@article {49827, title = {Dual Transcriptome Profiling of Leishmania-Infected Human Macrophages Reveals Distinct Reprogramming Signatures}, journal = {mBio}, volume = {7}, year = {2016}, month = {Jun-07-2016}, pages = {e00027-16}, doi = {10.1128/mBio.00027-16}, url = {http://mbio.asm.org/lookup/doi/10.1128/mBio.00027-16https://syndication.highwire.org/content/doi/10.1128/mBio.00027-16}, author = {Fernandes, Maria Cecilia and Dillon, Laura A. L. and Belew, Ashton Trey and Bravo, H{\'e}ctor Corrada and Mosser, David M. and El-Sayed, Najib M.} } @article {49668, title = {The fruRBA operon is necessary for Group A Streptococcal growth in fructose and for resistance to neutrophil killing during growth in whole human blood.}, journal = {Infect Immun}, year = {2016}, month = {2016 Jan 19}, abstract = {

Bacterial pathogens rely on the availability of nutrients for survival in the host environment. The phosphoenolpyruvate-phosphotransferase system (PTS) is a global regulatory network connecting sugar uptake with signal transduction. Since the fructose PTS has been shown to impact virulence in several Streptococci, including the human pathogen S. pyogenes (the group A Streptococcus, GAS), we characterized its role in carbon metabolism and pathogenesis in the M1T1 strain 5448. Growth in fructose as a sole carbon source resulted in 103 genes affected transcriptionally, where the fru locus (fruRBA) was the most induced. RT-PCR showed that fruRBA formed an operon, which was repressed by FruR in the absence of fructose, in addition to being under carbon catabolic repression. Growth assays and carbon utilization profiles revealed that although the entire fru operon was required for growth in fructose, FruA was the main transporter for fructose and was also involved in the utilization of three additional PTS sugars: cellobiose, mannitol, and N-acetyl-D-galactosamine. Inactivation of sloR, a fruA homolog that was also up regulated in presence of fructose, failed to reveal a role as a secondary fructose transporter. Whereas the ability of both ΔfruR and ΔfruB mutants to survive in the presence of whole human blood or neutrophils was impaired, the phenotype was not reproduced in murine whole blood, nor were those mutants attenuated in a mouse intraperitoneal infection. Since the ΔfruA mutant exhibited no phenotype in the human or mouse assays, we propose that FruR and FruB are important for GAS survival in a human-specific environment.

}, issn = {1098-5522}, doi = {10.1128/IAI.01296-15}, author = {Valdes, Kayla M and Sundar, Ganesh S and Vega, Luis A and Belew, Ashton T and Islam, Emrul and Binet, Rachel and El-Sayed, Najib M and Le Breton, Yoann and McIver, Kevin S} } @article {49731, title = {Functional Alignment of Metabolic Networks.}, journal = {J Comput Biol}, year = {2016}, month = {2016 Jan 13}, abstract = {

Network alignment has become a standard tool in comparative biology, allowing the inference of protein function, interaction, and orthology. However, current alignment techniques are based on topological properties of networks and do not take into account their functional implications. Here we propose, for the first time, an algorithm to align two metabolic networks by taking advantage of their coupled metabolic models. These models allow us to assess the functional implications of genes or reactions, captured by the metabolic fluxes that are altered following their deletion from the network. Such implications may spread far beyond the region of the network where the gene or reaction lies. We apply our algorithm to align metabolic networks from various organisms, ranging from bacteria to humans, showing that our alignment can reveal functional orthology relations that are missed by conventional topological alignments.

}, issn = {1557-8666}, doi = {10.1089/cmb.2015.0203}, author = {Mazza, Arnon and Wagner, Allon and Ruppin, Eytan and Sharan, Roded} } @article {49657, title = {Genome-scale study reveals reduced metabolic adaptability in patients with non-alcoholic fatty liver disease}, journal = {Nature Communications}, volume = {7}, year = {2016}, month = {Mar-02-2016}, pages = {8994}, doi = {10.1038/ncomms9994}, url = {http://www.nature.com/doifinder/10.1038/ncomms9994}, author = {{\"o}tyl{\"a}inen, Tuulia and Jerby, Livnat and {\"a}j{\"a}, Elina M. and Mattila, Ismo and {\"a}ntti, Sirkku and Auvinen, Petri and Gastaldelli, Amalia and {\"a}rvinen, Hannele and Ruppin, Eytan and {\v s}i{\v c}, Matej} } @article {49730, title = {Genome-scale study reveals reduced metabolic adaptability in patients with non-alcoholic fatty liver disease.}, journal = {Nat Commun}, volume = {7}, year = {2016}, month = {2016}, pages = {8994}, abstract = {

Non-alcoholic fatty liver disease (NAFLD) is a major risk factor leading to chronic liver disease and type 2 diabetes. Here we chart liver metabolic activity and functionality in NAFLD by integrating global transcriptomic data, from human liver biopsies, and metabolic flux data, measured across the human splanchnic vascular bed, within a genome-scale model of human metabolism. We show that an increased amount of liver fat induces mitochondrial metabolism, lipolysis, glyceroneogenesis and a switch from lactate to glycerol as substrate for gluconeogenesis, indicating an intricate balance of exacerbated opposite metabolic processes in glycemic regulation. These changes were associated with reduced metabolic adaptability on a network level in the sense that liver fat accumulation puts increasing demands on the liver to adaptively regulate metabolic responses to maintain basic liver functions. We propose that failure to meet excessive metabolic challenges coupled with reduced metabolic adaptability may lead to a vicious pathogenic cycle leading to the co-morbidities of NAFLD.

}, issn = {2041-1723}, doi = {10.1038/ncomms9994}, author = {Hy{\"o}tyl{\"a}inen, Tuulia and Jerby, Livnat and Pet{\"a}j{\"a}, Elina M and Mattila, Ismo and J{\"a}ntti, Sirkku and Auvinen, Petri and Gastaldelli, Amalia and Yki-J{\"a}rvinen, Hannele and Ruppin, Eytan and Ore{\v s}i{\v c}, Matej} } @article {49840, title = {Identification guide to the heterobranch sea slugs (Mollusca: Gastropoda) from Bocas del Toro, Panama}, journal = {Marine Biodiversity Records}, volume = {96737453830254034557880541418411912544728739317415779780725696418782226404216145163412560451520488424050829677}, year = {2016}, month = {Jan-12-2016}, doi = {10.1186/s41200-016-0048-z}, url = {http://mbr.biomedcentral.com/articles/10.1186/s41200-016-0048-zhttp://link.springer.com/content/pdf/10.1186/s41200-016-0048-z}, author = {Goodheart, Jessica and Ellingson, Ryan A. and Vital, Xochitl G. and {\~a}o Filho, Hilton C. and McCarthy, Jennifer B. and Medrano, Sabrina M. and Bhave, Vishal J. and {\'\i}a-M{\'e}ndez, Kimberly and {\'e}nez, Lina M. and {\'o}pez, Gina and Hoover, Craig A. and Awbrey, Jaymes D. and De Jesus, Jessika M. and Gowacki, William and Krug, Patrick J. and {\'e}s, {\'A}ngel} } @article {49795, title = {The fruRBA Operon Is Necessary for Group A Streptococcal Growth in Fructose and for Resistance to Neutrophil Killing during Growth in Whole Human Blood}, journal = {Infection and Immunity}, volume = {84}, year = {2016}, month = {Dec-04-2017}, pages = {1016 - 1031}, issn = {0019-9567}, doi = {10.1128/IAI.01296-15}, url = {http://iai.asm.org/lookup/doi/10.1128/IAI.01296-15}, author = {Valdes, Kayla M. and Sundar, Ganesh S. and Vega, Luis A. and Belew, Ashton T. and Islam, Emrul and Binet, Rachel and El-Sayed, Najib M. and Le Breton, Yoann and McIver, Kevin S.}, editor = {Camilli, A.} } @article {49821, title = {Longitudinal analysis of the lung microbiota of cynomolgous macaques during long-term SHIV infection}, journal = {Microbiome}, volume = {4320384718719152130282021211818418719223326578105723}, year = {2016}, month = {Jan-12-2016}, doi = {10.1186/s40168-016-0183-0}, url = {http://microbiomejournal.biomedcentral.com/articles/10.1186/s40168-016-0183-0http://link.springer.com/content/pdf/10.1186/s40168-016-0183-0}, author = {Morris, Alison and Paulson, Joseph N. and Talukder, Hisham and Tipton, Laura and Kling, Heather and Cui, Lijia and Fitch, Adam and Pop, Mihai and Norris, Karen A. and Ghedin, Elodie} } @article {49793, title = {Maligner: a fast ordered restriction map aligner.}, journal = {Bioinformatics}, volume = {32}, year = {2016}, month = {2016 Apr 1}, pages = {1016-22}, abstract = {

MOTIVATION: The Optical Mapping System discovers structural variants and potentiates sequence assembly of genomes via scaffolding and comparisons that globally validate or correct sequence assemblies. Despite its utility, there are few publicly available tools for aligning optical mapping datasets.

RESULTS: Here we present software, named {\textquoteright}Maligner{\textquoteright}, for the alignment of both single molecule restriction maps (Rmaps) and in silico restriction maps of sequence contigs to a reference. Maligner provides two modes of alignment: an efficient, sensitive dynamic programming implementation that scales to large eukaryotic genomes, and a faster indexed based implementation for finding alignments with unmatched sites in the reference but not the query. We compare our software to other publicly available tools on Rmap datasets and show that Maligner finds more correct alignments in comparable runtime. Lastly, we introduce the M-Score statistic for normalizing alignment scores across restriction maps and demonstrate its utility for selecting high quality alignments.

AVAILABILITY AND IMPLEMENTATION: The Maligner software is written in C ++ and is available at https://github.com/LeeMendelowitz/maligner under the GNU General Public License.

CONTACT: mpop@umiacs.umd.edu.

}, issn = {1367-4811}, doi = {10.1093/bioinformatics/btv711}, author = {Mendelowitz, Lee M and Schwartz, David C and Pop, Mihai} } @article {49800, title = {Mash: fast genome and metagenome distance estimation using MinHash}, journal = {Genome Biology}, year = {2016}, month = {Jan-12-2016}, doi = {10.1186/s13059-016-0997-x}, url = {http://genomebiology.biomedcentral.com/articles/10.1186/s13059-016-0997-xhttp://link.springer.com/content/pdf/10.1186/s13059-016-0997-x}, author = {Ondov, Brian D. and Todd Treangen and Melsted, {\'a}ll and Mallonee, Adam B. and Bergman, Nicholas H. and Koren, Sergey and Phillippy, Adam M.} } @article {49826, title = {methylFlow: cell-specific methylation pattern reconstruction from high-throughput bisulfite-converted DNA sequencing}, journal = {Bioinformatics}, volume = {32}, year = {2016}, month = {Jan-06-2016}, pages = {1618 - 1624}, issn = {1367-4803}, doi = {10.1093/bioinformatics/btw287}, url = {https://academic.oup.com/bioinformatics/article-lookup/doi/10.1093/bioinformatics/btw287https://academic.oup.com/bioinformatics/article/32/11/1618/1743421/methylFlow-cellspecific-methylation-pattern}, author = {Dorri, Faezeh and Mendelowitz, Lee and Corrada Bravo, {\'e}ctor} } @article {49812, title = {The Role of Temporal Trends in Growing Networks.}, journal = {PLoS One}, volume = {11}, year = {2016}, month = {2016}, pages = {e0156505}, abstract = {

The rich get richer principle, manifested by the Preferential attachment (PA) mechanism, is widely considered one of the major factors in the growth of real-world networks. PA stipulates that popular nodes are bound to be more attractive than less popular nodes; for example, highly cited papers are more likely to garner further citations. However, it overlooks the transient nature of popularity, which is often governed by trends. Here, we show that in a wide range of real-world networks the recent popularity of a node, i.e., the extent by which it accumulated links recently, significantly influences its attractiveness and ability to accumulate further links. We proceed to model this observation with a natural extension to PA, named Trending Preferential Attachment (TPA), in which edges become less influential as they age. TPA quantitatively parametrizes a fundamental network property, namely the network{\textquoteright}s tendency to trends. Through TPA, we find that real-world networks tend to be moderately to highly trendy. Networks are characterized by different susceptibilities to trends, which determine their structure to a large extent. Trendy networks display complex structural traits, such as modular community structure and degree-assortativity, occurring regularly in real-world networks. In summary, this work addresses an inherent trait of complex networks, which greatly affects their growth and structure, and develops a unified model to address its interaction with preferential attachment.

}, issn = {1932-6203}, doi = {10.1371/journal.pone.0156505}, author = {Mokryn, Osnat and Wagner, Allon and Blattner, Marcel and Ruppin, Eytan and Shavitt, Yuval} } @article {49817, title = {Therapeutic relevance of the protein phosphatase 2A in cancer}, journal = {Oncotarget.com}, year = {2016}, month = {Jul-09-2017}, doi = {10.18632/oncotarget.11399}, url = {https://www.oncotarget.com/article/11399}, author = {Cunningham, Chelsea E. and Li, Shuangshuang and Vizeacoumar, Frederick S. and Bhanumathy, Kalpana Kalyanasundaram and Lee, Joo Sang and Parameswaran, Sreejit and Furber, Levi and Abuhussein, Omar and Paul, James M. and McDonald, Megan and Templeton, Shaina D. and Shukla, Hersh and El Zawily, Amr M. and Boyd, Frederick and Alli, Nezeka and Mousseau, Darrell D. and Geyer, Ron and Bonham, Keith and Anderson, Deborah H. and Yan, Jiong and Yu-Lee, Li-Yuan and Weaver, Beth A. and Uppalapati, Maruti and Ruppin, Eytan and Sablina, Anna and Freywald, Andrew and Vizeacoumar, Franco J.} } @article {49623, title = {Bayesian integration of genetics and epigenetics detects causal regulatory SNPs underlying expression variability}, journal = {Nature Communications}, volume = {6}, year = {2015}, month = {Dec-10-2015}, pages = {8555}, doi = {10.1038/ncomms9555}, url = {http://www.nature.com/doifinder/10.1038/ncomms9555}, author = {Das, Avinash and Morley, Michael and Moravec, Christine S. and Tang, W. H. W. and Hakonarson, Hakon and Ashley, Euan A. and Brandimarto, Jeffrey and Hu, Ray and Li, Mingyao and Li, Hongzhe and Liu, Yichuan and Qu, Liming and Sanchez, Pablo and Margulies, Kenneth B. and Cappola, Thomas P. and Jensen, Shane and Hannenhalli, Sridhar} } @article {49537, title = {Essential Genes in the Core Genome of the Human Pathogen Streptococcus pyogenes.}, journal = {Sci Rep}, volume = {5}, year = {2015}, month = {2015}, pages = {9838}, abstract = {

Streptococcus pyogenes (Group A Streptococcus, GAS) remains a major public health burden worldwide, infecting over 750 million people leading to over 500,000 deaths annually. GAS pathogenesis is complex, involving genetically distinct GAS strains and multiple infection sites. To overcome fastidious genetic manipulations and accelerate pathogenesis investigations in GAS, we developed a mariner-based system (Krmit) for en masse monitoring of complex mutant pools by transposon sequencing (Tn-seq). Highly saturated transposant libraries (Krmit insertions in ca. every 25 nucleotides) were generated in two distinct GAS clinical isolates, a serotype M1T1 invasive strain 5448 and a nephritogenic serotype M49 strain NZ131, and analyzed using a Bayesian statistical model to predict GAS essential genes, identifying sets of 227 and 241 of those genes in 5448 and NZ131, respectively. A large proportion of GAS essential genes corresponded to key cellular processes and metabolic pathways, and 177 were found conserved within the GAS core genome established from 20 available GAS genomes. Selected essential genes were validated using conditional-expression mutants. Finally, comparison to previous essentiality analyses in S. sanguinis and S. pneumoniae revealed significant overlaps, providing valuable insights for the development of new antimicrobials to treat infections by GAS and other pathogenic streptococci.

}, issn = {2045-2322}, doi = {10.1038/srep09838}, author = {Le Breton, Yoann and Belew, Ashton T and Valdes, Kayla M and Islam, Emrul and Curry, Patrick and Tettelin, Herv{\'e} and Shirtliff, Mark E and El-Sayed, Najib M and McIver, Kevin S} } @article {49570, title = {Evaluation of BLAST-based edge-weighting metrics used for homology inference with the Markov Clustering algorithm.}, volume = {16}, year = {2015}, month = {2015}, pages = {218}, abstract = {

BACKGROUND: Clustering protein sequences according to inferred homology is a fundamental step in the analysis of many large data sets. Since the publication of the Markov Clustering (MCL) algorithm in 2002, it has been the centerpiece of several popular applications. Each of these approaches generates an undirected graph that represents sequences as nodes connected to each other by edges weighted with a BLAST-based metric. MCL is then used to infer clusters of homologous proteins by analyzing these graphs. The various approaches differ only by how they weight the edges, yet there has been very little direct examination of the relative performance of alternative edge-weighting metrics. This study compares the performance of four BLAST-based edge-weighting metrics: the bit score, bit score ratio (BSR), bit score over anchored length (BAL), and negative common log of the expectation value (NLE). Performance is tested using the Extended CEGMA KOGs (ECK) database, which we introduce here.

RESULTS: All metrics performed similarly when analyzing full-length sequences, but dramatic differences emerged as progressively larger fractions of the test sequences were split into fragments. The BSR and BAL successfully rescued subsets of clusters by strengthening certain types of alignments between fragmented sequences, but also shifted the largest correct scores down near the range of scores generated from spurious alignments. This penalty outweighed the benefits in most test cases, and was greatly exacerbated by increasing the MCL inflation parameter, making these metrics less robust than the bit score or the more popular NLE. Notably, the bit score performed as well or better than the other three metrics in all scenarios.

CONCLUSIONS: The results provide a strong case for use of the bit score, which appears to offer equivalent or superior performance to the more popular NLE. The insight that MCL-based clustering methods can be improved using a more tractable edge-weighting metric will greatly simplify future implementations. We demonstrate this with our own minimalist Python implementation: Porthos, which uses only standard libraries and can process a graph with 25 m + edges connecting the 60 k + KOG sequences in half a minute using less than half a gigabyte of memory.

}, issn = {1471-2105}, doi = {10.1186/s12859-015-0625-x}, author = {Gibbons, Theodore R and Mount, Stephen M and Cooper, Endymion D and Delwiche, Charles F} } @article {49579, title = {Fumarate induces redox-dependent senescence by modifying glutathione metabolism.}, volume = {6}, year = {2015}, month = {2015}, pages = {6001}, abstract = {

Mutations in the tricarboxylic acid (TCA) cycle enzyme fumarate hydratase (FH) are associated with a highly malignant form of renal cancer. We combined analytical chemistry and metabolic computational modelling to investigate the metabolic implications of FH loss in immortalized and primary mouse kidney cells. Here, we show that the accumulation of fumarate caused by the inactivation of FH leads to oxidative stress that is mediated by the formation of succinicGSH, a covalent adduct between fumarate and glutathione. Chronic succination of GSH, caused by the loss of FH, or by exogenous fumarate, leads to persistent oxidative stress and cellular senescence in vitro and in vivo. Importantly, the ablation of p21, a key mediator of senescence, in Fh1-deficient mice resulted in the transformation of benign renal cysts into a hyperplastic lesion, suggesting that fumarate-induced senescence needs to be bypassed for the initiation of renal cancers.

}, issn = {2041-1723}, doi = {10.1038/ncomms7001}, author = {Zheng, Liang and Cardaci, Simone and Jerby, Livnat and MacKenzie, Elaine D and Sciacovelli, Marco and Johnson, T Isaac and Gaude, Edoardo and King, Ayala and Leach, Joshua D G and Edrada-Ebel, RuAngelie and Hedley, Ann and Morrice, Nicholas A and Kalna, Gabriela and Blyth, Karen and Ruppin, Eytan and Frezza, Christian and Gottlieb, Eyal} } @article {49538, title = {The generation of macrophages with anti-inflammatory activity in the absence of STAT6 signaling.}, volume = {98}, year = {2015}, month = {2015 Sep}, pages = {395-407}, abstract = {

Macrophages readily change their phenotype in response to exogenous stimuli. In this work, macrophages were stimulated under a variety of experimental conditions, and phenotypic alterations were correlated with changes in gene expression. We identified 3 transcriptionally related populations of macrophages with immunoregulatory activity. They were generated by stimulating cells with TLR ligands in the presence of 3 different "reprogramming" signals: high-density ICs, PGE2, or Ado. All 3 of these cell populations produced high levels of transcripts for IL-10 and growth and angiogenic factors. They also secreted reduced levels of inflammatory cytokines IL-1β, IL-6, and IL-12. All 3 macrophage phenotypes could partially rescue mice from lethal endotoxemia, and therefore, we consider each to have anti-inflammatory activity. This ability to regulate innate-immune responses occurred equally well in macrophages from STAT6-deficient mice. The lack of STAT6 did not affect the ability of macrophages to change cytokine production reciprocally or to rescue mice from lethal endotoxemia. Furthermore, treatment of macrophages with IL-4 failed to induce similar phenotypic or transcriptional alterations. This work demonstrates that there are multiple ways to generate macrophages with immunoregulatory activity. These anti-inflammatory macrophages are transcriptionally and functionally related to each other and are quite distinct from macrophages treated with IL-4.

}, issn = {1938-3673}, doi = {10.1189/jlb.2A1114-560R}, author = {Fleming, Bryan D and Chandrasekaran, Prabha and Dillon, Laura A L and Dalby, Elizabeth and Suresh, Rahul and Sarkar, Arup and El-Sayed, Najib M and Mosser, David M} } @article {49734, title = {Genomic variation. Impact of regulatory variation from RNA to protein.}, journal = {Science}, volume = {347}, year = {2015}, month = {2015 Feb 6}, pages = {664-7}, abstract = {

The phenotypic consequences of expression quantitative trait loci (eQTLs) are presumably due to their effects on protein expression levels. Yet the impact of genetic variation, including eQTLs, on protein levels remains poorly understood. To address this, we mapped genetic variants that are associated with eQTLs, ribosome occupancy (rQTLs), or protein abundance (pQTLs). We found that most QTLs are associated with transcript expression levels, with consequent effects on ribosome and protein levels. However, eQTLs tend to have significantly reduced effect sizes on protein levels, which suggests that their potential impact on downstream phenotypes is often attenuated or buffered. Additionally, we identified a class of cis QTLs that affect protein abundance with little or no effect on messenger RNA or ribosome levels, which suggests that they may arise from differences in posttranslational regulation.

}, keywords = {3{\textquoteright} Flanking Region, 5{\textquoteright} Flanking Region, Cell Line, Exons, Gene Expression Regulation, Genetic Variation, HUMANS, PHENOTYPE, Protein Biosynthesis, Quantitative Trait Loci, Ribosomes, RNA, Messenger, Transcription, Genetic}, issn = {1095-9203}, doi = {10.1126/science.1260793}, author = {Battle, Alexis and Khan, Zia and Wang, Sidney H and Mitrano, Amy and Ford, Michael J and Pritchard, Jonathan K and Gilad, Yoav} } @article {49659, title = {Glutamine synthetase activity fuels nucleotide biosynthesis and supports growth of glutamine-restricted glioblastoma}, journal = {Nature Cell Biology}, volume = {17}, year = {2015}, month = {Nov-11-2016}, pages = {1556 - 1568}, issn = {1465-7392}, doi = {10.1038/ncb3272}, url = {http://www.nature.com/doifinder/10.1038/ncb3272}, author = {Tardito, Saverio and Oudin, {\"\i}s and Ahmed, Shafiq U. and Fack, Fred and Keunen, Olivier and Zheng, Liang and Miletic, Hrvoje and Sakariassen, {\O}ystein and Weinstock, Adam and Wagner, Allon and Lindsay, Susan L. and Hock, Andreas K. and Barnett, Susan C. and Ruppin, Eytan and {\o}rkve, Svein Harald and Lund-Johansen, Morten and Chalmers, Anthony J. and Bjerkvig, Rolf and Niclou, Simone P. and Gottlieb, Eyal} } @article {49540, title = {Impact of regulatory variation from RNA to protein}, volume = {347}, year = {2015}, month = {Jun-02-2015}, pages = {664 - 667}, issn = {0036-8075}, doi = {10.1126/science.1260793}, url = {http://www.sciencemag.org/cgi/doi/10.1126/science.1260793}, author = {Battle, A. and Khan, Z. and Wang, S. H. and Mitrano, A. and Ford, M. J. and Pritchard, J. K. and Gilad, Y.} } @article {49512, title = {Independent Emergence of Artemisinin Resistance Mutations Among Plasmodium falciparum in Southeast Asia}, journal = {Journal of Infectious Diseases}, volume = {211}, year = {2015}, month = {03/2015}, pages = {670 - 679}, issn = {1537-6613}, doi = {10.1093/infdis/jiu491}, author = {Takala-Harrison, S. and Jacob, C. G. and Arze, C. and Michael P. Cummings and Silva, J. C. and Dondorp, A. M. and Fukuda, M. M. and Hien, T. T. and Mayxay, M. and Noedl, H. and Nosten, F. and Kyaw, M. P. and Nhien, N. T. T. and Imwong, M. and Bethell, D. and Se, Y. and Lon, C. and Tyner, S. D. and Saunders, D. L. and Ariey, F. and Mercereau-Puijalon, O. and Menard, D. and Newton, P. N. and Khanthavong, M. and Hongvanthong, B. and Starzengruber, P. and Fuehrer, H.-P. and Swoboda, P. and Khan, W. A. and Phyo, A. P. and Nyunt, M. M. and Nyunt, M. H. and Brown, T. S. and Adams, M. and Pepin, C. S. and Bailey, J. and Tan, J. C. and Ferdig, M. T. and Clark, T. G. and Miotto, O. and MacInnis, B. and Kwiatkowski, D. P. and White, N. J. and Ringwald, P. and Plowe, CV} } @article {49571, title = {Insights from GWAS: emerging landscape of mechanisms underlying complex trait disease.}, volume = {16 Suppl 8}, year = {2015}, month = {2015}, pages = {S4}, abstract = {

BACKGROUND: There are now over 2000 loci in the human genome where genome wide association studies (GWAS) have found one or more SNPs to be associated with altered risk of a complex trait disease. At each of these loci, there must be some molecular level mechanism relevant to the disease. What are these mechanisms and how do they contribute to disease?

RESULTS: Here we consider the roles of three primary mechanism classes: changes that directly alter protein function (missense SNPs), changes that alter transcript abundance as a consequence of variants close-by in sequence, and changes that affect splicing. Missense SNPs are divided into those predicted to have a high impact on in vivo protein function, and those with a low impact. Splicing is divided into SNPs with a direct impact on splice sites, and those with a predicted effect on auxiliary splicing signals. The analysis was based on associations found for seven complex trait diseases in the classic Wellcome Trust Case Control Consortium (WTCCC1) GWA study and subsequent studies and meta-analyses, collected from the GWAS catalog. Linkage disequilibrium information was used to identify possible candidate SNPs for involvement in disease mechanism in each of the 356 loci associated with these seven diseases. With the parameters used, we find that 76\% of loci have at least of these mechanisms. Overall, except for the low incidence of direct impact on splice sites, the mechanisms are found at similar frequencies, with changes in transcript abundance the most common. But the distribution of mechanisms over diseases varies markedly, as does the fraction of loci with assigned mechanisms. Many of the implicated proteins have previously been suggested as relevant, but the specific mechanism assignments are new. In addition, a number of new disease relevant proteins are proposed.

CONCLUSIONS: The high fraction of GWAS loci with proposed mechanisms suggests that these classes of mechanism play a major role. Other mechanism types, such as variants affecting expression of genes remote in the DNA sequence, will contribute in other loci. Each of the identified putative mechanisms provides a hypothesis for further investigation.

}, issn = {1471-2164}, doi = {10.1186/1471-2164-16-S8-S4}, author = {Pal, Lipika R and Yu, Chen-Hsin and Mount, Stephen M and Moult, John} } @article {49758, title = {Maligner: a fast ordered restriction map aligner}, journal = {Bioinformatics}, year = {2015}, month = {Mar-12-2015}, pages = {btv711}, issn = {1367-4803}, doi = {10.1093/bioinformatics/btv711}, url = {http://bioinformatics.oxfordjournals.org/lookup/doi/10.1093/bioinformatics/btv711}, author = {Mendelowitz, Lee M. and Schwartz, David C. and Pop, Mihai} } @article {49612, title = {Microbiota that affect risk for shigellosis in children in low-income countries}, journal = {Emerg Infect DisEmerg Infect Dis}, volume = {21}, number = {2}, year = {2015}, note = {Lindsay, Brianna
Oundo, Joe
Hossain, M Anowar
Antonio, Martin
Tamboura, Boubou
Walker, Alan W
Paulson, Joseph N
Parkhill, Julian
Omore, Richard
Faruque, Abu S G
Das, Suman Kumar
Ikumapayi, Usman N
Adeyemi, Mitchell
Sanogo, Doh
Saha, Debasish
Sow, Samba
Farag, Tamer H
Nasrin, Dilruba
Li, Shan
Panchalingam, Sandra
Levine, Myron M
Kotloff, Karen
Magder, Laurence S
Hungerford, Laura
Sommerfelt, Halvor
Pop, Mihai
Nataro, James P
Stine, O Colin
U19 090873/PHS HHS/United States
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov{\textquoteright}t
Research Support, U.S. Gov{\textquoteright}t, Non-P.H.S.
United States
Emerg Infect Dis. 2015 Feb;21(2):242-50. doi: 10.3201/eid2101.140795.}, month = {Feb}, pages = {242-50}, edition = {2015/01/28}, abstract = {Pathogens in the gastrointestinal tract exist within a vast population of microbes. We examined associations between pathogens and composition of gut microbiota as they relate to Shigella spp./enteroinvasive Escherichia coli infection. We analyzed 3,035 stool specimens (1,735 nondiarrheal and 1,300 moderate-to-severe diarrheal) from the Global Enteric Multicenter Study for 9 enteropathogens. Diarrheal specimens had a higher number of enteropathogens (diarrheal mean 1.4, nondiarrheal mean 0.95; p<0.0001). Rotavirus showed a negative association with Shigella spp. in cases of diarrhea (odds ratio 0.31, 95\% CI 0.17-0.55) and had a large combined effect on moderate-to-severe diarrhea (odds ratio 29, 95\% CI 3.8-220). In 4 Lactobacillus taxa identified by 16S rRNA gene sequencing, the association between pathogen and disease was decreased, which is consistent with the possibility that Lactobacillus spp. are protective against Shigella spp.-induced diarrhea. Bacterial diversity of gut microbiota was associated with diarrhea status, not high levels of the Shigella spp. ipaH gene.}, isbn = {1080-6059 (Electronic)
1080-6040 (Linking)}, author = {Lindsay, B. and Oundo, J. and Hossain, M. A. and Antonio, M. and Tamboura, B. and Walker, A. W. and Paulson, J. N. and Parkhill, J. and Omore, R. and Faruque, A. S. and Das, S. K. and Ikumapayi, U. N. and Adeyemi, M. and Sanogo, D. and Saha, D. and Sow, S. and Farag, T. H. and Nasrin, D. and Li, S. and Panchalingam, S. and Levine, M. M. and Kotloff, K. and Magder, L. S. and Hungerford, L. and Sommerfelt, H. and Pop, M. and Nataro, J. P. and Stine, O. C.} } @article {49511, title = {A molecular phylogeny for the oldest (nonditrysian) lineages of extant Lepidoptera, with implications for classification, comparative morphology and life-history evolution}, journal = {Systematic Entomology}, year = {2015}, month = {05/2015}, pages = {n/a - n/a}, doi = {10.1111/syen.12129}, author = {Regier, Jerome C and Mitter, Charles and KRISTENSEN, NIELS P. and Davis, Donald R. and VAN NIEUKERKEN, ERIK J. and ROTA, JADRANKA and Simonsen, Thomas J. and Mitter, Kim T. and Kawahara, Akito Y. and Yen, Shen-Horn and Michael P. Cummings and Zwick, Andreas} } @article {49606, title = {Orchestrating high-throughput genomic analysis with Bioconductor.}, volume = {12}, year = {2015}, month = {2015 Feb}, pages = {115-21}, abstract = {

Bioconductor is an open-source, open-development software project for the analysis and comprehension of high-throughput data in genomics and molecular biology. The project aims to enable interdisciplinary research, collaboration and rapid development of scientific software. Based on the statistical programming language R, Bioconductor comprises 934 interoperable packages contributed by a large, diverse community of scientists. Packages cover a range of bioinformatic and statistical applications. They undergo formal initial review and continuous automated testing. We present an overview for prospective users and contributors.

}, keywords = {Computational Biology, Gene Expression Profiling, Genomics, High-Throughput Screening Assays, Programming Languages, software, User-Computer Interface}, issn = {1548-7105}, doi = {10.1038/nmeth.3252}, author = {Huber, Wolfgang and Carey, Vincent J and Gentleman, Robert and Anders, Simon and Carlson, Marc and Carvalho, Benilton S and Bravo, H{\'e}ctor Corrada and Davis, Sean and Gatto, Laurent and Girke, Thomas and Gottardo, Raphael and Hahne, Florian and Hansen, Kasper D and Irizarry, Rafael A and Lawrence, Michael and Love, Michael I and MacDonald, James and Obenchain, Valerie and Ole{\'s}, Andrzej K and Pag{\`e}s, Herv{\'e} and Reyes, Alejandro and Shannon, Paul and Smyth, Gordon K and Tenenbaum, Dan and Waldron, Levi and Morgan, Martin} } @article {49513, title = {Plasmodium falciparum field isolates from areas of repeated emergence of drug resistant malaria show no evidence of hypermutator phenotype}, journal = {Infection, Genetics and Evolution}, volume = {30}, year = {2015}, month = {03/2015}, pages = {318 - 322}, issn = {15671348}, doi = {10.1016/j.meegid.2014.12.010}, author = {Brown, Tyler S. and Jacob, Christopher G and Silva, Joana C and Takala-Harrison, Shannon and Djimd{\'e}, Abdoulaye and Dondorp, Arjen M and Fukuda, Mark and Noedl, Harald and Nyunt, Myaing Myaing and Kyaw, Myat Phone and Mayxay, Mayfong and Hien, Tran Tinh and Plowe, Christopher V and Michael P. Cummings} } @article {49577, title = {Proteomics-based metabolic modeling reveals that fatty acid oxidation (FAO) controls endothelial cell (EC) permeability.}, volume = {14}, year = {2015}, month = {2015 Mar}, pages = {621-34}, abstract = {

Endothelial cells (ECs) play a key role to maintain the functionality of blood vessels. Altered EC permeability causes severe impairment in vessel stability and is a hallmark of pathologies such as cancer and thrombosis. Integrating label-free quantitative proteomics data into genome-wide metabolic modeling, we built up a model that predicts the metabolic fluxes in ECs when cultured on a tridimensional matrix and organize into a vascular-like network. We discovered how fatty acid oxidation increases when ECs are assembled into a fully formed network that can be disrupted by inhibiting CPT1A, the fatty acid oxidation rate-limiting enzyme. Acute CPT1A inhibition reduces cellular ATP levels and oxygen consumption, which are restored by replenishing the tricarboxylic acid cycle. Remarkably, global phosphoproteomic changes measured upon acute CPT1A inhibition pinpointed altered calcium signaling. Indeed, CPT1A inhibition increases intracellular calcium oscillations. Finally, inhibiting CPT1A induces hyperpermeability in vitro and leakage of blood vessel in vivo, which were restored blocking calcium influx or replenishing the tricarboxylic acid cycle. Fatty acid oxidation emerges as central regulator of endothelial functions and blood vessel stability and druggable pathway to control pathological vascular permeability.

}, issn = {1535-9484}, doi = {10.1074/mcp.M114.045575}, author = {Patella, Francesca and Schug, Zachary T and Persi, Erez and Neilson, Lisa J and Erami, Zahra and Avanzato, Daniele and Maione, Federica and Hernandez-Fernaud, Juan R and Mackay, Gillian and Zheng, Liang and Reid, Steven and Frezza, Christian and Giraudo, Enrico and Fiorio Pla, Alessandra and Anderson, Kurt and Ruppin, Eytan and Gottlieb, Eyal and Zanivan, Sara} } @article {49673, title = {Recognizing the 35th anniversary of the proposal that snRNPs are involved in splicing.}, journal = {Mol Biol Cell}, volume = {26}, year = {2015}, month = {2015 Oct 15}, pages = {3557-60}, abstract = {

Thirty-five years ago, as young graduate students, we had the pleasure and privilege of being in Joan Steitz{\textquoteright}s laboratory at a pivotal point in the history of RNA molecular biology. Introns had recently been discovered in the laboratories of Philip Sharp and Richard Roberts, but the machinery for removing them from mRNA precursors was entirely unknown. This Retrospective describes our hypothesis that recently discovered snRNPs functioned in pre-mRNA splicing. The proposal was proven correct, as has Joan{\textquoteright}s intuition that small RNAs provide specificity to RNA processing reactions through base pairing in diverse settings. However, research over the intervening years has revealed that both splice site selection and splicing itself are much more complex and dynamic than we imagined.

}, issn = {1939-4586}, doi = {10.1091/mbc.E14-10-1486}, author = {Mount, Stephen M and Wolin, Sandra L} } @article {49591, title = {RNA-Seq identifies novel myocardial gene expression signatures of heart failure.}, volume = {105}, year = {2015}, month = {2015 Feb}, pages = {83-9}, abstract = {

Heart failure is a complex clinical syndrome and has become the most common reason for adult hospitalization in developed countries. Two subtypes of heart failure, ischemic heart disease (ISCH) and dilated cardiomyopathy (DCM), have been studied using microarray platforms. However, microarray has limited resolution. Here we applied RNA sequencing (RNA-Seq) to identify gene signatures for heart failure from six individuals, including three controls, one ISCH and two DCM patients. Using genes identified from this small RNA-Seq dataset, we were able to accurately classify heart failure status in a much larger set of 313 individuals. The identified genes significantly overlapped with genes identified via genome-wide association studies for cardiometabolic traits and the promoters of those genes were enriched for binding sites for transcriptions factors. Our results indicate that it is possible to use RNA-Seq to classify disease status for complex diseases such as heart failure using an extremely small training dataset.

}, issn = {1089-8646}, doi = {10.1016/j.ygeno.2014.12.002}, author = {Liu, Yichuan and Morley, Michael and Brandimarto, Jeffrey and Hannenhalli, Sridhar and Hu, Yu and Ashley, Euan A and Tang, W H Wilson and Moravec, Christine S and Margulies, Kenneth B and Cappola, Thomas P and Li, Mingyao} } @article {49796, title = {Simultaneous transcriptional profiling of Leishmania major and its murine macrophage host cell reveals insights into host-pathogen interactions.}, journal = {BMC Genomics}, volume = {16}, year = {2015}, month = {2015}, pages = {1108}, abstract = {

BACKGROUND: Parasites of the genus Leishmania are the causative agents of leishmaniasis, a group of diseases that range in manifestations from skin lesions to fatal visceral disease. The life cycle of Leishmania parasites is split between its insect vector and its mammalian host, where it resides primarily inside of macrophages. Once intracellular, Leishmania parasites must evade or deactivate the host{\textquoteright}s innate and adaptive immune responses in order to survive and replicate.

RESULTS: We performed transcriptome profiling using RNA-seq to simultaneously identify global changes in murine macrophage and L. major gene expression as the parasite entered and persisted within murine macrophages during the first 72 h of an infection. Differential gene expression, pathway, and gene ontology analyses enabled us to identify modulations in host and parasite responses during an infection. The most substantial and dynamic gene expression responses by both macrophage and parasite were observed during early infection. Murine genes related to both pro- and anti-inflammatory immune responses and glycolysis were substantially upregulated and genes related to lipid metabolism, biogenesis, and Fc gamma receptor-mediated phagocytosis were downregulated. Upregulated parasite genes included those aimed at mitigating the effects of an oxidative response by the host immune system while downregulated genes were related to translation, cell signaling, fatty acid biosynthesis, and flagellum structure.

CONCLUSIONS: The gene expression patterns identified in this work yield signatures that characterize multiple developmental stages of L. major parasites and the coordinated response of Leishmania-infected macrophages in the real-time setting of a dual biological system. This comprehensive dataset offers a clearer and more sensitive picture of the interplay between host and parasite during intracellular infection, providing additional insights into how pathogens are able to evade host defenses and modulate the biological functions of the cell in order to survive in the mammalian environment.

}, issn = {1471-2164}, doi = {10.1186/s12864-015-2237-2}, author = {Dillon, Laura A L and Suresh, Rahul and Okrah, Kwame and Corrada Bravo, Hector and Mosser, David M and El-Sayed, Najib M} } @article {49598, title = {Synthetic dosage lethality in the human metabolic network is highly predictive of tumor growth and cancer patient survival.}, journal = {Proc Natl Acad Sci U S A}, year = {2015}, month = {2015 Sep 14}, abstract = {

Synthetic dosage lethality (SDL) denotes a genetic interaction between two genes whereby the underexpression of gene A combined with the overexpression of gene B is lethal. SDLs offer a promising way to kill cancer cells by inhibiting the activity of SDL partners of activated oncogenes in tumors, which are often difficult to target directly. As experimental genome-wide SDL screens are still scarce, here we introduce a network-level computational modeling framework that quantitatively predicts human SDLs in metabolism. For each enzyme pair (A, B) we systematically knock out the flux through A combined with a stepwise flux increase through B and search for pairs that reduce cellular growth more than when either enzyme is perturbed individually. The predictive signal of the emerging network of 12,000 SDLs is demonstrated in five different ways. (i) It can be successfully used to predict gene essentiality in shRNA cancer cell line screens. Moving to clinical tumors, we show that (ii) SDLs are significantly underrepresented in tumors. Furthermore, breast cancer tumors with SDLs active (iii) have smaller sizes and (iv) result in increased patient survival, indicating that activation of SDLs increases cancer vulnerability. Finally, (v) patient survival improves when multiple SDLs are present, pointing to a cumulative effect. This study lays the basis for quantitative identification of cancer SDLs in a model-based mechanistic manner. The approach presented can be used to identify SDLs in species and cell types in which "omics" data necessary for data-driven identification are missing.

}, issn = {1091-6490}, doi = {10.1073/pnas.1508573112}, author = {Megchelenbrink, Wout and Katzir, Rotem and Lu, Xiaowen and Ruppin, Eytan and Notebaart, Richard A} } @article {49539, title = {Transcriptomic profiling of gene expression and RNA processing during Leishmania major differentiation.}, volume = {43}, year = {2015}, month = {2015 Aug 18}, pages = {6799-813}, abstract = {

Protozoan parasites of the genus Leishmania are the etiological agents of leishmaniasis, a group of diseases with a worldwide incidence of 0.9-1.6 million cases per year. We used RNA-seq to conduct a high-resolution transcriptomic analysis of the global changes in gene expression and RNA processing events that occur as L. major transforms from non-infective procyclic promastigotes to infective metacyclic promastigotes. Careful statistical analysis across multiple biological replicates and the removal of batch effects provided a high quality framework for comprehensively analyzing differential gene expression and transcriptome remodeling in this pathogen as it acquires its infectivity. We also identified precise 5{\textquoteright} and 3{\textquoteright} UTR boundaries for a majority of Leishmania genes and detected widespread alternative trans-splicing and polyadenylation. An investigation of possible correlations between stage-specific preferential trans-splicing or polyadenylation sites and differentially expressed genes revealed a lack of systematic association, establishing that differences in expression levels cannot be attributed to stage-regulated alternative RNA processing. Our findings build on and improve existing expression datasets and provide a substantially more detailed view of L. major biology that will inform the field and potentially provide a stronger basis for drug discovery and vaccine development efforts.

}, issn = {1362-4962}, doi = {10.1093/nar/gkv656}, author = {Dillon, Laura A L and Okrah, Kwame and Hughitt, V Keith and Suresh, Rahul and Li, Yuan and Fernandes, Maria Cecilia and Belew, A Trey and Corrada Bravo, Hector and Mosser, David M and El-Sayed, Najib M} } @article {49863, title = {Complete genome sequence of the quality control strain Staphylococcus aureus subsp. aureus ATCC 25923}, journal = {Genome announcements}, volume = {2}, year = {2014}, pages = {e01110{\textendash}14}, author = {Treangen, Todd J and Maybank, Rosslyn A and Enke, Sana and Friss, Mary Beth and Diviak, Lynn F and Karaolis, David KR and Koren, Sergey and Ondov, Brian and Phillippy, Adam M and Bergman, Nicholas H} } @article {49613, title = {Computational methods for optical mapping}, journal = {GigaScienceGigaScience}, volume = {3}, number = {1}, year = {2014}, pages = {33}, abstract = {Optical mapping and newer genome mapping technologies based on nicking enzymes provide low resolution but long-range genomic information. The optical mapping technique has been successfully used for assessing the quality of genome assemblies and for detecting large-scale structural variants and rearrangements that cannot be detected using current paired end sequencing protocols. Here, we review several algorithms and methods for building consensus optical maps and aligning restriction patterns to a reference map, as well as methods for using optical maps with sequence assemblies.}, isbn = {2047-217X}, author = {Mendelowitz, Lee and Pop, Mihai} } @article {49611, title = {Construction of a dairy microbial genome catalog opens new perspectives for the metagenomic analysis of dairy fermented products}, journal = {BMC GenomicsBMC Genomics}, volume = {15}, number = {1}, year = {2014}, pages = {1101}, abstract = {BACKGROUND:Microbial communities of traditional cheeses are complex and insufficiently characterized. The origin, safety and functional role in cheese making of these microbial communities are still not well understood. Metagenomic analysis of these communities by high throughput shotgun sequencing is a promising approach to characterize their genomic and functional profiles. Such analyses, however, critically depend on the availability of appropriate reference genome databases against which the sequencing reads can be aligned.RESULTS:We built a reference genome catalog suitable for short read metagenomic analysis using a low-cost sequencing strategy. We selected 142 bacteria isolated from dairy products belonging to 137 different species and 67 genera, and succeeded to reconstruct the draft genome of 117 of them at a standard or high quality level, including isolates from the genera Kluyvera, Luteococcus and Marinilactibacillus, still missing from public database. To demonstrate the potential of this catalog, we analysed the microbial composition of the surface of two smear cheeses and one blue-veined cheese, and showed that a significant part of the microbiota of these traditional cheeses was composed of microorganisms newly sequenced in our study.CONCLUSIONS:Our study provides data, which combined with publicly available genome references, represents the most expansive catalog to date of cheese-associated bacteria. Using this extended dairy catalog, we revealed the presence in traditional cheese of dominant microorganisms not deliberately inoculated, mainly Gram-negative genera such as Pseudoalteromonas haloplanktis or Psychrobacter immobilis, that may contribute to the characteristics of cheese produced through traditional methods.}, isbn = {1471-2164}, author = {Almeida, Mathieu and Hebert, Agnes and Abraham, Anne-Laure and Rasmussen, Simon and Monnet, Christophe and Pons, Nicolas and Delbes, Celine and Loux, Valentin and Batto, Jean-Michel and Leonard, Pierre and Kennedy, Sean and Ehrlich, Stanislas and Pop, Mihai and Montel, Marie-Christine and Irlinger, Francoise and Renault, Pierre} } @article {38584, title = {CTCF binding site sequence differences are associated with unique regulatory and functional trends during embryonic stem cell differentiation}, journal = {Nucleic Acids ResNucleic Acids ResNucleic Acids Res}, volume = {42}, number = {2}, year = {2014}, note = {Plasschaert, Robert N
Vigneau, Sebastien
Tempera, Italo
Gupta, Ravi
Maksimoska, Jasna
Everett, Logan
Davuluri, Ramana
Mamorstein, Ronen
Lieberman, Paul M
Schultz, David
Hannenhalli, Sridhar
Bartolomei, Marisa S
eng
K99AI099153/AI/NIAID NIH HHS/
P30 CA10815/CA/NCI NIH HHS/
R01 CA140652/CA/NCI NIH HHS/
R01-GM052880/GM/NIGMS NIH HHS/
R01CA140652/CA/NCI NIH HHS/
R01GM085226/GM/NIGMS NIH HHS/
R01HD042026/HD/NICHD NIH HHS/
T32GM008216/GM/NIGMS NIH HHS/
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov{\textquoteright}t
England
2013/10/15 06:00
Nucleic Acids Res. 2014 Jan;42(2):774-89. doi: 10.1093/nar/gkt910. Epub 2013 Oct 10.}, month = {Jan}, pages = {774-89}, abstract = {CTCF (CCCTC-binding factor) is a highly conserved multifunctional DNA-binding protein with thousands of binding sites genome-wide. Our previous work suggested that differences in CTCF{\textquoteright}s binding site sequence may affect the regulation of CTCF recruitment and its function. To investigate this possibility, we characterized changes in genome-wide CTCF binding and gene expression during differentiation of mouse embryonic stem cells. After separating CTCF sites into three classes (LowOc, MedOc and HighOc) based on similarity to the consensus motif, we found that developmentally regulated CTCF binding occurs preferentially at LowOc sites, which have lower similarity to the consensus. By measuring the affinity of CTCF for selected sites, we show that sites lost during differentiation are enriched in motifs associated with weaker CTCF binding in vitro. Specifically, enrichment for T at the 18(th) position of the CTCF binding site is associated with regulated binding in the LowOc class and can predictably reduce CTCF affinity for binding sites. Finally, by comparing changes in CTCF binding with changes in gene expression during differentiation, we show that LowOc and HighOc sites are associated with distinct regulatory functions. Our results suggest that the regulatory control of CTCF is dependent in part on specific motifs within its binding site.}, keywords = {*Gene Expression Regulation, *Regulatory Elements, Transcriptional, Animals, Binding Sites, Cell Differentiation/*genetics, Cells, Cultured, Embryonic Stem Cells/cytology/*metabolism, Mice, Nucleotide Motifs, Protein Binding, Repressor Proteins/*metabolism}, isbn = {1362-4962 (Electronic)
0305-1048 (Linking)}, author = {Plasschaert, R. N. and Vigneau, S. and Tempera, I. and Gupta, R. and Maksimoska, J. and Everett, L. and Davuluri, R. and Mamorstein, R. and Lieberman, P. M. and Schultz, D. and Sridhar Hannenhalli and Bartolomei, M. S.} } @article {49600, title = {Diarrhea in young children from low-income countries leads to large-scale alterations in intestinal microbiota composition.}, volume = {15}, year = {2014}, month = {2014}, pages = {R76}, abstract = {

BACKGROUND: Diarrheal diseases continue to contribute significantly to morbidity and mortality in infants and young children in developing countries. There is an urgent need to better understand the contributions of novel, potentially uncultured, diarrheal pathogens to severe diarrheal disease, as well as distortions in normal gut microbiota composition that might facilitate severe disease.

RESULTS: We use high throughput 16S rRNA gene sequencing to compare fecal microbiota composition in children under five years of age who have been diagnosed with moderate to severe diarrhea (MSD) with the microbiota from diarrhea-free controls. Our study includes 992 children from four low-income countries in West and East Africa, and Southeast Asia. Known pathogens, as well as bacteria currently not considered as important diarrhea-causing pathogens, are positively associated with MSD, and these include Escherichia/Shigella, and Granulicatella species, and Streptococcus mitis/pneumoniae groups. In both cases and controls, there tend to be distinct negative correlations between facultative anaerobic lineages and obligate anaerobic lineages. Overall genus-level microbiota composition exhibit a shift in controls from low to high levels of Prevotella and in MSD cases from high to low levels of Escherichia/Shigella in younger versus older children; however, there was significant variation among many genera by both site and age.

CONCLUSIONS: Our findings expand the current understanding of microbiota-associated diarrhea pathogenicity in young children from developing countries. Our findings are necessarily based on correlative analyses and must be further validated through epidemiological and molecular techniques.

}, keywords = {Bangladesh, Base Sequence, Case-Control Studies, Child, Preschool, Diarrhea, Infantile, Dysentery, Feces, Female, Gambia, HUMANS, Infant, Infant, Newborn, Intestines, Kenya, Male, Mali, Microbiota, Molecular Typing, Poverty, RNA, Bacterial, RNA, Ribosomal, 16S}, issn = {1474-760X}, doi = {10.1186/gb-2014-15-6-r76}, author = {Pop, Mihai and Walker, Alan W and Paulson, Joseph and Lindsay, Brianna and Antonio, Martin and Hossain, M Anowar and Oundo, Joseph and Tamboura, Boubou and Mai, Volker and Astrovskaya, Irina and Corrada Bravo, Hector and Rance, Richard and Stares, Mark and Levine, Myron M and Panchalingam, Sandra and Kotloff, Karen and Ikumapayi, Usman N and Ebruke, Chinelo and Adeyemi, Mitchell and Ahmed, Dilruba and Ahmed, Firoz and Alam, Meer Taifur and Amin, Ruhul and Siddiqui, Sabbir and Ochieng, John B and Ouma, Emmanuel and Juma, Jane and Mailu, Euince and Omore, Richard and Morris, J Glenn and Breiman, Robert F and Saha, Debasish and Parkhill, Julian and Nataro, James P and Stine, O Colin} } @article {49604, title = {Large hypomethylated blocks as a universal defining epigenetic alteration in human solid tumors.}, volume = {6}, year = {2014}, month = {2014}, pages = {61}, abstract = {

BACKGROUND: One of the most provocative recent observations in cancer epigenetics is the discovery of large hypomethylated blocks, including single copy genes, in colorectal cancer, that correspond in location to heterochromatic LOCKs (large organized chromatin lysine-modifications) and LADs (lamin-associated domains).

METHODS: Here we performed a comprehensive genome-scale analysis of 10 breast, 28 colon, nine lung, 38 thyroid, 18 pancreas cancers, and five pancreas neuroendocrine tumors as well as matched normal tissue from most of these cases, as well as 51 premalignant lesions. We used a new statistical approach that allows the identification of large hypomethylated blocks on the Illumina HumanMethylation450 BeadChip platform.

RESULTS: We find that hypomethylated blocks are a universal feature of common solid human cancer, and that they occur at the earliest stage of premalignant tumors and progress through clinical stages of thyroid and colon cancer development. We also find that the disrupted CpG islands widely reported previously, including hypermethylated island bodies and hypomethylated shores, are enriched in hypomethylated blocks, with flattening of the methylation signal within and flanking the islands. Finally, we found that genes showing higher between individual gene expression variability are enriched within these hypomethylated blocks.

CONCLUSION: Thus hypomethylated blocks appear to be a universal defining epigenetic alteration in human cancer, at least for common solid tumors.

}, issn = {1756-994X}, doi = {10.1186/s13073-014-0061-y}, author = {Timp, Winston and Bravo, H{\'e}ctor Corrada and McDonald, Oliver G and Goggins, Michael and Umbricht, Chris and Zeiger, Martha and Feinberg, Andrew P and Irizarry, Rafael A} } @article {49514, title = {A molecular phylogeny and revised classification for the oldest ditrysian moth lineages (Lepidoptera: Tineoidea), with implications for ancestral feeding habits of the mega-diverse Ditrysia}, journal = {Systematic Entomology}, volume = {40}, year = {2014}, month = {04/2015}, pages = {409 - 432}, doi = {10.1111/syen.12110}, author = {Regier, Jerome C and Mitter, Charles and Davis, Donald R. and HARRISON, TERRY L. and Sohn, Jae-Cheon and Michael P. Cummings and Zwick, Andreas and Mitter, Kim T.} } @article {49862, title = {A new rhesus macaque assembly and annotation for next-generation sequencing analyses}, journal = {Biology direct}, volume = {9}, year = {2014}, pages = {20}, author = {Zimin, Aleksey V and Cornish, Adam S and Maudhoo, Mnirnal D and Gibbs, Robert M and Zhang, Xiongfei and Pandey, Sanjit and Meehan, Daniel T and Wipfler, Kristin and Bosinger, Steven E and Johnson, Zachary P and Todd Treangen} } @article {49587, title = {A Novel Nutritional Predictor Links Microbial Fastidiousness with Lowered Ubiquity, Growth Rate, and Cooperativeness}, journal = {PLoS Computational Biology}, volume = {10}, year = {2014}, month = {May-07-2015}, pages = {e1003726}, doi = {10.1371/journal.pcbi.1003726}, url = {http://journals.plos.org/ploscompbiol/article?id=10.1371/journal.pcbi.1003726}, author = {Zarecki, Raphy and Oberhardt, Matthew A. and Reshef, Leah and Gophna, Uri and Ruppin, Eytan}, editor = {Maranas, Costas D.} } @article {49726, title = {Predicting cancer-specific vulnerability via data-driven detection of synthetic lethality.}, journal = {Cell}, volume = {158}, year = {2014}, month = {2014 Aug 28}, pages = {1199-209}, abstract = {

Synthetic lethality occurs when the inhibition of two genes is lethal while the inhibition of each single gene is not. It can be harnessed to selectively treat cancer by identifying inactive genes in a given cancer and targeting their synthetic lethal (SL) partners. We present a data-driven computational pipeline for the genome-wide identification of SL interactions in cancer by analyzing large volumes of cancer genomic data. First, we show that the approach successfully captures known SL partners of tumor suppressors and oncogenes. We then validate SL predictions obtained for the tumor suppressor VHL. Next, we construct a genome-wide network of SL interactions in cancer and demonstrate its value in predicting gene essentiality and clinical prognosis. Finally, we identify synthetic lethality arising from gene overactivation and use it to predict drug efficacy. These results form a computational basis for exploiting synthetic lethality to uncover cancer-specific susceptibilities.

}, keywords = {Breast Neoplasms, Cell Line, Tumor, Computational Biology, Data Mining, Genes, Tumor Suppressor, HUMANS, Neoplasms, Oncogenes, RNA, Small Interfering, workflow}, issn = {1097-4172}, doi = {10.1016/j.cell.2014.07.027}, author = {Jerby-Arnon, Livnat and Pfetzer, Nadja and Waldman, Yedael Y and McGarry, Lynn and James, Daniel and Shanks, Emma and Seashore-Ludlow, Brinton and Weinstock, Adam and Geiger, Tamar and Clemons, Paul A and Gottlieb, Eyal and Ruppin, Eytan} } @article {49608, title = {RNA-sequencing of the brain transcriptome implicates dysregulation of neuroplasticity, circadian rhythms and GTPase binding in bipolar disorder.}, volume = {19}, year = {2014}, month = {2014 Nov}, pages = {1179-85}, abstract = {

RNA-sequencing (RNA-seq) is a powerful technique to investigate the complexity of gene expression in the human brain. We used RNA-seq to survey the brain transcriptome in high-quality postmortem dorsolateral prefrontal cortex from 11 individuals diagnosed with bipolar disorder (BD) and from 11 age- and gender-matched controls. Deep sequencing was performed, with over 350 million reads per specimen. At a false discovery rate of <5\%, we detected five differentially expressed (DE) genes and 12 DE transcripts, most of which have not been previously implicated in BD. Among these, Prominin 1/CD133 and ATP-binding cassette-sub-family G-member2 (ABCG2) have important roles in neuroplasticity. We also show for the first time differential expression of long noncoding RNAs (lncRNAs) in BD. DE transcripts include those of serine/arginine-rich splicing factor 5 (SRSF5) and regulatory factor X4 (RFX4), which along with lncRNAs have a role in mammalian circadian rhythms. The DE genes were significantly enriched for several Gene Ontology categories. Of these, genes involved with GTPase binding were also enriched for BD-associated SNPs from previous genome-wide association studies, suggesting that differential expression of these genes is not simply a consequence of BD or its treatment. Many of these findings were replicated by microarray in an independent sample of 60 cases and controls. These results highlight common pathways for inherited and non-inherited influences on disease risk that may constitute good targets for novel therapies.

}, keywords = {Adult, Aged, Bipolar Disorder, Circadian Rhythm, Female, Genome-Wide Association Study, GTP Phosphohydrolases, HUMANS, Male, Meta-Analysis as Topic, Microarray Analysis, Middle Aged, Neuronal Plasticity, Polymerase Chain Reaction, Prefrontal Cortex, Principal Component Analysis, Sequence Analysis, RNA, Transcriptome, Young Adult}, issn = {1476-5578}, doi = {10.1038/mp.2013.170}, author = {Akula, N and Barb, J and Jiang, X and Wendland, J R and Choi, K H and Sen, S K and Hou, L and Chen, D T W and Laje, G and Johnson, K and Lipska, B K and Kleinman, J E and Corrada-Bravo, H and Detera-Wadleigh, S and Munson, P J and McMahon, F J} } @article {38469, title = {RNA-sequencing of the brain transcriptome implicates dysregulation of neuroplasticity, circadian rhythms and GTPase binding in bipolar disorder}, journal = {Molecular psychiatry}, year = {2014}, note = {http://www.ncbi.nlm.nih.gov/pubmed/24393808?dopt=Abstract}, type = {10.1038/mp.2013.170}, abstract = {RNA-sequencing (RNA-seq) is a powerful technique to investigate the complexity of gene expression in the human brain. We used RNA-seq to survey the brain transcriptome in high-quality postmortem dorsolateral prefrontal cortex from 11 individuals diagnosed with bipolar disorder (BD) and from 11 age- and gender-matched controls. Deep sequencing was performed, with over 350 million reads per specimen. At a false discovery rate of <5\%, we detected five differentially expressed (DE) genes and 12 DE transcripts, most of which have not been previously implicated in BD. Among these, Prominin 1/CD133 and ATP-binding cassette-sub-family G-member2 (ABCG2) have important roles in neuroplasticity. We also show for the first time differential expression of long noncoding RNAs (lncRNAs) in BD. DE transcripts include those of serine/arginine-rich splicing factor 5 (SRSF5) and regulatory factor X4 (RFX4), which along with lncRNAs have a role in mammalian circadian rhythms. The DE genes were significantly enriched for several Gene Ontology categories. Of these, genes involved with GTPase binding were also enriched for BD-associated SNPs from previous genome-wide association studies, suggesting that differential expression of these genes is not simply a consequence of BD or its treatment. Many of these findings were replicated by microarray in an independent sample of 60 cases and controls. These results highlight common pathways for inherited and non-inherited influences on disease risk that may constitute good targets for novel therapies.Molecular Psychiatry advance online publication, 7 January 2014; doi:10.1038/mp.2013.170.}, author = {Akula, N. and Barb, J. and Jiang, X. and Wendland, J. R. and Choi, K. H. and Sen, S. K. and Hou, L. and Chen, D. T. W. and Laje, G. and Johnson, K. and Lipska, B. K. and Kleinman, J. E. and H{\'e}ctor Corrada Bravo and Detera-Wadleigh, S. and Munson, P. J. and McMahon, F. J.} } @article {49572, title = {Sailfish enables alignment-free isoform quantification from RNA-seq reads using lightweight algorithms.}, volume = {32}, year = {2014}, month = {2014 May}, pages = {462-4}, abstract = {

We introduce Sailfish, a computational method for quantifying the abundance of previously annotated RNA isoforms from RNA-seq data. Because Sailfish entirely avoids mapping reads, a time-consuming step in all current methods, it provides quantification estimates much faster than do existing approaches (typically 20 times faster) without loss of accuracy. By facilitating frequent reanalysis of data and reducing the need to optimize parameters, Sailfish exemplifies the potential of lightweight algorithms for efficiently processing sequencing reads.

}, keywords = {algorithms, Brain Chemistry, Computational Biology, HUMANS, Models, Biological, RNA Isoforms, Sequence Analysis, RNA, software}, issn = {1546-1696}, doi = {10.1038/nbt.2862}, author = {Patro, Rob and Mount, Stephen M and Kingsford, Carl} } @article {49737, title = {Stable isotope labeling of phosphoproteins for large-scale phosphorylation rate determination.}, journal = {Mol Cell Proteomics}, volume = {13}, year = {2014}, month = {2014 Apr}, pages = {1106-18}, abstract = {

Signals that control responses to stimuli and cellular function are transmitted through the dynamic phosphorylation of thousands of proteins by protein kinases. Many techniques have been developed to study phosphorylation dynamics, including several mass spectrometry (MS)-based methods. Over the past few decades, substantial developments have been made in MS techniques for the large-scale identification of proteins and their post-translational modifications. Nevertheless, all of the current MS-based techniques for quantifying protein phosphorylation dynamics rely on the measurement of changes in peptide abundance levels, and many methods suffer from low confidence in phosphopeptide identification due to poor fragmentation. Here we have optimized an approach for the stable isotope labeling of amino acids by phosphate using [γ-{\textonesuperior}$^{8}$O$_{4}$]ATP in nucleo to determine global site-specific phosphorylation rates. The advantages of this metabolic labeling technique are increased confidence in phosphorylated peptide identification, direct labeling of phosphorylation sites, measurement phosphorylation rates, and the identification of actively phosphorylated sites in a cell-like environment. In this study we calculated approximate rate constants for over 1,000 phosphorylation sites based on labeling progress curves. We measured a wide range of phosphorylation rate constants from 0.34 min$^{-}${\textonesuperior} to 0.001 min$^{-}${\textonesuperior}. Finally, we applied stable isotope labeling of amino acids by phosphate to identify sites that have different phosphorylation kinetics during G1/S and M phase. We found that most sites had very similar phosphorylation rates under both conditions; however, a small subset of sites on proteins involved in the mitotic spindle were more actively phosphorylated during M phase, whereas proteins involved in DNA replication and transcription were more actively phosphorylated during G1/S phase. The data have been deposited to the ProteomeXchange with the identifier PXD000680.

}, keywords = {cell cycle, HEK293 Cells, HeLa Cells, HUMANS, Isotope Labeling, Kinetics, Peptide Mapping, Phosphoproteins, Phosphorylation, proteomics, Tandem Mass Spectrometry}, issn = {1535-9484}, doi = {10.1074/mcp.O113.036145}, author = {Molden, Rosalynn C and Goya, Jonathan and Khan, Zia and Garcia, Benjamin A} } @article {49614, title = {TIPP:Taxonomic Identification and Phylogenetic Profiling}, journal = {BioinformaticsBioinformatics}, year = {2014}, month = {October 29, 2014}, abstract = {Motivation: Abundance profiling (also called {\textquotedblleft}phylogenetic profiling{\textquotedblright}) is a crucial step in understanding the diversity of a metagenomic sample, and one of the basic techniques used for this is taxonomic identification of the metagenomic reads.Results: We present TIPP (taxon identification and phylogenetic profiling), a new marker-based taxon identification and abundance profiling method. TIPP combines SEPP, a phylogenetic placement method, with statistical techniques to control the classification precision and recall, and results in improved abundance profiles. TIPP is highly accurate even in the presence of high indel errors and novel genomes, and matches or improves on previous approaches, including NBC, mOTU, PhymmBL, MetaPhyler, and MetaPhlAn.Availability: Software and supplementary materials are available at http://www.cs.utexas.edu/users/phylo/software/sepp/tipp-submission/.Contact: warnow@illinois.edu}, author = {Nguyen, Nam-phuong and Mirarab, Siavash and Liu, Bo and Pop, Mihai and Warnow, Tandy} } @article {38142, title = {Can RNA-Seq resolve the rapid radiation of advanced moths and butterflies (Hexapoda: Lepidoptera: Apoditrysia)? An exploratory study}, journal = {PLoS One}, volume = {8}, year = {2013}, type = {10.1371/journal.pone.0082615}, abstract = {

Recent molecular phylogenetic studies of the insect order Lepidoptera have robustly resolved family-level divergences within most superfamilies, and most divergences among the relatively species-poor early-arising superfamilies. In sharp contrast, relationships among the superfamilies of more advanced moths and butterflies that comprise the mega-diverse clade Apoditrysia (ca. 145,000 spp.) remain mostly poorly supported. This uncertainty, in turn, limits our ability to discern the origins, ages and evolutionary consequences of traits hypothesized to promote the spectacular diversification of Apoditrysia. Low support along the apoditrysian "backbone" probably reflects rapid diversification. If so, it may be feasible to strengthen resolution by radically increasing the gene sample, but case studies have been few. We explored the potential of next-generation sequencing to conclusively resolve apoditrysian relationships. We used transcriptome RNA-Seq to generate 1579 putatively orthologous gene sequences across a broad sample of 40 apoditrysians plus four outgroups, to which we added two taxa from previously published data. Phylogenetic analysis of a 46-taxon, 741-gene matrix, resulting from a strict filter that eliminated ortholog groups containing any apparent paralogs, yielded dramatic overall increase in bootstrap support for deeper nodes within Apoditrysia as compared to results from previous and concurrent 19-gene analyses. High support was restricted mainly to the huge subclade Obtectomera broadly defined, in which 11 of 12 nodes subtending multiple superfamilies had bootstrap support of 100\%. The strongly supported nodes showed little conflict with groupings from previous studies, and were little affected by changes in taxon sampling, suggesting that they reflect true signal rather than artifacts of massive gene sampling. In contrast, strong support was seen at only 2 of 11 deeper nodes among the "lower", non-obtectomeran apoditrysians. These represent a much harder phylogenetic problem, for which one path to resolution might include further increase in gene sampling, together with improved orthology assignments.

}, author = {Adam L. Bazinet and Michael P. Cummings and Mitter, Kim T. and Mitter, Charles W.} } @article {38183, title = {Correlated evolution of positions within mammalian cis elements }, volume = {8}, year = {2013}, pages = {e55521}, author = {R. Mukherjee and L. N. S. Singh and Evans, P. and Sridhar Hannenhalli} } @conference {45868, title = {De novo likelihood-based measures for comparing metagenomic assemblies}, booktitle = {2013 IEEE International Conference on Bioinformatics and Biomedicine (BIBM)}, year = {2013}, month = {12/2013}, publisher = {IEEE}, organization = {IEEE}, address = {Shanghai, China}, author = {Hill, Christopher M and Irina Astrovskaya and Huang, Howard and Koren, Sergey and Memon, Atif and Todd Treangen and Pop, Mihai} } @article {38583, title = {Enhancer networks revealed by correlated DNAse hypersensitivity states of enhancers}, journal = {Nucleic Acids ResNucleic Acids ResNucleic Acids Res}, volume = {41}, number = {14}, year = {2013}, note = {Malin, Justin
Aniba, Mohamed Radhouane
Hannenhalli, Sridhar
eng
R01 GM100335/GM/NIGMS NIH HHS/
R01GM100335/GM/NIGMS NIH HHS/
Research Support, N.I.H., Extramural
England
2013/05/24 06:00
Nucleic Acids Res. 2013 Aug;41(14):6828-38. doi: 10.1093/nar/gkt374. Epub 2013 May 21.}, month = {Aug}, pages = {6828-38}, abstract = {Mammalian gene expression is often regulated by distal enhancers. However, little is known about higher order functional organization of enhancers. Using approximately 100 K P300-bound regions as candidate enhancers, we investigated their correlated activity across 72 cell types based on DNAse hypersensitivity. We found widespread correlated activity between enhancers, which decreases with increasing inter-enhancer genomic distance. We found that correlated enhancers tend to share common transcription factor (TF) binding motifs, and several chromatin modification enzymes preferentially interact with these TFs. Presence of shared motifs in enhancer pairs can predict correlated activity with 73\% accuracy. Also, genes near correlated enhancers exhibit correlated expression and share common function. Correlated enhancers tend to be spatially proximal. Interestingly, weak enhancers tend to correlate with significantly greater numbers of other enhancers relative to strong enhancers. Furthermore, strong/weak enhancers preferentially correlate with strong/weak enhancers, respectively. We constructed enhancer networks based on shared motif and correlated activity and show significant functional enrichment in their putative target gene clusters. Overall, our analyses show extensive correlated activity among enhancers and reveal clusters of enhancers whose activities are coordinately regulated by multiple potential mechanisms involving shared TF binding, chromatin modifying enzymes and 3D chromatin structure, which ultimately co-regulate functionally linked genes.}, keywords = {*Deoxyribonucleases, *Enhancer Elements, Genetic, Chromatin/chemistry, Gene expression, Gene Regulatory Networks, HUMANS, Transcription Factors/metabolism}, isbn = {1362-4962 (Electronic)
0305-1048 (Linking)}, author = {Malin, J. and Aniba, M. R. and Sridhar Hannenhalli} } @article {38284, title = {Genetic loci associated with delayed clearance of Plasmodium falciparum following artemisinin treatment in Southeast Asia}, journal = {Proceedings of the National Academy of Sciences of the United States of AmericaProceedings of the National Academy of Sciences of the United States of America}, volume = {110}, year = {2013}, type = {10.1073/pnas.1211205110}, abstract = {The recent emergence of artemisinin-resistant Plasmodium falciparum malaria in western Cambodia could threaten prospects for malaria elimination. Identification of the genetic basis of resistance would provide tools for molecular surveillance, aiding efforts to contain resistance. Clinical trials of artesunate efficacy were conducted in Bangladesh, in northwestern Thailand near the Myanmar border, and at two sites in western Cambodia. Parasites collected from trial participants were genotyped at 8,079 single nucleotide polymorphisms (SNPs) using a P. falciparum-specific SNP array. Parasite genotypes were examined for signatures of recent positive selection and association with parasite clearance phenotypes to identify regions of the genome associated with artemisinin resistance. Four SNPs on chromosomes 10 (one), 13 (two), and 14 (one) were significantly associated with delayed parasite clearance. The two SNPs on chromosome 13 are in a region of the genome that appears to be under strong recent positive selection in Cambodia. The SNPs on chromosomes 10 and 13 lie in or near genes involved in postreplication repair, a DNA damage-tolerance pathway. Replication and validation studies are needed to refine the location of loci responsible for artemisinin resistance and to understand the mechanism behind it; however, two SNPs on chromosomes 10 and 13 may be useful markers of delayed parasite clearance in surveillance for artemisinin resistance in Southeast Asia.}, author = {Takala-Harrison, Shannon and Clark, Taane G. and Jacob, Christopher G. and Michael P. Cummings and Miotto, Olivo and Dondorp, Arjen M. and Fukuda, Mark M. and Nosten, Francois and Noedl, Harald and Imwong, Mallika and Bethell, Delia and Se, Youry and Lon, Chanthap and Tyner, Stuart D. and Saunders, David L. and Socheat, Duong and Ariey, Frederic and Phyo, Aung Pyae and Starzengruber, Peter and Fuehrer, Hans-Peter and Swoboda, Paul and Stepniewska, Kasia and Flegg, Jennifer and Arze, Cesar and Cerqueira, Gustavo C. and Silva, Joana C. and Ricklefs, Stacy M. and Porcella, Stephen F. and Stephens, Robert M. and Adams, Matthew and Kenefic, Leo J. and Campino, Susana and Auburn, Sarah and Macinnis, Bronwyn and Kwiatkowski, Dominic P. and Su, Xin-Zhuan and White, Nicholas J. and Ringwald, Pascal and Plowe, Christopher V.} } @article {38306, title = {Genome sequencing of four strains of Rickettsia prowazekii, the causative agent of epidemic typhus, including one flying squirrel isolate}, journal = {Genome announcementsGenome announcements}, volume = {1}, year = {2013}, publisher = {American Society for Microbiology}, isbn = {2169-8287}, author = {Bishop-Lilly, Kimberly A. and Ge, Hong and Butani, Amy and Osborne, Brian and Verratti, Kathleen and Mokashi, Vishwesh and Nagarajan, Niranjan and M. Pop and Read, Timothy D. and Richards, Allen L.} } @article {38354, title = {Intrinsically disordered proteins and conformational noise: Implications in cancer}, journal = {Cell CycleCell Cycle}, volume = {12}, year = {2013}, note = {cc}, type = {10.4161/cc10.4161/cc.23178}, author = {Mahmoudabadi, Gita and Rajagopalan, Krithika and Getzenberg, Robert H. and Sridhar Hannenhalli and Rangarajan, Govindan and Kulkarni, Prakash} } @article {38358, title = {A large-scale, higher-level, molecular phylogenetic study of the insect order Lepidoptera (moths and butterflies)}, journal = {PLoS OnePLoS One}, volume = {8}, year = {2013}, type = {10.1371/journal.pone.0058568}, abstract = {

BACKGROUND: Higher-level relationships within the Lepidoptera, and particularly within the species-rich subclade Ditrysia, are generally not well understood, although recent studies have yielded progress. We present the most comprehensive molecular analysis of lepidopteran phylogeny to date, focusing on relationships among superfamilies.

METHODOLOGY PRINCIPAL FINDINGS: 483 taxa spanning 115 of 124 families were sampled for 19 protein-coding nuclear genes, from which maximum likelihood tree estimates and bootstrap percentages were obtained using GARLI. Assessment of heuristic search effectiveness showed that better trees and higher bootstrap percentages probably remain to be discovered even after 1000 or more search replicates, but further search proved impractical even with grid computing. Other analyses explored the effects of sampling nonsynonymous change only versus partitioned and unpartitioned total nucleotide change; deletion of rogue taxa; and compositional heterogeneity. Relationships among the non-ditrysian lineages previously inferred from morphology were largely confirmed, plus some new ones, with strong support. Robust support was also found for divergences among non-apoditrysian lineages of Ditrysia, but only rarely so within Apoditrysia. Paraphyly for Tineoidea is strongly supported by analysis of nonsynonymous-only signal; conflicting, strong support for tineoid monophyly when synonymous signal was added back is shown to result from compositional heterogeneity. CONCLUSIONS SIGNIFICANCE: Support for among-superfamily relationships outside the Apoditrysia is now generally strong. Comparable support is mostly lacking within Apoditrysia, but dramatically increased bootstrap percentages for some nodes after rogue taxon removal, and concordance with other evidence, strongly suggest that our picture of apoditrysian phylogeny is approximately correct. This study highlights the challenge of finding optimal topologies when analyzing hundreds of taxa. It also shows that some nodes get strong support only when analysis is restricted to nonsynonymous change, while total change is necessary for strong support of others. Thus, multiple types of analyses will be necessary to fully resolve lepidopteran phylogeny.

}, keywords = {Animals, Butterflies, Moths, Phylogeny}, author = {Regier, Jerome C. and Mitter, Charles and Zwick, Andreas and Adam L. Bazinet and Michael P. Cummings and Kawahara, Akito Y. and Sohn, Jae-Cheon and Zwickl, Derrick J. and Cho, Soowon and Davis, Donald R. and Baixeras, Joaquin and Brown, John and Parr, Cynthia and Weller, Susan and Lees, David C. and Mitter, Kim T.} } @article {38389, title = {A molecular phylogeny for Yponomeutoidea (Insecta, Lepidoptera, Ditrysia) and its implications for classification, biogeography and\ the evolution of host plant use}, journal = {PLoS One}, year = {2013}, author = {J. C. Sohn and Regier, J. C. and Mitter, C. and D. Davis and J. F. Landry and Zwick, A. and Michael P. Cummings} } @article {49738, title = {Primate transcript and protein expression levels evolve under compensatory selection pressures.}, journal = {Science}, volume = {342}, year = {2013}, month = {2013 Nov 29}, pages = {1100-4}, abstract = {

Changes in gene regulation have likely played an important role in the evolution of primates. Differences in messenger RNA (mRNA) expression levels across primates have often been documented; however, it is not yet known to what extent measurements of divergence in mRNA levels reflect divergence in protein expression levels, which are probably more important in determining phenotypic differences. We used high-resolution, quantitative mass spectrometry to collect protein expression measurements from human, chimpanzee, and rhesus macaque lymphoblastoid cell lines and compared them to transcript expression data from the same samples. We found dozens of genes with significant expression differences between species at the mRNA level yet little or no difference in protein expression. Overall, our data suggest that protein expression levels evolve under stronger evolutionary constraint than mRNA levels.

}, keywords = {Animals, Evolution, Molecular, Gene Expression Regulation, HUMANS, Macaca mulatta, Pan troglodytes, Protein Biosynthesis, RNA, Messenger, Selection, Genetic, Species Specificity, Transcription, Genetic}, issn = {1095-9203}, doi = {10.1126/science.1242379}, author = {Khan, Zia and Ford, Michael J and Cusanovich, Darren A and Mitrano, Amy and Pritchard, Jonathan K and Gilad, Yoav} } @article {49545, title = {Primate Transcript and Protein Expression Levels Evolve Under Compensatory Selection Pressures}, volume = {342}, year = {2013}, month = {May-11-2015}, pages = {1100 - 1104}, issn = {0036-8075}, doi = {10.1126/science.1242379}, url = {http://www.sciencemag.org/cgi/doi/10.1126/science.1242379}, author = {Khan, Z. and Ford, M. J. and Cusanovich, D. A. and Mitrano, A. and Pritchard, J. K. and Gilad, Y.} } @article {38509, title = {Somatic alterations contributing to metastasis of a castration-resistant prostate cancer}, journal = {Human mutationHuman mutation}, volume = {34}, year = {2013}, note = {http://www.ncbi.nlm.nih.gov/pubmed/23636849?dopt=Abstract}, type = {10.1002/humu.22346}, abstract = {Metastatic castration-resistant prostate cancer (mCRPC) is a lethal disease, and molecular markers that differentiate indolent from aggressive subtypes are needed. We sequenced the exomes of five metastatic tumors and healthy kidney tissue from an index case with mCRPC to identify lesions associated with disease progression and metastasis. An Ashkenazi Jewish (AJ) germline founder mutation, del185AG in BRCA1, was observed and AJ ancestry was confirmed. Sixty-two somatic variants altered proteins in tumors, including cancer-associated genes, TMPRSS2-ERG, PBRM1, and TET2. The majority (n = 53) of somatic variants were present in all metastases and only a subset (n = 31) was observed in the primary tumor. Integrating tumor next-generation sequencing and DNA copy number showed somatic loss of BRCA1 and TMPRSS2-ERG. We sequenced 19 genes with deleterious mutations in the index case in additional mCRPC samples and detected a frameshift, two somatic missense alterations, tumor loss of heterozygosity, and combinations of germline missense SNPs in TET2. In summary, genetic analysis of metastases from an index case permitted us to infer a chronology for the clonal spread of disease based on sequential accrual of somatic lesions. The role of TET2 in mCRPC deserves additional analysis and may define a subset of metastatic disease.}, author = {Nickerson, Michael L. and Im, Kate M. and Misner, Kevin J. and Tan, Wei and Lou, Hong and Gold, Bert and Wells, David W. and H{\'e}ctor Corrada Bravo and Fredrikson, Karin M. and Harkins, Timothy T. and Milos, Patrice and Zbar, Berton and Linehan, W. Marston and Yeager, Meredith and Andresson, Thorkell and Dean, Michael and Bova, G. Steven} } @article {38519, title = {Survey of Culture, GoldenGate Assay, Universal Biosensor Assay, and 16S rRNA Gene Sequencing as Alternative Methods of Bacterial Pathogen Detection}, journal = {Journal of Clinical MicrobiologyJournal of Clinical Microbiology}, volume = {51}, year = {2013}, publisher = {American Society for Microbiology}, isbn = {0095-1137}, author = {Lindsay, Brianna and M. Pop and Antonio, Martin and Walker, Alan W. and Mai, Volker and Ahmed, Dilruba and Oundo, Joseph and Tamboura, Boubou and Panchalingam, Sandra and Levine, Myron M.} } @article {38107, title = {AGORA: Assembly Guided by Optical Restriction Alignment}, journal = {BMC bioinformaticsBMC Bioinformatics}, volume = {13}, year = {2012}, publisher = {BioMed Central Ltd}, author = {Lin, H. C. and Goldstein, S. and L. Mendelowitz and Zhou, S. and Wetzel, J. and Schwartz, D. C. and M. Pop} } @article {49741, title = {BclAF1 restriction factor is neutralized by proteasomal degradation and microRNA repression during human cytomegalovirus infection.}, journal = {Proc Natl Acad Sci U S A}, volume = {109}, year = {2012}, month = {2012 Jun 12}, pages = {9575-80}, abstract = {

Cell proteins can restrict the replication of viruses. Here, we identify the cellular BclAF1 protein as a human cytomegalovirus restriction factor and describe two independent mechanisms the virus uses to decrease its steady-state levels. Immediately following infection, the viral pp71 and UL35 proteins, which are delivered to cells within virions, direct the proteasomal degradation of BclAF1. Although BclAF1 reaccumulates through the middle stages of infection, it is subsequently down-regulated at late times by miR-UL112-1, a virus-encoded microRNA. In the absence of BclAF1 neutralization, viral gene expression and replication are inhibited. These data identify two temporally and mechanistically distinct functions used by human cytomegalovirus to down-regulate a cellular antiviral protein.

}, keywords = {Cytomegalovirus, Cytomegalovirus Infections, Genes, Immediate-Early, HUMANS, Hydrolysis, MicroRNAs, Proteasome Endopeptidase Complex, Repressor Proteins, Tumor Suppressor Proteins}, issn = {1091-6490}, doi = {10.1073/pnas.1207496109}, author = {Lee, Song Hee and Kalejta, Robert F and Kerry, Julie and Semmes, Oliver John and O{\textquoteright}Connor, Christine M and Khan, Zia and Garcia, Benjamin A and Shenk, Thomas and Murphy, Eain} } @article {49551, title = {BclAF1 restriction factor is neutralized by proteasomal degradation and microRNA repression during human cytomegalovirus infection}, volume = {109}, year = {2012}, month = {Dec-06-2012}, pages = {9575 - 9580}, issn = {0027-8424}, doi = {10.1073/pnas.1207496109}, url = {http://www.pnas.org/cgi/doi/10.1073/pnas.1207496109}, author = {Lee, S. H. and Kalejta, R. F. and Kerry, J. and Semmes, O. J. and O{\textquoteright}Connor, C. M. and Khan, Z. and Garcia, B. A. and Shenk, T. and Murphy, E.} } @article {49550, title = {BclAF1 restriction factor is neutralized by proteasomal degradation and microRNA repression during human cytomegalovirus infection}, journal = {Proceedings of the National Academy of Sciences}, volume = {109}, year = {2012}, month = {Dec-06-2012}, pages = {9575 - 9580}, issn = {0027-8424}, doi = {10.1073/pnas.1207496109}, url = {http://www.pnas.org/cgi/doi/10.1073/pnas.1207496109}, author = {Lee, S. H. and Kalejta, R. F. and Kerry, J. and Semmes, O. J. and O{\textquoteright}Connor, C. M. and Khan, Z. and Garcia, B. A. and Shenk, T. and Murphy, E.} } @article {38195, title = {Deep Sequencing of the Oral Microbiome Reveals Signatures of Periodontal Disease}, journal = {PloS onePLoS One}, volume = {7}, year = {2012}, publisher = {Public Library of Science}, author = {Liu, B. and Faller, L. L. and Klitgord, N. and Mazumdar, V. and Ghodsi, M. and Sommer, D. D. and Gibbons, T. R. and Todd Treangen and Chang, Y. C. and Li, S. and others,} } @article {49743, title = {Drosophila Src regulates anisotropic apical surface growth to control epithelial tube size.}, journal = {Nat Cell Biol}, volume = {14}, year = {2012}, month = {2012 May}, pages = {518-25}, abstract = {

Networks of epithelial and endothelial tubes are essential for the function of organs such as the lung, kidney and vascular system. The sizes and shapes of these tubes are highly regulated to match their individual functions. Defects in tube size can cause debilitating diseases such as polycystic kidney disease and ischaemia. It is therefore critical to understand how tube dimensions are regulated. Here we identify the tyrosine kinase Src as an instructive regulator of epithelial-tube length in the Drosophila tracheal system. Loss-of-function Src42 mutations shorten tracheal tubes, whereas Src42 overexpression elongates them. Surprisingly, Src42 acts distinctly from known tube-size pathways and regulates both the amount of apical surface growth and, with the conserved formin dDaam, the direction of growth. Quantitative three-dimensional image analysis reveals that Src42- and dDaam-mutant tracheal cells expand more in the circumferential than the axial dimension, resulting in tubes that are shorter in length-but larger in diameter-than wild-type tubes. Thus, Src42 and dDaam control tube dimensions by regulating the direction of anisotropic growth, a mechanism that has not previously been described.

}, keywords = {Animals, Drosophila, Epithelium, src-Family Kinases}, issn = {1476-4679}, doi = {10.1038/ncb2467}, author = {Nelson, Kevin S and Khan, Zia and Moln{\'a}r, Imre and Mih{\'a}ly, J{\'o}zsef and Kaschube, Matthias and Beitel, Greg J} } @article {38251, title = {Exploiting sparseness in de novo genome assembly}, journal = {BMC bioinformaticsBMC Bioinformatics}, volume = {13}, year = {2012}, publisher = {BioMed Central Ltd}, author = {Chengxi Ye and Ma, Z. S. and Cannon, C. H. and M. Pop and Yu, D. W.} } @article {38264, title = {A framework for human microbiome research}, journal = {NatureNature}, volume = {486}, year = {2012}, author = {Meth{\'e}, B. A. and Nelson, K. E. and M. Pop and Creasy, H. H. and Giglio, M. G. and Huttenhower, C. and Gevers, D. and Petrosino, J. F. and Abubucker, S. and Badger, J. H. and others,} } @article {38272, title = {GAGE: A critical evaluation of genome assemblies and assembly algorithms}, journal = {Genome researchGenome Research}, volume = {22}, year = {2012}, publisher = {Cold Spring Harbor Lab}, author = {Salzberg, S. L. and Phillippy, A. M. and Zimin, A. and Puiu, D. and Magoc, T. and Koren, S. and Todd Treangen and Schatz, M. C. and Delcher, A. L. and Roberts, M. and others,} } @article {38276, title = {Gene expression anti-profiles as a basis for accurate universal cancer signatures}, journal = {BMC bioinformaticsBMC Bioinformatics}, volume = {13}, year = {2012}, note = {http://www.ncbi.nlm.nih.gov/pubmed/23088656?dopt=Abstract}, type = {10.1186/1471-2105-13-272}, abstract = {BACKGROUND: Early screening for cancer is arguably one of the greatest public health advances over the last fifty years. However, many cancer screening tests are invasive (digital rectal exams), expensive (mammograms, imaging) or both (colonoscopies). This has spurred growing interest in developing genomic signatures that can be used for cancer diagnosis and prognosis. However, progress has been slowed by heterogeneity in cancer profiles and the lack of effective computational prediction tools for this type of data. RESULTS: We developed anti-profiles as a first step towards translating experimental findings suggesting that stochastic across-sample hyper-variability in the expression of specific genes is a stable and general property of cancer into predictive and diagnostic signatures. Using single-chip microarray normalization and quality assessment methods, we developed an anti-profile for colon cancer in tissue biopsy samples. To demonstrate the translational potential of our findings, we applied the signature developed in the tissue samples, without any further retraining or normalization, to screen patients for colon cancer based on genomic measurements from peripheral blood in an independent study (AUC of 0.89). This method achieved higher accuracy than the signature underlying commercially available peripheral blood screening tests for colon cancer (AUC of 0.81). We also confirmed the existence of hyper-variable genes across a range of cancer types and found that a significant proportion of tissue-specific genes are hyper-variable in cancer. Based on these observations, we developed a universal cancer anti-profile that accurately distinguishes cancer from normal regardless of tissue type (ten-fold cross-validation AUC > 0.92). CONCLUSIONS: We have introduced anti-profiles as a new approach for developing cancer genomic signatures that specifically takes advantage of gene expression heterogeneity. We have demonstrated that anti-profiles can be successfully applied to develop peripheral-blood based diagnostics for cancer and used anti-profiles to develop a highly accurate universal cancer signature. By using single-chip normalization and quality assessment methods, no further retraining of signatures developed by the anti-profile approach would be required before their application in clinical settings. Our results suggest that anti-profiles may be used to develop inexpensive and non-invasive universal cancer screening tests.}, keywords = {Area Under Curve, Colonic Neoplasms, Gene Expression Profiling, Genetic Variation, Genomics, HUMANS, Oligonucleotide Array Sequence Analysis, Prognosis, Transcriptome, Tumor Markers, Biological}, author = {H{\'e}ctor Corrada Bravo and Pihur, Vasyl and McCall, Matthew and Irizarry, Rafael A. and Leek, Jeffrey T.} } @article {38314, title = {Genomic analysis of sleep deprivation reveals translational regulation in the hippocampus}, journal = {Physiological GenomicsPhysiological Genomics}, year = {2012}, author = {Christopher, G. Vecsey and Lucia, Peixoto and Jennifer, H. K. Choi and Mathieu, Wimmer and Devan, Jaganath and Pepe, J. Hernandez and Jennifer, Blackwell and Karuna, Meda and Alan, J. Park and Sridhar Hannenhalli and Abel, Ted} } @article {38352, title = {InterPro in 2011: new developments in the family and domain prediction database}, journal = {Nucleic acids researchNucleic Acids Research}, volume = {40}, year = {2012}, note = {http://www.ncbi.nlm.nih.gov/pubmed/22096229?dopt=Abstract}, type = {10.1093/nar/gkr948}, abstract = {InterPro (http://www.ebi.ac.uk/interpro/) is a database that integrates diverse information about protein families, domains and functional sites, and makes it freely available to the public via Web-based interfaces and services. Central to the database are diagnostic models, known as signatures, against which protein sequences can be searched to determine their potential function. InterPro has utility in the large-scale analysis of whole genomes and meta-genomes, as well as in characterizing individual protein sequences. Herein we give an overview of new developments in the database and its associated software since 2009, including updates to database content, curation processes and Web and programmatic interfaces.}, keywords = {Databases, Protein, Protein Structure, Tertiary, Proteins, Sequence Analysis, Protein, software, Terminology as Topic, User-Computer Interface}, author = {Hunter, Sarah and Jones, Philip and Mitchell, Alex and Apweiler, Rolf and Attwood, Teresa K. and Bateman, Alex and Bernard, Thomas and Binns, David and Bork, Peer and Burge, Sarah and de Castro, Edouard and Coggill, Penny and Corbett, Matthew and Das, Ujjwal and Daugherty, Louise and Duquenne, Lauranne and Finn, Robert D. and Fraser, Matthew and Gough, Julian and Haft, Daniel and Hulo, Nicolas and Kahn, Daniel and Kelly, Elizabeth and Letunic, Ivica and Lonsdale, David and Lopez, Rodrigo and Madera, Martin and Maslen, John and McAnulla, Craig and McDowall, Jennifer and McMenamin, Conor and Mi, Huaiyu and Mutowo-Muellenet, Prudence and Mulder, Nicola and Natale, Darren and Orengo, Christine and Pesseat, Sebastien and Punta, Marco and Quinn, Antony F. and Rivoire, Catherine and Sangrador-Vegas, Amaia and J. Selengut and Sigrist, Christian J. A. and Scheremetjew, Maxim and Tate, John and Thimmajanarthanan, Manjulapramila and Thomas, Paul D. and Wu, Cathy H. and Yeats, Corin and Yong, Siew-Yit} } @article {49765, title = {InterPro in 2011: new developments in the family and domain prediction database.}, journal = {Nucleic Acids Res}, volume = {40}, year = {2012}, month = {2012 Jan}, pages = {D306-12}, abstract = {

InterPro (http://www.ebi.ac.uk/interpro/) is a database that integrates diverse information about protein families, domains and functional sites, and makes it freely available to the public via Web-based interfaces and services. Central to the database are diagnostic models, known as signatures, against which protein sequences can be searched to determine their potential function. InterPro has utility in the large-scale analysis of whole genomes and meta-genomes, as well as in characterizing individual protein sequences. Herein we give an overview of new developments in the database and its associated software since 2009, including updates to database content, curation processes and Web and programmatic interfaces.

}, keywords = {Databases, Protein, Protein Structure, Tertiary, Proteins, Sequence Analysis, Protein, software, Terminology as Topic, User-Computer Interface}, issn = {1362-4962}, doi = {10.1093/nar/gkr948}, author = {Hunter, Sarah and Jones, Philip and Mitchell, Alex and Apweiler, Rolf and Attwood, Teresa K and Bateman, Alex and Bernard, Thomas and Binns, David and Bork, Peer and Burge, Sarah and de Castro, Edouard and Coggill, Penny and Corbett, Matthew and Das, Ujjwal and Daugherty, Louise and Duquenne, Lauranne and Finn, Robert D and Fraser, Matthew and Gough, Julian and Haft, Daniel and Hulo, Nicolas and Kahn, Daniel and Kelly, Elizabeth and Letunic, Ivica and Lonsdale, David and Lopez, Rodrigo and Madera, Martin and Maslen, John and McAnulla, Craig and McDowall, Jennifer and McMenamin, Conor and Mi, Huaiyu and Mutowo-Muellenet, Prudence and Mulder, Nicola and Natale, Darren and Orengo, Christine and Pesseat, Sebastien and Punta, Marco and Quinn, Antony F and Rivoire, Catherine and Sangrador-Vegas, Amaia and Selengut, Jeremy D and Sigrist, Christian J A and Scheremetjew, Maxim and Tate, John and Thimmajanarthanan, Manjulapramila and Thomas, Paul D and Wu, Cathy H and Yeats, Corin and Yong, Siew-Yit} } @article {49517, title = {A molecular phylogeny for the leaf-roller moths (Lepidoptera: Tortricidae) and its implications for classification and life history evolution.}, journal = {PloS one}, volume = {7}, year = {2012}, month = {2012}, pages = {e35574}, abstract = {Tortricidae, one of the largest families of microlepidopterans, comprise about 10,000 described species worldwide, including important pests, biological control agents and experimental models. Understanding of tortricid phylogeny, the basis for a predictive classification, is currently provisional. We present the first detailed molecular estimate of relationships across the tribes and subfamilies of Tortricidae, assess its concordance with previous morphological evidence, and re-examine postulated evolutionary trends in host plant use and biogeography.}, author = {Regier, Jerome C and Brown, John W and Mitter, Charles and Baixeras, Joaquin and Cho, Soowon and Michael P. Cummings and Zwick, Andreas} } @article {49515, title = {A molecular phylogeny for the pyraloid moths (Lepidoptera: Pyraloidea) and its implications for higher-level classification}, journal = {Systematic Entomology}, volume = {37}, year = {2012}, month = {Jan-10-2012}, pages = {635 - 656}, doi = {10.1111/sen.2012.37.issue-410.1111/j.1365-3113.2012.00641.x}, url = {http://doi.wiley.com/10.1111/sen.2012.37.issue-4http://doi.wiley.com/10.1111/j.1365-3113.2012.00641.x}, author = {Regier, Jerome C. and Mitter, Charles and SOLIS, M. ALMA and HAYDEN, JAMES E. and LANDRY, BERNARD and NUSS, MATTHIAS and Simonsen, Thomas J. and Yen, Shen-Horn and Zwick, Andreas and Michael P. Cummings} } @article {38393, title = {Myocardin-like Protein (MKL)-2 Regulates TGF-beta Signaling}, journal = {Embryonic Stem Cells and the Developing Vasculature DevelopmentEmbryonic Stem Cells and the Developing Vasculature Development}, year = {2012}, author = {Li, Jian and Nina, Bowens and Lan, Cheng and Mary, Chen and Sridhar Hannenhalli and Xiaohong, Zhu and Thomas, P. Cappola and Parmacek, Michael S.} } @article {38412, title = {Occurrence of protozoans \& their limnological relationships in some ponds of Mathbaria, Bangladesh}, journal = {University Journal of Zoology, Rajshahi UniversityUniversity Journal of Zoology, Rajshahi University}, volume = {29}, year = {2012}, isbn = {1023-6104}, author = {Mozumder, P. K. and Banu, M. A. and Naser, M. N. and Ali, M. S. and Alam, M. and Sack, R. B. and Rita R. Colwell and Huq, A.} } @article {49531, title = {Plasmodium falciparum merozoite surface protein 1 blocks the proinflammatory protein S100P.}, volume = {109}, year = {2012}, month = {2012 Apr 3}, pages = {5429-34}, abstract = {

The malaria parasite, Plasmodium falciparum, and the human immune system have coevolved to ensure that the parasite is not eliminated and reinfection is not resisted. This relationship is likely mediated through a myriad of host-parasite interactions, although surprisingly few such interactions have been identified. Here we show that the 33-kDa fragment of P. falciparum merozoite surface protein 1 (MSP1(33)), an abundant protein that is shed during red blood cell invasion, binds to the proinflammatory protein, S100P. MSP1(33) blocks S100P-induced NFκB activation in monocytes and chemotaxis in neutrophils. Remarkably, S100P binds to both dimorphic alleles of MSP1, estimated to have diverged >27 Mya, suggesting an ancient, conserved relationship between these parasite and host proteins that may serve to attenuate potentially damaging inflammatory responses.

}, keywords = {Amino Acid Sequence, Animals, Calcium-Binding Proteins, Chromatography, Gel, Electrophoresis, Polyacrylamide Gel, Enzyme-Linked Immunosorbent Assay, HUMANS, Merozoite Surface Protein 1, Microscopy, Confocal, Molecular Sequence Data, Neoplasm Proteins, Plasmodium falciparum, Sequence Homology, Amino Acid, Surface Plasmon Resonance}, issn = {1091-6490}, doi = {10.1073/pnas.1202689109}, author = {Waisberg, Michael and Cerqueira, Gustavo C and Yager, Stephanie B and Francischetti, Ivo M B and Lu, Jinghua and Gera, Nidhi and Srinivasan, Prakash and Miura, Kazutoyo and Rada, Balazs and Lukszo, Jan and Barbian, Kent D and Leto, Thomas L and Porcella, Stephen F and Narum, David L and El-Sayed, Najib and Miller, Louis H and Pierce, Susan K} } @article {38526, title = {Temporal and Spatial Variability in the Distribution of Vibrio vulnificus in the Chesapeake Bay: A Hindcast Study}, journal = {EcoHealthEcoHealth}, year = {2012}, type = {10.1007/s10393-011-0736-4}, abstract = {Vibrio vulnificus, an estuarine bacterium, is the causative agent of seafood-related gastroenteritis, primary septicemia, and wound infections worldwide. It occurs as part of the normal microflora of coastal marine environments and can be isolated from water, sediment, and oysters. Hindcast prediction was undertaken to determine spatial and temporal variability in the likelihood of occurrence of V. vulnificus in surface waters of the Chesapeake Bay. Hindcast predictions were achieved by forcing a multivariate habitat suitability model with simulated sea surface temperature and salinity in the Bay for the period between 1991 and 2005 and the potential hotspots of occurrence of V. vulnificus in the Chesapeake Bay were identified. The likelihood of occurrence of V. vulnificus during high and low rainfall years was analyzed. From results of the study, it is concluded that hindcast prediction yields an improved understanding of environmental conditions associated with occurrence of V. vulnificus in the Chesapeake Bay.}, author = {Banakar, V. and Constantin de Magny, G. and Jacobs, J. and Murtugudde, R. and Huq, A. and J. Wood, R. and Rita R. Colwell} } @article {38566, title = {Vibrio Cholerae Classical Biotype Strains Reveal Distinct Signatures in Mexico}, journal = {Journal of Clinical MicrobiologyJ. Clin. Microbiol.Journal of Clinical MicrobiologyJ. Clin. Microbiol.}, year = {2012}, type = {10.1128/JCM.00189-12}, abstract = {Vibrio cholerae O1 Classical (CL) biotype caused the 5th and 6th, and probably the earlier cholera pandemics, before the El Tor (ET) biotype initiated the 7th pandemic in Asia in the 1970{\textquoteright}s by completely displacing the CL biotype. Although the CL biotype was thought to be extinct in Asia, and it had never been reported from Latin America, V. cholerae CL and ET biotypes, including hybrid ET were found associated with endemic cholera in Mexico between 1991 and 1997. In this study, CL biotype strains isolated from endemic cholera in Mexico, between 1983 and 1997 were characterized in terms of major phenotypic and genetic traits, and compared with CL biotype strains isolated in Bangladesh between 1962 and 1989. According to sero- and bio-typing data, all V. cholerae strains tested had the major phenotypic and genotypic characteristics specific for the CL biotype. Antibiograms revealed the majority of the Bangladeshi strains to be resistant to trimethoprim/sulfamethoxazole, furazolidone, ampicillin, and gentamycin, while the Mexican strains were sensitive to all of these drugs, as well as to ciprofloxacin, erythromycin, and tetracycline. Pulsed-field gel electrophoresis (PFGE) of NotI-digested genomic DNA revealed characteristic banding patterns for all the CL biotype strains, although the Mexican strains differed with the Bangladeshi strains in 1-2 DNA bands. The difference may be subtle, but consistent, as confirmed by the sub-clustering patterns in the PFGE-based dendrogram, and can serve as regional signature, suggesting pre-1991 existence and evolution of the CL biotype strains in the Americas, independent from that of Asia.}, isbn = {0095-1137, 1098-660X}, author = {Alam, Munirul and Islam, M. Tarequl and Rashed, Shah Manzur and Johura, Fatema-Tuz and Bhuiyan, Nurul A. and Delgado, Gabriela and Morales, Rosario and Mendez, Jose Luis and Navarro, Armando and Watanabe, Haruo and Hasan, Nur- A. and Rita R. Colwell and Cravioto, Alejandro} } @article {38573, title = {Whole genome analysis of Leptospira licerasiae provides insight into leptospiral evolution and pathogenicity}, journal = {PLoS neglected tropical diseasesPLoS neglected tropical diseases}, volume = {6}, year = {2012}, note = {http://www.ncbi.nlm.nih.gov/pubmed/23145189?dopt=Abstract}, type = {10.1371/journal.pntd.0001853}, abstract = {The whole genome analysis of two strains of the first intermediately pathogenic leptospiral species to be sequenced (Leptospira licerasiae strains VAR010 and MMD0835) provides insight into their pathogenic potential and deepens our understanding of leptospiral evolution. Comparative analysis of eight leptospiral genomes shows the existence of a core leptospiral genome comprising 1547 genes and 452 conserved genes restricted to infectious species (including L. licerasiae) that are likely to be pathogenicity-related. Comparisons of the functional content of the genomes suggests that L. licerasiae retains several proteins related to nitrogen, amino acid and carbohydrate metabolism which might help to explain why these Leptospira grow well in artificial media compared with pathogenic species. L. licerasiae strains VAR010(T) and MMD0835 possess two prophage elements. While one element is circular and shares homology with LE1 of L. biflexa, the second is cryptic and homologous to a previously identified but unnamed region in L. interrogans serovars Copenhageni and Lai. We also report a unique O-antigen locus in L. licerasiae comprised of a 6-gene cluster that is unexpectedly short compared with L. interrogans in which analogous regions may include >90 such genes. Sequence homology searches suggest that these genes were acquired by lateral gene transfer (LGT). Furthermore, seven putative genomic islands ranging in size from 5 to 36 kb are present also suggestive of antecedent LGT. How Leptospira become naturally competent remains to be determined, but considering the phylogenetic origins of the genes comprising the O-antigen cluster and other putative laterally transferred genes, L. licerasiae must be able to exchange genetic material with non-invasive environmental bacteria. The data presented here demonstrate that L. licerasiae is genetically more closely related to pathogenic than to saprophytic Leptospira and provide insight into the genomic bases for its infectiousness and its unique antigenic characteristics.}, keywords = {DNA, Bacterial, Evolution, Molecular, Gene Transfer, Horizontal, Genome, Bacterial, Genomic islands, HUMANS, Leptospira, Molecular Sequence Data, Multigene Family, Prophages, Sequence Analysis, DNA, Virulence factors}, author = {Ricaldi, Jessica N. and Fouts, Derrick E. and J. Selengut and Harkins, Derek M. and Patra, Kailash P. and Moreno, Angelo and Lehmann, Jason S. and Purushe, Janaki and Sanka, Ravi and Torres, Michael and Webster, Nicholas J. and Vinetz, Joseph M. and Matthias, Michael A.} } @article {49776, title = {Whole genome analysis of Leptospira licerasiae provides insight into leptospiral evolution and pathogenicity.}, journal = {PLoS Negl Trop Dis}, volume = {6}, year = {2012}, month = {2012}, pages = {e1853}, abstract = {

The whole genome analysis of two strains of the first intermediately pathogenic leptospiral species to be sequenced (Leptospira licerasiae strains VAR010 and MMD0835) provides insight into their pathogenic potential and deepens our understanding of leptospiral evolution. Comparative analysis of eight leptospiral genomes shows the existence of a core leptospiral genome comprising 1547 genes and 452 conserved genes restricted to infectious species (including L. licerasiae) that are likely to be pathogenicity-related. Comparisons of the functional content of the genomes suggests that L. licerasiae retains several proteins related to nitrogen, amino acid and carbohydrate metabolism which might help to explain why these Leptospira grow well in artificial media compared with pathogenic species. L. licerasiae strains VAR010(T) and MMD0835 possess two prophage elements. While one element is circular and shares homology with LE1 of L. biflexa, the second is cryptic and homologous to a previously identified but unnamed region in L. interrogans serovars Copenhageni and Lai. We also report a unique O-antigen locus in L. licerasiae comprised of a 6-gene cluster that is unexpectedly short compared with L. interrogans in which analogous regions may include >90 such genes. Sequence homology searches suggest that these genes were acquired by lateral gene transfer (LGT). Furthermore, seven putative genomic islands ranging in size from 5 to 36 kb are present also suggestive of antecedent LGT. How Leptospira become naturally competent remains to be determined, but considering the phylogenetic origins of the genes comprising the O-antigen cluster and other putative laterally transferred genes, L. licerasiae must be able to exchange genetic material with non-invasive environmental bacteria. The data presented here demonstrate that L. licerasiae is genetically more closely related to pathogenic than to saprophytic Leptospira and provide insight into the genomic bases for its infectiousness and its unique antigenic characteristics.

}, keywords = {DNA, Bacterial, Evolution, Molecular, Gene Transfer, Horizontal, Genome, Bacterial, Genomic islands, HUMANS, Leptospira, Molecular Sequence Data, Multigene Family, Prophages, Sequence Analysis, DNA, Virulence factors}, issn = {1935-2735}, doi = {10.1371/journal.pntd.0001853}, author = {Ricaldi, Jessica N and Fouts, Derrick E and Selengut, Jeremy D and Harkins, Derek M and Patra, Kailash P and Moreno, Angelo and Lehmann, Jason S and Purushe, Janaki and Sanka, Ravi and Torres, Michael and Webster, Nicholas J and Vinetz, Joseph M and Matthias, Michael A} } @article {38141, title = {Can Deliberately Incomplete Gene Sample Augmentation Improve a Phylogeny Estimate for the Advanced Moths and Butterflies (Hexapoda: Lepidoptera)?}, journal = {Systematic BiologySyst BiolSystematic BiologySyst Biol}, volume = {60}, year = {2011}, type = {10.1093/sysbio/syr079}, abstract = {This paper addresses the question of whether one can economically improve the robustness of a molecular phylogeny estimate by increasing gene sampling in only a subset of taxa, without having the analysis invalidated by artifacts arising from large blocks of missing data. Our case study stems from an ongoing effort to resolve poorly understood deeper relationships in the large clade Ditrysia ( > 150,000 species) of the insect order Lepidoptera (butterflies and moths). Seeking to remedy the overall weak support for deeper divergences in an initial study based on five nuclear genes (6.6 kb) in 123 exemplars, we nearly tripled the total gene sample (to 26 genes, 18.4 kb) but only in a third (41) of the taxa. The resulting partially augmented data matrix (45\% intentionally missing data) consistently increased bootstrap support for groupings previously identified in the five-gene (nearly) complete matrix, while introducing no contradictory groupings of the kind that missing data have been predicted to produce. Our results add to growing evidence that data sets differing substantially in gene and taxon sampling can often be safely and profitably combined. The strongest overall support for nodes above the family level came from including all nucleotide changes, while partitioning sites into sets undergoing mostly nonsynonymous versus mostly synonymous change. In contrast, support for the deepest node for which any persuasive molecular evidence has yet emerged (78{\textendash}85\% bootstrap) was weak or nonexistent unless synonymous change was entirely excluded, a result plausibly attributed to compositional heterogeneity. This node (Gelechioidea + Apoditrysia), tentatively proposed by previous authors on the basis of four morphological synapomorphies, is the first major subset of ditrysian superfamilies to receive strong statistical support in any phylogenetic study. A {\textquotedblleft}more-genes-only{\textquotedblright} data set (41 taxa{\texttimes}26 genes) also gave strong signal for a second deep grouping (Macrolepidoptera) that was obscured, but not strongly contradicted, in more taxon-rich analyses.}, keywords = {Ditrysia, gene sampling, Hexapoda, Lepidoptera, missing data, molecular phylogenetics, nuclear genes, taxon sampling}, isbn = {1063-5157, 1076-836X}, author = {Cho, Soowon and Zwick, Andreas and Regier, Jerome C. and Mitter, Charles and Michael P. Cummings and Yao, Jianxiu and Du, Zaile and Zhao, Hong and Kawahara, Akito Y. and Weller, Susan and Davis, Donald R. and Baixeras, Joaquin and Brown, John W. and Parr, Cynthia} } @article {49854, title = {Complete Columbian mammoth mitogenome suggests interbreeding with woolly mammoths}, journal = {Genome biology}, volume = {12}, year = {2011}, pages = {R51}, author = {Enk, Jacob and Devault, Alison and Debruyne, Regis and King, Christine E and Todd Treangen and O{\textquoteright}Rourke, Dennis and Salzberg, Steven L and Fisher, Daniel and MacPhee, Ross and Poinar, Hendrik} } @article {49556, title = {Direct targeting of Sec23a by miR-200s influences cancer cell secretome and promotes metastatic colonization}, volume = {17}, year = {2011}, month = {Jul-08-2011}, pages = {1101 - 1108}, issn = {1078-8956}, doi = {10.1038/nm.2401}, url = {http://www.nature.com/doifinder/10.1038/nm.2401}, author = {Korpal, Manav and Ell, Brian J and Buffa, Francesca M and Ibrahim, Toni and Blanco, Mario A and {\`a}-Terrassa, Toni and Mercatali, Laura and Khan, Zia and Goodarzi, Hani and Hua, Yuling and Wei, Yong and Hu, Guohong and Garcia, Benjamin A and Ragoussis, Jiannis and Amadori, Dino and Harris, Adrian L and Kang, Yibin} } @article {49746, title = {Direct targeting of Sec23a by miR-200s influences cancer cell secretome and promotes metastatic colonization.}, journal = {Nat Med}, volume = {17}, year = {2011}, month = {2011 Sep}, pages = {1101-8}, abstract = {

Although the role of miR-200s in regulating E-cadherin expression and epithelial-to-mesenchymal transition is well established, their influence on metastatic colonization remains controversial. Here we have used clinical and experimental models of breast cancer metastasis to discover a pro-metastatic role of miR-200s that goes beyond their regulation of E-cadherin and epithelial phenotype. Overexpression of miR-200s is associated with increased risk of metastasis in breast cancer and promotes metastatic colonization in mouse models, phenotypes that cannot be recapitulated by E-cadherin expression alone. Genomic and proteomic analyses revealed global shifts in gene expression upon miR-200 overexpression toward that of highly metastatic cells. miR-200s promote metastatic colonization partly through direct targeting of Sec23a, which mediates secretion of metastasis-suppressive proteins, including Igfbp4 and Tinagl1, as validated by functional and clinical correlation studies. Overall, these findings suggest a pleiotropic role of miR-200s in promoting metastatic colonization by influencing E-cadherin-dependent epithelial traits and Sec23a-mediated tumor cell secretome.

}, keywords = {Animals, Cadherins, Cell Line, Tumor, Female, Gene Expression Profiling, Gene Expression Regulation, Neoplastic, HUMANS, Mass Spectrometry, Mice, Mice, Inbred BALB C, Microarray Analysis, MicroRNAs, Neoplasm Metastasis, Statistics, Nonparametric, Vesicular Transport Proteins}, issn = {1546-170X}, doi = {10.1038/nm.2401}, author = {Korpal, Manav and Ell, Brian J and Buffa, Francesca M and Ibrahim, Toni and Blanco, Mario A and Celi{\`a}-Terrassa, Toni and Mercatali, Laura and Khan, Zia and Goodarzi, Hani and Hua, Yuling and Wei, Yong and Hu, Guohong and Garcia, Benjamin A and Ragoussis, Jiannis and Amadori, Dino and Harris, Adrian L and Kang, Yibin} } @article {49727, title = {Haem oxygenase is synthetically lethal with the tumour suppressor fumarate hydratase.}, journal = {Nature}, volume = {477}, year = {2011}, month = {2011 Sep 8}, pages = {225-8}, abstract = {

Fumarate hydratase (FH) is an enzyme of the tricarboxylic acid cycle (TCA cycle) that catalyses the hydration of fumarate into malate. Germline mutations of FH are responsible for hereditary leiomyomatosis and renal-cell cancer (HLRCC). It has previously been demonstrated that the absence of FH leads to the accumulation of fumarate, which activates hypoxia-inducible factors (HIFs) at normal oxygen tensions. However, so far no mechanism that explains the ability of cells to survive without a functional TCA cycle has been provided. Here we use newly characterized genetically modified kidney mouse cells in which Fh1 has been deleted, and apply a newly developed computer model of the metabolism of these cells to predict and experimentally validate a linear metabolic pathway beginning with glutamine uptake and ending with bilirubin excretion from Fh1-deficient cells. This pathway, which involves the biosynthesis and degradation of haem, enables Fh1-deficient cells to use the accumulated TCA cycle metabolites and permits partial mitochondrial NADH production. We predicted and confirmed that targeting this pathway would render Fh1-deficient cells non-viable, while sparing wild-type Fh1-containing cells. This work goes beyond identifying a metabolic pathway that is induced in Fh1-deficient cells to demonstrate that inhibition of haem oxygenation is synthetically lethal when combined with Fh1 deficiency, providing a new potential target for treating HLRCC patients.

}, keywords = {Animals, Bilirubin, Cell Line, Cells, Cultured, Citric Acid Cycle, Computer simulation, Fumarate Hydratase, Fumarates, Genes, Lethal, Genes, Tumor Suppressor, Glutamine, Heme, Heme Oxygenase (Decyclizing), Kidney Neoplasms, Leiomyomatosis, Mice, Mitochondria, Mutation, NAD, Neoplastic Syndromes, Hereditary, Skin Neoplasms, Uterine Neoplasms}, issn = {1476-4687}, doi = {10.1038/nature10363}, author = {Frezza, Christian and Zheng, Liang and Folger, Ori and Rajagopalan, Kartik N and MacKenzie, Elaine D and Jerby, Livnat and Micaroni, Massimo and Chaneton, Barbara and Adam, Julie and Hedley, Ann and Kalna, Gabriela and Tomlinson, Ian P M and Pollard, Patrick J and Watson, Dave G and Deberardinis, Ralph J and Shlomi, Tomer and Ruppin, Eytan and Gottlieb, Eyal} } @article {38341, title = {Increased gene sampling provides stronger support for higher-level groups within gracillariid leaf mining moths and relatives (Lepidoptera: Gracillariidae)}, journal = {BMC Evol BiolBMC Evol Biol}, volume = {11:182}, year = {2011}, author = {Kawahara, A. Y. and Ohshima, I. and Kawakita, A. and Regier, J. C. and Mitter, C. and Michael P. Cummings and Davis, D. R. and Wagner, D. L. and De Prinis, J. and Lopez-Vaamonde, C.} } @article {38342, title = {Increased gene sampling yields robust support for higher-level clades within Bombycoidea (Lepidoptera)}, journal = {Systematic EntomologySystematic Entomology}, volume = {36}, year = {2011}, type = {10.1111/j.1365-3113.2010.00543.x}, abstract = {This study has as its primary aim the robust resolution of higher-level relationships within the lepidopteran superfamily Bombycoidea. Our study builds on an earlier analysis of five genes (\~{}6.6 kbp) sequenced for 50 taxa from Bombycoidea and its sister group Lasiocampidae, plus representatives of other macrolepidoteran superfamilies. The earlier study failed to yield strong support for the monophyly of and basal splits within Bombycoidea, among others. Therefore, in an effort to increase support specifically for higher-level nodes, we generated 11.7 kbp of additional data from 20 genes for 24 of 50 bombycoid and lasiocampid taxa. The data from the genes are all derived from protein-coding nuclear genes previously used to resolve other lepidopteran relationships. With these additional data, all but a few higher-level nodes are strongly supported. Given our decision to minimize project costs by augmenting genes for only 24 of the 50 taxa, we explored whether the resulting pattern of missing data in the combined-gene matrix introduced a nonphylogenetic bias, a possibility reported by others. This was achieved by comparing node support values (i.e. nonparametric bootstrap values) based on likelihood and parsimony analyses of three datasets that differ in their number of taxa and level of missing data: 50 taxa/5 genes (dataset A), 50 taxa/25 genes (dataset B) and 24 taxa/25 genes (dataset C). Whereas datasets B and C provided similar results for common nodes, both frequently yielded higher node support relative to dataset A, arguing that: (i) more data yield increased node support and (ii) partial gene augmentation does not introduce an obvious nonphylogenetic bias. A comparison of single-gene bootstrap analyses identified four nodes for which one or two of the 25 genes provided modest to strong support for a grouping not recovered by the combined-gene result. As a summary proposal, two of these four groupings (one each within Bombycoidea and Lasiocampidae) were deemed sufficiently problematic to regard them as unresolved trichotomies. Since the alternative groupings were always highly localized on the tree, we did not judge a combined-gene analysis to present a problem outside those regions. Based on our robustly resolved results, we have revised the classification of Bombycoidea: the family Bombycidae is restricted to its nominate subfamily, and its tribe Epiini is elevated to subfamily rank (Epiinae stat.rev.), whereas the bombycid subfamily Phiditiinae is reinstated as a separate family (Phiditiidae stat.rev.). The bombycid subfamilies Oberthueriinae Kuznetzov \& Stekolnikov, 1985, syn.nov. and Prismostictinae Forbes, 1955, syn.nov., and the family Mirinidae Kozlov, 1985, syn.nov. are established as subjective junior synonyms of Endromidae Boisduval, 1828. The family Anthelidae (Lasiocampoidea) is reincluded in the superfamily Bombycoidea.}, isbn = {1365-3113}, author = {Zwick, Andreas and Regier, Jerome C. and Mitter, Charles and Michael P. Cummings} } @article {49831, title = {Increased methylation variation in epigenetic domains across cancer types}, journal = {Nature Genetics}, volume = {43}, year = {2011}, month = {Feb-06-2013}, pages = {768 - 775}, issn = {1061-4036}, doi = {10.1038/ng.865}, url = {http://www.nature.com/doifinder/10.1038/ng.865}, author = {Hansen, Kasper Daniel and Timp, Winston and Bravo, H{\'e}ctor Corrada and Sabunciyan, Sarven and Langmead, Benjamin and McDonald, Oliver G and Wen, Bo and Wu, Hao and Liu, Yun and Diep, Dinh and Briem, Eirikur and Zhang, Kun and Irizarry, Rafael A and Feinberg, Andrew P} } @article {38347, title = {Influence of host gene transcription level and orientation on HIV-1 latency in a primary-cell model}, journal = {Journal of virologyJournal of virology}, volume = {85}, year = {2011}, note = {http://www.ncbi.nlm.nih.gov/pubmed/21430059?dopt=Abstract}, type = {10.1128/JVI.02536-10}, abstract = {Human immunodeficiency virus type 1 (HIV-1) establishes a latent reservoir in resting memory CD4(+) T cells. This latent reservoir is a major barrier to the eradication of HIV-1 in infected individuals and is not affected by highly active antiretroviral therapy (HAART). Reactivation of latent HIV-1 is a possible strategy for elimination of this reservoir. The mechanisms with which latency is maintained are unclear. In the analysis of the regulation of HIV-1 gene expression, it is important to consider the nature of HIV-1 integration sites. In this study, we analyzed the integration and transcription of latent HIV-1 in a primary CD4(+) T cell model of latency. The majority of integration sites in latently infected cells were in introns of transcription units. Serial analysis of gene expression (SAGE) demonstrated that more than 90\% of those host genes harboring a latent integrated provirus were transcriptionally active, mostly at high levels. For latently infected cells, we observed a modest preference for integration in the same transcriptional orientation as the host gene (63.8\% versus 36.2\%). In contrast, this orientation preference was not observed in acutely infected or persistently infected cells. These results suggest that transcriptional interference may be one of the important factors in the establishment and maintenance of HIV-1 latency. Our findings suggest that disrupting the negative control of HIV-1 transcription by upstream host promoters could facilitate the reactivation of latent HIV-1 in some resting CD4(+) T cells.}, keywords = {CD4-Positive T-Lymphocytes, Cells, Cultured, Gene Expression Profiling, Gene Expression Regulation, Viral, HIV-1, HUMANS, Transcription, Genetic, Virus Integration, Virus Latency}, author = {Shan, Liang and Yang, Hung-Chih and Rabi, S. Alireza and H{\'e}ctor Corrada Bravo and Shroff, Neeta S. and Irizarry, Rafael A. and Zhang, Hao and Margolick, Joseph B. and Siliciano, Janet D. and Siliciano, Robert F.} } @article {49832, title = {Influence of Host Gene Transcription Level and Orientation on HIV-1 Latency in a Primary-Cell Model}, journal = {Journal of Virology}, volume = {85}, year = {2011}, month = {Jan-06-2011}, pages = {5384 - 5393}, issn = {0022-538X}, doi = {10.1128/JVI.02536-10}, url = {http://jvi.asm.org/cgi/doi/10.1128/JVI.02536-10https://syndication.highwire.org/content/doi/10.1128/JVI.02536-10}, author = {Shan, L. and Yang, H.-C. and Rabi, S. A. and Bravo, H. C. and Shroff, N. S. and Irizarry, R. A. and Zhang, H. and Margolick, J. B. and Siliciano, J. D. and Siliciano, R. F.} } @article {38370, title = {Metagenomic 16S rDNA Targeted PCR-DGGE in Determining Bacterial Diversity in Aquatic Ecosystem}, journal = {Bangladesh Journal of MicrobiologyBangladesh Journal of Microbiology}, volume = {27}, year = {2011}, type = {10.3329/bjm.v27i2.9171}, abstract = {Bacterial numbers in surface water samples, collected randomly from six different water bodies, were estimated by acridine orange direct counting (AODC) and conventional culture-based heterotrophic plate counting (HPC). Bacterial genomic DNA was prepared from water samples by employing methods used for stool samples, including the population dynamics, were determined by primer extension of the 16S rDNA (V6/V8 region) using polymerase chain reaction (PCR), followed by denaturing gradient gel electrophoresis (DGGE), a metagenomic tool that is capable of separating unrelated DNAs based on the differences in their sequences and GC contents. The bacterial numbers in water samples ranged from 103 {\textendash} 106 CFU/ mL for HPC and 104 {\textendash} 107 cells/ mL for AODC, showing that a great majority of bacteria prevail as uncultivable which do not respond to culture methods that are used widely for tracking bacterial pathogens. The acridine orange-stained bacteria varied in sizes and shapes, and appeared either as planktonic (solitary) cells or as clusters of biofilms, showing the presence of diverse community under the epifluorescence microscope. The DGGE of the ca. 457 bp amplicons, as confirmed by agarose gel electrophoresis, produced bands that ranged in intensities and numbers from 18 to 31, with each band possibly indicating the presence of one or more closely related bacterial species. The enrichment of pathogenic bacteria in the aquatic ecosystem is known to precede the seasonal diarrhoeal outbreaks; therefore, bacterial community dynamics determined by Metagenomic 16S PCR-DGGE during pre-epidemic enrichment appears promising in predicting the upcoming diarrheal outbreaks.}, isbn = {1011-9981}, author = {Hasan, Nur A. and Chowdhury, W. Bari and Rahim, Niaz and Sultana, Marzia and Shabnam, S. Antara and Mai, Volker and Ali, Afsar and Morris, Glen J. and Sack, R. Bradley and Huq, Anwar and Rita R. Colwell and Endtz, Hubert Ph and Cravioto, Alejandro and Alam, Munirul} } @article {38440, title = {Population Dynamics of Vibrio Cholerae and Cholera in the Bangladesh Sundarbans: Role of Zooplankton Diversity}, journal = {Applied and Environmental MicrobiologyAppl. Environ. Microbiol.Applied and Environmental MicrobiologyAppl. Environ. Microbiol.}, year = {2011}, type = {10.1128/AEM.01472-10}, abstract = {Vibrio cholerae, a bacterium autochthonous to the aquatic environment, is the causative agent of cholera, a severe watery, life-threatening diarrhoeal disease occurring predominantly in developing countries. V. cholerae, including both serogroup O1 and O139, i.e. found in association with crustacean zooplankton, mainly copepods, and notably in ponds, rivers, and estuarine systems globally. The incidence of cholera and occurrence of V. cholerae pathogenic strains with zooplankton were studied in two areas of Bangladesh: Bakerganj and Mathbaria. Chitinous zooplankton communities of several bodies of water were analyzed in order to understand the interaction of zooplankton population composition with the population dynamics of pathogenic V. cholerae and incidence of cholera. Two dominant zooplankton groups were found to be consistently associated with detection of V. cholerae and/or occurrence of cholera cases, namely rotifers, and cladocerans, in addition to copepods. Local differences indicate there are subtle ecological factors that can influence interactions between V. cholerae, its plankton hosts, and the incidence of cholera.}, isbn = {0099-2240, 1098-5336}, author = {De Magny, Guillaume Constantin and Mozumder, Pronob K. and Grim, Christopher J. and Hasan, Nur A. and Naser, M. Niamul and Alam, Munirul and Sack, Bradley and Huq, Anwar and Rita R. Colwell} } @article {38460, title = {Regulation of Lung Endoderm Progenitor Cell Behavior by miR302/367}, journal = {DevelopmentDevelopmentDevelopmentDevelopment}, volume = {138}, year = {2011}, type = {10.1242/dev.061762}, abstract = {The temporal and spatial control of organ-specific endoderm progenitor development is poorly understood. miRNAs affect cell function by regulating programmatic changes in protein expression levels. We show that the miR302/367 cluster is a target of the transcription factor Gata6 in mouse lung endoderm and regulates multiple aspects of early lung endoderm progenitor development. miR302/367 is expressed at early stages of lung development, but its levels decline rapidly as development proceeds. Gain- and loss-of-function studies show that altering miR302/367 expression disrupts the balance of lung endoderm progenitor proliferation and differentiation, as well as apical-basal polarity. Increased miR302/367 expression results in the formation of an undifferentiated multi-layered lung endoderm, whereas loss of miR302/367 activity results in decreased proliferation and enhanced lung endoderm differentiation. miR302/367 coordinates the balance between proliferation and differentiation, in part, through direct regulation of Rbl2 and Cdkn1a, whereas apical-basal polarity is controlled by regulation of Tiam1 and Lis1. Thus, miR302/367 directs lung endoderm development by coordinating multiple aspects of progenitor cell behavior, including proliferation, differentiation and apical-basal polarity.}, keywords = {Lung, MicroRNA, mouse, Progenitor}, isbn = {0950-1991, 1477-9129}, author = {Tian, Ying and Zhang, Yuzhen and Hurd, Laura and Sridhar Hannenhalli and Liu, Feiyan and Lu, Min Min and Morrisey, Edward E.} } @article {38470, title = {A robust and rotationally invariant local surface descriptor with applications to non-local mesh processing}, journal = {Graphical ModelsGraphical Models}, volume = {73}, year = {2011}, type = {10.1016/j.gmod.2011.05.002}, abstract = {In recent years, we have witnessed a striking increase in research concerning how to describe a meshed surface. These descriptors are commonly used to encode mesh properties or guide mesh processing, not to augment existing computations by replication. In this work, we first define a robust surface descriptor based on a local height field representation, and present a transformation via the extraction of Zernike moments. Unlike previous work, our local surface descriptor is innately rotationally invariant. Second, equipped with this novel descriptor, we present SAMPLE {\textendash} similarity augmented mesh processing using local exemplars {\textendash} a method which uses feature neighbourhoods to propagate mesh processing done in one part of the mesh, the local exemplar, to many others. Finally, we show that SAMPLE can be used in a number of applications, such as detail transfer and parameterization.}, keywords = {Local descriptors, Non-local mesh processing, shape analysis, Similarity processing}, isbn = {1524-0703}, author = {Maximo, A. and Patro, R. and Varshney, Amitabh and Farias, R.} } @article {38473, title = {Role of Zooplankton Diversity in Vibrio Cholerae Population Dynamics and in the Incidence of Cholera in the Bangladesh Sundarbans}, journal = {Applied and Environmental MicrobiologyAppl. Environ. Microbiol.Applied and Environmental MicrobiologyAppl. Environ. Microbiol.}, volume = {77}, year = {2011}, type = {10.1128/AEM.01472-10}, abstract = {Vibrio cholerae, a bacterium autochthonous to the aquatic environment, is the causative agent of cholera, a severe watery, life-threatening diarrheal disease occurring predominantly in developing countries. V. cholerae, including both serogroups O1 and O139, is found in association with crustacean zooplankton, mainly copepods, and notably in ponds, rivers, and estuarine systems globally. The incidence of cholera and occurrence of pathogenic V. cholerae strains with zooplankton were studied in two areas of Bangladesh: Bakerganj and Mathbaria. Chitinous zooplankton communities of several bodies of water were analyzed in order to understand the interaction of the zooplankton population composition with the population dynamics of pathogenic V. cholerae and incidence of cholera. Two dominant zooplankton groups were found to be consistently associated with detection of V. cholerae and/or occurrence of cholera cases, namely, rotifers and cladocerans, in addition to copepods. Local differences indicate there are subtle ecological factors that can influence interactions between V. cholerae, its plankton hosts, and the incidence of cholera.}, isbn = {0099-2240, 1098-5336}, author = {De Magny, Guillaume Constantin and Mozumder, Pronob K. and Grim, Christopher J. and Hasan, Nur A. and Naser, M. Niamul and Alam, Munirul and Sack, R. Bradley and Huq, Anwar and Rita R. Colwell} } @article {38524, title = {Temperature regulation of virulence factors in the pathogen Vibrio coralliilyticus}, journal = {The ISME JournalThe ISME journal}, volume = {6}, year = {2011}, type = {10.1038/ismej.2011.154}, abstract = {Sea surface temperatures (SST) are rising because of global climate change. As a result, pathogenic Vibrio species that infect humans and marine organisms during warmer summer months are of growing concern. Coral reefs, in particular, are already experiencing unprecedented degradation worldwide due in part to infectious disease outbreaks and bleaching episodes that are exacerbated by increasing SST. For example, Vibrio coralliilyticus, a globally distributed bacterium associated with multiple coral diseases, infects corals at temperatures above 27 {\textdegree}C. The mechanisms underlying this temperature-dependent pathogenicity, however, are unknown. In this study, we identify potential virulence mechanisms using whole genome sequencing of V. coralliilyticus ATCC (American Type Culture Collection) BAA-450. Furthermore, we demonstrate direct temperature regulation of numerous virulence factors using proteomic analysis and bioassays. Virulence factors involved in motility, host degradation, secretion, antimicrobial resistance and transcriptional regulation are upregulated at the higher virulent temperature of 27 {\textdegree}C, concurrent with phenotypic changes in motility, antibiotic resistance, hemolysis, cytotoxicity and bioluminescence. These results provide evidence that temperature regulates multiple virulence mechanisms in V. coralliilyticus, independent of abundance. The ecological and biological significance of this temperature-dependent virulence response is reinforced by climate change models that predict tropical SST to consistently exceed 27 {\textdegree}C during the spring, summer and fall seasons. We propose V. coralliilyticus as a model Gram-negative bacterium to study temperature-dependent pathogenicity in Vibrio-related diseases.}, keywords = {ecophysiology, ecosystems, environmental biotechnology, geomicrobiology, ISME J, microbe interactions, microbial communities, microbial ecology, microbial engineering, microbial epidemiology, microbial genomics, microorganisms}, isbn = {1751-7362}, author = {Kimes, Nikole E. and Grim, Christopher J. and Johnson, Wesley R. and Hasan, Nur A. and Tall, Ben D. and Kothary, Mahendra H. and Kiss, Hajnalka and Munk, A. Christine and Tapia, Roxanne and Green, Lance and Detter, Chris and Bruce, David C. and Brettin, Thomas S. and Rita R. Colwell and Morris, Pamela J.} } @article {38160, title = {Comparative Genomics of Clinical and Environmental Vibrio Mimicus}, journal = {Proceedings of the National Academy of SciencesPNASProceedings of the National Academy of SciencesPNAS}, volume = {107}, year = {2010}, type = {10.1073/pnas.1013825107}, abstract = {Whether Vibrio mimicus is a variant of Vibrio cholerae or a separate species has been the subject of taxonomic controversy. A genomic analysis was undertaken to resolve the issue. The genomes of V. mimicus MB451, a clinical isolate, and VM223, an environmental isolate, comprise ca. 4,347,971 and 4,313,453 bp and encode 3,802 and 3,290 ORFs, respectively. As in other vibrios, chromosome I (C-I) predominantly contains genes necessary for growth and viability, whereas chromosome II (C-II) bears genes for adaptation to environmental change. C-I harbors many virulence genes, including some not previously reported in V. mimicus, such as mannose-sensitive hemagglutinin (MSHA), and enterotoxigenic hemolysin (HlyA); C-II encodes a variant of Vibrio pathogenicity island 2 (VPI-2), and Vibrio seventh pandemic island II (VSP-II) cluster of genes. Extensive genomic rearrangement in C-II indicates it is a hot spot for evolution and genesis of speciation for the genus Vibrio. The number of virulence regions discovered in this study (VSP-II, MSHA, HlyA, type IV pilin, PilE, and integron integrase, IntI4) with no notable difference in potential virulence genes between clinical and environmental strains suggests these genes also may play a role in the environment and that pathogenic strains may arise in the environment. Significant genome synteny with prototypic pre-seventh pandemic strains of V. cholerae was observed, and the results of phylogenetic analysis support the hypothesis that, in the course of evolution, V. mimicus and V. cholerae diverged from a common ancestor with a prototypic sixth pandemic genomic backbone.}, isbn = {0027-8424, 1091-6490}, author = {Hasan, Nur A. and Grim, Christopher J. and Haley, Bradd J. and Jongsik, Chun and Alam, Munirul and Taviani, Elisa and Mozammel, Hoq and Munk, A. Christine and Rita R. Colwell} } @article {38210, title = {Diversity and distribution of cholix toxin, a novel ADP-ribosylating factor from Vibrio cholerae}, journal = {Environmental Microbiology ReportsEnvironmental Microbiology Reports}, volume = {2}, year = {2010}, type = {10.1111/j.1758-2229.2010.00139.x}, abstract = {Non-toxigenic non-O1, non-O139 Vibrio cholerae strains isolated from both environmental and clinical settings carry a suite of virulence factors aside from cholera toxin. Among V. cholerae strains isolated from coastal waters of southern California, this includes cholix toxin, an ADP-ribosylating factor that is capable of halting protein synthesis in eukaryotic cells. The prevalence of the gene encoding cholix toxin, chxA, was assessed among a collection of 155 diverse V. cholerae strains originating from both clinical and environmental settings in Bangladesh and Mexico and other countries around the globe. The chxA gene was present in 47\% of 83 non-O1, non-O139 strains and 16\% of 72 O1/O139 strains screened as part of this study. A total of 86 chxA gene sequences were obtained, and phylogenetic analysis revealed that they fall into two distinct clades. These two clades were also observed in the phylogenies of several housekeeping genes, suggesting that the divergence observed in chxA extends to other regions of the V. cholerae genome, and most likely has arisen from vertical descent rather than horizontal transfer. Our results clearly indicate that ChxA is a major toxin of V. cholerae with a worldwide distribution that is preferentially associated with non-pandemic strains.}, isbn = {1758-2229}, author = {Purdy, Alexandra E. and Balch, Deborah and Liz{\'a}rraga-Partida, Marcial Leonardo and Islam, Mohammad Sirajul and Martinez-Urtaza, Jaime and Huq, Anwar and Rita R. Colwell and Bartlett, Douglas H.} } @article {49674, title = {Evolutionary dynamics of U12-type spliceosomal introns.}, journal = {BMC Evol Biol}, volume = {10}, year = {2010}, month = {2010}, pages = {47}, abstract = {

BACKGROUND: Many multicellular eukaryotes have two types of spliceosomes for the removal of introns from messenger RNA precursors. The major (U2) spliceosome processes the vast majority of introns, referred to as U2-type introns, while the minor (U12) spliceosome removes a small fraction (less than 0.5\%) of introns, referred to as U12-type introns. U12-type introns have distinct sequence elements and usually occur together in genes with U2-type introns. A phylogenetic distribution of U12-type introns shows that the minor splicing pathway appeared very early in eukaryotic evolution and has been lost repeatedly.

RESULTS: We have investigated the evolution of U12-type introns among eighteen metazoan genomes by analyzing orthologous U12-type intron clusters. Examination of gain, loss, and type switching shows that intron type is remarkably conserved among vertebrates. Among 180 intron clusters, only eight show intron loss in any vertebrate species and only five show conversion between the U12 and the U2-type. Although there are only nineteen U12-type introns in Drosophila melanogaster, we found one case of U2 to U12-type conversion, apparently mediated by the activation of cryptic U12 splice sites early in the dipteran lineage. Overall, loss of U12-type introns is more common than conversion to U2-type and the U12 to U2 conversion occurs more frequently among introns of the GT-AG subtype than among introns of the AT-AC subtype. We also found support for natural U12-type introns with non-canonical terminal dinucleotides (CT-AC, GG-AG, and GA-AG) that have not been previously reported.

CONCLUSIONS: Although complete loss of the U12-type spliceosome has occurred repeatedly, U12 introns are extremely stable in some taxa, including eutheria. Loss of U12 introns or the genes containing them is more common than conversion to the U2-type. The degeneracy of U12-type terminal dinucleotides among natural U12-type introns is higher than previously thought.

}, keywords = {Animals, Arabidopsis, Evolution, Molecular, HUMANS, Introns, RNA, Small Nuclear, Spliceosomes}, issn = {1471-2148}, doi = {10.1186/1471-2148-10-47}, author = {Lin, Chiao-Feng and Mount, Stephen M and Jarmo{\l}owski, Artur and Maka{\l}owski, Wojciech} } @inbook {38246, title = {Evolutionary framework for Lepidoptera model systems}, booktitle = {Genetics and Molecular Biology of LepidopteraGenetics and Molecular Biology of Lepidoptera}, year = {2010}, publisher = {Taylor \& Francis}, organization = {Taylor \& Francis}, address = {Boca Raton}, abstract = {{\textquotedblleft}Model systems{\textquotedblright} are specific organisms upon which detailed studies have been conducted examining a fundamental biological question. If the studies are robust, their results can be extrapolated among an array of organisms that possess features in common with the subject organism. The true power of model systems lies in the ability to extrapolate these details across larger groups of organisms. In order to generalize these results, comparative studies are essential and require that model systems be placed into their evolutionary or phylogenetic context. This chapter examines model systems in the insect order Lepidoptera from the perspective of several different superfamilies. Historically, many species of Lepidoptera have been essential in the development of invaluable model systems in the fields of development biology, genetics, molecular biology, physiology, co-evolution, population dynamics, and ecology.}, author = {Roe, A. and Weller, S. and Baixeras, J. and Brown, J. W. and Michael P. Cummings and Davis, D. R. and Horak, M. and Kawahara, A. Y. and Mitter, C. and Parr, C. S. and Regier, J. C. and Rubinoff, D. and Simonsen, T. J. and Wahlberg, N. and Zwick, A.}, editor = {Goldsmith, M. and Marec, F.} } @article {38282, title = {Genetic and Physiological Activation of Osmosensitive Gene Expression Mimics Transcriptional Signatures of Pathogen Infection in C. elegans}, journal = {PLoS ONEPLoS One}, volume = {5}, year = {2010}, type = {10.1371/journal.pone.0009010}, abstract = {The soil-dwelling nematode C. elegans is a powerful system for comparative molecular analyses of environmental stress response mechanisms. Infection of worms with bacterial and fungal pathogens causes the activation of well-characterized innate immune transcriptional programs in pathogen-exposed hypodermal and intestinal tissues. However, the pathophysiological events that drive such transcriptional responses are not understood. Here, we show that infection-activated transcriptional responses are, in large part, recapitulated by either physiological or genetic activation of the osmotic stress response. Microarray profiling of wild type worms exposed to non-lethal hypertonicity identified a suite of genes that were also regulated by infection. Expression profiles of five different osmotic stress resistant (osr) mutants under isotonic conditions reiterated the wild type transcriptional response to osmotic stress and also showed substantial similarity to infection-induced gene expression under isotonic conditions. Computational, transgenic, and functional approaches revealed that two GATA transcription factors previously implicated in infection-induced transcriptional responses, elt-2 and elt-3, are also essential for coordinated tissue-specific activation of osmosensitive gene expression and promote survival under osmotically stressful conditions. Together, our data suggest infection and osmotic adaptation share previously unappreciated transcriptional similarities which might be controlled via regulation of tissue-specific GATA transcription factors.}, author = {Rohlfing, Anne-Katrin and Miteva, Yana and Sridhar Hannenhalli and Lamitina, Todd} } @article {49649, title = {Genome-wide analysis reveals novel genes essential for heme homeostasis in Caenorhabditis elegans.}, journal = {PLoS Genet}, volume = {6}, year = {2010}, month = {2010 Jul}, pages = {e1001044}, abstract = {

Heme is a cofactor in proteins that function in almost all sub-cellular compartments and in many diverse biological processes. Heme is produced by a conserved biosynthetic pathway that is highly regulated to prevent the accumulation of heme--a cytotoxic, hydrophobic tetrapyrrole. Caenorhabditis elegans and related parasitic nematodes do not synthesize heme, but instead require environmental heme to grow and develop. Heme homeostasis in these auxotrophs is, therefore, regulated in accordance with available dietary heme. We have capitalized on this auxotrophy in C. elegans to study gene expression changes associated with precisely controlled dietary heme concentrations. RNA was isolated from cultures containing 4, 20, or 500 microM heme; derived cDNA probes were hybridized to Affymetrix C. elegans expression arrays. We identified 288 heme-responsive genes (hrgs) that were differentially expressed under these conditions. Of these genes, 42\% had putative homologs in humans, while genomes of medically relevant heme auxotrophs revealed homologs for 12\% in both Trypanosoma and Leishmania and 24\% in parasitic nematodes. Depletion of each of the 288 hrgs by RNA-mediated interference (RNAi) in a transgenic heme-sensor worm strain identified six genes that regulated heme homeostasis. In addition, seven membrane-spanning transporters involved in heme uptake were identified by RNAi knockdown studies using a toxic heme analog. Comparison of genes that were positive in both of the RNAi screens resulted in the identification of three genes in common that were vital for organismal heme homeostasis in C. elegans. Collectively, our results provide a catalog of genes that are essential for metazoan heme homeostasis and demonstrate the power of C. elegans as a genetic animal model to dissect the regulatory circuits which mediate heme trafficking in both vertebrate hosts and their parasites, which depend on environmental heme for survival.

}, keywords = {Animals, Caenorhabditis elegans, Dose-Response Relationship, Drug, Gene Expression Profiling, Gene Expression Regulation, genes, Genome-Wide Association Study, Heme, Homeostasis, HUMANS, Leishmania, Nematoda, Trypanosoma}, issn = {1553-7404}, doi = {10.1371/journal.pgen.1001044}, author = {Severance, Scott and Rajagopal, Abbhirami and Rao, Anita U and Cerqueira, Gustavo C and Mitreva, Makedonka and El-Sayed, Najib M and Krause, Michael and Hamza, Iqbal} } @article {38315, title = {Genomic characterization of the Yersinia genus}, journal = {Genome BiologyGenome Biology}, volume = {11}, year = {2010}, type = {10.1186/gb-2010-11-1-r1}, abstract = {New DNA sequencing technologies have enabled detailed comparative genomic analyses of entire genera of bacterial pathogens. Prior to this study, three species of the enterobacterial genus Yersinia that cause invasive human diseases (Yersinia pestis, Yersinia pseudotuberculosis, and Yersinia enterocolitica) had been sequenced. However, there were no genomic data on the Yersinia species with more limited virulence potential, frequently found in soil and water environments.}, isbn = {1465-6906}, author = {Chen, Peter E. and Cook, Christopher and Stewart, Andrew C. and Nagarajan, Niranjan and Sommer, Dan D. and M. Pop and Thomason, Brendan and Thomason, Maureen P. K. and Lentz, Shannon and Nolan, Nichole and Sozhamannan, Shanmuga and Sulakvelidze, Alexander and Mateczun, Alfred and Du, Lei and Zwick, Michael E. and Read, Timothy D.} } @article {38335, title = {Identification of Pathogenic Vibrio Species by Multilocus PCR-Electrospray Ionization Mass Spectrometry and Its Application to Aquatic Environments of the Former Soviet Republic of Georgia}, journal = {Applied and Environmental MicrobiologyAppl. Environ. Microbiol.Applied and Environmental MicrobiologyAppl. Environ. Microbiol.}, volume = {76}, year = {2010}, type = {10.1128/AEM.01919-09}, abstract = {The Ibis T5000 is a novel diagnostic platform that couples PCR and mass spectrometry. In this study, we developed an assay that can identify all known pathogenic Vibrio species and field-tested it using natural water samples from both freshwater lakes and the Georgian coastal zone of the Black Sea. Of the 278 total water samples screened, 9 different Vibrio species were detected, 114 (41\%) samples were positive for V. cholerae, and 5 (0.8\%) samples were positive for the cholera toxin A gene (ctxA). All ctxA-positive samples were from two freshwater lakes, and no ctxA-positive samples from any of the Black Sea sites were detected.}, isbn = {0099-2240, 1098-5336}, author = {Whitehouse, Chris A. and Baldwin, Carson and Sampath, Rangarajan and Blyn, Lawrence B. and Melton, Rachael and Li, Feng and Hall, Thomas A. and Harpin, Vanessa and Matthews, Heather and Tediashvili, Marina and Jaiani, Ekaterina and Kokashvili, Tamar and Janelidze, Nino and Grim, Christopher and Rita R. Colwell and Huq, Anwar} } @article {49650, title = {A model for using a concept inventory as a tool for students{\textquoteright} assessment and faculty professional development.}, journal = {CBE Life Sci Educ}, volume = {9}, year = {2010}, month = {2010 Winter}, pages = {408-16}, abstract = {

This essay describes how the use of a concept inventory has enhanced professional development and curriculum reform efforts of a faculty teaching community. The Host Pathogen Interactions (HPI) teaching team is composed of research and teaching faculty with expertise in HPI who share the goal of improving the learning experience of students in nine linked undergraduate microbiology courses. To support evidence-based curriculum reform, we administered our HPI Concept Inventory as a pre- and postsurvey to approximately 400 students each year since 2006. The resulting data include student scores as well as their open-ended explanations for distractor choices. The data have enabled us to address curriculum reform goals of 1) reconciling student learning with our expectations, 2) correlating student learning with background variables, 3) understanding student learning across institutions, 4) measuring the effect of teaching techniques on student learning, and 5) demonstrating how our courses collectively form a learning progression. The analysis of the concept inventory data has anchored and deepened the team{\textquoteright}s discussions of student learning. Reading and discussing students{\textquoteright} responses revealed the gap between our understanding and the students{\textquoteright} understanding. We provide evidence to support the concept inventory as a tool for assessing student understanding of HPI concepts and faculty development.

}, keywords = {Curriculum, Faculty, Models, Theoretical, Research, Students, Teaching}, issn = {1931-7913}, doi = {10.1187/cbe.10-05-0069}, author = {Marbach-Ad, Gili and McAdams, Katherine C and Benson, Spencer and Briken, Volker and Cathcart, Laura and Chase, Michael and El-Sayed, Najib M and Frauwirth, Kenneth and Fredericksen, Brenda and Joseph, Sam W and Lee, Vincent and McIver, Kevin S and Mosser, David and Quimby, B Booth and Shields, Patricia and Song, Wenxia and Stein, Daniel C and Stewart, Richard and Thompson, Katerina V and Smith, Ann C} } @article {38114, title = {Analysis of clonally related environmental Vibrio cholerae O1 El Tor isolated before 1992 from Varanasi, India reveals origin of SXT-ICEs belonging to O139 and O1 serogroups}, journal = {Environmental Microbiology ReportsEnvironmental Microbiology Reports}, volume = {2}, year = {2009}, type = {10.1111/j.1758-2229.2009.00051.x}, abstract = {In this study, we report the presence of SXT in environmental Vibrio cholerae O1 El Tor strains isolated before 1992 from Varanasi, India. All isolates, except one, were resistant to Tm, and/or Sul, Sm, Fr, Na and Am. None contained plasmids. PCR and DNA sequencing revealed the presence of SXT containing dfrA1 and/or sulII, strAB in six isolates and dfr18, sulII and strAB in five isolates. Three clinical V. cholerae O1 isolated during 1992 contained the antibiotic resistance gene cassette aadA1 in the class 1 integron. Conjugation experiments, followed by PCR analysis of transconjugants, provided evidence of the transferable nature of SXT and associated antibiotic resistance genes, and its integration into the prfC site. Results of phylogenetic analysis of the intSXT gene of clonally similar V. cholerae showed a clear difference between dfr18+ and dfrA1+V. cholerae O1 isolates. This is the first report of the occurrence of SXT harbouring sulII, strAB, dfr18 and/or dfrA1 genes in environmental V. cholerae O1 isolated prior to 1992 from Varanasi, India, and suggests emergence of SXT+ antibiotic-resistant V. cholerae O139 and O1 from an environmental V. cholerae progenitor by acquisition of SXT and antibiotic-resistant gene clusters.}, isbn = {1758-2229}, author = {Mohapatra, Saswat S. and Mantri, Chinmay K. and Mohapatra, Harapriya and Rita R. Colwell and Singh, Durg V.} } @article {49645, title = {Assessing Student Understanding of Host Pathogen Interactions Using a Concept Inventory}, journal = {J. Microbiol. Biol. Ed.}, volume = {10}, year = {2009}, pages = {43-50}, author = {Marbach-Ad, G. and Briken, V. and El-Sayed, N.M. and Frauwirth, K. and Fredericksen, B. and Hutcheson, S. and Gao, L.-Y. and Joseph, S. and Lee, V. and McIver, K.S. and Mosser, D. and Quimby, B.B. and Shields, P. and Song, W. and Stein, D.C. and Yuan, R.T. and Smith, A.C.} } @article {38202, title = {Determination of relationships among non-toxigenic Vibrio cholerae O1 biotype El Tor strains from housekeeping gene sequences and ribotype patterns}, journal = {Research in MicrobiologyResearch in Microbiology}, volume = {160}, year = {2009}, type = {10.1016/j.resmic.2008.10.008}, abstract = {Sequencing of three housekeeping genes, mdh, dnaE and recA, and ribotyping for seven non-toxigenic Vibrio cholerae O1 strains isolated from different geographic sources indicate a phylogenetic relationship among the strains. Results of MLST and ribotyping indicate a clear difference between three toxigenic strains (N16961, O395, and 569B) and three non-toxigenic strains from India (GS1, GS2, and GW87) and one Guam strain (X392), the latter of which were similar in both MLST and ribotyping, while two other non-toxigenic strains from the USA and India (2740-80 and OR69) appeared to be more closely related to toxigenic strains than to non-toxigenic strains, although this was not supported by ribotyping. These results provide clues to the emergence of toxigenic strains from a non-toxigenic progenitor by acquisition of virulence gene clusters. Results of split decomposition analysis suggest that widespread recombination occurs among the three housekeeping genes and that recombination plays an important role in the emergence of toxigenic strains of V. cholerae O1.}, keywords = {Housekeeping genes, Ribotyping, sequencing, Vibrio cholerae}, isbn = {0923-2508}, author = {Mohapatra, Saswat S. and Ramachandran, Dhanya and Mantri, Chinmay K. and Rita R. Colwell and Singh, Durg V.} } @article {38239, title = {Evidence for Coregulation of Myocardial Gene Expression by MEF2 and NFAT in Human Heart FailureCLINICAL PERSPECTIVE}, journal = {Circulation: Cardiovascular GeneticsCirculation: Cardiovascular Genetics}, volume = {2}, year = {2009}, publisher = {Am Heart Assoc}, author = {Putt, M. E. and Sridhar Hannenhalli and Lu, Y. and Haines, P. and Chandrupatla, H. R. and Morrisey, E. E. and Margulies, K. B. and Cappola, T. P.} } @article {38278, title = {Gene Profiling of Human Adipose Tissue During Evoked Inflammation In Vivo}, journal = {DiabetesDiabetesDiabetesDiabetes}, volume = {58}, year = {2009}, type = {10.2337/db09-0256}, abstract = {OBJECTIVE Adipose inflammation plays a central role in obesity-related metabolic and cardiovascular complications. However, few human adipose-secreted proteins are known to mediate these processes. We hypothesized that microarray mRNA profiling of human adipose during evoked inflammation could identify novel adipocytokines.RESEARCH DESIGN AND METHODS Healthy human volunteers (n = 14) were treated with intravenous endotoxin (3 ng/kg lipopolysaccharide [LPS]) and underwent subcutaneous adipose biopsies before and after LPS. On Affymetrix U133Plus 2.0 arrays, adipose mRNAs modulated >1.5-fold (with P < 0.00001) were selected. SignalP 3.0 and SecretomeP 2.0 identified genes predicted to encode secreted proteins. Of these, 86 candidates were chosen for validation in adipose from an independent human endotoxemia protocol (N = 7, with 0.6 ng/kg LPS) and for exploration of cellular origin in primary human adipocytes and macrophages in vitro. RESULTS Microarray identified 776 adipose genes modulated by LPS; 298 were predicted to be secreted. Of detectable prioritized genes, 82 of 85 (96\% [95\% CI 90{\textendash}99]) were upregulated (fold changes >1.0) during the lower-dose (LPS 0.6 ng/kg) validation study and 51 of 85 (59\% [49{\textendash}70]) were induced greater than 1.5-fold. Treatment of primary adipocytes with LPS and macrophage polarization to M1 proinflammatory phenotype increased expression by 1.5-fold for 58 and 73\% of detectable genes, respectively. CONCLUSIONS We demonstrate that evoked inflammation of human adipose in vivo modulated expression of multiple genes likely secreted by adipocytes and monocytes. These included established adipocytokines and chemokines implicated in recruitment and activation of lymphocytes, adhesion molecules, antioxidants, and several novel genes with unknown function. Such candidates may represent biomarkers and therapeutic targets for obesity-related complications.}, isbn = {0012-1797, 1939-327X}, author = {Shah, Rachana and Lu, Yun and Hinkle, Christine C. and McGillicuddy, Fiona C. and Kim, Roy and Sridhar Hannenhalli and Cappola, Thomas P. and Heffron, Sean and Wang, XingMei and Mehta, Nehal N. and Putt, Mary and Reilly, Muredach P.} } @article {38290, title = {Genome assortment, not serogroup, defines Vibrio cholerae pandemic strains}, journal = {NatureNature}, year = {2009}, abstract = {Vibrio cholerae, the causative agent of cholera, is a bacterium autochthonous to the aquatic environment, and a serious public health threat. V. cholerae serogroup O1 is responsible for the previous two cholera pandemics, in which classical and El Tor biotypes were dominant in the 6th and the current 7th pandemics, respectively. Cholera researchers continually face newly emerging and re-emerging pathogenic clones carrying combinations of new serogroups as well as of phenotypic and genotypic properties. These genotype and phenotype changes have hampered control of the disease. Here we compare the complete genome sequences of 23 strains of V. cholerae isolated from a variety of sources and geographical locations over the past 98 years in an effort to elucidate the evolutionary mechanisms governing genetic diversity and genesis of new pathogenic clones. The genome-based phylogeny revealed 12 distinct V. cholerae phyletic lineages, of which one, designated the V. cholerae core genome (CG), comprises both O1 classical and EI Tor biotypes. All 7th pandemic clones share nearly identical gene content, i.e., the same genome backbone. The transition from 6th to 7th pandemic strains is defined here as a {\textquoteright}shift{\textquoteright} between pathogenic clones belonging to the same O1 serogroup, but from significantly different phyletic lineages within the CG clade. In contrast, transition among clones during the present 7th pandemic period can be characterized as a {\textquoteright}drift{\textquoteright} between clones, differentiated mainly by varying composition of laterally transferred genomic islands, resulting in emergence of variants, exemplified by V.cholerae serogroup O139 and V.cholerae O1 El Tor hybrid clones that produce cholera toxin of classical biotype. Based on the comprehensive comparative genomics presented in this study it is concluded that V. cholerae undergoes extensive genetic recombination via lateral gene transfer, and, therefore, genome assortment, not serogroup, should be used to define pathogenic V. cholerae clones.}, keywords = {59, CHOLERA, genes, Genetics, GENOTYPE, ISLANDS, ORIGIN, PHENOTYPE, PUBLIC HEALTH, recombination, STRAINS, Toxins}, author = {Brettin, Thomas S. and Bruce, David C. and Challacombe, Jean F. and Detter, John C. and Han, Cliff S. and Munik, A. C. and Chertkov, Olga and Meincke, Linda and Saunders, Elizabeth and Choi, Seon Y. and Haley, Bradd J. and Taviani, Elisa and Jeon, Yoon-Seong and Kim, Dong Wook and Lee, Jae-Hak and Walters, Ronald A. and Hug, Anwar and Rita R. Colwell} } @article {49646, title = {The genome of the blood fluke Schistosoma mansoni.}, journal = {Nature}, volume = {460}, year = {2009}, month = {2009 Jul 16}, pages = {352-8}, abstract = {

Schistosoma mansoni is responsible for the neglected tropical disease schistosomiasis that affects 210 million people in 76 countries. Here we present analysis of the 363 megabase nuclear genome of the blood fluke. It encodes at least 11,809 genes, with an unusual intron size distribution, and new families of micro-exon genes that undergo frequent alternative splicing. As the first sequenced flatworm, and a representative of the Lophotrochozoa, it offers insights into early events in the evolution of the animals, including the development of a body pattern with bilateral symmetry, and the development of tissues into organs. Our analysis has been informed by the need to find new drug targets. The deficits in lipid metabolism that make schistosomes dependent on the host are revealed, and the identification of membrane receptors, ion channels and more than 300 proteases provide new insights into the biology of the life cycle and new targets. Bioinformatics approaches have identified metabolic chokepoints, and a chemogenomic screen has pinpointed schistosome proteins for which existing drugs may be active. The information generated provides an invaluable resource for the research community to develop much needed new control tools for the treatment and eradication of this important and neglected disease.

}, keywords = {Animals, Biological Evolution, Exons, Genes, Helminth, Genome, Helminth, Host-Parasite Interactions, Introns, Molecular Sequence Data, Physical Chromosome Mapping, Schistosoma mansoni, Schistosomiasis mansoni}, issn = {1476-4687}, doi = {10.1038/nature08160}, author = {Berriman, Matthew and Haas, Brian J and LoVerde, Philip T and Wilson, R Alan and Dillon, Gary P and Cerqueira, Gustavo C and Mashiyama, Susan T and Al-Lazikani, Bissan and Andrade, Luiza F and Ashton, Peter D and Aslett, Martin A and Bartholomeu, Daniella C and Blandin, Ga{\"e}lle and Caffrey, Conor R and Coghlan, Avril and Coulson, Richard and Day, Tim A and Delcher, Art and DeMarco, Ricardo and Djikeng, Appolinaire and Eyre, Tina and Gamble, John A and Ghedin, Elodie and Gu, Yong and Hertz-Fowler, Christiane and Hirai, Hirohisha and Hirai, Yuriko and Houston, Robin and Ivens, Alasdair and Johnston, David A and Lacerda, Daniela and Macedo, Camila D and McVeigh, Paul and Ning, Zemin and Oliveira, Guilherme and Overington, John P and Parkhill, Julian and Pertea, Mihaela and Pierce, Raymond J and Protasio, Anna V and Quail, Michael A and Rajandream, Marie-Ad{\`e}le and Rogers, Jane and Sajid, Mohammed and Salzberg, Steven L and Stanke, Mario and Tivey, Adrian R and White, Owen and Williams, David L and Wortman, Jennifer and Wu, Wenjie and Zamanian, Mostafa and Zerlotini, Adhemar and Fraser-Liggett, Claire M and Barrell, Barclay G and El-Sayed, Najib M} } @article {49644, title = {Genomic organization and expression profile of the mucin-associated surface protein (masp) family of the human pathogen Trypanosoma cruzi.}, journal = {Nucleic Acids Res}, volume = {37}, year = {2009}, month = {2009 Jun}, pages = {3407-17}, abstract = {

A novel large multigene family was recently identified in the human pathogen Trypanosoma cruzi, causative agent of Chagas disease, and corresponds to approximately 6\% of the parasite diploid genome. The predicted gene products, mucin-associated surface proteins (MASPs), are characterized by highly conserved N- and C-terminal domains and a strikingly variable and repetitive central region. We report here an analysis of the genomic organization and expression profile of masp genes. Masps are not randomly distributed throughout the genome but instead are clustered with genes encoding mucin and other surface protein families. Masp transcripts vary in size, are preferentially expressed during the trypomastigote stage and contain highly conserved 5{\textquoteright} and 3{\textquoteright} untranslated regions. A sequence analysis of a trypomastigote cDNA library reveals the expression of multiple masp variants with a bias towards a particular masp subgroup. Immunofluorescence assays using antibodies generated against a MASP peptide reveals that the expression of particular MASPs at the cell membrane is limited to subsets of the parasite population. Western blots of phosphatidylinositol-specific phospholipase C (PI-PLC)-treated parasites suggest that MASP may be GPI-anchored and shed into the medium culture, thus contributing to the large repertoire of parasite polypeptides that are exposed to the host immune system.

}, keywords = {3{\textquoteright} Flanking Region, 5{\textquoteright} Flanking Region, Amino Acid Sequence, Animals, Base Sequence, Conserved Sequence, Gene Expression Profiling, Genes, Protozoan, Genome, Protozoan, Membrane Proteins, Molecular Sequence Data, Mucins, Multigene Family, Protozoan Proteins, RNA, Messenger, Trypanosoma cruzi}, issn = {1362-4962}, doi = {10.1093/nar/gkp172}, author = {Bartholomeu, Daniella C and Cerqueira, Gustavo C and Le{\~a}o, Ana Carolina A and daRocha, Wanderson D and Pais, Fabiano S and Macedo, Camila and Djikeng, Appolinaire and Teixeira, Santuza M R and El-Sayed, Najib M} } @article {49781, title = {InterPro: the integrative protein signature database.}, journal = {Nucleic Acids Res}, volume = {37}, year = {2009}, month = {2009 Jan}, pages = {D211-5}, abstract = {

The InterPro database (http://www.ebi.ac.uk/interpro/) integrates together predictive models or {\textquoteright}signatures{\textquoteright} representing protein domains, families and functional sites from multiple, diverse source databases: Gene3D, PANTHER, Pfam, PIRSF, PRINTS, ProDom, PROSITE, SMART, SUPERFAMILY and TIGRFAMs. Integration is performed manually and approximately half of the total approximately 58,000 signatures available in the source databases belong to an InterPro entry. Recently, we have started to also display the remaining un-integrated signatures via our web interface. Other developments include the provision of non-signature data, such as structural data, in new XML files on our FTP site, as well as the inclusion of matchless UniProtKB proteins in the existing match XML files. The web interface has been extended and now links out to the ADAN predicted protein-protein interaction database and the SPICE and Dasty viewers. The latest public release (v18.0) covers 79.8\% of UniProtKB (v14.1) and consists of 16 549 entries. InterPro data may be accessed either via the web address above, via web services, by downloading files by anonymous FTP or by using the InterProScan search software (http://www.ebi.ac.uk/Tools/InterProScan/).

}, keywords = {Databases, Protein, Proteins, Sequence Analysis, Protein, Systems Integration}, issn = {1362-4962}, doi = {10.1093/nar/gkn785}, author = {Hunter, Sarah and Apweiler, Rolf and Attwood, Teresa K and Bairoch, Amos and Bateman, Alex and Binns, David and Bork, Peer and Das, Ujjwal and Daugherty, Louise and Duquenne, Lauranne and Finn, Robert D and Gough, Julian and Haft, Daniel and Hulo, Nicolas and Kahn, Daniel and Kelly, Elizabeth and Laugraud, Aur{\'e}lie and Letunic, Ivica and Lonsdale, David and Lopez, Rodrigo and Madera, Martin and Maslen, John and McAnulla, Craig and McDowall, Jennifer and Mistry, Jaina and Mitchell, Alex and Mulder, Nicola and Natale, Darren and Orengo, Christine and Quinn, Antony F and Selengut, Jeremy D and Sigrist, Christian J A and Thimma, Manjula and Thomas, Paul D and Valentin, Franck and Wilson, Derek and Wu, Cathy H and Yeats, Corin} } @article {38353, title = {InterPro: the integrative protein signature database}, journal = {Nucleic acids researchNucleic Acids Research}, volume = {37}, year = {2009}, note = {http://www.ncbi.nlm.nih.gov/pubmed/18940856?dopt=Abstract}, type = {10.1093/nar/gkn785}, abstract = {The InterPro database (http://www.ebi.ac.uk/interpro/) integrates together predictive models or {\textquoteright}signatures{\textquoteright} representing protein domains, families and functional sites from multiple, diverse source databases: Gene3D, PANTHER, Pfam, PIRSF, PRINTS, ProDom, PROSITE, SMART, SUPERFAMILY and TIGRFAMs. Integration is performed manually and approximately half of the total approximately 58,000 signatures available in the source databases belong to an InterPro entry. Recently, we have started to also display the remaining un-integrated signatures via our web interface. Other developments include the provision of non-signature data, such as structural data, in new XML files on our FTP site, as well as the inclusion of matchless UniProtKB proteins in the existing match XML files. The web interface has been extended and now links out to the ADAN predicted protein-protein interaction database and the SPICE and Dasty viewers. The latest public release (v18.0) covers 79.8\% of UniProtKB (v14.1) and consists of 16 549 entries. InterPro data may be accessed either via the web address above, via web services, by downloading files by anonymous FTP or by using the InterProScan search software (http://www.ebi.ac.uk/Tools/InterProScan/).}, keywords = {Databases, Protein, Proteins, Sequence Analysis, Protein, Systems Integration}, author = {Hunter, Sarah and Apweiler, Rolf and Attwood, Teresa K. and Bairoch, Amos and Bateman, Alex and Binns, David and Bork, Peer and Das, Ujjwal and Daugherty, Louise and Duquenne, Lauranne and Finn, Robert D. and Gough, Julian and Haft, Daniel and Hulo, Nicolas and Kahn, Daniel and Kelly, Elizabeth and Laugraud, Aur{\'e}lie and Letunic, Ivica and Lonsdale, David and Lopez, Rodrigo and Madera, Martin and Maslen, John and McAnulla, Craig and McDowall, Jennifer and Mistry, Jaina and Mitchell, Alex and Mulder, Nicola and Natale, Darren and Orengo, Christine and Quinn, Antony F. and J. Selengut and Sigrist, Christian J. A. and Thimma, Manjula and Thomas, Paul D. and Valentin, Franck and Wilson, Derek and Wu, Cathy H. and Yeats, Corin} } @conference {49856, title = {Novel computational methods for large scale genome comparison}, booktitle = {2nd International Workshop on Practical Applications of Computational Biology and Bioinformatics (IWPACBB 2008)}, year = {2009}, publisher = {Springer}, organization = {Springer}, author = {Todd Treangen and Messeguer, Xavier} } @article {49869, title = {A Novel Heuristic for Local Multiple Alignment of Interspersed DNA Repeats}, journal = {IEEE/ACM Transactions on Computational Biology and Bioinformatics}, volume = {6}, year = {2009}, month = {Jan-04-2009}, pages = {180 - 189}, issn = {1545-5963}, doi = {10.1109/TCBB.2009.9}, url = {http://ieeexplore.ieee.org/document/4770094/http://xplorestaging.ieee.org/ielx5/8857/4907697/04770094.pdf?arnumber=4770094}, author = {Todd Treangen and Darling, A.E. and Achaz, G. and Ragan, M.A. and Messeguer, X. and Rocha, E.P.C.} } @article {49853, title = {A novel heuristic for local multiple alignment of interspersed DNA repeats}, journal = {IEEE/ACM Transactions on Computational Biology and Bioinformatics (TCBB)}, volume = {6}, year = {2009}, pages = {180{\textendash}189}, author = {Todd Treangen and Darling, Aaron E and Achaz, Guillaume and Ragan, Mark A and Messeguer, Xavier and Rocha, Eduardo PC} } @article {38446, title = {Predicting the distribution of Vibrio spp. in the Chesapeake Bay: a Vibrio cholerae case study}, journal = {EcoHealthEcoHealth}, volume = {6}, year = {2009}, type = {10.1007/s10393-009-0273-6}, abstract = {Vibrio cholerae, the causative agent of cholera, is a naturally occurring inhabitant of the Chesapeake Bay and serves as a predictor for other clinically important vibrios, including Vibrio parahaemolyticus and Vibrio vulnificus. A system was constructed to predict the likelihood of the presence of V. cholerae in surface waters of the Chesapeake Bay, with the goal to provide forecasts of the occurrence of this and related pathogenic Vibrio spp. Prediction was achieved by driving an available multivariate empirical habitat model estimating the probability of V. cholerae within a range of temperatures and salinities in the Bay, with hydrodynamically generated predictions of ambient temperature and salinity. The experimental predictions provided both an improved understanding of the in situ variability of V. cholerae, including identification of potential hotspots of occurrence, and usefulness as an early warning system. With further development of the system, prediction of the probability of the occurrence of related pathogenic vibrios in the Chesapeake Bay, notably V. parahaemolyticus and V. vulnificus, will be possible, as well as its transport to any geographical location where sufficient relevant data are available.}, author = {Constantin de Magny, G. and Long, W. and Brown, C. W. and Hood, R. R. and Huq, A. and Murtugudde, R. and Rita R. Colwell} } @article {38462, title = {Resistin gene variation is associated with systemic inflammation but not plasma adipokine levels, metabolic syndrome or coronary atherosclerosis in nondiabetic Caucasians}, journal = {Clinical EndocrinologyClinical Endocrinology}, volume = {70}, year = {2009}, type = {10.1111/j.1365-2265.2008.03375.x}, abstract = {Objective Resistin causes insulin resistance and diabetes in mice whereas in humans it is linked to inflammation and atherosclerosis. Few human genetic studies of resistin in inflammation and atherosclerosis have been performed. We hypothesized that the {\textendash}420C>G putative gain-of-function resistin variant would be associated with inflammatory markers and atherosclerosis but not with metabolic syndrome or adipokines in humans.Design and methods We examined the association of three resistin polymorphisms, {\textendash}852A>G, {\textendash}420C>G and +157C>T, and related haplotypes with plasma resistin, cytokines, C-reactive protein (CRP), adipokines, plasma lipoproteins, metabolic syndrome and coronary artery calcification (CAC) in nondiabetic Caucasians (n~=~851). Results Resistin levels were higher, dose-dependently, with the {\textendash}420G allele (CC 5{\textperiodcentered}9~{\textpm}~2{\textperiodcentered}7~ng/ml, GC 6{\textperiodcentered}5~{\textpm}~4{\textperiodcentered}0~ng/ml and GG 7{\textperiodcentered}2~{\textpm}~4{\textperiodcentered}8~ng/ml, trend P~=~0{\textperiodcentered}04) after age and gender adjustment [fold higher for GC~+~GG vs. CC; 1{\textperiodcentered}07~(1{\textperiodcentered}00{\textendash}1{\textperiodcentered}15), P~<~0{\textperiodcentered}05)]. The {\textendash}852A>G single nucleotide polymorphism (SNP) was associated with higher soluble tumour necrosis factor-receptor~2 (sol-TNFR2) levels in fully adjusted models [1{\textperiodcentered}06~(95\%~CI 1{\textperiodcentered}01{\textendash}1{\textperiodcentered}11), P~=~0{\textperiodcentered}01)]. The estimated resistin haplotype (GGT) was associated with sol-TNFR2 (P~=~0{\textperiodcentered}04) and the AGT haplotype was related to CRP (P~=~0{\textperiodcentered}04) in the fully adjusted models. Resistin SNPs and haplotypes were not associated with body mass index (BMI), fasting glucose, insulin resistance, metabolic syndrome, adipokines or CAC scores. Conclusions Despite modest associations with plasma resistin and inflammatory biomarkers, resistin 5' variants were not associated with metabolic parameters or coronary calcification. This suggests that resistin is an inflammatory cytokine in humans but has little influence on adiposity, metabolic syndrome or atherosclerosis.}, isbn = {1365-2265}, author = {Qasim, Atif N. and Metkus, Thomas S. and Tadesse, Mahlet and Lehrke, Michael and Restine, Stephanie and Wolfe, Megan L. and Sridhar Hannenhalli and Cappola, Thomas and Rader, Daniel J. and Reilly, Muredach P.} } @article {38468, title = {RNA Colony Blot Hybridization Method for Enumeration of Culturable Vibrio Cholerae and Vibrio Mimicus Bacteria}, journal = {Applied and Environmental MicrobiologyAppl. Environ. Microbiol.Applied and Environmental MicrobiologyAppl. Environ. Microbiol.}, volume = {75}, year = {2009}, type = {10.1128/AEM.02007-08}, abstract = {A species-specific RNA colony blot hybridization protocol was developed for enumeration of culturable Vibrio cholerae and Vibrio mimicus bacteria in environmental water samples. Bacterial colonies on selective or nonselective plates were lysed by sodium dodecyl sulfate, and the lysates were immobilized on nylon membranes. A fluorescently labeled oligonucleotide probe targeting a phylogenetic signature sequence of 16S rRNA of V. cholerae and V. mimicus was hybridized to rRNA molecules immobilized on the nylon colony lift blots. The protocol produced strong positive signals for all colonies of the 15 diverse V. cholerae-V. mimicus strains tested, indicating 100\% sensitivity of the probe for the targeted species. For visible colonies of 10 nontarget species, the specificity of the probe was calculated to be 90\% because of a weak positive signal produced by Grimontia (Vibrio) hollisae, a marine bacterium. When both the sensitivity and specificity of the assay were evaluated using lake water samples amended with a bioluminescent V. cholerae strain, no false-negative or false-positive results were found, indicating 100\% sensitivity and specificity for culturable bacterial populations in freshwater samples when G. hollisae was not present. When the protocol was applied to laboratory microcosms containing V. cholerae attached to live copepods, copepods were found to carry approximately 10,000 to 50,000 CFU of V. cholerae per copepod. The protocol was also used to analyze pond water samples collected in an area of cholera endemicity in Bangladesh over a 9-month period. Water samples collected from six ponds demonstrated a peak in abundance of total culturable V. cholerae bacteria 1 to 2 months prior to observed increases in pathogenic V. cholerae and in clinical cases recorded by the area health clinic. The method provides a highly specific and sensitive tool for monitoring the dynamics of V. cholerae in the environment. The RNA blot hybridization protocol can also be applied to detection of other gram-negative bacteria for taxon-specific enumeration.}, isbn = {0099-2240, 1098-5336}, author = {Grim, Christopher J. and Zo, Young-Gun and Hasan, Nur A. and Ali, Afsar and Chowdhury, Wasimul B. and Islam, Atiqul and Rashid, Mohammed H. and Alam, Munirul and Morris, J. Glenn and Huq, Anwar and Rita R. Colwell} } @article {38521, title = {A synthesis for exactly 3-edge-connected graphs}, journal = {Arxiv preprint arXiv:0905.1053Arxiv preprint arXiv:0905.1053}, year = {2009}, author = {Kingsford, Carl and Mar{\c c}ais, G.} } @article {38528, title = {Three genomes from the phylum Acidobacteria provide insight into the lifestyles of these microorganisms in soils}, journal = {Applied and environmental microbiologyApplied and environmental microbiology}, volume = {75}, year = {2009}, note = {http://www.ncbi.nlm.nih.gov/pubmed/19201974?dopt=Abstract}, type = {10.1128/AEM.02294-08}, abstract = {The complete genomes of three strains from the phylum Acidobacteria were compared. Phylogenetic analysis placed them as a unique phylum. They share genomic traits with members of the Proteobacteria, the Cyanobacteria, and the Fungi. The three strains appear to be versatile heterotrophs. Genomic and culture traits indicate the use of carbon sources that span simple sugars to more complex substrates such as hemicellulose, cellulose, and chitin. The genomes encode low-specificity major facilitator superfamily transporters and high-affinity ABC transporters for sugars, suggesting that they are best suited to low-nutrient conditions. They appear capable of nitrate and nitrite reduction but not N(2) fixation or denitrification. The genomes contained numerous genes that encode siderophore receptors, but no evidence of siderophore production was found, suggesting that they may obtain iron via interaction with other microorganisms. The presence of cellulose synthesis genes and a large class of novel high-molecular-weight excreted proteins suggests potential traits for desiccation resistance, biofilm formation, and/or contribution to soil structure. Polyketide synthase and macrolide glycosylation genes suggest the production of novel antimicrobial compounds. Genes that encode a variety of novel proteins were also identified. The abundance of acidobacteria in soils worldwide and the breadth of potential carbon use by the sequenced strains suggest significant and previously unrecognized contributions to the terrestrial carbon cycle. Combining our genomic evidence with available culture traits, we postulate that cells of these isolates are long-lived, divide slowly, exhibit slow metabolic rates under low-nutrient conditions, and are well equipped to tolerate fluctuations in soil hydration.}, keywords = {Anti-Bacterial Agents, bacteria, Biological Transport, Carbohydrate Metabolism, Cyanobacteria, DNA, Bacterial, Fungi, Genome, Bacterial, Macrolides, Molecular Sequence Data, Nitrogen, Phylogeny, Proteobacteria, Sequence Analysis, DNA, Sequence Homology, Soil Microbiology}, author = {Ward, Naomi L. and Challacombe, Jean F. and Janssen, Peter H. and Henrissat, Bernard and Coutinho, Pedro M. and Wu, Martin and Xie, Gary and Haft, Daniel H. and Sait, Michelle and Badger, Jonathan and Barabote, Ravi D. and Bradley, Brent and Brettin, Thomas S. and Brinkac, Lauren M. and Bruce, David and Creasy, Todd and Daugherty, Sean C. and Davidsen, Tanja M. and DeBoy, Robert T. and Detter, J. Chris and Dodson, Robert J. and Durkin, A. Scott and Ganapathy, Anuradha and Gwinn-Giglio, Michelle and Han, Cliff S. and Khouri, Hoda and Kiss, Hajnalka and Kothari, Sagar P. and Madupu, Ramana and Nelson, Karen E. and Nelson, William C. and Paulsen, Ian and Penn, Kevin and Ren, Qinghu and Rosovitz, M. J. and J. Selengut and Shrivastava, Susmita and Sullivan, Steven A. and Tapia, Roxanne and Thompson, L. Sue and Watkins, Kisha L. and Yang, Qi and Yu, Chunhui and Zafar, Nikhat and Zhou, Liwei and Kuske, Cheryl R.} } @article {49780, title = {Three genomes from the phylum Acidobacteria provide insight into the lifestyles of these microorganisms in soils.}, journal = {Appl Environ Microbiol}, volume = {75}, year = {2009}, month = {2009 Apr}, pages = {2046-56}, abstract = {

The complete genomes of three strains from the phylum Acidobacteria were compared. Phylogenetic analysis placed them as a unique phylum. They share genomic traits with members of the Proteobacteria, the Cyanobacteria, and the Fungi. The three strains appear to be versatile heterotrophs. Genomic and culture traits indicate the use of carbon sources that span simple sugars to more complex substrates such as hemicellulose, cellulose, and chitin. The genomes encode low-specificity major facilitator superfamily transporters and high-affinity ABC transporters for sugars, suggesting that they are best suited to low-nutrient conditions. They appear capable of nitrate and nitrite reduction but not N(2) fixation or denitrification. The genomes contained numerous genes that encode siderophore receptors, but no evidence of siderophore production was found, suggesting that they may obtain iron via interaction with other microorganisms. The presence of cellulose synthesis genes and a large class of novel high-molecular-weight excreted proteins suggests potential traits for desiccation resistance, biofilm formation, and/or contribution to soil structure. Polyketide synthase and macrolide glycosylation genes suggest the production of novel antimicrobial compounds. Genes that encode a variety of novel proteins were also identified. The abundance of acidobacteria in soils worldwide and the breadth of potential carbon use by the sequenced strains suggest significant and previously unrecognized contributions to the terrestrial carbon cycle. Combining our genomic evidence with available culture traits, we postulate that cells of these isolates are long-lived, divide slowly, exhibit slow metabolic rates under low-nutrient conditions, and are well equipped to tolerate fluctuations in soil hydration.

}, keywords = {Anti-Bacterial Agents, bacteria, Biological Transport, Carbohydrate Metabolism, Cyanobacteria, DNA, Bacterial, Fungi, Genome, Bacterial, Macrolides, Molecular Sequence Data, Nitrogen, Phylogeny, Proteobacteria, Sequence Analysis, DNA, Sequence Homology, Soil Microbiology}, issn = {1098-5336}, doi = {10.1128/AEM.02294-08}, author = {Ward, Naomi L and Challacombe, Jean F and Janssen, Peter H and Henrissat, Bernard and Coutinho, Pedro M and Wu, Martin and Xie, Gary and Haft, Daniel H and Sait, Michelle and Badger, Jonathan and Barabote, Ravi D and Bradley, Brent and Brettin, Thomas S and Brinkac, Lauren M and Bruce, David and Creasy, Todd and Daugherty, Sean C and Davidsen, Tanja M and DeBoy, Robert T and Detter, J Chris and Dodson, Robert J and Durkin, A Scott and Ganapathy, Anuradha and Gwinn-Giglio, Michelle and Han, Cliff S and Khouri, Hoda and Kiss, Hajnalka and Kothari, Sagar P and Madupu, Ramana and Nelson, Karen E and Nelson, William C and Paulsen, Ian and Penn, Kevin and Ren, Qinghu and Rosovitz, M J and Selengut, Jeremy D and Shrivastava, Susmita and Sullivan, Steven A and Tapia, Roxanne and Thompson, L Sue and Watkins, Kisha L and Yang, Qi and Yu, Chunhui and Zafar, Nikhat and Zhou, Liwei and Kuske, Cheryl R} } @article {38533, title = {Toward reconstructing the evolution of advanced moths and butterflies (Lepidoptera: Ditrysia): an initial molecular study}, journal = {BMC Evol BiolBMC Evol Biol}, volume = {9}, year = {2009}, type = {10.1186/1471-2148-9-280}, abstract = {BACKGROUND: In the mega-diverse insect order Lepidoptera (butterflies and moths; 165,000 described species), deeper relationships are little understood within the clade Ditrysia, to which 98\% of the species belong. To begin addressing this problem, we tested the ability of five protein-coding nuclear genes (6.7 kb total), and character subsets therein, to resolve relationships among 123 species representing 27 (of 33) superfamilies and 55 (of 100) families of Ditrysia under maximum likelihood analysis. RESULTS: Our trees show broad concordance with previous morphological hypotheses of ditrysian phylogeny, although most relationships among superfamilies are weakly supported. There are also notable surprises, such as a consistently closer relationship of Pyraloidea than of butterflies to most Macrolepidoptera. Monophyly is significantly rejected by one or more character sets for the putative clades Macrolepidoptera as currently defined (P < 0.05) and Macrolepidoptera excluding Noctuoidea and Bombycoidea sensu lato (P < or = 0.005), and nearly so for the superfamily Drepanoidea as currently defined (P < 0.08). Superfamilies are typically recovered or nearly so, but usually without strong support. Relationships within superfamilies and families, however, are often robustly resolved. We provide some of the first strong molecular evidence on deeper splits within Pyraloidea, Tortricoidea, Geometroidea, Noctuoidea and others.Separate analyses of mostly synonymous versus non-synonymous character sets revealed notable differences (though not strong conflict), including a marked influence of compositional heterogeneity on apparent signal in the third codon position (nt3). As available model partitioning methods cannot correct for this variation, we assessed overall phylogeny resolution through separate examination of trees from each character set. Exploration of "tree space" with GARLI, using grid computing, showed that hundreds of searches are typically needed to find the best-feasible phylogeny estimate for these data. CONCLUSION: Our results (a) corroborate the broad outlines of the current working phylogenetic hypothesis for Ditrysia, (b) demonstrate that some prominent features of that hypothesis, including the position of the butterflies, need revision, and (c) resolve the majority of family and subfamily relationships within superfamilies as thus far sampled. Much further gene and taxon sampling will be needed, however, to strongly resolve individual deeper nodes.}, author = {Regier, J. C. and Zwick, A. and Michael P. Cummings and Kawahara, A. Y. and Cho, S. and Weller, S. and Roe, A. and Baixeras, J. and Brown, J. W. and Parr, C. and Davis, D. R. and Epstein, M. and Hallwachs, W. and Hausmann, A. and Janzen, D. H. and Kitching, I. J. and Solis, M. A. and Yen, S. H. and Adam L. Bazinet and Mitter, C.} } @article {49675, title = {Two alternatively spliced isoforms of the Arabidopsis SR45 protein have distinct roles during normal plant development.}, journal = {Plant Physiol}, volume = {150}, year = {2009}, month = {2009 Jul}, pages = {1450-8}, abstract = {

The serine-arginine-rich (SR) proteins constitute a conserved family of pre-mRNA splicing factors. In Arabidopsis (Arabidopsis thaliana), they are encoded by 19 genes, most of which are themselves alternatively spliced. In the case of SR45, the use of alternative 3{\textquoteright} splice sites 21 nucleotides apart generates two alternatively spliced isoforms. Isoform 1 (SR45.1) has an insertion relative to isoform 2 (SR45.2) that replaces a single arginine with eight amino acids (TSPQRKTG). The biological implications of SR45 alternative splicing have been unclear. A previously described loss-of-function mutant affecting both isoforms, sr45-1, shows several developmental defects, including defects in petal development and root growth. We found that the SR45 promoter is highly active in regions with actively growing and dividing cells. We also tested the ability of each SR45 isoform to complement the sr45-1 mutant by overexpression of isoform-specific green fluorescent protein (GFP) fusion proteins. As expected, transgenic plants overexpressing either isoform displayed both nuclear speckles and GFP fluorescence throughout the nucleoplasm. We found that SR45.1-GFP complements the flower petal phenotype, but not the root growth phenotype. Conversely, SR45.2-GFP complements root growth but not floral morphology. Mutation of a predicted phosphorylation site within the alternatively spliced segment, SR45.1-S219A-GFP, does not affect complementation. However, a double mutation affecting both serine-219 and the adjacent threonine-218 (SR45.1-T218A + S219A-GFP) behaves like isoform 2, complementing the root but not the floral phenotype. In conclusion, our study provides evidence that the two alternatively spliced isoforms of SR45 have distinct biological functions.

}, keywords = {Alternative Splicing, Amino Acid Sequence, Arabidopsis, Arabidopsis Proteins, Carrier Proteins, Flowers, Molecular Sequence Data, Mutation, Plant Roots, Protein Isoforms, Ribonucleoproteins, RNA-Binding Proteins, sequence alignment}, issn = {0032-0889}, doi = {10.1104/pp.109.138180}, author = {Zhang, Xiao-Ning and Mount, Stephen M} } @article {38559, title = {Using Satellite Images of Environmental Changes to Predict Infectious Disease Outbreaks}, journal = {Emerging Infectious DiseasesEmerg Infect DisEmerging Infectious DiseasesEmerg Infect Dis}, volume = {15}, year = {2009}, type = {10.3201/eid/1509.081334}, abstract = {A strong global satellite imaging system is essential for predicting outbreaks., Recent events clearly illustrate a continued vulnerability of large populations to infectious diseases, which is related to our changing human-constructed and natural environments. A single person with multidrug-resistant tuberculosis in 2007 provided a wake-up call to the United States and global public health infrastructure, as the health professionals and the public realized that today{\textquoteright}s ease of airline travel can potentially expose hundreds of persons to an untreatable disease associated with an infectious agent. Ease of travel, population increase, population displacement, pollution, agricultural activity, changing socioeconomic structures, and international conflicts worldwide have each contributed to infectious disease events. Today, however, nothing is larger in scale, has more potential for long-term effects, and is more uncertain than the effects of climate change on infectious disease outbreaks, epidemics, and pandemics. We discuss advances in our ability to predict these events and, in particular, the critical role that satellite imaging could play in mounting an effective response.}, isbn = {1080-6040}, author = {Ford, Timothy E. and Rita R. Colwell and Rose, Joan B. and Morse, Stephen S. and Rogers, David J. and Yates, Terry L.} } @article {49676, title = {The draft genome of the transgenic tropical fruit tree papaya (Carica papaya Linnaeus).}, journal = {Nature}, volume = {452}, year = {2008}, month = {2008 Apr 24}, pages = {991-6}, abstract = {

Papaya, a fruit crop cultivated in tropical and subtropical regions, is known for its nutritional benefits and medicinal applications. Here we report a 3x draft genome sequence of {\textquoteright}SunUp{\textquoteright} papaya, the first commercial virus-resistant transgenic fruit tree to be sequenced. The papaya genome is three times the size of the Arabidopsis genome, but contains fewer genes, including significantly fewer disease-resistance gene analogues. Comparison of the five sequenced genomes suggests a minimal angiosperm gene set of 13,311. A lack of recent genome duplication, atypical of other angiosperm genomes sequenced so far, may account for the smaller papaya gene number in most functional groups. Nonetheless, striking amplifications in gene number within particular functional groups suggest roles in the evolution of tree-like habit, deposition and remobilization of starch reserves, attraction of seed dispersal agents, and adaptation to tropical daylengths. Transgenesis at three locations is closely associated with chloroplast insertions into the nuclear genome, and with topoisomerase I recognition sites. Papaya offers numerous advantages as a system for fruit-tree functional genomics, and this draft genome sequence provides the foundation for revealing the basis of Carica{\textquoteright}s distinguishing morpho-physiological, medicinal and nutritional properties.

}, keywords = {Arabidopsis, Carica, Contig Mapping, Databases, Genetic, Genes, Plant, Genome, Plant, Molecular Sequence Data, Plants, Genetically Modified, sequence alignment, Sequence Analysis, DNA, Transcription Factors, Tropical Climate}, issn = {1476-4687}, doi = {10.1038/nature06856}, author = {Ming, Ray and Hou, Shaobin and Feng, Yun and Yu, Qingyi and Dionne-Laporte, Alexandre and Saw, Jimmy H and Senin, Pavel and Wang, Wei and Ly, Benjamin V and Lewis, Kanako L T and Salzberg, Steven L and Feng, Lu and Jones, Meghan R and Skelton, Rachel L and Murray, Jan E and Chen, Cuixia and Qian, Wubin and Shen, Junguo and Du, Peng and Eustice, Moriah and Tong, Eric and Tang, Haibao and Lyons, Eric and Paull, Robert E and Michael, Todd P and Wall, Kerr and Rice, Danny W and Albert, Henrik and Wang, Ming-Li and Zhu, Yun J and Schatz, Michael and Nagarajan, Niranjan and Acob, Ricelle A and Guan, Peizhu and Blas, Andrea and Wai, Ching Man and Ackerman, Christine M and Ren, Yan and Liu, Chao and Wang, Jianmei and Wang, Jianping and Na, Jong-Kuk and Shakirov, Eugene V and Haas, Brian and Thimmapuram, Jyothi and Nelson, David and Wang, Xiyin and Bowers, John E and Gschwend, Andrea R and Delcher, Arthur L and Singh, Ratnesh and Suzuki, Jon Y and Tripathi, Savarni and Neupane, Kabi and Wei, Hairong and Irikura, Beth and Paidi, Maya and Jiang, Ning and Zhang, Wenli and Presting, Gernot and Windsor, Aaron and Navajas-P{\'e}rez, Rafael and Torres, Manuel J and Feltus, F Alex and Porter, Brad and Li, Yingjun and Burroughs, A Max and Luo, Ming-Cheng and Liu, Lei and Christopher, David A and Mount, Stephen M and Moore, Paul H and Sugimura, Tak and Jiang, Jiming and Schuler, Mary A and Friedman, Vikki and Mitchell-Olds, Thomas and Shippen, Dorothy E and dePamphilis, Claude W and Palmer, Jeffrey D and Freeling, Michael and Paterson, Andrew H and Gonsalves, Dennis and Wang, Lei and Alam, Maqsudul} } @article {38232, title = {Environmental signatures associated with cholera epidemics}, journal = {Proceedings of the National Academy of SciencesProceedings of the National Academy of Sciences}, volume = {105}, year = {2008}, type = {10.1073/pnas.0809654105}, abstract = {The causative agent of cholera, Vibrio cholerae, has been shown to be autochthonous to riverine, estuarine, and coastal waters along with its host, the copepod, a significant member of the zooplankton community. Temperature, salinity, rainfall and plankton have proven to be important factors in the ecology of V. cholerae, influencing the transmission of the disease in those regions of the world where the human population relies on untreated water as a source of drinking water. In this study, the pattern of cholera outbreaks during 1998{\textendash}2006 in Kolkata, India, and Matlab, Bangladesh, and the earth observation data were analyzed with the objective of developing a prediction model for cholera. Satellite sensors were used to measure chlorophyll a concentration (CHL) and sea surface temperature (SST). In addition, rainfall data were obtained from both satellite and in situ gauge measurements. From the analyses, a statistically significant relationship between the time series for cholera in Kolkata, India, and CHL and rainfall anomalies was determined. A statistically significant one month lag was observed between CHL anomaly and number of cholera cases in Matlab, Bangladesh. From the results of the study, it is concluded that ocean and climate patterns are useful predictors of cholera epidemics, with the dynamics of endemic cholera being related to climate and/or changes in the aquatic ecosystem. When the ecology of V. cholerae is considered in predictive models, a robust early warning system for cholera in endemic regions of the world can be developed for public health planning and decision making.ecology epidemiology microbiology remote sensing}, isbn = {0027-8424, 1091-6490}, author = {Constantin de Magny, G. and Murtugudde, R. and Sapiano, M. R. P. and Nizam, A. and Brown, C. W. and Busalacchi, A. J. and Yunus, M. and Nair, G. B. and Gil, A. I. and Lanata, C. F. and Rita R. Colwell} } @inbook {38248, title = {Expanding the reach of Grid computing: combining Globus- and BOINC-based systems}, booktitle = {Grids for Bioinformatics and Computational BiologyGrids for Bioinformatics and Computational Biology}, series = {Wiley Book Series on Bioinformatics: Computational Techniques and Engineering}, year = {2008}, publisher = {Wiley-Interscience}, organization = {Wiley-Interscience}, address = {Hoboken}, author = {Myers, D. S. and Adam L. Bazinet and Michael P. Cummings}, editor = {Talbi, E. G. and Zomaya, A. Y.} } @article {38309, title = {Genome-wide analysis of repetitive elements in papaya}, journal = {Tropical Plant BiologyTropical Plant Biology}, volume = {1}, year = {2008}, publisher = {Springer}, author = {Nagarajan, N. and Navajas-P{\'e}rez, R. and M. Pop and Alam, M. and Ming, R. and Paterson, A. H. and Salzberg, S. L.} } @book {49868, title = {Lecture Notes in Computer ScienceBioinformatics Research and ApplicationsGapped Extension for Local Multiple Alignment of Interspersed DNA Repeats}, volume = {4983}, year = {2008}, pages = {74 - 86}, publisher = {Springer Berlin Heidelberg}, organization = {Springer Berlin Heidelberg}, address = {Berlin, Heidelberg}, isbn = {978-3-540-79449-3}, doi = {10.1007/978-3-540-79450-910.1007/978-3-540-79450-9_8}, url = {http://www.springerlink.com/index/10.1007/978-3-540-79450-9http://link.springer.com/10.1007/978-3-540-79450-9_8http://www.springerlink.com/index/pdf/10.1007/978-3-540-79450-9_8}, author = {Todd Treangen and Darling, Aaron E. and Ragan, Mark A. and Messeguer, Xavier} } @article {38366, title = {Maternal depletion of CTCF reveals multiple functions during oocyte and preimplantation embryo development}, journal = {DevelopmentDevelopment}, volume = {135}, year = {2008}, publisher = {The Company of Biologists Limited}, author = {Wan, L. B. and Pan, H. and Sridhar Hannenhalli and Cheng, Y. and Ma, J. and Fedoriw, A. and Lobanenkov, V. and Latham, K. E. and Schultz, R. M. and Bartolomei, M. S.} } @article {38383, title = {The minimum information about a genome sequence (MIGS) specification}, journal = {Nature biotechnologyNature biotechnology}, volume = {26}, year = {2008}, note = {http://www.ncbi.nlm.nih.gov/pubmed/18464787?dopt=Abstract}, type = {10.1038/nbt1360}, abstract = {With the quantity of genomic data increasing at an exponential rate, it is imperative that these data be captured electronically, in a standard format. Standardization activities must proceed within the auspices of open-access and international working bodies. To tackle the issues surrounding the development of better descriptions of genomic investigations, we have formed the Genomic Standards Consortium (GSC). Here, we introduce the minimum information about a genome sequence (MIGS) specification with the intent of promoting participation in its development and discussing the resources that will be required to develop improved mechanisms of metadata capture and exchange. As part of its wider goals, the GSC also supports improving the {\textquoteright}transparency{\textquoteright} of the information contained in existing genomic databases.}, keywords = {Chromosome mapping, Databases, Factual, information dissemination, Information Storage and Retrieval, Information Theory, Internationality}, author = {Field, Dawn and Garrity, George and Gray, Tanya and Morrison, Norman and J. Selengut and Sterk, Peter and Tatusova, Tatiana and Thomson, Nicholas and Allen, Michael J. and Angiuoli, Samuel V. and Ashburner, Michael and Axelrod, Nelson and Baldauf, Sandra and Ballard, Stuart and Boore, Jeffrey and Cochrane, Guy and Cole, James and Dawyndt, Peter and De Vos, Paul and DePamphilis, Claude and Edwards, Robert and Faruque, Nadeem and Feldman, Robert and Gilbert, Jack and Gilna, Paul and Gl{\"o}ckner, Frank Oliver and Goldstein, Philip and Guralnick, Robert and Haft, Dan and Hancock, David and Hermjakob, Henning and Hertz-Fowler, Christiane and Hugenholtz, Phil and Joint, Ian and Kagan, Leonid and Kane, Matthew and Kennedy, Jessie and Kowalchuk, George and Kottmann, Renzo and Kolker, Eugene and Kravitz, Saul and Kyrpides, Nikos and Leebens-Mack, Jim and Lewis, Suzanna E. and Li, Kelvin and Lister, Allyson L. and Lord, Phillip and Maltsev, Natalia and Markowitz, Victor and Martiny, Jennifer and Methe, Barbara and Mizrachi, Ilene and Moxon, Richard and Nelson, Karen and Parkhill, Julian and Proctor, Lita and White, Owen and Sansone, Susanna-Assunta and Spiers, Andrew and Stevens, Robert and Swift, Paul and Taylor, Chris and Tateno, Yoshio and Tett, Adrian and Turner, Sarah and Ussery, David and Vaughan, Bob and Ward, Naomi and Whetzel, Trish and San Gil, Ingio and Wilson, Gareth and Wipat, Anil} } @article {38463, title = {Resolving arthropod phylogeny: exploring phylogenetic signal within 41 kb of protein-coding nuclear gene sequence}, journal = {Syst BiolSyst Biol}, volume = {57}, year = {2008}, type = {10.1080/10635150802570791}, abstract = {This study attempts to resolve relationships among and within the four basal arthropod lineages (Pancrustacea, Myriapoda, Euchelicerata, Pycnogonida) and to assess the widespread expectation that remaining phylogenetic problems will yield to increasing amounts of sequence data. Sixty-eight regions of 62 protein-coding nuclear genes (approximately 41 kilobases (kb)/taxon) were sequenced for 12 taxonomically diverse arthropod taxa and a tardigrade outgroup. Parsimony, likelihood, and Bayesian analyses of total nucleotide data generally strongly supported the monophyly of each of the basal lineages represented by more than one species. Other relationships within the Arthropoda were also supported, with support levels depending on method of analysis and inclusion/exclusion of synonymous changes. Removing third codon positions, where the assumption of base compositional homogeneity was rejected, altered the results. Removing the final class of synonymous mutations{\textendash}first codon positions encoding leucine and arginine, which were also compositionally heterogeneous{\textendash}yielded a data set that was consistent with a hypothesis of base compositional homogeneity. Furthermore, under such a data-exclusion regime, all 68 gene regions individually were consistent with base compositional homogeneity. Restricting likelihood analyses to nonsynonymous change recovered trees with strong support for the basal lineages but not for other groups that were variably supported with more inclusive data sets. In a further effort to increase phylogenetic signal, three types of data exploration were undertaken. (1) Individual genes were ranked by their average rate of nonsynonymous change, and three rate categories were assigned{\textendash}fast, intermediate, and slow. Then, bootstrap analysis of each gene was performed separately to see which taxonomic groups received strong support. Five taxonomic groups were strongly supported independently by two or more genes, and these genes mostly belonged to the slow or intermediate categories, whereas groups supported only by a single gene region tended to be from genes of the fast category, arguing that fast genes provide a less consistent signal. (2) A sensitivity analysis was performed in which increasing numbers of genes were excluded, beginning with the fastest. The number of strongly supported nodes increased up to a point and then decreased slightly. Recovery of Hexapoda required removal of fast genes. Support for Mandibulata (Pancrustacea + Myriapoda) also increased, at times to "strong" levels, with removal of the fastest genes. (3) Concordance selection was evaluated by clustering genes according to their ability to recover Pancrustacea, Euchelicerata, or Myriapoda and analyzing the three clusters separately. All clusters of genes recovered the three concordance clades but were at times inconsistent in the relationships recovered among and within these clades, a result that indicates that the a priori concordance criteria may bias phylogenetic signal in unexpected ways. In a further attempt to increase support of taxonomic relationships, sequence data from 49 additional taxa for three slow genes (i.e., EF-1 alpha, EF-2, and Pol II) were combined with the various 13-taxon data sets. The 62-taxon analyses supported the results of the 13-taxon analyses and provided increased support for additional pancrustacean clades found in an earlier analysis including only EF-1 alpha, EF-2, and Pol II.}, author = {Regier, J. C. and Shultz, J. W. and Ganley, A. R. D. and Hussey, A. and Shi, D. and Ball, B. and Zwick, A. and Stajich, J. E. and Michael P. Cummings and Martin, J. W. and Cunningham, C. W.} } @article {38484, title = {Seasonal Cholera from Multiple Small Outbreaks, Rural Bangladesh}, journal = {Emerging Infectious DiseasesEmerg Infect DisEmerging Infectious DiseasesEmerg Infect Dis}, volume = {14}, year = {2008}, type = {10.3201/eid1405.071116}, abstract = {Clinical and environmental Vibrio cholerae organisms collected from February 2004 through April 2005 were systematically isolated from 2 rural Bangladeshi locales. Their genetic relatedness was evaluated at 5 loci that contained a variable number of tandem repeats (VNTR). The observed minimal overlap in VNTR patterns between the 2 communities was consistent with sequential, small outbreaks from local sources.}, isbn = {1080-6040}, author = {Stine, O. Colin and Alam, Munirul and Tang, Li and Nair, G. Balakrish and Siddique, A. Kasem and Faruque, Shah M. and Huq, Anwar and Rita R. Colwell and Sack, R. Bradley and Morris, J. Glenn} } @article {38491, title = {Sequence diversity and evolution of multigene families in Trypanosoma cruzi}, journal = {Molecular and Biochemical ParasitologyMolecular and Biochemical Parasitology}, volume = {157}, year = {2008}, type = {16/j.molbiopara.2007.10.002}, abstract = {Several copies of genes belonging to three multigene families present in the genome of Trypanosoma cruzi were sequenced and comparatively analyzed across six different strains of the parasite belonging to the T. cruzi I lineage (Colombiana, Silvio X10 and Dm28c), the T. cruzi II lineage (Esmeraldo and JG) and a hybrid strain (CL Brener). For all three gene families analyzed, our results support the division in T. cruzi I and II lineages. Furthermore, in agreement with its hybrid nature, sequences derived from the CL Brener clone clustered together with T. cruzi II sequences as well as with a third group of sequences. Paralogous sequences encoding Amastin, an amastigote surface glycoprotein and TcAG48, an antigenic RNA binding protein, which are clustered in the parasite genome, present higher intragenomic variability in T. cruzi II and CL Brener strains, when compared to T. cruzi I strains. Paralogous sequences derived from the TcADC gene family, which encode various isoforms of adenylyl cyclases and are dispersed throughout the T. cruzi genome, exhibit similar degree of variability in all strains, except in the CL Brener strain, in which the sequences were more divergent. Several factors including mutation rates and gene conversion mechanisms, acting differently within the T. cruzi population, may contribute to create such distinct levels of sequence diversity in multigene families that are clustered in the T. cruzi genome.}, keywords = {Amastin, Gene conversion, Genetic diversity, Multigene families, Trypanosoma cruzi}, isbn = {0166-6851}, author = {Cerqueira, Gustavo C. and Bartholomeu, Daniella C. and DaRocha, Wanderson D. and Hou, Lihua and Freitas-Silva, Danielle M. and Machado, Carlos Renato and Najib M. El-Sayed and Teixeira, Santuza M. R.} } @article {38499, title = {Sex and age dimorphism of myocardial gene expression in nonischemic human heart failure}, journal = {Circulation: Cardiovascular GeneticsCirculation: Cardiovascular Genetics}, volume = {1}, year = {2008}, publisher = {Am Heart Assoc}, author = {Fermin, D. R. and Barac, A. and Lee, S. and Polster, S. P. and Sridhar Hannenhalli and Bergemann, T. L. and Grindle, S. and Dyke, D. B. and Pagani, F. and Miller, L. W. and others,} } @article {38567, title = {Vibrio cholerae non-O1, non-O139 strains isolated before 1992 from Varanasi, India are multiple drug resistant, contain intSXT, dfr18 and aadA5 genes}, journal = {Environmental MicrobiologyEnvironmental Microbiology}, volume = {10}, year = {2008}, type = {10.1111/j.1462-2920.2007.01502.x}, abstract = {In this study, we report the presence of the SXT element and Class I integron in Vibrio cholerae non-O1, non-O139 strains isolated from Varanasi, India. Isolates were resistant to cotrimoxazole, trimethoprim and/or streptomycin, furazolidone and ampicillin. None contained plasmids. Polymerase chain reaction (PCR) and DNA sequencing revealed the presence of antibiotic resistance gene cassettes, aadA1, aadA2, aadA5 and dfrA15, in the Class I integron and SXT, an integrative conjugative element containing dfr18, sulII and strAB, in three and six of the isolates respectively. Conjugation experiments, followed by PCR analysis of transconjugants, provided evidence for the transferable nature of intSXT and associated antibiotic resistance gene cassettes. This is the first report of the occurrence of SXT ICE, dfr18, sulII, strAB and aadA5 genes in environmental V.~cholerae non-O1, non-O139 strains from Varanasi, India, that had been isolated before 1992.}, isbn = {1462-2920}, author = {Mohapatra, Harapriya and Mohapatra, Saswat S. and Mantri, Chinmay K. and Rita R. Colwell and Singh, Durg V.} } @article {49852, title = {Analyzing patterns of microbial evolution using the mauve genome alignment system}, journal = {Comparative Genomics}, year = {2007}, pages = {135{\textendash}152}, author = {Darling, Aaron E and Todd Treangen and Messeguer, Xavier and Perna, Nicole T} } @article {38172, title = {COMPUTATIONAL BIOLOGY}, journal = {Nucleic acids researchNucleic Acids Research}, volume = {35}, year = {2007}, publisher = {Information Retrieval Ltd}, author = {Leparc, G. G. and Mitra, R. D. and Vardhanabhuti, S. and Wang, J. and Sridhar Hannenhalli and Smit, S. and Widmann, J. and Knight, R. and Wu, S. and Zhang, Y. and others,} } @article {49680, title = {A computational survey of candidate exonic splicing enhancer motifs in the model plant Arabidopsis thaliana.}, journal = {BMC Bioinformatics}, volume = {8}, year = {2007}, month = {2007}, pages = {159}, abstract = {

BACKGROUND: Algorithmic approaches to splice site prediction have relied mainly on the consensus patterns found at the boundaries between protein coding and non-coding regions. However exonic splicing enhancers have been shown to enhance the utilization of nearby splice sites.

RESULTS: We have developed a new computational technique to identify significantly conserved motifs involved in splice site regulation. First, 84 putative exonic splicing enhancer hexamers are identified in Arabidopsis thaliana. Then a Gibbs sampling program called ELPH was used to locate conserved motifs represented by these hexamers in exonic regions near splice sites in confirmed genes. Oligomers containing 35 of these motifs have been shown experimentally to induce significant inclusion of A. thaliana exons. Second, integration of our regulatory motifs into two different splice site recognition programs significantly improved the ability of the software to correctly predict splice sites in a large database of confirmed genes. We have released GeneSplicerESE, the improved splice site recognition code, as open source software.

CONCLUSION: Our results show that the use of the ESE motifs consistently improves splice site prediction accuracy.

}, keywords = {Alternative Splicing, Arabidopsis, Computational Biology, Enhancer Elements, Genetic, Exons, Genes, Plant, RNA, Plant}, issn = {1471-2105}, doi = {10.1186/1471-2105-8-159}, author = {Pertea, Mihaela and Mount, Stephen M and Salzberg, Steven L} } @article {38215, title = {Draft genome of the filarial nematode parasite Brugia malayi}, journal = {ScienceScience}, volume = {317}, year = {2007}, publisher = {American Association for the Advancement of Science}, author = {Ghedin, E. and Wang, S. and Spiro, D. and Caler, E. and Zhao, Q. and Crabtree, J. and Allen, J. E. and Delcher, A. L. and Guiliano, D. B. and Miranda-Saavedra, D. and others,} } @article {38242, title = {Evolution of genes and genomes on the Drosophila phylogeny}, journal = {NatureNature}, volume = {450}, year = {2007}, note = {[szlig]}, type = {10.1038/nature06341}, abstract = {Comparative analysis of multiple genomes in a phylogenetic framework dramatically improves the precision and sensitivity of evolutionary inference, producing more robust results than single-genome analyses can provide. The genomes of 12 Drosophila species, ten of which are presented here for the first time (sechellia, simulans, yakuba, erecta, ananassae, persimilis, willistoni, mojavensis, virilis and grimshawi), illustrate how rates and patterns of sequence divergence across taxa can illuminate evolutionary processes on a genomic scale. These genome sequences augment the formidable genetic tools that have made Drosophila melanogaster a pre-eminent model for animal genetics, and will further catalyse fundamental research on mechanisms of development, cell biology, genetics, disease, neurobiology, behaviour, physiology and evolution. Despite remarkable similarities among these Drosophila species, we identified many putatively non-neutral changes in protein-coding genes, non-coding RNA genes, and cis-regulatory regions. These may prove to underlie differences in the ecology and behaviour of these diverse species.}, isbn = {0028-0836}, author = {Clark, Andrew G. and Eisen, Michael B. and Smith, Douglas R. and Bergman, Casey M. and Oliver, Brian and Markow, Therese A. and Kaufman, Thomas C. and Kellis, Manolis and Gelbart, William and Iyer, Venky N. and Pollard, Daniel A. and Sackton, Timothy B. and Larracuente, Amanda M. and Singh, Nadia D. and Abad, Jose P. and Abt, Dawn N. and Adryan, Boris and Aguade, Montserrat and Akashi, Hiroshi and Anderson, Wyatt W. and Aquadro, Charles F. and Ardell, David H. and Arguello, Roman and Artieri, Carlo G. and Barbash, Daniel A. and Barker, Daniel and Barsanti, Paolo and Batterham, Phil and Batzoglou, Serafim and Begun, Dave and Bhutkar, Arjun and Blanco, Enrico and Bosak, Stephanie A. and Bradley, Robert K. and Brand, Adrianne D. and Brent, Michael R. and Brooks, Angela N. and Brown, Randall H. and Butlin, Roger K. and Caggese, Corrado and Calvi, Brian R. and Carvalho, A. Bernardo de and Caspi, Anat and Castrezana, Sergio and Celniker, Susan E. and Chang, Jean L. and Chapple, Charles and Chatterji, Sourav and Chinwalla, Asif and Civetta, Alberto and Clifton, Sandra W. and Comeron, Josep M. and Costello, James C. and Coyne, Jerry A. and Daub, Jennifer and David, Robert G. and Delcher, Arthur L. and Delehaunty, Kim and Do, Chuong B. and Ebling, Heather and Edwards, Kevin and Eickbush, Thomas and Evans, Jay D. and Filipski, Alan and Findei, and Sven and Freyhult, Eva and Fulton, Lucinda and Fulton, Robert and Garcia, Ana C. L. and Gardiner, Anastasia and Garfield, David A. and Garvin, Barry E. and Gibson, Greg and Gilbert, Don and Gnerre, Sante and Godfrey, Jennifer and Good, Robert and Gotea, Valer and Gravely, Brenton and Greenberg, Anthony J. and Griffiths-Jones, Sam and Gross, Samuel and Guigo, Roderic and Gustafson, Erik A. and Haerty, Wilfried and Hahn, Matthew W. and Halligan, Daniel L. and Halpern, Aaron L. and Halter, Gillian M. and Han, Mira V. and Heger, Andreas and Hillier, LaDeana and Hinrichs, Angie S. and Holmes, Ian and Hoskins, Roger A. and Hubisz, Melissa J. and Hultmark, Dan and Huntley, Melanie A. and Jaffe, David B. and Jagadeeshan, Santosh and Jeck, William R. and Johnson, Justin and Jones, Corbin D. and Jordan, William C. and Karpen, Gary H. and Kataoka, Eiko and Keightley, Peter D. and Kheradpour, Pouya and Kirkness, Ewen F. and Koerich, Leonardo B. and Kristiansen, Karsten and Kudrna, Dave and Kulathinal, Rob J. and Kumar, Sudhir and Kwok, Roberta and Lander, Eric and Langley, Charles H. and Lapoint, Richard and Lazzaro, Brian P. and Lee, So-Jeong and Levesque, Lisa and Li, Ruiqiang and Lin, Chiao-Feng and Lin, Michael F. and Lindblad-Toh, Kerstin and Llopart, Ana and Long, Manyuan and Low, Lloyd and Lozovsky, Elena and Lu, Jian and Luo, Meizhong and Machado, Carlos A. and Makalowski, Wojciech and Marzo, Mar and Matsuda, Muneo and Matzkin, Luciano and McAllister, Bryant and McBride, Carolyn S. and McKernan, Brendan and McKernan, Kevin and Mendez-Lago, Maria and Minx, Patrick and Mollenhauer, Michael U. and Montooth, Kristi and Stephen M. Mount and Mu, Xu and Myers, Eugene and Negre, Barbara and Newfeld, Stuart and Nielsen, Rasmus and Noor, Mohamed A. F. and O{\textquoteright}Grady, Patrick and Pachter, Lior and Papaceit, Montserrat and Parisi, Matthew J. and Parisi, Michael and Parts, Leopold and Pedersen, Jakob S. and Pesole, Graziano and Phillippy, Adam M. and Ponting, Chris P. and M. Pop and Porcelli, Damiano and Powell, Jeffrey R. and Prohaska, Sonja and Pruitt, Kim and Puig, Marta and Quesneville, Hadi and Ram, Kristipati Ravi and Rand, David and Rasmussen, Matthew D. and Reed, Laura K. and Reenan, Robert and Reily, Amy and Remington, Karin A. and Rieger, Tania T. and Ritchie, Michael G. and Robin, Charles and Rogers, Yu-Hui and Rohde, Claudia and Rozas, Julio and Rubenfield, Marc J. and Ruiz, Alfredo and Russo, Susan and Salzberg, Steven L. and Sanchez-Gracia, Alejandro and Saranga, David J. and Sato, Hajime and Schaeffer, Stephen W. and Schatz, Michael C. and Schlenke, Todd and Schwartz, Russell and Segarra, Carmen and Singh, Rama S. and Sirot, Laura and Sirota, Marina and Sisneros, Nicholas B. and Smith, Chris D. and Smith, Temple F. and Spieth, John and Stage, Deborah E. and Stark, Alexander and Stephan, Wolfgang and Strausberg, Robert L. and Strempel, Sebastian and Sturgill, David and Sutton, Granger and Sutton, Granger G. and Tao, Wei and Teichmann, Sarah and Tobari, Yoshiko N. and Tomimura, Yoshihiko and Tsolas, Jason M. and Valente, Vera L. S. and Venter, Eli and Venter, J. Craig and Vicario, Saverio and Vieira, Filipe G. and Vilella, Albert J. and Villasante, Alfredo and Walenz, Brian and Wang, Jun and Wasserman, Marvin and Watts, Thomas and Wilson, Derek and Wilson, Richard K. and Wing, Rod A. and Wolfner, Mariana F. and Wong, Alex and Wong, Gane Ka-Shu and Wu, Chung- I. and Wu, Gabriel and Yamamoto, Daisuke and Yang, Hsiao-Pei and Yang, Shiaw-Pyng and Yorke, James A. and Yoshida, Kiyohito and Zdobnov, Evgeny and Zhang, Peili and Zhang, Yu and Zimin, Aleksey V. and Baldwin, Jennifer and Abdouelleil, Amr and Abdulkadir, Jamal and Abebe, Adal and Abera, Brikti and Abreu, Justin and Acer, St Christophe and Aftuck, Lynne and Alexander, Allen and An, Peter and Anderson, Erica and Anderson, Scott and Arachi, Harindra and Azer, Marc and Bachantsang, Pasang and Barry, Andrew and Bayul, Tashi and Berlin, Aaron and Bessette, Daniel and Bloom, Toby and Blye, Jason and Boguslavskiy, Leonid and Bonnet, Claude and Boukhgalter, Boris and Bourzgui, Imane and Brown, Adam and Cahill, Patrick and Channer, Sheridon and Cheshatsang, Yama and Chuda, Lisa and Citroen, Mieke and Collymore, Alville and Cooke, Patrick and Costello, Maura and D{\textquoteright}Aco, Katie and Daza, Riza and Haan, Georgius De and DeGray, Stuart and DeMaso, Christina and Dhargay, Norbu and Dooley, Kimberly and Dooley, Erin and Doricent, Missole and Dorje, Passang and Dorjee, Kunsang and Dupes, Alan and Elong, Richard and Falk, Jill and Farina, Abderrahim and Faro, Susan and Ferguson, Diallo and Fisher, Sheila and Foley, Chelsea D. and Franke, Alicia and Friedrich, Dennis and Gadbois, Loryn and Gearin, Gary and Gearin, Christina R. and Giannoukos, Georgia and Goode, Tina and Graham, Joseph and Grandbois, Edward and Grewal, Sharleen and Gyaltsen, Kunsang and Hafez, Nabil and Hagos, Birhane and Hall, Jennifer and Henson, Charlotte and Hollinger, Andrew and Honan, Tracey and Huard, Monika D. and Hughes, Leanne and Hurhula, Brian and Husby, M. Erii and Kamat, Asha and Kanga, Ben and Kashin, Seva and Khazanovich, Dmitry and Kisner, Peter and Lance, Krista and Lara, Marcia and Lee, William and Lennon, Niall and Letendre, Frances and LeVine, Rosie and Lipovsky, Alex and Liu, Xiaohong and Liu, Jinlei and Liu, Shangtao and Lokyitsang, Tashi and Lokyitsang, Yeshi and Lubonja, Rakela and Lui, Annie and MacDonald, Pen and Magnisalis, Vasilia and Maru, Kebede and Matthews, Charles and McCusker, William and McDonough, Susan and Mehta, Teena and Meldrim, James and Meneus, Louis and Mihai, Oana and Mihalev, Atanas and Mihova, Tanya and Mittelman, Rachel and Mlenga, Valentine and Montmayeur, Anna and Mulrain, Leonidas and Navidi, Adam and Naylor, Jerome and Negash, Tamrat and Nguyen, Thu and Nguyen, Nga and Nicol, Robert and Norbu, Choe and Norbu, Nyima and Novod, Nathaniel and O{\textquoteright}Neill, Barry and Osman, Sahal and Markiewicz, Eva and Oyono, Otero L. and Patti, Christopher and Phunkhang, Pema and Pierre, Fritz and Priest, Margaret and Raghuraman, Sujaa and Rege, Filip and Reyes, Rebecca and Rise, Cecil and Rogov, Peter and Ross, Keenan and Ryan, Elizabeth and Settipalli, Sampath and Shea, Terry and Sherpa, Ngawang and Shi, Lu and Shih, Diana and Sparrow, Todd and Spaulding, Jessica and Stalker, John and Stange-Thomann, Nicole and Stavropoulos, Sharon and Stone, Catherine and Strader, Christopher and Tesfaye, Senait and Thomson, Talene and Thoulutsang, Yama and Thoulutsang, Dawa and Topham, Kerri and Topping, Ira and Tsamla, Tsamla and Vassiliev, Helen and Vo, Andy and Wangchuk, Tsering and Wangdi, Tsering and Weiand, Michael and Wilkinson, Jane and Wilson, Adam and Yadav, Shailendra and Young, Geneva and Yu, Qing and Zembek, Lisa and Zhong, Danni and Zimmer, Andrew and Zwirko, Zac and Jaffe, David B. and Alvarez, Pablo and Brockman, Will and Butler, Jonathan and Chin, CheeWhye and Gnerre, Sante and Grabherr, Manfred and Kleber, Michael and Mauceli, Evan and MacCallum, Iain} } @article {49677, title = {Evolution of genes and genomes on the Drosophila phylogeny.}, journal = {Nature}, volume = {450}, year = {2007}, month = {2007 Nov 8}, pages = {203-18}, abstract = {

Comparative analysis of multiple genomes in a phylogenetic framework dramatically improves the precision and sensitivity of evolutionary inference, producing more robust results than single-genome analyses can provide. The genomes of 12 Drosophila species, ten of which are presented here for the first time (sechellia, simulans, yakuba, erecta, ananassae, persimilis, willistoni, mojavensis, virilis and grimshawi), illustrate how rates and patterns of sequence divergence across taxa can illuminate evolutionary processes on a genomic scale. These genome sequences augment the formidable genetic tools that have made Drosophila melanogaster a pre-eminent model for animal genetics, and will further catalyse fundamental research on mechanisms of development, cell biology, genetics, disease, neurobiology, behaviour, physiology and evolution. Despite remarkable similarities among these Drosophila species, we identified many putatively non-neutral changes in protein-coding genes, non-coding RNA genes, and cis-regulatory regions. These may prove to underlie differences in the ecology and behaviour of these diverse species.

}, keywords = {Animals, Codon, DNA Transposable Elements, Drosophila, Drosophila Proteins, Evolution, Molecular, Gene Order, Genes, Insect, Genome, Insect, Genome, Mitochondrial, Genomics, Immunity, Multigene Family, Phylogeny, Reproduction, RNA, Untranslated, sequence alignment, Sequence Analysis, DNA, Synteny}, issn = {1476-4687}, doi = {10.1038/nature06341}, author = {Clark, Andrew G and Eisen, Michael B and Smith, Douglas R and Bergman, Casey M and Oliver, Brian and Markow, Therese A and Kaufman, Thomas C and Kellis, Manolis and Gelbart, William and Iyer, Venky N and Pollard, Daniel A and Sackton, Timothy B and Larracuente, Amanda M and Singh, Nadia D and Abad, Jose P and Abt, Dawn N and Adryan, Boris and Aguade, Montserrat and Akashi, Hiroshi and Anderson, Wyatt W and Aquadro, Charles F and Ardell, David H and Arguello, Roman and Artieri, Carlo G and Barbash, Daniel A and Barker, Daniel and Barsanti, Paolo and Batterham, Phil and Batzoglou, Serafim and Begun, Dave and Bhutkar, Arjun and Blanco, Enrico and Bosak, Stephanie A and Bradley, Robert K and Brand, Adrianne D and Brent, Michael R and Brooks, Angela N and Brown, Randall H and Butlin, Roger K and Caggese, Corrado and Calvi, Brian R and Bernardo de Carvalho, A and Caspi, Anat and Castrezana, Sergio and Celniker, Susan E and Chang, Jean L and Chapple, Charles and Chatterji, Sourav and Chinwalla, Asif and Civetta, Alberto and Clifton, Sandra W and Comeron, Josep M and Costello, James C and Coyne, Jerry A and Daub, Jennifer and David, Robert G and Delcher, Arthur L and Delehaunty, Kim and Do, Chuong B and Ebling, Heather and Edwards, Kevin and Eickbush, Thomas and Evans, Jay D and Filipski, Alan and Findeiss, Sven and Freyhult, Eva and Fulton, Lucinda and Fulton, Robert and Garcia, Ana C L and Gardiner, Anastasia and Garfield, David A and Garvin, Barry E and Gibson, Greg and Gilbert, Don and Gnerre, Sante and Godfrey, Jennifer and Good, Robert and Gotea, Valer and Gravely, Brenton and Greenberg, Anthony J and Griffiths-Jones, Sam and Gross, Samuel and Guigo, Roderic and Gustafson, Erik A and Haerty, Wilfried and Hahn, Matthew W and Halligan, Daniel L and Halpern, Aaron L and Halter, Gillian M and Han, Mira V and Heger, Andreas and Hillier, LaDeana and Hinrichs, Angie S and Holmes, Ian and Hoskins, Roger A and Hubisz, Melissa J and Hultmark, Dan and Huntley, Melanie A and Jaffe, David B and Jagadeeshan, Santosh and Jeck, William R and Johnson, Justin and Jones, Corbin D and Jordan, William C and Karpen, Gary H and Kataoka, Eiko and Keightley, Peter D and Kheradpour, Pouya and Kirkness, Ewen F and Koerich, Leonardo B and Kristiansen, Karsten and Kudrna, Dave and Kulathinal, Rob J and Kumar, Sudhir and Kwok, Roberta and Lander, Eric and Langley, Charles H and Lapoint, Richard and Lazzaro, Brian P and Lee, So-Jeong and Levesque, Lisa and Li, Ruiqiang and Lin, Chiao-Feng and Lin, Michael F and Lindblad-Toh, Kerstin and Llopart, Ana and Long, Manyuan and Low, Lloyd and Lozovsky, Elena and Lu, Jian and Luo, Meizhong and Machado, Carlos A and Makalowski, Wojciech and Marzo, Mar and Matsuda, Muneo and Matzkin, Luciano and McAllister, Bryant and McBride, Carolyn S and McKernan, Brendan and McKernan, Kevin and Mendez-Lago, Maria and Minx, Patrick and Mollenhauer, Michael U and Montooth, Kristi and Mount, Stephen M and Mu, Xu and Myers, Eugene and Negre, Barbara and Newfeld, Stuart and Nielsen, Rasmus and Noor, Mohamed A F and O{\textquoteright}Grady, Patrick and Pachter, Lior and Papaceit, Montserrat and Parisi, Matthew J and Parisi, Michael and Parts, Leopold and Pedersen, Jakob S and Pesole, Graziano and Phillippy, Adam M and Ponting, Chris P and Pop, Mihai and Porcelli, Damiano and Powell, Jeffrey R and Prohaska, Sonja and Pruitt, Kim and Puig, Marta and Quesneville, Hadi and Ram, Kristipati Ravi and Rand, David and Rasmussen, Matthew D and Reed, Laura K and Reenan, Robert and Reily, Amy and Remington, Karin A and Rieger, Tania T and Ritchie, Michael G and Robin, Charles and Rogers, Yu-Hui and Rohde, Claudia and Rozas, Julio and Rubenfield, Marc J and Ruiz, Alfredo and Russo, Susan and Salzberg, Steven L and Sanchez-Gracia, Alejandro and Saranga, David J and Sato, Hajime and Schaeffer, Stephen W and Schatz, Michael C and Schlenke, Todd and Schwartz, Russell and Segarra, Carmen and Singh, Rama S and Sirot, Laura and Sirota, Marina and Sisneros, Nicholas B and Smith, Chris D and Smith, Temple F and Spieth, John and Stage, Deborah E and Stark, Alexander and Stephan, Wolfgang and Strausberg, Robert L and Strempel, Sebastian and Sturgill, David and Sutton, Granger and Sutton, Granger G and Tao, Wei and Teichmann, Sarah and Tobari, Yoshiko N and Tomimura, Yoshihiko and Tsolas, Jason M and Valente, Vera L S and Venter, Eli and Venter, J Craig and Vicario, Saverio and Vieira, Filipe G and Vilella, Albert J and Villasante, Alfredo and Walenz, Brian and Wang, Jun and Wasserman, Marvin and Watts, Thomas and Wilson, Derek and Wilson, Richard K and Wing, Rod A and Wolfner, Mariana F and Wong, Alex and Wong, Gane Ka-Shu and Wu, Chung-I and Wu, Gabriel and Yamamoto, Daisuke and Yang, Hsiao-Pei and Yang, Shiaw-Pyng and Yorke, James A and Yoshida, Kiyohito and Zdobnov, Evgeny and Zhang, Peili and Zhang, Yu and Zimin, Aleksey V and Baldwin, Jennifer and Abdouelleil, Amr and Abdulkadir, Jamal and Abebe, Adal and Abera, Brikti and Abreu, Justin and Acer, St Christophe and Aftuck, Lynne and Alexander, Allen and An, Peter and Anderson, Erica and Anderson, Scott and Arachi, Harindra and Azer, Marc and Bachantsang, Pasang and Barry, Andrew and Bayul, Tashi and Berlin, Aaron and Bessette, Daniel and Bloom, Toby and Blye, Jason and Boguslavskiy, Leonid and Bonnet, Claude and Boukhgalter, Boris and Bourzgui, Imane and Brown, Adam and Cahill, Patrick and Channer, Sheridon and Cheshatsang, Yama and Chuda, Lisa and Citroen, Mieke and Collymore, Alville and Cooke, Patrick and Costello, Maura and D{\textquoteright}Aco, Katie and Daza, Riza and De Haan, Georgius and DeGray, Stuart and DeMaso, Christina and Dhargay, Norbu and Dooley, Kimberly and Dooley, Erin and Doricent, Missole and Dorje, Passang and Dorjee, Kunsang and Dupes, Alan and Elong, Richard and Falk, Jill and Farina, Abderrahim and Faro, Susan and Ferguson, Diallo and Fisher, Sheila and Foley, Chelsea D and Franke, Alicia and Friedrich, Dennis and Gadbois, Loryn and Gearin, Gary and Gearin, Christina R and Giannoukos, Georgia and Goode, Tina and Graham, Joseph and Grandbois, Edward and Grewal, Sharleen and Gyaltsen, Kunsang and Hafez, Nabil and Hagos, Birhane and Hall, Jennifer and Henson, Charlotte and Hollinger, Andrew and Honan, Tracey and Huard, Monika D and Hughes, Leanne and Hurhula, Brian and Husby, M Erii and Kamat, Asha and Kanga, Ben and Kashin, Seva and Khazanovich, Dmitry and Kisner, Peter and Lance, Krista and Lara, Marcia and Lee, William and Lennon, Niall and Letendre, Frances and LeVine, Rosie and Lipovsky, Alex and Liu, Xiaohong and Liu, Jinlei and Liu, Shangtao and Lokyitsang, Tashi and Lokyitsang, Yeshi and Lubonja, Rakela and Lui, Annie and MacDonald, Pen and Magnisalis, Vasilia and Maru, Kebede and Matthews, Charles and McCusker, William and McDonough, Susan and Mehta, Teena and Meldrim, James and Meneus, Louis and Mihai, Oana and Mihalev, Atanas and Mihova, Tanya and Mittelman, Rachel and Mlenga, Valentine and Montmayeur, Anna and Mulrain, Leonidas and Navidi, Adam and Naylor, Jerome and Negash, Tamrat and Nguyen, Thu and Nguyen, Nga and Nicol, Robert and Norbu, Choe and Norbu, Nyima and Novod, Nathaniel and O{\textquoteright}Neill, Barry and Osman, Sahal and Markiewicz, Eva and Oyono, Otero L and Patti, Christopher and Phunkhang, Pema and Pierre, Fritz and Priest, Margaret and Raghuraman, Sujaa and Rege, Filip and Reyes, Rebecca and Rise, Cecil and Rogov, Peter and Ross, Keenan and Ryan, Elizabeth and Settipalli, Sampath and Shea, Terry and Sherpa, Ngawang and Shi, Lu and Shih, Diana and Sparrow, Todd and Spaulding, Jessica and Stalker, John and Stange-Thomann, Nicole and Stavropoulos, Sharon and Stone, Catherine and Strader, Christopher and Tesfaye, Senait and Thomson, Talene and Thoulutsang, Yama and Thoulutsang, Dawa and Topham, Kerri and Topping, Ira and Tsamla, Tsamla and Vassiliev, Helen and Vo, Andy and Wangchuk, Tsering and Wangdi, Tsering and Weiand, Michael and Wilkinson, Jane and Wilson, Adam and Yadav, Shailendra and Young, Geneva and Yu, Qing and Zembek, Lisa and Zhong, Danni and Zimmer, Andrew and Zwirko, Zac and Jaffe, David B and Alvarez, Pablo and Brockman, Will and Butler, Jonathan and Chin, CheeWhye and Gnerre, Sante and Grabherr, Manfred and Kleber, Michael and Mauceli, Evan and MacCallum, Iain} } @article {38258, title = {Features generated for computational splice-site prediction correspond to functional elements}, journal = {BMC BioinformaticsBMC Bioinformatics}, volume = {8}, year = {2007}, type = {10.1186/1471-2105-8-410}, abstract = {BackgroundAccurate selection of splice sites during the splicing of precursors to messenger RNA requires both relatively well-characterized signals at the splice sites and auxiliary signals in the adjacent exons and introns. We previously described a feature generation algorithm (FGA) that is capable of achieving high classification accuracy on human 3{\textquoteright} splice sites. In this paper, we extend the splice-site prediction to 5{\textquoteright} splice sites and explore the generated features for biologically meaningful splicing signals. Results We present examples from the observed features that correspond to known signals, both core signals (including the branch site and pyrimidine tract) and auxiliary signals (including GGG triplets and exon splicing enhancers). We present evidence that features identified by FGA include splicing signals not found by other methods. Conclusion Our generated features capture known biological signals in the expected sequence interval flanking splice sites. The method can be easily applied to other species and to similar classification problems, such as tissue-specific regulatory elements, polyadenylation sites, promoters, etc.}, isbn = {14712105}, author = {Dogan, Rezarta Islamaj and Getoor, Lise and Wilbur, W. John and Stephen M. Mount} } @article {49678, title = {Features generated for computational splice-site prediction correspond to functional elements.}, journal = {BMC Bioinformatics}, volume = {8}, year = {2007}, month = {2007}, pages = {410}, abstract = {

BACKGROUND: Accurate selection of splice sites during the splicing of precursors to messenger RNA requires both relatively well-characterized signals at the splice sites and auxiliary signals in the adjacent exons and introns. We previously described a feature generation algorithm (FGA) that is capable of achieving high classification accuracy on human 3{\textquoteright} splice sites. In this paper, we extend the splice-site prediction to 5{\textquoteright} splice sites and explore the generated features for biologically meaningful splicing signals.

RESULTS: We present examples from the observed features that correspond to known signals, both core signals (including the branch site and pyrimidine tract) and auxiliary signals (including GGG triplets and exon splicing enhancers). We present evidence that features identified by FGA include splicing signals not found by other methods.

CONCLUSION: Our generated features capture known biological signals in the expected sequence interval flanking splice sites. The method can be easily applied to other species and to similar classification problems, such as tissue-specific regulatory elements, polyadenylation sites, promoters, etc.

}, keywords = {Computational Biology, HUMANS, Predictive Value of Tests, RNA Splice Sites, RNA, Messenger}, issn = {1471-2105}, doi = {10.1186/1471-2105-8-410}, author = {Dogan, Rezarta Islamaj and Getoor, Lise and Wilbur, W John and Mount, Stephen M} } @article {38273, title = {GATA and Nkx factors synergistically regulate tissue-specific gene expression and development in vivo}, journal = {DevelopmentDevelopment}, volume = {134}, year = {2007}, type = {10.1242/dev.02720}, abstract = {In vitro studies have suggested that members of the GATA and Nkx transcription factor families physically interact, and synergistically activate pulmonary epithelial- and cardiac-gene promoters. However, the relevance of this synergy has not been demonstrated in vivo. We show that Gata6-Titf1 (Gata6-Nkx2.1) double heterozygous (G6-Nkx DH) embryos and mice have severe defects in pulmonary epithelial differentiation and distal airway development, as well as reduced phospholipid production. The defects in G6-Nkx DH embryos and mice are similar to those observed in human neonates with respiratory distress syndromes, including bronchopulmonary dysplasia, and differential gene expression analysis reveals essential developmental pathways requiring synergistic regulation by both Gata6 and Titf1 (Nkx2.1). These studies indicate that Gata6 and Nkx2.1 act in a synergistic manner to direct pulmonary epithelial differentiation and development in vivo, providing direct evidence that interactions between these two transcription factor families are crucial for the development of the tissues in which they are co-expressed.}, author = {Zhang, Yuzhen and Rath, Nibedita and Sridhar Hannenhalli and Wang, Zhishan and Cappola, Thomas and Kimura, Shioko and Atochina-Vasserman, Elena and Lu, Min Min and Beers, Michael F. and Morrisey, Edward E.} } @article {49782, title = {Genome sequence and identification of candidate vaccine antigens from the animal pathogen Dichelobacter nodosus.}, journal = {Nat Biotechnol}, volume = {25}, year = {2007}, month = {2007 May}, pages = {569-75}, abstract = {

Dichelobacter nodosus causes ovine footrot, a disease that leads to severe economic losses in the wool and meat industries. We sequenced its 1.4-Mb genome, the smallest known genome of an anaerobe. It differs markedly from small genomes of intracellular bacteria, retaining greater biosynthetic capabilities and lacking any evidence of extensive ongoing genome reduction. Comparative genomic microarray studies and bioinformatic analysis suggested that, despite its small size, almost 20\% of the genome is derived from lateral gene transfer. Most of these regions seem to be associated with virulence. Metabolic reconstruction indicated unsuspected capabilities, including carbohydrate utilization, electron transfer and several aerobic pathways. Global transcriptional profiling and bioinformatic analysis enabled the prediction of virulence factors and cell surface proteins. Screening of these proteins against ovine antisera identified eight immunogenic proteins that are candidate antigens for a cross-protective vaccine.

}, keywords = {Animals, Antigens, Chromosome mapping, Dichelobacter nodosus, Foot Rot, Genome, Bacterial, Sequence Analysis, DNA}, issn = {1087-0156}, doi = {10.1038/nbt1302}, author = {Myers, Garry S A and Parker, Dane and Al-Hasani, Keith and Kennan, Ruth M and Seemann, Torsten and Ren, Qinghu and Badger, Jonathan H and Selengut, Jeremy D and DeBoy, Robert T and Tettelin, Herv{\'e} and Boyce, John D and McCarl, Victoria P and Han, Xiaoyan and Nelson, William C and Madupu, Ramana and Mohamoud, Yasmin and Holley, Tara and Fedorova, Nadia and Khouri, Hoda and Bottomley, Steven P and Whittington, Richard J and Adler, Ben and Songer, J Glenn and Rood, Julian I and Paulsen, Ian T} } @article {38296, title = {Genome sequence and identification of candidate vaccine antigens from the animal pathogen Dichelobacter nodosus}, journal = {Nature biotechnologyNature biotechnology}, volume = {25}, year = {2007}, note = {http://www.ncbi.nlm.nih.gov/pubmed/17468768?dopt=Abstract}, type = {10.1038/nbt1302}, abstract = {Dichelobacter nodosus causes ovine footrot, a disease that leads to severe economic losses in the wool and meat industries. We sequenced its 1.4-Mb genome, the smallest known genome of an anaerobe. It differs markedly from small genomes of intracellular bacteria, retaining greater biosynthetic capabilities and lacking any evidence of extensive ongoing genome reduction. Comparative genomic microarray studies and bioinformatic analysis suggested that, despite its small size, almost 20\% of the genome is derived from lateral gene transfer. Most of these regions seem to be associated with virulence. Metabolic reconstruction indicated unsuspected capabilities, including carbohydrate utilization, electron transfer and several aerobic pathways. Global transcriptional profiling and bioinformatic analysis enabled the prediction of virulence factors and cell surface proteins. Screening of these proteins against ovine antisera identified eight immunogenic proteins that are candidate antigens for a cross-protective vaccine.}, keywords = {Animals, Antigens, Chromosome mapping, Dichelobacter nodosus, Foot Rot, Genome, Bacterial, Sequence Analysis, DNA}, author = {Myers, Garry S. A. and Parker, Dane and Al-Hasani, Keith and Kennan, Ruth M. and Seemann, Torsten and Ren, Qinghu and Badger, Jonathan H. and J. Selengut and DeBoy, Robert T. and Tettelin, Herv{\'e} and Boyce, John D. and McCarl, Victoria P. and Han, Xiaoyan and Nelson, William C. and Madupu, Ramana and Mohamoud, Yasmin and Holley, Tara and Fedorova, Nadia and Khouri, Hoda and Bottomley, Steven P. and Whittington, Richard J. and Adler, Ben and Songer, J. Glenn and Rood, Julian I. and Paulsen, Ian T.} } @article {38323, title = {Grid Services Base Library: A high-level, procedural application programming interface for writing Globus-based Grid services}, journal = {Future Generation Comp SystFuture Generation Comp Syst}, volume = {23}, year = {2007}, abstract = {The Grid Services Base Library (GSBL) is a procedural application programming interface (API) that abstracts many of the high-level functions performed by Globus Grid services, thus dramatically lowering the barriers to writing Grid services. The library has been extensively tested and used for computational biology research in a Globus Toolkit-based Grid system, in which no fewer than twenty Grid services written with this API are deployed.}, author = {Adam L. Bazinet and Myers, D. S. and Fuetsch, J. and Michael P. Cummings} } @article {49642, title = {Members of a large retroposon family are determinants of post-transcriptional gene expression in Leishmania.}, journal = {PLoS Pathog}, volume = {3}, year = {2007}, month = {2007 Sep 7}, pages = {1291-307}, abstract = {

Trypanosomatids are unicellular protists that include the human pathogens Leishmania spp. (leishmaniasis), Trypanosoma brucei (sleeping sickness), and Trypanosoma cruzi (Chagas disease). Analysis of their recently completed genomes confirmed the presence of non-long-terminal repeat retrotransposons, also called retroposons. Using the 79-bp signature sequence common to all trypanosomatid retroposons as bait, we identified in the Leishmania major genome two new large families of small elements--LmSIDER1 (785 copies) and LmSIDER2 (1,073 copies)--that fulfill all the characteristics of extinct trypanosomatid retroposons. LmSIDERs are approximately 70 times more abundant in L. major compared to T. brucei and are found almost exclusively within the 3{\textquoteright}-untranslated regions (3{\textquoteright}UTRs) of L. major mRNAs. We provide experimental evidence that LmSIDER2 act as mRNA instability elements and that LmSIDER2-containing mRNAs are generally expressed at lower levels compared to the non-LmSIDER2 mRNAs. The considerable expansion of LmSIDERs within 3{\textquoteright}UTRs in an organism lacking transcriptional control and their role in regulating mRNA stability indicate that Leishmania have probably recycled these short retroposons to globally modulate the expression of a number of genes. To our knowledge, this is the first example in eukaryotes of the domestication and expansion of a family of mobile elements that have evolved to fulfill a critical cellular function.

}, keywords = {3{\textquoteright} Untranslated Regions, Animals, Base Sequence, Biological Evolution, Down-Regulation, Gene Expression Regulation, Genome, Protozoan, Leishmania, Leishmania major, Molecular Sequence Data, Retroelements, RNA, Messenger, sequence alignment, Trypanosoma brucei brucei, Trypanosoma cruzi}, issn = {1553-7374}, doi = {10.1371/journal.ppat.0030136}, author = {Bringaud, Frederic and M{\"u}ller, Michaela and Cerqueira, Gustavo Coutinho and Smith, Martin and Rochette, Annie and el-Sayed, Najib M A and Papadopoulou, Barbara and Ghedin, Elodie} } @book {49866, title = {Methods in Molecular BiologyComparative GenomicsAnalyzing Patterns of Microbial Evolution Using the Mauve Genome Alignment System}, volume = {396}, year = {2007}, pages = {135 - 152}, publisher = {Humana Press}, organization = {Humana Press}, address = {Totowa, NJ}, isbn = {978-1-934115-37-4}, issn = {1064-3745}, doi = {10.1007/978-1-59745-515-210.1007/978-1-59745-515-2_10}, url = {http://www.springerlink.com/index/10.1007/978-1-59745-515-2http://www.springerlink.com/index/pdf/10.1007/978-1-59745-515-2http://link.springer.com/10.1007/978-1-59745-515-2_10http://www.springerlink.com/index/pdf/10.1007/978-1-59745-515-2_10}, author = {Darling, Aaron E and Todd Treangen and Messeguer, Xavier and Perna, Nicole T}, editor = {Walker, John M. and Bergman, Nicholas H.} } @article {49783, title = {New developments in the InterPro database.}, journal = {Nucleic Acids Res}, volume = {35}, year = {2007}, month = {2007 Jan}, pages = {D224-8}, abstract = {

InterPro is an integrated resource for protein families, domains and functional sites, which integrates the following protein signature databases: PROSITE, PRINTS, ProDom, Pfam, SMART, TIGRFAMs, PIRSF, SUPERFAMILY, Gene3D and PANTHER. The latter two new member databases have been integrated since the last publication in this journal. There have been several new developments in InterPro, including an additional reading field, new database links, extensions to the web interface and additional match XML files. InterPro has always provided matches to UniProtKB proteins on the website and in the match XML file on the FTP site. Additional matches to proteins in UniParc (UniProt archive) are now available for download in the new match XML files only. The latest InterPro release (13.0) contains more than 13 000 entries, covering over 78\% of all proteins in UniProtKB. The database is available for text- and sequence-based searches via a webserver (http://www.ebi.ac.uk/interpro), and for download by anonymous FTP (ftp://ftp.ebi.ac.uk/pub/databases/interpro). The InterProScan search tool is now also available via a web service at http://www.ebi.ac.uk/Tools/webservices/WSInterProScan.html.

}, keywords = {Databases, Protein, Internet, Protein Structure, Tertiary, Proteins, Sequence Analysis, Protein, Systems Integration, User-Computer Interface}, issn = {1362-4962}, doi = {10.1093/nar/gkl841}, author = {Mulder, Nicola J and Apweiler, Rolf and Attwood, Teresa K and Bairoch, Amos and Bateman, Alex and Binns, David and Bork, Peer and Buillard, Virginie and Cerutti, Lorenzo and Copley, Richard and Courcelle, Emmanuel and Das, Ujjwal and Daugherty, Louise and Dibley, Mark and Finn, Robert and Fleischmann, Wolfgang and Gough, Julian and Haft, Daniel and Hulo, Nicolas and Hunter, Sarah and Kahn, Daniel and Kanapin, Alexander and Kejariwal, Anish and Labarga, Alberto and Langendijk-Genevaux, Petra S and Lonsdale, David and Lopez, Rodrigo and Letunic, Ivica and Madera, Martin and Maslen, John and McAnulla, Craig and McDowall, Jennifer and Mistry, Jaina and Mitchell, Alex and Nikolskaya, Anastasia N and Orchard, Sandra and Orengo, Christine and Petryszak, Robert and Selengut, Jeremy D and Sigrist, Christian J A and Thomas, Paul D and Valentin, Franck and Wilson, Derek and Wu, Cathy H and Yeats, Corin} } @article {38405, title = {New Trypanosoma cruzi Repeated Element That Shows Site Specificity for Insertion}, journal = {Eukaryotic CellEukaryotic Cell}, volume = {6}, year = {2007}, type = {

10.1128/EC.00036-07

}, abstract = {A new family of site-specific repeated elements identified in Trypanosoma cruzi, which we named TcTREZO, is described here. TcTREZO appears to be a composite repeated element, since three subregions may be defined within it on the basis of sequence similarities with other T. cruzi sequences. Analysis of the distribution of TcTREZO in the genome clearly indicates that it displays site specificity for insertion. Most TcTREZO elements are flanked by conserved sequences. There is a highly conserved 68-bp sequence at the 5{\textquoteright} end of the element and a sequence domain of [~]500 bp without a well-defined borderline at the 3{\textquoteright} end. Northern blot hybridization and reverse transcriptase PCR analyses showed that TcTREZO transcripts are expressed as oligo(A)-terminated transcripts whose length corresponds to the unit size of the element (1.6 kb). Transcripts of [~]0.2 kb derived from a small part of TcTREZO are also detected in steady-state RNA. TcTREZO transcripts are unspliced and not translated. The copy number of TcTREZO sequences was estimated to be [~]173 copies per haploid genome. TcTREZO appears to have been assembled by insertions of sequences into a progenitor element. Once associated with each other, these subunits were amplified as a new transposable element. TcTREZO shows site specificity for insertion, suggesting that a sequence-specific endonuclease could be responsible for its insertion at a unique site.}, author = {Souza, Renata T. and Santos, Marcia R. M. and Lima, Fabio M. and Najib M. El-Sayed and Myler, Peter J. and Ruiz, Jeronimo C. and da Silveira, Jose Franco} } @article {49681, title = {Spliceosomal small nuclear RNA genes in 11 insect genomes.}, journal = {RNA}, volume = {13}, year = {2007}, month = {2007 Jan}, pages = {5-14}, abstract = {

The removal of introns from the primary transcripts of protein-coding genes is accomplished by the spliceosome, a large macromolecular complex of which small nuclear RNAs (snRNAs) are crucial components. Following the recent sequencing of the honeybee (Apis mellifera) genome, we used various computational methods, ranging from sequence similarity search to RNA secondary structure prediction, to search for putative snRNA genes (including their promoters) and to examine their pattern of conservation among 11 available insect genomes (A. mellifera, Tribolium castaneum, Bombyx mori, Anopheles gambiae, Aedes aegypti, and six Drosophila species). We identified candidates for all nine spliceosomal snRNA genes in all the analyzed genomes. All the species contain a similar number of snRNA genes, with the exception of A. aegypti, whose genome contains more U1, U2, and U5 genes, and A. mellifera, whose genome contains fewer U2 and U5 genes. We found that snRNA genes are generally more closely related to homologs within the same genus than to those in other genera. Promoter regions for all spliceosomal snRNA genes within each insect species share similar sequence motifs that are likely to correspond to the PSEA (proximal sequence element A), the binding site for snRNA activating protein complex, but these promoter elements vary in sequence among the five insect families surveyed here. In contrast to the other insect species investigated, Dipteran genomes are characterized by a rapid evolution (or loss) of components of the U12 spliceosome and a striking loss of U12-type introns.

}, keywords = {Animals, Base Sequence, Bees, Computational Biology, Diptera, Evolution, Molecular, Genes, Insect, Genome, Insect, Molecular Sequence Data, Nucleic Acid Conformation, Phylogeny, Promoter Regions, Genetic, RNA Splicing, RNA, Small Nuclear, Sequence Analysis, RNA, Spliceosomes}, issn = {1355-8382}, doi = {10.1261/rna.259207}, author = {Mount, Stephen M and Gotea, Valer and Lin, Chiao-Feng and Hernandez, Kristina and Makalowski, Wojciech} } @article {49679, title = {SplicePort--an interactive splice-site analysis tool.}, journal = {Nucleic Acids Res}, volume = {35}, year = {2007}, month = {2007 Jul}, pages = {W285-91}, abstract = {

SplicePort is a web-based tool for splice-site analysis that allows the user to make splice-site predictions for submitted sequences. In addition, the user can also browse the rich catalog of features that underlies these predictions, and which we have found capable of providing high classification accuracy on human splice sites. Feature selection is optimized for human splice sites, but the selected features are likely to be predictive for other mammals as well. With our interactive feature browsing and visualization tool, the user can view and explore subsets of features used in splice-site prediction (either the features that account for the classification of a specific input sequence or the complete collection of features). Selected feature sets can be searched, ranked or displayed easily. The user can group features into clusters and frequency plot WebLogos can be generated for each cluster. The user can browse the identified clusters and their contributing elements, looking for new interesting signals, or can validate previously observed signals. The SplicePort web server can be accessed at http://www.cs.umd.edu/projects/SplicePort and http://www.spliceport.org.

}, keywords = {Base Sequence, Chromosome mapping, Computational Biology, Computer simulation, DNA, Genome, HUMANS, Internet, Models, Genetic, Molecular Sequence Data, Pattern Recognition, Automated, RNA Splice Sites, sequence alignment, Sequence Analysis, DNA, User-Computer Interface}, issn = {1362-4962}, doi = {10.1093/nar/gkm407}, author = {Dogan, Rezarta Islamaj and Getoor, Lise and Wilbur, W John and Mount, Stephen M} } @article {38511, title = {SplicePort--An interactive splice-site analysis tool}, journal = {Nucleic Acids ResearchNucleic Acids Research}, volume = {35}, year = {2007}, type = {10.1093/nar/gkm407}, abstract = {SplicePort is a web-based tool for splice-site analysis that allows the user to make splice-site predictions for submitted sequences. In addition, the user can also browse the rich catalog of features that underlies these predictions, and which we have found capable of providing high classification accuracy on human splice sites. Feature selection is optimized for human splice sites, but the selected features are likely to be predictive for other mammals as well. With our interactive feature browsing and visualization tool, the user can view and explore subsets of features used in splice-site prediction (either the features that account for the classification of a specific input sequence or the complete collection of features). Selected feature sets can be searched, ranked or displayed easily. The user can group features into clusters and frequency plot WebLogos can be generated for each cluster. The user can browse the identified clusters and their contributing elements, looking for new interesting signals, or can validate previously observed signals. The SplicePort web server can be accessed at http://www.cs.umd.edu/projects/SplicePort and http://www.spliceport.org.}, isbn = {0305-1048, 1362-4962}, author = {Dogan, R. I. and Getoor, Lise and Wilbur, W. J. and Stephen M. Mount} } @article {38554, title = {Ultrastructure of coccoid viable but non-culturable Vibrio cholerae}, journal = {Environmental MicrobiologyEnvironmental Microbiology}, volume = {9}, year = {2007}, type = {10.1111/j.1462-2920.2006.01150.x}, abstract = {Morphology of viable but non-culturable Vibrio cholerae was monitored for 2~years by scanning and transmission electron microscopy. Morphological changes included very small coccoid forms, after extended incubation at 4{\textdegree}C and room temperature, and sequential transformation from curved rods to irregular (\~{}1~μm) rods to \~{}0.8~μm coccoid cells and, ultimately, to tiny coccoid forms (0.07{\textendash}0.4~μm). Irregular rod-shaped and coccoid cells were equally distributed in microcosms during the first 30{\textendash}60~days of incubation at both temperatures, but only coccoid cells were observed after incubation for 60~days at 4{\textdegree}C. When V.~cholerae O1 and O139, maintained for 30{\textendash}60~days at both temperatures, were heated to 45{\textdegree}C for 60~s, after serial passage through 0.45~μm and 0.1~μm filters, and plating on Luria{\textendash}Bertania (LB) agar, only cells larger than 1~μm yielded colonies on LB agar. Approximately 0.1\% of heat-treated cultures were culturable. Cell division in the smallest coccoid cells was observed, yielding daughter cells of equal size, whereas other coccoid cells revealed bleb-like, cell wall evagination, followed by transfer of nuclear material. Coccoid cells of V.~cholerae O1 and O139 incubated at 4{\textdegree}C for more than 1~year remained substrate responsive and antigenic.}, isbn = {1462-2920}, author = {Chaiyanan, Saipin and Chaiyanan, Sitthipan and Grim, Christopher and Maugel, Timothy and Huq, Anwar and Rita R. Colwell} } @article {38563, title = {Variola virus topoisomerase: DNA cleavage specificity and distribution of sites in Poxvirus genomes}, journal = {VirologyVirology}, volume = {365}, year = {2007}, type = {16/j.virol.2007.02.037}, abstract = {Topoisomerase enzymes regulate superhelical tension in DNA resulting from transcription, replication, repair, and other molecular transactions. Poxviruses encode an unusual type IB topoisomerase that acts only at conserved DNA sequences containing the core pentanucleotide 5{\textquoteright}-(T/C)CCTT-3{\textquoteright}. In X-ray structures of the variola virus topoisomerase bound to DNA, protein-DNA contacts were found to extend beyond the core pentanucleotide, indicating that the full recognition site has not yet been fully defined in functional studies. Here we report quantitation of DNA cleavage rates for an optimized 13~bp site and for all possible single base substitutions (40 total sites), with the goals of understanding the molecular mechanism of recognition and mapping topoisomerase sites in poxvirus genome sequences. The data allow a precise definition of enzyme-DNA interactions and the energetic contributions of each. We then used the resulting "action matrix" to show that favorable topoisomerase sites are distributed all along the length of poxvirus DNA sequences, consistent with a requirement for local release of superhelical tension in constrained topological domains. In orthopox genomes, an additional central cluster of sites was also evident. A negative correlation of predicted topoisomerase sites was seen relative to early terminators, but no correlation was seen with early or late promoters. These data define the full variola virus topoisomerase recognition site and provide a new window on topoisomerase function in vivo.}, keywords = {Annotation of topoisomerase sites, Sequence specific recognition, Topoisomerase IB, Variola virus}, isbn = {0042-6822}, author = {Minkah, Nana and Hwang, Young and Perry, Kay and Van Duyne, Gregory D. and Hendrickson, Robert and Lefkowitz, Elliot J. and Sridhar Hannenhalli and Bushman, Frederic D.} } @article {38159, title = {Comparative genomic evidence for a close relationship between the dimorphic prosthecate bacteria Hyphomonas neptunium and Caulobacter crescentus}, journal = {Journal of bacteriologyJournal of bacteriology}, volume = {188}, year = {2006}, note = {http://www.ncbi.nlm.nih.gov/pubmed/16980487?dopt=Abstract}, type = {10.1128/JB.00111-06}, abstract = {The dimorphic prosthecate bacteria (DPB) are alpha-proteobacteria that reproduce in an asymmetric manner rather than by binary fission and are of interest as simple models of development. Prior to this work, the only member of this group for which genome sequence was available was the model freshwater organism Caulobacter crescentus. Here we describe the genome sequence of Hyphomonas neptunium, a marine member of the DPB that differs from C. crescentus in that H. neptunium uses its stalk as a reproductive structure. Genome analysis indicates that this organism shares more genes with C. crescentus than it does with Silicibacter pomeroyi (a closer relative according to 16S rRNA phylogeny), that it relies upon a heterotrophic strategy utilizing a wide range of substrates, that its cell cycle is likely to be regulated in a similar manner to that of C. crescentus, and that the outer membrane complements of H. neptunium and C. crescentus are remarkably similar. H. neptunium swarmer cells are highly motile via a single polar flagellum. With the exception of cheY and cheR, genes required for chemotaxis were absent in the H. neptunium genome. Consistent with this observation, H. neptunium swarmer cells did not respond to any chemotactic stimuli that were tested, which suggests that H. neptunium motility is a random dispersal mechanism for swarmer cells rather than a stimulus-controlled navigation system for locating specific environments. In addition to providing insights into bacterial development, the H. neptunium genome will provide an important resource for the study of other interesting biological processes including chromosome segregation, polar growth, and cell aging.}, keywords = {Alphaproteobacteria, Bacterial Outer Membrane Proteins, Caulobacter crescentus, cell cycle, Chemotaxis, DNA, Bacterial, Flagella, Genome, Bacterial, Microbial Viability, Molecular Sequence Data, Movement, Sequence Analysis, DNA, Sequence Homology, signal transduction}, author = {Badger, Jonathan H. and Hoover, Timothy R. and Brun, Yves V. and Weiner, Ronald M. and Laub, Michael T. and Alexandre, Gladys and Mr{\'a}zek, Jan and Ren, Qinghu and Paulsen, Ian T. and Nelson, Karen E. and Khouri, Hoda M. and Radune, Diana and Sosa, Julia and Dodson, Robert J. and Sullivan, Steven A. and Rosovitz, M. J. and Madupu, Ramana and Brinkac, Lauren M. and Durkin, A. Scott and Daugherty, Sean C. and Kothari, Sagar P. and Giglio, Michelle Gwinn and Zhou, Liwei and Haft, Daniel H. and J. Selengut and Davidsen, Tanja M. and Yang, Qi and Zafar, Nikhat and Ward, Naomi L.} } @article {38161, title = {Comparative genomics of emerging human ehrlichiosis agents}, journal = {PLoS geneticsPLoS genetics}, volume = {2}, year = {2006}, note = {http://www.ncbi.nlm.nih.gov/pubmed/16482227?dopt=Abstract}, type = {10.1371/journal.pgen.0020021}, abstract = {Anaplasma (formerly Ehrlichia) phagocytophilum, Ehrlichia chaffeensis, and Neorickettsia (formerly Ehrlichia) sennetsu are intracellular vector-borne pathogens that cause human ehrlichiosis, an emerging infectious disease. We present the complete genome sequences of these organisms along with comparisons to other organisms in the Rickettsiales order. Ehrlichia spp. and Anaplasma spp. display a unique large expansion of immunodominant outer membrane proteins facilitating antigenic variation. All Rickettsiales have a diminished ability to synthesize amino acids compared to their closest free-living relatives. Unlike members of the Rickettsiaceae family, these pathogenic Anaplasmataceae are capable of making all major vitamins, cofactors, and nucleotides, which could confer a beneficial role in the invertebrate vector or the vertebrate host. Further analysis identified proteins potentially involved in vacuole confinement of the Anaplasmataceae, a life cycle involving a hematophagous vector, vertebrate pathogenesis, human pathogenesis, and lack of transovarial transmission. These discoveries provide significant insights into the biology of these obligate intracellular pathogens.}, keywords = {Animals, Biotin, DNA Repair, Ehrlichia, Ehrlichiosis, Genome, Genomics, HUMANS, Models, Biological, Phylogeny, Rickettsia, Ticks}, author = {Dunning Hotopp, Julie C. and Lin, Mingqun and Madupu, Ramana and Crabtree, Jonathan and Angiuoli, Samuel V. and Eisen, Jonathan A. and Eisen, Jonathan and Seshadri, Rekha and Ren, Qinghu and Wu, Martin and Utterback, Teresa R. and Smith, Shannon and Lewis, Matthew and Khouri, Hoda and Zhang, Chunbin and Niu, Hua and Lin, Quan and Ohashi, Norio and Zhi, Ning and Nelson, William and Brinkac, Lauren M. and Dodson, Robert J. and Rosovitz, M. J. and Sundaram, Jaideep and Daugherty, Sean C. and Davidsen, Tanja and Durkin, Anthony S. and Gwinn, Michelle and Haft, Daniel H. and J. Selengut and Sullivan, Steven A. and Zafar, Nikhat and Zhou, Liwei and Benahmed, Faiza and Forberger, Heather and Halpin, Rebecca and Mulligan, Stephanie and Robinson, Jeffrey and White, Owen and Rikihisa, Yasuko and Tettelin, Herv{\'e}} } @article {49682, title = {Comprehensive analysis of alternative splicing in rice and comparative analyses with Arabidopsis.}, journal = {BMC Genomics}, volume = {7}, year = {2006}, month = {2006}, pages = {327}, abstract = {

BACKGROUND: Recently, genomic sequencing efforts were finished for Oryza sativa (cultivated rice) and Arabidopsis thaliana (Arabidopsis). Additionally, these two plant species have extensive cDNA and expressed sequence tag (EST) libraries. We employed the Program to Assemble Spliced Alignments (PASA) to identify and analyze alternatively spliced isoforms in both species.

RESULTS: A comprehensive analysis of alternative splicing was performed in rice that started with >1.1 million publicly available spliced ESTs and over 30,000 full length cDNAs in conjunction with the newly enhanced PASA software. A parallel analysis was performed with Arabidopsis to compare and ascertain potential differences between monocots and dicots. Alternative splicing is a widespread phenomenon (observed in greater than 30\% of the loci with transcript support) and we have described nine alternative splicing variations. While alternative splicing has the potential to create many RNA isoforms from a single locus, the majority of loci generate only two or three isoforms and transcript support indicates that these isoforms are generally not rare events. For the alternate donor (AD) and acceptor (AA) classes, the distance between the splice sites for the majority of events was found to be less than 50 basepairs (bp). In both species, the most frequent distance between AA is 3 bp, consistent with reports in mammalian systems. Conversely, the most frequent distance between AD is 4 bp in both plant species, as previously observed in mouse. Most alternative splicing variations are localized to the protein coding sequence and are predicted to significantly alter the coding sequence.

CONCLUSION: Alternative splicing is widespread in both rice and Arabidopsis and these species share many common features. Interestingly, alternative splicing may play a role beyond creating novel combinations of transcripts that expand the proteome. Many isoforms will presumably have negative consequences for protein structure and function, suggesting that their biological role involves post-transcriptional regulation of gene expression.

}, keywords = {Alternative Splicing, Arabidopsis, DNA, Complementary, Expressed Sequence Tags, Oryza}, issn = {1471-2164}, doi = {10.1186/1471-2164-7-327}, author = {Campbell, Matthew A and Haas, Brian J and Hamilton, John P and Mount, Stephen M and Buell, C Robin} } @article {38332, title = {Identification and cross-species comparison of canine osteoarthritic gene regulatory cis-elements}, journal = {Osteoarthritis and cartilage/OARS, Osteoarthritis Research SocietyOsteoarthritis and cartilage/OARS, Osteoarthritis Research Society}, volume = {14}, year = {2006}, author = {Sridhar Hannenhalli and Middleton, R. P. and Levy, S. and Perroud, B. and Holzwarth, J. A. and McDonald, K. and Hannah, S. S. and others,} } @article {49847, title = {M-GCAT: interactively and efficiently constructing large-scale multiple genome comparison frameworks in closely related species}, journal = {BMC bioinformatics}, volume = {7}, year = {2006}, pages = {433}, author = {Todd Treangen and Messeguer, Xavier} } @article {38427, title = {Patterns of sequence conservation in presynaptic neural genes}, journal = {Genome BiolGenome Biol}, volume = {7}, year = {2006}, author = {Hadley, D. and Murphy, T. and Valladares, O. and Sridhar Hannenhalli and Ungar, L. and Kim, J. and Bucan, M. and others,} } @book {49867, title = {Procrastination Leads to Efficient Filtration for Local Multiple Alignment}, volume = {4175}, year = {2006}, pages = {126 - 137}, publisher = {Springer Berlin Heidelberg}, organization = {Springer Berlin Heidelberg}, address = {Berlin, Heidelberg}, isbn = {978-3-540-39583-6}, issn = {0302-9743}, doi = {10.1007/1185156110.1007/11851561_12}, url = {http://www.springerlink.com/index/10.1007/11851561http://www.springerlink.com/index/pdf/10.1007/11851561http://link.springer.com/10.1007/11851561_12http://www.springerlink.com/index/pdf/10.1007/11851561_12}, author = {Darling, Aaron E. and Todd Treangen and Zhang, Louxin and Kuiken, Carla and Messeguer, Xavier and Perna, Nicole T.} } @conference {49851, title = {Procrastination leads to efficient filtration for local multiple alignment}, booktitle = {International Workshop on Algorithms in Bioinformatics}, year = {2006}, publisher = {Springer Berlin Heidelberg}, organization = {Springer Berlin Heidelberg}, author = {Darling, Aaron E and Todd Treangen and Zhang, Louxin and Kuiken, Carla and Messeguer, Xavier and Perna, Nicole T} } @article {38464, title = {Retroviral DNA integration: viral and cellular determinants of target-site selection}, journal = {PLoS pathogensPLoS pathogens}, volume = {2}, year = {2006}, publisher = {Public Library of Science}, author = {Lewinski, M. K. and Yamashita, M. and Emerman, M. and Ciuffi, A. and Marshall, H. and Crawford, G. and Collins, F. and Shinn, P. and Leipzig, J. and Sridhar Hannenhalli and others,} } @article {38488, title = {Septaplex PCR assay for rapid identification of Vibrio cholerae including detection of virulence and int SXT genes}, journal = {FEMS Microbiology LettersFEMS Microbiology Letters}, volume = {265}, year = {2006}, type = {10.1111/j.1574-6968.2006.00491.x}, abstract = {In this study, we describe a septaplex PCR assay for rapid identification of Vibrio cholerae including detection of the virulence and intsxt genes. Conditions were optimized to amplify fragments of ISRrRNA (encoding for 16S{\textendash}23S rRNA gene, Intergenic spacer regions), O1rfb (O1 serogroup specific rfb), O139rfb (O139 serogroup specific rfb), ctxA (cholera toxin subunit A), tcpA (toxin coregulated pilus), and intsxt (sxt integron) simultaneously in a single PCR. The septaplex PCR was evaluated using 211 strains of V. cholerae and six water samples for in situ testing. PCR results were correlated with genotype data obtained by individual PCR and slot-blot assays. The one-step PCR described here can be used to identify V. cholerae accurately and rapidly. Also, the virulence and intsxt genes can be simultaneously detected, providing a useful method for monitoring pathogenic, intsxt-positive and nonpathogenic, intsxt-negative V. cholerae serogroups both in the environment and clinical settings.}, keywords = {DETECTION, intsxt, septaplex PCR, Vibrio cholerae, virulence}, isbn = {1574-6968}, author = {Mantri, Chinmay K. and Mohapatra, Saswat S. and Ramamurthy, Thandavarayan and Ghosh, Raikamal and Rita R. Colwell and Singh, Durg V.} } @article {38537, title = {Transcriptional Genomics Associates FOX Transcription Factors With Human Heart Failure}, journal = {CirculationCirculation}, volume = {114}, year = {2006}, type = {10.1161/CIRCULATIONAHA.106.632430}, abstract = {Background{\textemdash} Specific transcription factors (TFs) modulate cardiac gene expression in murine models of heart failure, but their relevance in human subjects remains untested. We developed and applied a computational approach called transcriptional genomics to test the hypothesis that a discrete set of cardiac TFs is associated with human heart failure.Methods and Results{\textemdash} RNA isolates from failing (n=196) and nonfailing (n=16) human hearts were hybridized with Affymetrix HU133A arrays, and differentially expressed heart failure genes were determined. TF binding sites overrepresented in the -5-kb promoter sequences of these heart failure genes were then determined with the use of public genome sequence databases. Binding sites for TFs identified in murine heart failure models (MEF2, NKX, NF-AT, and GATA) were significantly overrepresented in promoters of human heart failure genes (P<0.002; false discovery rate 2\% to 4\%). In addition, binding sites for FOX TFs showed substantial overrepresentation in both advanced human and early murine heart failure (P<0.002 and false discovery rate <4\% for each). A role for FOX TFs was supported further by expression of FOXC1, C2, P1, P4, and O1A in failing human cardiac myocytes at levels similar to established hypertrophic TFs and by abundant FOXP1 protein in failing human cardiac myocyte nuclei.Conclusions{\textemdash} Our results provide the first evidence that specific TFs identified in murine models (MEF2, NKX, NFAT, and GATA) are associated with human heart failure. Moreover, these data implicate specific members of the FOX family of TFs (FOXC1, C2, P1, P4, and O1A) not previously suggested in heart failure pathogenesis. These findings provide a crucial link between animal models and human disease and suggest a specific role for FOX signaling in modulating the hypertrophic response of the heart to stress in humans.}, author = {Sridhar Hannenhalli and Putt, Mary E. and Gilmore, Joan M. and Wang, Junwen and Parmacek, Michael S. and Epstein, Jonathan A. and Morrisey, Edward E. and Margulies, Kenneth B. and Cappola, Thomas P.} } @article {38162, title = {Comparative Genomics of Trypanosomatid Parasitic Protozoa}, journal = {ScienceScience}, volume = {309}, year = {2005}, type = {10.1126/science.1112181}, abstract = {A comparison of gene content and genome architecture of Trypanosoma brucei, Trypanosoma cruzi, and Leishmania major, three related pathogens with different life cycles and disease pathology, revealed a conserved core proteome of about 6200 genes in large syntenic polycistronic gene clusters. Many species-specific genes, especially large surface antigen families, occur at nonsyntenic chromosome-internal and subtelomeric regions. Retroelements, structural RNAs, and gene family expansion are often associated with syntenic discontinuities that{\textemdash}along with gene divergence, acquisition and loss, and rearrangement within the syntenic regions{\textemdash}have shaped the genomes of each parasite. Contrary to recent reports, our analyses reveal no evidence that these species are descended from an ancestor that contained a photosynthetic endosymbiont.}, author = {Najib M. El-Sayed and Myler, Peter J. and Blandin, Ga{\"e}lle and Berriman, Matthew and Crabtree, Jonathan and Aggarwal, Gautam and Caler, Elisabet and Renauld, Hubert and Worthey, Elizabeth A. and Hertz-Fowler, Christiane and Ghedin, Elodie and Peacock, Christopher and Bartholomeu, Daniella C. and Haas, Brian J. and Tran, Anh-Nhi and Wortman, Jennifer R. and Alsmark, U. Cecilia M. and Angiuoli, Samuel and Anupama, Atashi and Badger, Jonathan and Bringaud, Frederic and Cadag, Eithon and Carlton, Jane M. and Cerqueira, Gustavo C. and Creasy, Todd and Delcher, Arthur L. and Djikeng, Appolinaire and Embley, T. Martin and Hauser, Christopher and Ivens, Alasdair C. and Kummerfeld, Sarah K. and Pereira-Leal, Jose B. and Nilsson, Daniel and Peterson, Jeremy and Salzberg, Steven L. and Shallom, Joshua and Silva, Joana C. and Sundaram, Jaideep and Westenberger, Scott and White, Owen and Melville, Sara E. and Donelson, John E. and Andersson, Bj{\"o}rn and Stuart, Kenneth D. and Hall, Neil} } @article {38188, title = {Critical Factors Influencing the Occurrence of Vibrio Cholerae in the Environment of Bangladesh}, journal = {Applied and Environmental MicrobiologyAppl. Environ. Microbiol.Applied and Environmental MicrobiologyAppl. Environ. Microbiol.}, volume = {71}, year = {2005}, type = {10.1128/AEM.71.8.4645-4654.2005}, abstract = {The occurrence of outbreaks of cholera in Africa in 1970 and in Latin America in 1991, mainly in coastal communities, and the appearance of the new serotype Vibrio cholerae O139 in India and subsequently in Bangladesh have stimulated efforts to understand environmental factors influencing the growth and geographic distribution of epidemic Vibrio cholerae serotypes. Because of the severity of recent epidemics, cholera is now being considered by some infectious disease investigators as a {\textquotedblleft}reemerging{\textquotedblright} disease, prompting new work on the ecology of vibrios. Epidemiological and ecological surveillance for cholera has been under way in four rural, geographically separated locations in Bangladesh for the past 4 years, during which both clinical and environmental samples were collected at biweekly intervals. The clinical epidemiology portion of the research has been published (Sack et al., J. Infect. Dis. 187:96-101, 2003). The results of environmental sampling and analysis of the environmental and clinical data have revealed significant correlations of water temperature, water depth, rainfall, conductivity, and copepod counts with the occurrence of cholera toxin-producing bacteria (presumably V. cholerae). The lag periods between increases or decreases in units of factors, such as temperature and salinity, and occurrence of cholera correlate with biological parameters, e.g., plankton population blooms. The new information on the ecology of V. cholerae is proving useful in developing environmental models for the prediction of cholera epidemics.}, isbn = {0099-2240, 1098-5336}, author = {Huq, Anwar and Sack, R. Bradley and Nizam, Azhar and Longini, Ira M. and Nair, G. Balakrish and Ali, Afsar and Morris, J. Glenn and Khan, M. N. Huda and Siddique, A. Kasem and Yunus, Mohammed and Albert, M. John and Sack, David A. and Rita R. Colwell} } @article {38219, title = {Dynamic Querying for Pattern Identification in Microarray and Genomic Data (2003)}, journal = {Institute for Systems Research Technical ReportsInstitute for Systems Research Technical Reports}, year = {2005}, abstract = {Data sets involving linear ordered sequences are a recurring theme in bioinformatics. Dynamic query tools that support exploration of these data sets can be useful for identifying patterns of interest. This paper describes the use of one such tool TimeSearcher - to interactively explore linear sequence data sets taken from two bioinformatics problems. Microarray time course data sets involve expression levels for large numbers of genes over multiple time points. TimeSearcher can be used to interactively search these data sets for genes with expression profiles of interest. The occurrence frequencies of short sequences of DNA in aligned exons can be used to identify sequences that play a role in the pre-mRNA splicing. TimeSearcher can be used to search these data sets for candidate splicing signals.}, keywords = {Technical Report}, author = {Hochheiser, Harry and Baehrecke, Eric H. and Stephen M. Mount and Shneiderman, Ben} } @article {38227, title = {eGenomics: Cataloguing our Complete Genome Collection}, journal = {Comparative and functional genomicsComparative and functional genomics}, volume = {6}, year = {2005}, note = {http://www.ncbi.nlm.nih.gov/pubmed/18629208?dopt=Abstract}, type = {10.1002/cfg.494}, author = {Field, Dawn and Garrity, George and Morrison, Norman and J. Selengut and Sterk, Peter and Tatusova, Tatiana and Thomson, Nick} } @article {38285, title = {The genetic map and comparative analysis with the physical map of Trypanosoma brucei}, journal = {Nucleic acids researchNucleic Acids Research}, volume = {33}, year = {2005}, author = {MacLeod, A. and Tweedie, A. and McLellan, S. and Taylor, S. and Hall, N. and Berriman, M. and Najib M. El-Sayed and Hope, M. and Turner, C. M. R. and Tait, A.} } @article {38287, title = {Genome analysis of multiple pathogenic isolates of Streptococcus agalactiae: implications for the microbial "pan-genome"}, journal = {Proceedings of the National Academy of Sciences of the United States of AmericaProceedings of the National Academy of Sciences of the United States of America}, volume = {102}, year = {2005}, note = {http://www.ncbi.nlm.nih.gov/pubmed/16172379?dopt=Abstract}, type = {10.1073/pnas.0506758102}, abstract = {The development of efficient and inexpensive genome sequencing methods has revolutionized the study of human bacterial pathogens and improved vaccine design. Unfortunately, the sequence of a single genome does not reflect how genetic variability drives pathogenesis within a bacterial species and also limits genome-wide screens for vaccine candidates or for antimicrobial targets. We have generated the genomic sequence of six strains representing the five major disease-causing serotypes of Streptococcus agalactiae, the main cause of neonatal infection in humans. Analysis of these genomes and those available in databases showed that the S. agalactiae species can be described by a pan-genome consisting of a core genome shared by all isolates, accounting for approximately 80\% of any single genome, plus a dispensable genome consisting of partially shared and strain-specific genes. Mathematical extrapolation of the data suggests that the gene reservoir available for inclusion in the S. agalactiae pan-genome is vast and that unique genes will continue to be identified even after sequencing hundreds of genomes.}, keywords = {Amino Acid Sequence, Bacterial Capsules, Base Sequence, Gene expression, Genes, Bacterial, Genetic Variation, Genome, Bacterial, Molecular Sequence Data, Phylogeny, sequence alignment, Sequence Analysis, DNA, Streptococcus agalactiae, virulence}, author = {Tettelin, Herv{\'e} and Masignani, Vega and Cieslewicz, Michael J. and Donati, Claudio and Medini, Duccio and Ward, Naomi L. and Angiuoli, Samuel V. and Crabtree, Jonathan and Jones, Amanda L. and Durkin, A. Scott and DeBoy, Robert T. and Davidsen, Tanja M. and Mora, Marirosa and Scarselli, Maria and Margarit y Ros, Immaculada and Peterson, Jeremy D. and Hauser, Christopher R. and Sundaram, Jaideep P. and Nelson, William C. and Madupu, Ramana and Brinkac, Lauren M. and Dodson, Robert J. and Rosovitz, Mary J. and Sullivan, Steven A. and Daugherty, Sean C. and Haft, Daniel H. and J. Selengut and Gwinn, Michelle L. and Zhou, Liwei and Zafar, Nikhat and Khouri, Hoda and Radune, Diana and Dimitrov, George and Watkins, Kisha and O{\textquoteright}Connor, Kevin J. B. and Smith, Shannon and Utterback, Teresa R. and White, Owen and Rubens, Craig E. and Grandi, Guido and Madoff, Lawrence C. and Kasper, Dennis L. and Telford, John L. and Wessels, Michael R. and Rappuoli, Rino and Fraser, Claire M.} } @article {38293, title = {The genome of the protist parasite Entamoeba histolytica}, journal = {NatureNature}, volume = {433}, year = {2005}, publisher = {Nature Publishing Group}, author = {Loftus, B. and Anderson, I. and Davies, R. and Alsmark, U. C. M. and Samuelson, J. and Amedeo, P. and Roncaglia, P. and Berriman, M. and Hirt, R. P. and Mann, B. J. and others,} } @article {38305, title = {The genome sequence of Trypanosoma cruzi, etiologic agent of Chagas disease}, journal = {ScienceScience}, volume = {309}, year = {2005}, publisher = {American Association for the Advancement of Science}, author = {Najib M. El-Sayed and Myler, P. J. and Bartholomeu, D. C. and Nilsson, D. and Aggarwal, G. and Tran, A. N. and Ghedin, E. and Worthey, E. A. and Delcher, A. L. and Blandin, G. and others,} } @article {38325, title = {A guild of 45 CRISPR-associated (Cas) protein families and multiple CRISPR/Cas subtypes exist in prokaryotic genomes}, journal = {PLoS computational biologyPLOS Computational Biology}, volume = {1}, year = {2005}, note = {http://www.ncbi.nlm.nih.gov/pubmed/16292354?dopt=Abstract}, type = {10.1371/journal.pcbi.0010060}, abstract = {Clustered regularly interspaced short palindromic repeats (CRISPRs) are a family of DNA direct repeats found in many prokaryotic genomes. Repeats of 21-37 bp typically show weak dyad symmetry and are separated by regularly sized, nonrepetitive spacer sequences. Four CRISPR-associated (Cas) protein families, designated Cas1 to Cas4, are strictly associated with CRISPR elements and always occur near a repeat cluster. Some spacers originate from mobile genetic elements and are thought to confer "immunity" against the elements that harbor these sequences. In the present study, we have systematically investigated uncharacterized proteins encoded in the vicinity of these CRISPRs and found many additional protein families that are strictly associated with CRISPR loci across multiple prokaryotic species. Multiple sequence alignments and hidden Markov models have been built for 45 Cas protein families. These models identify family members with high sensitivity and selectivity and classify key regulators of development, DevR and DevS, in Myxococcus xanthus as Cas proteins. These identifications show that CRISPR/cas gene regions can be quite large, with up to 20 different, tandem-arranged cas genes next to a repeat cluster or filling the region between two repeat clusters. Distinctive subsets of the collection of Cas proteins recur in phylogenetically distant species and correlate with characteristic repeat periodicity. The analyses presented here support initial proposals of mobility of these units, along with the likelihood that loci of different subtypes interact with one another as well as with host cell defensive, replicative, and regulatory systems. It is evident from this analysis that CRISPR/cas loci are larger, more complex, and more heterogeneous than previously appreciated.}, keywords = {Genes, Archaeal, Genes, Bacterial, Genes, Fungal, Genome, Genome, Bacterial, Haloarcula marismortui, Markov chains, Multigene Family, Oligonucleotide Array Sequence Analysis, Phylogeny, Prokaryotic Cells, Proteins, Repetitive Sequences, Nucleic Acid, Yersinia pestis}, author = {Haft, Daniel H. and J. Selengut and Mongodin, Emmanuel F. and Nelson, Karen E.} } @article {38363, title = {Magic bullets and golden rules: data sampling in molecular phylogenetics}, journal = {Zoology (Jena)Zoology (Jena)}, volume = {108}, year = {2005}, type = {10.1016/j.zool.2005.09.006}, abstract = {Data collection for molecular phylogenetic studies is based on samples of both genes and taxa. In an ideal world, with no limitations to resources, as many genes could be sampled as deemed necessary to address phylogenetic problems. Given limited resources in the real world, inadequate (in terms of choice of genes or number of genes) sequences or restricted taxon sampling can adversely affect the reliability or information gained in phylogenetics. Recent empirical and simulation-based studies of data sampling in molecular phylogenetics have reached differing conclusions on how to deal with these problems. Some advocated sampling more genes, others more taxa. There is certainly no {\textquoteright}magic bullet{\textquoteright} that will fit all phylogenetic problems, and no specific {\textquoteright}golden rules{\textquoteright} have been deduced, other than that single genes may not always contain sufficient phylogenetic information. However, several general conclusions and suggestions can be made. One suggestion is that the determination of a multiple, but moderate number (e.g., 6-10) of gene sequences might take precedence over sequencing a larger set of genes and thereby permit the sampling of more taxa for a phylogenetic study.}, author = {Michael P. Cummings and Meyer, A.} } @article {49636, title = {Telomere and subtelomere of Trypanosoma cruzi chromosomes are enriched in (pseudo)genes of retrotransposon hot spot and trans-sialidase-like gene families: the origins of T. cruzi telomeres.}, journal = {Gene}, volume = {346}, year = {2005}, month = {2005 Feb 14}, pages = {153-61}, abstract = {

Here, we sequenced two large telomeric regions obtained from the pathogen protozoan Trypanosoma cruzi. These sequences, together with in silico assembled contigs, allowed us to establish the general features of telomeres and subtelomeres of this parasite. Our findings can be summarized as follows: We confirmed the presence of two types of telomeric ends; subtelomeric regions appeared to be enriched in (pseudo)genes of RHS (retrotransposon hot spot), TS (trans-sialidase)-like proteins, and putative surface protein DGF-1 (dispersed gene family-1). Sequence analysis of the ts-like genes located at the telomeres suggested that T. cruzi chromosomal ends could have been the site for generation of new gp85 variants, an important adhesin molecule involved in the invasion of mammalian cells by T. cruzi. Finally, a mechanism for generation of T. cruzi telomere by chromosome breakage and telomere healing is proposed.

}, keywords = {Amino Acid Sequence, Animals, Base Sequence, Chromosomes, Chromosomes, Artificial, Bacterial, DNA, Protozoan, Genes, Protozoan, Glycoproteins, Molecular Sequence Data, Multigene Family, Neuraminidase, Pseudogenes, Retroelements, Sequence Homology, Amino Acid, Sequence Homology, Nucleic Acid, Telomere, Trypanosoma cruzi}, issn = {0378-1119}, doi = {10.1016/j.gene.2004.10.014}, author = {Kim, Dong and Chiurillo, Miguel Angel and El-Sayed, Najib and Jones, Kristin and Santos, M{\'a}rcia R M and Porcile, Patricio E and Andersson, Bj{\"o}rn and Myler, Peter and da Silveira, Jose Franco and Ram{\'\i}rez, Jos{\'e} Luis} } @article {49638, title = {What the genome sequence is revealing about trypanosome antigenic variation.}, journal = {Biochem Soc Trans}, volume = {33}, year = {2005}, month = {2005 Nov}, pages = {986-9}, abstract = {

African trypanosomes evade humoral immunity through antigenic variation, whereby they switch expression of the gene encoding their VSG (variant surface glycoprotein) coat. Switching proceeds by duplication of silent VSG genes into a transcriptionally active locus. The genome project has revealed that most of the silent archive consists of hundreds of subtelomeric VSG tandem arrays, and that most of these are not functional genes. Precedent suggests that they can contribute combinatorially to the formation of expressed, functional genes through segmental gene conversion. These findings from the genome project have major implications for evolution of the VSG archive and for transmission of the parasite in the field.

}, keywords = {Animals, Antigens, Protozoan, Evolution, Molecular, Genetic Variation, Genome, Trypanosomatina, Variant Surface Glycoproteins, Trypanosoma}, issn = {0300-5127}, doi = {10.1042/BST20050986}, author = {Barry, J D and Marcello, L and Morrison, L J and Read, A F and Lythgoe, K and Jones, N and Carrington, M and Blandin, G and B{\"o}hme, U and Caler, E and Hertz-Fowler, C and Renauld, H and El-Sayed, N and Berriman, M} } @article {38575, title = {Whole-genome sequence analysis of Pseudomonas syringae pv. phaseolicola 1448A reveals divergence among pathovars in genes involved in virulence and transposition}, journal = {Journal of bacteriologyJournal of bacteriology}, volume = {187}, year = {2005}, note = {http://www.ncbi.nlm.nih.gov/pubmed/16159782?dopt=Abstract}, type = {10.1128/JB.187.18.6488-6498.2005}, abstract = {Pseudomonas syringae pv. phaseolicola, a gram-negative bacterial plant pathogen, is the causal agent of halo blight of bean. In this study, we report on the genome sequence of P. syringae pv. phaseolicola isolate 1448A, which encodes 5,353 open reading frames (ORFs) on one circular chromosome (5,928,787 bp) and two plasmids (131,950 bp and 51,711 bp). Comparative analyses with a phylogenetically divergent pathovar, P. syringae pv. tomato DC3000, revealed a strong degree of conservation at the gene and genome levels. In total, 4,133 ORFs were identified as putative orthologs in these two pathovars using a reciprocal best-hit method, with 3,941 ORFs present in conserved, syntenic blocks. Although these two pathovars are highly similar at the physiological level, they have distinct host ranges; 1448A causes disease in beans, and DC3000 is pathogenic on tomato and Arabidopsis. Examination of the complement of ORFs encoding virulence, fitness, and survival factors revealed a substantial, but not complete, overlap between these two pathovars. Another distinguishing feature between the two pathovars is their distinctive sets of transposable elements. With access to a fifth complete pseudomonad genome sequence, we were able to identify 3,567 ORFs that likely comprise the core Pseudomonas genome and 365 ORFs that are P. syringae specific.}, keywords = {Bacterial Proteins, DNA, Bacterial, Genes, Bacterial, Genome, Bacterial, Molecular Sequence Data, Pseudomonas syringae, Species Specificity, virulence}, author = {Joardar, Vinita and Lindeberg, Magdalen and Jackson, Robert W. and J. Selengut and Dodson, Robert and Brinkac, Lauren M. and Daugherty, Sean C. and Deboy, Robert and Durkin, A. Scott and Giglio, Michelle Gwinn and Madupu, Ramana and Nelson, William C. and Rosovitz, M. J. and Sullivan, Steven and Crabtree, Jonathan and Creasy, Todd and Davidsen, Tanja and Haft, Dan H. and Zafar, Nikhat and Zhou, Liwei and Halpin, Rebecca and Holley, Tara and Khouri, Hoda and Feldblyum, Tamara and White, Owen and Fraser, Claire M. and Chatterjee, Arun K. and Cartinhour, Sam and Schneider, David J. and Mansfield, John and Collmer, Alan and Buell, C. Robin} } @article {38117, title = {Applying permutation tests to tree-based statistical models: extending the R package rpart}, volume = {2004-24}, year = {2004}, institution = {University of Maryland Institute for Advanced Computer Studies}, abstract = {Tree-based statistical models are useful for evaluating relationships between predictor and response variables and for generating predictions when the response is unknown. However, current methods of constructing tree-based models do not provide a probabilistic assessment of the models produced. Here we describe our work to use permutation tests to quantitatively estimate the probability of tree-based statistical models. We have extended the rpart (recursive partitioning) package of the R system for statistical data analysis. This extension, rpart.permutation, executes the permutations in parallel, using MPI (Message Passing Interface) to greatly decrease the time necessary to complete the analysis.}, author = {Michael P. Cummings and Myers, D. S. and Mangelson, M.} } @article {38149, title = {CHARACTERIZATION OF< i> Ath17, A QUANTITATIVE TRAIT LOCUS FOR ATHEROSCLEROSIS SUSCEPTIBILITY BETWEEN C57BL/6J AND 129S1/SvImJ; SINGLE-NUCLEOTIDE POLYMORPHISMS HAVE IMPORTANT IMPLICATIONS ON IDENTIFYING ATHEROSCLEROSIS MODIFIER GENES}, journal = {Cardiovascular PathologyCardiovascular Pathology}, volume = {13}, year = {2004}, publisher = {Elsevier}, author = {Ishimori, N. and Walsh, K. and Zheng, X. and Lu, F. and Sridhar Hannenhalli and Nusskern, D. and Mural, R. and Paigen, B.} } @article {38165, title = {Comparison of the genome of the oral pathogen Treponema denticola with other spirochete genomes}, journal = {Proceedings of the National Academy of Sciences of the United States of AmericaProceedings of the National Academy of Sciences of the United States of America}, volume = {101}, year = {2004}, note = {http://www.ncbi.nlm.nih.gov/pubmed/15064399?dopt=Abstract}, type = {10.1073/pnas.0307639101}, abstract = {We present the complete 2,843,201-bp genome sequence of Treponema denticola (ATCC 35405) an oral spirochete associated with periodontal disease. Analysis of the T. denticola genome reveals factors mediating coaggregation, cell signaling, stress protection, and other competitive and cooperative measures, consistent with its pathogenic nature and lifestyle within the mixed-species environment of subgingival dental plaque. Comparisons with previously sequenced spirochete genomes revealed specific factors contributing to differences and similarities in spirochete physiology as well as pathogenic potential. The T. denticola genome is considerably larger in size than the genome of the related syphilis-causing spirochete Treponema pallidum. The differences in gene content appear to be attributable to a combination of three phenomena: genome reduction, lineage-specific expansions, and horizontal gene transfer. Genes lost due to reductive evolution appear to be largely involved in metabolism and transport, whereas some of the genes that have arisen due to lineage-specific expansions are implicated in various pathogenic interactions, and genes acquired via horizontal gene transfer are largely phage-related or of unknown function.}, keywords = {ATP-Binding Cassette Transporters, Bacterial Proteins, Base Sequence, Borrelia burgdorferi, Genes, Bacterial, Genome, Bacterial, Leptospira interrogans, Models, Genetic, Molecular Sequence Data, Mouth, Sequence Homology, Amino Acid, Treponema, Treponema pallidum}, author = {Seshadri, Rekha and Myers, Garry S. A. and Tettelin, Herv{\'e} and Eisen, Jonathan A. and Heidelberg, John F. and Dodson, Robert J. and Davidsen, Tanja M. and DeBoy, Robert T. and Fouts, Derrick E. and Haft, Dan H. and J. Selengut and Ren, Qinghu and Brinkac, Lauren M. and Madupu, Ramana and Kolonay, Jamie and Durkin, A. Scott and Daugherty, Sean C. and Shetty, Jyoti and Shvartsbeyn, Alla and Gebregeorgis, Elizabeth and Geer, Keita and Tsegaye, Getahun and Malek, Joel and Ayodeji, Bola and Shatsman, Sofiya and McLeod, Michael P. and Smajs, David and Howell, Jerrilyn K. and Pal, Sangita and Amin, Anita and Vashisth, Pankaj and McNeill, Thomas Z. and Xiang, Qin and Sodergren, Erica and Baca, Ernesto and Weinstock, George M. and Norris, Steven J. and Fraser, Claire M. and Paulsen, Ian T.} } @article {38209, title = {Divergent Gene Copies in the Asexual Class Bdelloidea (Rotifera) Separated Before the Bdelloid Radiation or Within Bdelloid Families}, journal = {Proceedings of the National Academy of Sciences of the United States of AmericaPNASProceedings of the National Academy of Sciences of the United States of AmericaPNAS}, volume = {101}, year = {2004}, type = {10.1073/pnas.2136686100}, abstract = {Rotifers of the asexual class Bdelloidea are unusual in possessing two or more divergent copies of every gene that has been examined. Phylogenetic analysis of the heat-shock gene hsp82 and the TATA-box-binding protein gene tbp in multiple bdelloid species suggested that for each gene, each copy belonged to one of two lineages that began to diverge before the bdelloid radiation. Such gene trees are consistent with the two lineages having descended from former alleles that began to diverge after meiotic segregation ceased or from subgenomes of an alloploid ancestor of the bdelloids. However, the original analyses of bdelloid gene-copy divergence used only a single outgroup species and were based on parsimony and neighbor joining. We have now used maximum likelihood and Bayesian inference methods and, for hsp82, multiple outgroups in an attempt to produce more robust gene trees. Here we report that the available data do not unambiguously discriminate between gene trees that root the origin of hsp82 and tbp copy divergence before the bdelloid radiation and those which indicate that the gene copies began to diverge within bdelloid families. The remarkable presence of multiple diverged gene copies in individual genomes is nevertheless consistent with the loss of sex in an ancient ancestor of bdelloids.}, isbn = {0027-8424, 1091-6490}, author = {Welch, David B. Mark and Michael P. Cummings and Hillis, David M. and Meselson, Matthew} } @article {49684, title = {The Drosophila U1-70K protein is required for viability, but its arginine-rich domain is dispensable.}, journal = {Genetics}, volume = {168}, year = {2004}, month = {2004 Dec}, pages = {2059-65}, abstract = {

The conserved spliceosomal U1-70K protein is thought to play a key role in RNA splicing by linking the U1 snRNP particle to regulatory RNA-binding proteins. Although these protein interactions are mediated by repeating units rich in arginines and serines (RS domains) in vitro, tests of this domain{\textquoteright}s importance in intact multicellular organisms have not been carried out. Here we report a comprehensive genetic analysis of U1-70K function in Drosophila. Consistent with the idea that U1-70K is an essential splicing factor, we find that loss of U1-70K function results in lethality during embryogenesis. Surprisingly, and contrary to the current view of U1-70K function, animals carrying a mutant U1-70K protein lacking the arginine-rich domain, which includes two embedded sets of RS dipeptide repeats, have no discernible mutant phenotype. Through double-mutant studies, however, we show that the U1-70K RS domain deletion no longer supports viability when combined with a viable mutation in another U1 snRNP component. Together our studies demonstrate that while the protein interactions mediated by the U1-70K RS domain are not essential for viability, they nevertheless contribute to an essential U1 snRNP function.

}, keywords = {Amino Acid Sequence, Animals, Animals, Genetically Modified, Arginine, Drosophila, Drosophila Proteins, Molecular Sequence Data, Mutation, Protein Structure, Tertiary, Ribonucleoprotein, U1 Small Nuclear, RNA-Binding Proteins}, issn = {0016-6731}, doi = {10.1534/genetics.104.032532}, author = {Salz, Helen K and Mancebo, Ricardo S Y and Nagengast, Alexis A and Speck, Olga and Psotka, Mitchell and Mount, Stephen M} } @article {49635, title = {Gene synteny and evolution of genome architecture in trypanosomatids.}, journal = {Mol Biochem Parasitol}, volume = {134}, year = {2004}, month = {2004 Apr}, pages = {183-91}, abstract = {

The trypanosomatid protozoa Trypanosoma brucei, Trypanosoma cruzi and Leishmania major are related human pathogens that cause markedly distinct diseases. Using information from genome sequencing projects currently underway, we have compared the sequences of large chromosomal fragments from each species. Despite high levels of divergence at the sequence level, these three species exhibit a striking conservation of gene order, suggesting that selection has maintained gene order among the trypanosomatids over hundreds of millions of years of evolution. The few sites of genome rearrangement between these species are marked by the presence of retrotransposon-like elements, suggesting that retrotransposons may have played an important role in shaping trypanosomatid genome organization. A degenerate retroelement was identified in L. major by examining the regions near breakage points of the synteny. This is the first such element found in L. major suggesting that retroelements were found in the common ancestor of all three species.

}, keywords = {Animals, Computational Biology, Evolution, Molecular, Gene Order, Genome, Protozoan, Genomics, Leishmania major, Multigene Family, Recombination, Genetic, Retroelements, Selection, Genetic, Synteny, Trypanosoma brucei brucei, Trypanosoma cruzi, Trypanosomatina}, issn = {0166-6851}, doi = {10.1016/j.molbiopara.2003.11.012}, author = {Ghedin, Elodie and Bringaud, Frederic and Peterson, Jeremy and Myler, Peter and Berriman, Matthew and Ivens, Alasdair and Andersson, Bj{\"o}rn and Bontempi, Esteban and Eisen, Jonathan and Angiuoli, Sam and Wanless, David and Von Arx, Anna and Murphy, Lee and Lennard, Nicola and Salzberg, Steven and Adams, Mark D and White, Owen and Hall, Neil and Stuart, Kenneth and Fraser, Claire M and el-Sayed, Najib M A} } @article {38302, title = {Genome sequence of Silicibacter pomeroyi reveals adaptations to the marine environment}, journal = {NatureNature}, volume = {432}, year = {2004}, note = {http://www.ncbi.nlm.nih.gov/pubmed/15602564?dopt=Abstract}, type = {10.1038/nature03170}, abstract = {Since the recognition of prokaryotes as essential components of the oceanic food web, bacterioplankton have been acknowledged as catalysts of most major biogeochemical processes in the sea. Studying heterotrophic bacterioplankton has been challenging, however, as most major clades have never been cultured or have only been grown to low densities in sea water. Here we describe the genome sequence of Silicibacter pomeroyi, a member of the marine Roseobacter clade (Fig. 1), the relatives of which comprise approximately 10-20\% of coastal and oceanic mixed-layer bacterioplankton. This first genome sequence from any major heterotrophic clade consists of a chromosome (4,109,442 base pairs) and megaplasmid (491,611 base pairs). Genome analysis indicates that this organism relies upon a lithoheterotrophic strategy that uses inorganic compounds (carbon monoxide and sulphide) to supplement heterotrophy. Silicibacter pomeroyi also has genes advantageous for associations with plankton and suspended particles, including genes for uptake of algal-derived compounds, use of metabolites from reducing microzones, rapid growth and cell-density-dependent regulation. This bacterium has a physiology distinct from that of marine oligotrophs, adding a new strategy to the recognized repertoire for coping with a nutrient-poor ocean.}, keywords = {Adaptation, Physiological, Carrier Proteins, Genes, Bacterial, Genome, Bacterial, marine biology, Molecular Sequence Data, Oceans and Seas, Phylogeny, plankton, RNA, Ribosomal, 16S, Roseobacter, Seawater}, author = {Moran, Mary Ann and Buchan, Alison and Gonz{\'a}lez, Jos{\'e} M. and Heidelberg, John F. and Whitman, William B. and Kiene, Ronald P. and Henriksen, James R. and King, Gary M. and Belas, Robert and Fuqua, Clay and Brinkac, Lauren and Lewis, Matt and Johri, Shivani and Weaver, Bruce and Pai, Grace and Eisen, Jonathan A. and Rahe, Elisha and Sheldon, Wade M. and Ye, Wenying and Miller, Todd R. and Carlton, Jane and Rasko, David A. and Paulsen, Ian T. and Ren, Qinghu and Daugherty, Sean C. and DeBoy, Robert T. and Dodson, Robert J. and Durkin, A. Scott and Madupu, Ramana and Nelson, William C. and Sullivan, Steven A. and Rosovitz, M. J. and Haft, Daniel H. and J. Selengut and Ward, Naomi} } @article {38303, title = {The genome sequence of the anaerobic, sulfate-reducing bacterium Desulfovibrio vulgaris Hildenborough}, journal = {Nature biotechnologyNature biotechnology}, volume = {22}, year = {2004}, note = {http://www.ncbi.nlm.nih.gov/pubmed/15077118?dopt=Abstract}, type = {10.1038/nbt959}, abstract = {Desulfovibrio vulgaris Hildenborough is a model organism for studying the energy metabolism of sulfate-reducing bacteria (SRB) and for understanding the economic impacts of SRB, including biocorrosion of metal infrastructure and bioremediation of toxic metal ions. The 3,570,858 base pair (bp) genome sequence reveals a network of novel c-type cytochromes, connecting multiple periplasmic hydrogenases and formate dehydrogenases, as a key feature of its energy metabolism. The relative arrangement of genes encoding enzymes for energy transduction, together with inferred cellular location of the enzymes, provides a basis for proposing an expansion to the {\textquoteright}hydrogen-cycling{\textquoteright} model for increasing energy efficiency in this bacterium. Plasmid-encoded functions include modification of cell surface components, nitrogen fixation and a type-III protein secretion system. This genome sequence represents a substantial step toward the elucidation of pathways for reduction (and bioremediation) of pollutants such as uranium and chromium and offers a new starting point for defining this organism{\textquoteright}s complex anaerobic respiration.}, keywords = {Desulfovibrio vulgaris, Energy Metabolism, Genome, Bacterial, Molecular Sequence Data}, author = {Heidelberg, John F. and Seshadri, Rekha and Haveman, Shelley A. and Hemme, Christopher L. and Paulsen, Ian T. and Kolonay, James F. and Eisen, Jonathan A. and Ward, Naomi and Methe, Barbara and Brinkac, Lauren M. and Daugherty, Sean C. and DeBoy, Robert T. and Dodson, Robert J. and Durkin, A. Scott and Madupu, Ramana and Nelson, William C. and Sullivan, Steven A. and Fouts, Derrick and Haft, Daniel H. and J. Selengut and Peterson, Jeremy D. and Davidsen, Tanja M. and Zafar, Nikhat and Zhou, Liwei and Radune, Diana and Dimitrov, George and Hance, Mark and Tran, Kevin and Khouri, Hoda and Gill, John and Utterback, Terry R. and Feldblyum, Tamara V. and Wall, Judy D. and Voordouw, Gerrit and Fraser, Claire M.} } @article {38348, title = {The ingi and RIME non-LTR retrotransposons are not randomly distributed in the genome of Trypanosoma brucei}, journal = {Molecular biology and evolutionMolecular biology and evolution}, volume = {21}, year = {2004}, author = {Bringaud, F. and Biteau, N. and Zuiderwijk, E. and Berriman, M. and Najib M. El-Sayed and Ghedin, E. and Melville, S. E. and Hall, N. and Baltz, T.} } @article {49634, title = {The ingi and RIME non-LTR retrotransposons are not randomly distributed in the genome of Trypanosoma brucei.}, journal = {Mol Biol Evol}, volume = {21}, year = {2004}, month = {2004 Mar}, pages = {520-8}, abstract = {

The ingi (long and autonomous) and RIME (short and nonautonomous) non--long-terminal repeat retrotransposons are the most abundant mobile elements characterized to date in the genome of the African trypanosome Trypanosoma brucei. These retrotransposons were thought to be randomly distributed, but a detailed and comprehensive analysis of their genomic distribution had not been performed until now. To address this question, we analyzed the ingi/RIME sequences and flanking sequences from the ongoing T. brucei genome sequencing project (TREU927/4 strain). Among the 81 ingi/RIME elements analyzed, 60\% are complete, and 7\% of the ingi elements (approximately 15 copies per haploid genome) appear to encode for their own transposition. The size of the direct repeat flanking the ingi/RIME retrotransposons is conserved (i.e., 12-bp), and a strong 11-bp consensus pattern precedes the 5{\textquoteright}-direct repeat. The presence of a consensus pattern upstream of the retroelements was confirmed by the analysis of the base occurrence in 294 GSS containing 5{\textquoteright}-adjacent ingi/RIME sequences. The conserved sequence is present upstream of ingis and RIMEs, suggesting that ingi-encoded enzymatic activities are used for retrotransposition of RIMEs, which are short nonautonomous retroelements. In conclusion, the ingi and RIME retroelements are not randomly distributed in the genome of T. brucei and are preceded by a conserved sequence, which may be the recognition site of the ingi-encoded endonuclease.

}, keywords = {Amino Acid Sequence, Animals, Base Sequence, Consensus Sequence, Genome, Protozoan, Molecular Sequence Data, Retroelements, Sequence Analysis, Trypanosoma brucei brucei}, issn = {0737-4038}, doi = {10.1093/molbev/msh045}, author = {Bringaud, Frederic and Biteau, Nicolas and Zuiderwijk, Eduard and Berriman, Matthew and El-Sayed, Najib M and Ghedin, Elodie and Melville, Sara E and Hall, Neil and Baltz, Th{\'e}o} } @book {49567, title = {Lecture Notes in Computer ScienceComputer Vision - ECCV 2004An MCMC-Based Particle Filter for Tracking Multiple Interacting Targets}, volume = {3024}, year = {2004}, pages = {279 - 290}, publisher = {Springer Berlin Heidelberg}, organization = {Springer Berlin Heidelberg}, address = {Berlin, Heidelberg}, isbn = {978-3-540-21981-1}, issn = {0302-9743}, doi = {10.1007/b9787310.1007/978-3-540-24673-2_23}, url = {http://www.springerlink.com/index/10.1007/b97873http://www.springerlink.com/index/pdf/10.1007/b97873http://link.springer.com/10.1007/978-3-540-24673-2_23http://www.springerlink.com/index/pdf/10.1007/978-3-540-24673-2_23}, author = {Khan, Zia and Balch, Tucker and Dellaert, Frank}, editor = {Kanade, Takeo and Kittler, Josef and Kleinberg, Jon M. and Mattern, Friedemann and Mitchell, John C. and Nierstrasz, Oscar and Pandu Rangan, C. and Steffen, Bernhard and Sudan, Madhu and Terzopoulos, Demetri and Tygar, Dough and Vardi, Moshe Y. and Weikum, Gerhard and Pajdla, {\'a}s and Matas, {\v r}{\'\i}} } @article {38418, title = {Pandemic strains of O3:K6 Vibrio parahaemolyticus in the aquatic environment of Bangladesh}, journal = {Canadian Journal of MicrobiologyCanadian Journal of Microbiology}, volume = {50}, year = {2004}, abstract = {A total of 1500 environmental strains of Vibrio parahaemolyticus, isolated from the aquatic environment of Bangladesh, were screened for the presence of a major V. parahaemolyticus virulence factor, the thermostable direct haemolysin (tdh) gene, by the colony blot hybridization method using a digoxigenin-labeled tdh gene probe. Of 1500 strains, 5 carried the tdh sequence, which was further confirmed by PCR using primers specific for the tdh gene. Examination by PCR confirmed that the 5 strains were V. parahamolyticus and lacked the thermostable direct haemolysin-related haemolysin (trh) gene, the alternative major virulence gene known to be absent in pandemic strains. All 5 strains gave positive Kanagawa phenomenon reaction with characteristic beta-haemolysis on Wagatsuma agar medium. Southern blot analysis of the HindIII-digested chromosomal DNA demonstrated, in all 5 strains, the presence of 2 tdh genes common to strains positive for Kanagawa phenomenon. However, the 5 strains were found to belong to 3 different serotypes (O3:K29, O4:K37, and O3:K6). The 2 with pandemic serotype O3:K6 gave positive results in group-specific PCR and ORF8 PCR assays, characteristics unique to the pandemic clone. Clonal variations among the 5 isolates were analyzed by comparing RAPD and ribotyping patterns. Results showed different patterns for the 3 serotypes, but the pattern was identical among the O3:K6 strains. This is the first report on the isolation of pandemic O3:K6 strains of V. parahaemolyticus from the aquatic environment of Bangladesh.}, author = {Islam, M. S. and Tasmin, Rizwana and Khan, Sirajul I. s l a m and Bakht, Habibul B. M. and Mahmood, Zahid H. a y a t and Rahman, M. Z. i a u r and Bhuiyan, Nurul A. m i n and Nishibuchi, Mitsuaki and Nair, G. B. a l a k r i s h and Sack, R. B. r a d l e y and Huq, Anwar and Rita R. Colwell and Sack, David A.} } @article {49683, title = {Reducing storage requirements for biological sequence comparison.}, journal = {Bioinformatics}, volume = {20}, year = {2004}, month = {2004 Dec 12}, pages = {3363-9}, abstract = {

MOTIVATION: Comparison of nucleic acid and protein sequences is a fundamental tool of modern bioinformatics. A dominant method of such string matching is the {\textquoteright}seed-and-extend{\textquoteright} approach, in which occurrences of short subsequences called {\textquoteright}seeds{\textquoteright} are used to search for potentially longer matches in a large database of sequences. Each such potential match is then checked to see if it extends beyond the seed. To be effective, the seed-and-extend approach needs to catalogue seeds from virtually every substring in the database of search strings. Projects such as mammalian genome assemblies and large-scale protein matching, however, have such large sequence databases that the resulting list of seeds cannot be stored in RAM on a single computer. This significantly slows the matching process.

RESULTS: We present a simple and elegant method in which only a small fraction of seeds, called {\textquoteright}minimizers{\textquoteright}, needs to be stored. Using minimizers can speed up string-matching computations by a large factor while missing only a small fraction of the matches found using all seeds.

}, keywords = {algorithms, Databases, Genetic, Information Storage and Retrieval, Numerical Analysis, Computer-Assisted, sequence alignment, Sequence Analysis}, issn = {1367-4803}, doi = {10.1093/bioinformatics/bth408}, author = {Roberts, Michael and Hayes, Wayne and Hunt, Brian R and Mount, Stephen M and Yorke, James A} } @article {38480, title = {Schistosoma mansoni genome project: an update}, journal = {Parasitology InternationalParasitology International}, volume = {53}, year = {2004}, type = {16/j.parint.2004.01.009}, abstract = {A schistosome genome project was initiated by the World Health Organization in 1994 with the notion that the best prospects for identifying new targets for drugs, vaccines, and diagnostic development lie in schistosome gene discovery, development of chromosome maps, whole genome sequencing and genome analysis. Schistosoma mansoni has a haploid genome of 270 Mb contained on 8 pairs of chromosomes. It is estimated that the S. mansoni genome contains between 15~000 and 25~000 genes. There are approximately 16~689 ESTs obtained from diverse libraries representing different developmental stages of S. mansoni, deposited in the NCBI EST database. More than half of the deposited sequences correspond to genes of unknown function. Approximately 40-50\% of the sequences form unique clusters, suggesting that approximately 20-25\% of the total schistosome genes have been discovered. Efforts to develop low resolution chromosome maps are in progress. There is a genome sequencing program underway that will provide 3X sequence coverage of the S. mansoni genome that will result in approximately 95\% gene discovery. The genomics era has provided the resources to usher in the era of functional genomics that will involve microarrays to focus on specific metabolic pathways, proteomics to identify relevant proteins and protein-protein interactions to understand critical parasite pathways. Functional genomics is expected to accelerate the development of control and treatment strategies for schistosomiasis.}, keywords = {Chromosome mapping, Gene discovery, Genomics, Schistosoma mansoni}, isbn = {1383-5769}, author = {LoVerde, Philip T. and Hirai, Hirohisa and Merrick, Joseph M. and Lee, Norman H. and Najib M. El-Sayed} } @article {38494, title = {Sequencing Strategies for Parasite Genomes}, journal = {METHODS IN MOLECULAR BIOLOGY-CLIFTON THEN TOTOWA-METHODS IN MOLECULAR BIOLOGY-CLIFTON THEN TOTOWA-}, volume = {270}, year = {2004}, author = {Bartholomeu, D. and Najib M. El-Sayed and Melville, S. E.} } @article {38505, title = {Simple statistical models predict C-to-U edited sites in plant mitochondrial RNA}, journal = {BMC BioinformaticsBMC Bioinformatics}, volume = {5}, year = {2004}, type = {10.1186/1471-2105-5-132}, abstract = {BACKGROUND: RNA editing is the process whereby an RNA sequence is modified from the sequence of the corresponding DNA template. In the mitochondria of land plants, some cytidines are converted to uridines before translation. Despite substantial study, the molecular biological mechanism by which C-to-U RNA editing proceeds remains relatively obscure, although several experimental studies have implicated a role for cis-recognition. A highly non-random distribution of nucleotides is observed in the immediate vicinity of edited sites (within 20 nucleotides 5{\textquoteright} and 3{\textquoteright}), but no precise consensus motif has been identified. RESULTS: Data for analysis were derived from the the complete mitochondrial genomes of Arabidopsis thaliana, Brassica napus, and Oryza sativa; additionally, a combined data set of observations across all three genomes was generated. We selected datasets based on the 20 nucleotides 5{\textquoteright} and the 20 nucleotides 3{\textquoteright} of edited sites and an equivalently sized and appropriately constructed null-set of non-edited sites. We used tree-based statistical methods and random forests to generate models of C-to-U RNA editing based on the nucleotides surrounding the edited/non-edited sites and on the estimated folding energies of those regions. Tree-based statistical methods based on primary sequence data surrounding edited/non-edited sites and estimates of free energy of folding yield models with optimistic re-substitution-based estimates of approximately 0.71 accuracy, approximately 0.64 sensitivity, and approximately 0.88 specificity. Random forest analysis yielded better models and more exact performance estimates with approximately 0.74 accuracy, approximately 0.72 sensitivity, and approximately 0.81 specificity for the combined observations. CONCLUSIONS: Simple models do moderately well in predicting which cytidines will be edited to uridines, and provide the first quantitative predictive models for RNA edited sites in plant mitochondria. Our analysis shows that the identity of the nucleotide -1 to the edited C and the estimated free energy of folding for a 41 nt region surrounding the edited C are the most important variables that distinguish most edited from non-edited sites. However, the results suggest that primary sequence data and simple free energy of folding calculations alone are insufficient to make highly accurate predictions.}, author = {Michael P. Cummings and Myers, D. S.} } @article {38514, title = {Structural flexibility in the Burkholderia mallei genome}, journal = {Proceedings of the National Academy of Sciences of the United States of AmericaProceedings of the National Academy of Sciences of the United States of America}, volume = {101}, year = {2004}, note = {http://www.ncbi.nlm.nih.gov/pubmed/15377793?dopt=Abstract}, type = {10.1073/pnas.0403306101}, abstract = {The complete genome sequence of Burkholderia mallei ATCC 23344 provides insight into this highly infectious bacterium{\textquoteright}s pathogenicity and evolutionary history. B. mallei, the etiologic agent of glanders, has come under renewed scientific investigation as a result of recent concerns about its past and potential future use as a biological weapon. Genome analysis identified a number of putative virulence factors whose function was supported by comparative genome hybridization and expression profiling of the bacterium in hamster liver in vivo. The genome contains numerous insertion sequence elements that have mediated extensive deletions and rearrangements of the genome relative to Burkholderia pseudomallei. The genome also contains a vast number (>12,000) of simple sequence repeats. Variation in simple sequence repeats in key genes can provide a mechanism for generating antigenic variation that may account for the mammalian host{\textquoteright}s inability to mount a durable adaptive immune response to a B. mallei infection.}, keywords = {Animals, Base Composition, Base Sequence, Burkholderia mallei, Chromosomes, Bacterial, Cricetinae, Genome, Bacterial, Glanders, Liver, Mesocricetus, Molecular Sequence Data, Multigene Family, Oligonucleotide Array Sequence Analysis, Open Reading Frames, virulence}, author = {Nierman, William C. and DeShazer, David and Kim, H. Stanley and Tettelin, Herv{\'e} and Nelson, Karen E. and Feldblyum, Tamara and Ulrich, Ricky L. and Ronning, Catherine M. and Brinkac, Lauren M. and Daugherty, Sean C. and Davidsen, Tanja D. and DeBoy, Robert T. and Dimitrov, George and Dodson, Robert J. and Durkin, A. Scott and Gwinn, Michelle L. and Haft, Daniel H. and Khouri, Hoda and Kolonay, James F. and Madupu, Ramana and Mohammoud, Yasmin and Nelson, William C. and Radune, Diana and Romero, Claudia M. and Sarria, Saul and J. Selengut and Shamblin, Christine and Sullivan, Steven A. and White, Owen and Yu, Yan and Zafar, Nikhat and Zhou, Liwei and Fraser, Claire M.} } @article {38562, title = {Variation of toxigenic Vibrio cholerae O1 in the aquatic environment of Bangladesh and its correlation with the clinical strains}, journal = {Microbiology and immunologyMicrobiology and Immunology}, volume = {48}, year = {2004}, author = {Islam, M. S. and Talukder, K. A. and Khan, N. H. and Mahmud, Z. H. and Rahman, M. Z. and Nair, G. B. and Siddique, A. K. M. and Yunus, M. and Sack, D. A. and Sack, R. B. and Rita R. Colwell} } @article {38574, title = {Whole genome comparisons of serotype 4b and 1/2a strains of the food-borne pathogen Listeria monocytogenes reveal new insights into the core genome components of this species}, journal = {Nucleic acids researchNucleic Acids Research}, volume = {32}, year = {2004}, note = {http://www.ncbi.nlm.nih.gov/pubmed/15115801?dopt=Abstract}, type = {10.1093/nar/gkh562}, abstract = {The genomes of three strains of Listeria monocytogenes that have been associated with food-borne illness in the USA were subjected to whole genome comparative analysis. A total of 51, 97 and 69 strain-specific genes were identified in L.monocytogenes strains F2365 (serotype 4b, cheese isolate), F6854 (serotype 1/2a, frankfurter isolate) and H7858 (serotype 4b, meat isolate), respectively. Eighty-three genes were restricted to serotype 1/2a and 51 to serotype 4b strains. These strain- and serotype-specific genes probably contribute to observed differences in pathogenicity, and the ability of the organisms to survive and grow in their respective environmental niches. The serotype 1/2a-specific genes include an operon that encodes the rhamnose biosynthetic pathway that is associated with teichoic acid biosynthesis, as well as operons for five glycosyl transferases and an adenine-specific DNA methyltransferase. A total of 8603 and 105 050 high quality single nucleotide polymorphisms (SNPs) were found on the draft genome sequences of strain H7858 and strain F6854, respectively, when compared with strain F2365. Whole genome comparative analyses revealed that the L.monocytogenes genomes are essentially syntenic, with the majority of genomic differences consisting of phage insertions, transposable elements and SNPs.}, keywords = {Base Composition, Chromosomes, Bacterial, DNA Transposable Elements, Food Microbiology, Genes, Bacterial, Genome, Bacterial, Genomics, Listeria monocytogenes, Meat, Open Reading Frames, Physical Chromosome Mapping, Polymorphism, Single Nucleotide, Prophages, Serotyping, Species Specificity, Synteny, virulence}, author = {Nelson, Karen E. and Fouts, Derrick E. and Mongodin, Emmanuel F. and Ravel, Jacques and DeBoy, Robert T. and Kolonay, James F. and Rasko, David A. and Angiuoli, Samuel V. and Gill, Steven R. and Paulsen, Ian T. and Peterson, Jeremy and White, Owen and Nelson, William C. and Nierman, William and Beanan, Maureen J. and Brinkac, Lauren M. and Daugherty, Sean C. and Dodson, Robert J. and Durkin, A. Scott and Madupu, Ramana and Haft, Daniel H. and J. Selengut and Van Aken, Susan and Khouri, Hoda and Fedorova, Nadia and Forberger, Heather and Tran, Bao and Kathariou, Sophia and Wonderling, Laura D. and Uhlich, Gaylen A. and Bayles, Darrell O. and Luchansky, John B. and Fraser, Claire M.} } @article {38576, title = {Whole-genome shotgun assembly and comparison of human genome assemblies}, journal = {Proceedings of the National Academy of Sciences of the United States of AmericaProceedings of the National Academy of Sciences of the United States of America}, volume = {101}, year = {2004}, publisher = {National Acad Sciences}, author = {Istrail, S. and Sutton, G. G. and Florea, L. and Halpern, A. L. and Mobarry, C. M. and Lippert, R. and Walenz, B. and Shatkay, H. and Dew, I. and Miller, J. R. and others,} } @article {38098, title = {A 4-Year Study of the Epidemiology of Vibrio Cholerae in Four Rural Areas of Bangladesh}, journal = {Journal of Infectious DiseasesJ Infect Dis.Journal of Infectious DiseasesJ Infect Dis.}, volume = {187}, year = {2003}, type = {10.1086/345865}, abstract = {How Vibrio cholerae spreads around the world and what determines its seasonal peaks in endemic areas are not known. These features of cholera have been hypothesized to be primarily the result of environmental factors associated with aquatic habitats that can now be identified. Since 1997, fortnightly surveillance in 4 widely separated geographic locations in Bangladesh has been performed to identify patients with cholera and to collect environmental data. A total of 5670 patients (53\% <5 years of age) have been studied; 14.3\% had cholera (10.4\% due to V. cholerae O1 El Tor, 3.8\% due to O139). Both serogroups were found in all locations; outbreaks were seasonal and often occurred simultaneously. Water-use patterns showed that bathing and washing clothes in tube-well water was significantly protective in two of the sites. These data will be correlated with environmental factors, to develop a model for prediction of cholera outbreaks}, isbn = {0022-1899, 1537-6613}, author = {Sack, R. Bradley and Siddique, A. Kasem and Longini, Ira M. and Nizam, Azhar and Yunus, Md and M. Sirajul Islam and Morris and Ali, Afsar and Huq, Anwar and Nair, G. Balakrish and Qadri, Firdausi and Faruque, Shah M. and Sack, David A. and Rita R. Colwell} } @article {38164, title = {Comparing bootstrap and posterior probability values in the four-taxon case}, journal = {Syst BiolSyst Biol}, volume = {52}, year = {2003}, abstract = {Assessment of the reliability of a given phylogenetic hypothesis is an important step in phylogenetic analysis. Historically, the nonparametric bootstrap procedure has been the most frequently used method for assessing the support for specific phylogenetic relationships. The recent employment of Bayesian methods for phylogenetic inference problems has resulted in clade support being expressed in terms of posterior probabilities. We used simulated data and the four-taxon case to explore the relationship between nonparametric bootstrap values (as inferred by maximum likelihood) and posterior probabilities (as inferred by Bayesian analysis). The results suggest a complex association between the two measures. Three general regions of tree space can be identified: (1) the neutral zone, where differences between mean bootstrap and mean posterior probability values are not significant, (2) near the two-branch corner, and (3) deep in the two-branch corner. In the last two regions, significant differences occur between mean bootstrap and mean posterior probability values. Whether bootstrap or posterior probability values are higher depends on the data in support of alternative topologies. Examination of star topologies revealed that both bootstrap and posterior probability values differ significantly from theoretical expectations; in particular, there are more posterior probability values in the range 0.85-1 than expected by theory. Therefore, our results corroborate the findings of others that posterior probability values are excessively high. Our results also suggest that extrapolations from single topology branch-length studies are unlikely to provide any general conclusions regarding the relationship between bootstrap and posterior probability values.}, author = {Michael P. Cummings and Handley, S. A. and Myers, D. S. and Reed, D. L. and Rokas, A. and Winka, K.} } @article {38168, title = {The complete genome sequence of the Arabidopsis and tomato pathogen Pseudomonas syringae pv. tomato DC3000}, journal = {Proceedings of the National Academy of Sciences of the United States of AmericaProceedings of the National Academy of Sciences of the United States of America}, volume = {100}, year = {2003}, note = {http://www.ncbi.nlm.nih.gov/pubmed/12928499?dopt=Abstract}, type = {10.1073/pnas.1731982100}, abstract = {We report the complete genome sequence of the model bacterial pathogen Pseudomonas syringae pathovar tomato DC3000 (DC3000), which is pathogenic on tomato and Arabidopsis thaliana. The DC3000 genome (6.5 megabases) contains a circular chromosome and two plasmids, which collectively encode 5,763 ORFs. We identified 298 established and putative virulence genes, including several clusters of genes encoding 31 confirmed and 19 predicted type III secretion system effector proteins. Many of the virulence genes were members of paralogous families and also were proximal to mobile elements, which collectively comprise 7\% of the DC3000 genome. The bacterium possesses a large repertoire of transporters for the acquisition of nutrients, particularly sugars, as well as genes implicated in attachment to plant surfaces. Over 12\% of the genes are dedicated to regulation, which may reflect the need for rapid adaptation to the diverse environments encountered during epiphytic growth and pathogenesis. Comparative analyses confirmed a high degree of similarity with two sequenced pseudomonads, Pseudomonas putida and Pseudomonas aeruginosa, yet revealed 1,159 genes unique to DC3000, of which 811 lack a known function.}, keywords = {Arabidopsis, Base Sequence, Biological Transport, Genome, Bacterial, Lycopersicon esculentum, Molecular Sequence Data, Plant Growth Regulators, Plasmids, Pseudomonas, Reactive Oxygen Species, Siderophores, virulence}, author = {Buell, C. Robin and Joardar, Vinita and Lindeberg, Magdalen and J. Selengut and Paulsen, Ian T. and Gwinn, Michelle L. and Dodson, Robert J. and DeBoy, Robert T. and Durkin, A. Scott and Kolonay, James F. and Madupu, Ramana and Daugherty, Sean and Brinkac, Lauren and Beanan, Maureen J. and Haft, Daniel H. and Nelson, William C. and Davidsen, Tanja and Zafar, Nikhat and Zhou, Liwei and Liu, Jia and Yuan, Qiaoping and Khouri, Hoda and Fedorova, Nadia and Tran, Bao and Russell, Daniel and Berry, Kristi and Utterback, Teresa and Aken, Susan E. van and Feldblyum, Tamara V. and D{\textquoteright}Ascenzo, Mark and Deng, Wen-Ling and Ramos, Adela R. and Alfano, James R. and Cartinhour, Samuel and Chatterjee, Arun K. and Delaney, Terrence P. and Lazarowitz, Sondra G. and Martin, Gregory B. and Schneider, David J. and Tang, Xiaoyan and Bender, Carol L. and White, Owen and Fraser, Claire M. and Collmer, Alan} } @proceedings {38218, title = {Dynamic querying for pattern identification in microarray and genomic data}, volume = {3}, year = {2003}, month = {2003}, publisher = {IEEE}, type = {10.1109/ICME.2003.1221346}, abstract = {Data sets involving linear ordered sequences are a recurring theme in bioinformatics. Dynamic query tools that support exploration of these data sets can be useful for identifying patterns of interest. This paper describes the use of one such tool - timesearcher - to interactively explore linear sequence data sets taken from two bioinformatics problems. Microarray time course data sets involve expression levels for large numbers of genes over multiple time points. Timesearcher can be used to interactively search these data sets for genes with expression profiles of interest. The occurrence frequencies of short sequences of DNA in aligned exons can be used to identify sequences that play a role in the pre-mRNA splicing. Timesearcher can be used to search these data sets for candidate splicing signals.}, keywords = {Bioinformatics, data sets, Displays, dynamic querying, expression profiles, Frequency, Gene expression, genes, Genetics, genomic data, Genomics, linear ordered sequences, macromolecules, medical signal processing, Mice, Microarray, pattern identification, pattern recognition, premRNA splicing, Query processing, sequences, Signal processing, splicing, TimeSearcher}, isbn = {0-7803-7965-9}, author = {Hochheiser, H. and Baehrecke, E. H. and Stephen M. Mount and Shneiderman, Ben} } @article {38291, title = {Genome of Geobacter sulfurreducens: metal reduction in subsurface environments}, journal = {Science (New York, N.Y.)Science (New York, N.Y.)}, volume = {302}, year = {2003}, note = {http://www.ncbi.nlm.nih.gov/pubmed/14671304?dopt=Abstract}, type = {10.1126/science.1088727}, abstract = {The complete genome sequence of Geobacter sulfurreducens, a delta-proteobacterium, reveals unsuspected capabilities, including evidence of aerobic metabolism, one-carbon and complex carbon metabolism, motility, and chemotactic behavior. These characteristics, coupled with the possession of many two-component sensors and many c-type cytochromes, reveal an ability to create alternative, redundant, electron transport networks and offer insights into the process of metal ion reduction in subsurface environments. As well as playing roles in the global cycling of metals and carbon, this organism clearly has the potential for use in bioremediation of radioactive metals and in the generation of electricity.}, keywords = {Acetates, Acetyl Coenzyme A, Aerobiosis, Anaerobiosis, Bacterial Proteins, Carbon, Chemotaxis, Chromosomes, Bacterial, Cytochromes c, Electron Transport, Energy Metabolism, Genes, Bacterial, Genes, Regulator, Genome, Bacterial, Geobacter, Hydrogen, Metals, Movement, Open Reading Frames, Oxidation-Reduction, Phylogeny}, author = {Meth{\'e}, B. A. and Nelson, K. E. and Eisen, J. A. and Paulsen, I. T. and Nelson, W. and Heidelberg, J. F. and Wu, D. and Wu, M. and Ward, N. and Beanan, M. J. and Dodson, R. J. and Madupu, R. and Brinkac, L. M. and Daugherty, S. C. and DeBoy, R. T. and Durkin, A. S. and Gwinn, M. and Kolonay, J. F. and Sullivan, S. A. and Haft, D. H. and J. Selengut and Davidsen, T. M. and Zafar, N. and White, O. and Tran, B. and Romero, C. and Forberger, H. A. and Weidman, J. and Khouri, H. and Feldblyum, T. V. and Utterback, T. R. and Van Aken, S. E. and Lovley, D. R. and Fraser, C. M.} } @article {38300, title = {The genome sequence of Bacillus anthracis Ames and comparison to closely related bacteria}, journal = {NatureNature}, volume = {423}, year = {2003}, note = {[eacute]
[Oslash]}, type = {10.1038/nature01586}, abstract = {Bacillus anthracis is an endospore-forming bacterium that causes inhalational anthrax1. Key virulence genes are found on plasmids (extra-chromosomal, circular, double-stranded DNA molecules) pXO1 (ref. 2) and pXO2 (ref. 3). To identify additional genes that might contribute to virulence, we analysed the complete sequence of the chromosome of B. anthracis Ames (about 5.23 megabases). We found several chromosomally encoded proteins that may contribute to pathogenicity{\textemdash}including haemolysins, phospholipases and iron acquisition functions{\textemdash}and identified numerous surface proteins that might be important targets for vaccines and drugs. Almost all these putative chromosomal virulence and surface proteins have homologues in Bacillus cereus, highlighting the similarity of B. anthracis to near-neighbours that are not associated with anthrax4. By performing a comparative genome hybridization of 19 B. cereus and Bacillus thuringiensis strains against a B. anthracis DNA microarray, we confirmed the general similarity of chromosomal genes among this group of close relatives. However, we found that the gene sequences of pXO1 and pXO2 were more variable between strains, suggesting plasmid mobility in the group. The complete sequence of B. anthracis is a step towards a better understanding of anthrax pathogenesis.}, isbn = {0028-0836}, author = {Read, Timothy D. and Peterson, Scott N. and Tourasse, Nicolas and Baillie, Les W. and Paulsen, Ian T. and Nelson, Karen E. and Tettelin, Herv and Fouts, Derrick E. and Eisen, Jonathan A. and Gill, Steven R. and Holtzapple, Erik K. and kstad, Ole Andreas and Helgason, Erlendur and Rilstone, Jennifer and Wu, Martin and Kolonay, James F. and Beanan, Maureen J. and Dodson, Robert J. and Brinkac, Lauren M. and Gwinn, Michelle and DeBoy, Robert T. and Madpu, Ramana and Daugherty, Sean C. and Durkin, A. Scott and Haft, Daniel H. and Nelson, William C. and Peterson, Jeremy D. and M. Pop and Khouri, Hoda M. and Radune, Diana and Benton, Jonathan L. and Mahamoud, Yasmin and Jiang, Lingxia and Hance, Ioana R. and Weidman, Janice F. and Berry, Kristi J. and Plaut, Roger D. and Wolf, Alex M. and Watkins, Kisha L. and Nierman, William C. and Hazen, Alyson and Cline, Robin and Redmond, Caroline and Thwaite, Joanne E. and White, Owen and Salzberg, Steven L. and Thomason, Brendan and Friedlander, Arthur M. and Koehler, Theresa M. and Hanna, Philip C. and Kolst, and Anne-Brit and Fraser, Claire M.} } @article {49685, title = {Improving the Arabidopsis genome annotation using maximal transcript alignment assemblies.}, journal = {Nucleic Acids Res}, volume = {31}, year = {2003}, month = {2003 Oct 1}, pages = {5654-66}, abstract = {

The spliced alignment of expressed sequence data to genomic sequence has proven a key tool in the comprehensive annotation of genes in eukaryotic genomes. A novel algorithm was developed to assemble clusters of overlapping transcript alignments (ESTs and full-length cDNAs) into maximal alignment assemblies, thereby comprehensively incorporating all available transcript data and capturing subtle splicing variations. Complete and partial gene structures identified by this method were used to improve The Institute for Genomic Research Arabidopsis genome annotation (TIGR release v.4.0). The alignment assemblies permitted the automated modeling of several novel genes and >1000 alternative splicing variations as well as updates (including UTR annotations) to nearly half of the approximately 27 000 annotated protein coding genes. The algorithm of the Program to Assemble Spliced Alignments (PASA) tool is described, as well as the results of automated updates to Arabidopsis gene annotations.

}, keywords = {algorithms, Alternative Splicing, Arabidopsis, DNA, Complementary, Expressed Sequence Tags, Genome, Plant, Introns, Plant Proteins, RNA, Plant, sequence alignment, software, Transcription, Genetic, Untranslated Regions}, issn = {1362-4962}, author = {Haas, Brian J and Delcher, Arthur L and Mount, Stephen M and Wortman, Jennifer R and Smith, Roger K and Hannick, Linda I and Maiti, Rama and Ronning, Catherine M and Rusch, Douglas B and Town, Christopher D and Salzberg, Steven L and White, Owen} } @article {38394, title = {Necessity is the mother of invention: a simple grid computing system using commodity tools}, journal = {J Parallel Distr ComJ Parallel Distr Com}, volume = {63}, year = {2003}, type = {DOI 10.1016/S0743-7315(03)00004-2}, abstract = {Access to sufficient resources is a barrier to scientific progress for many researchers facing large computational problems. Gaining access to large-scale resources (i.e., university-wide or federally supported computer centers) can be difficult, given their limited availability, particular architectures, and request/review/approval cycles. Simultaneously, researchers often find themselves with access to workstations and older clusters overlooked by their owners in favor of newer hardware. Software to tie these resources into a coherent Grid, however, has been problematic. Here, we describe our experiences building a Grid computing system to conduct a large-scale simulation study using "borrowed" computing resources distributed over a wide area. Using standard software components, we have produced a Grid computing system capable of coupling several hundred processors spanning multiple continents and administrative domains. We believe that this system fills an important niche between a closely coupled local system and a heavyweight, highly customized wide area system. (C) 2003 Elsevier Science (USA). All rights reserved.}, keywords = {Apache, computing, distributed, Grid, HTTP, java, Linux, Perl, SQL, Unix, XML-RPC}, author = {Myers, D. S. and Michael P. Cummings} } @article {38424, title = {Pathogenic Potential of Environmental Vibrio Cholerae Strains Carrying Genetic Variants of the Toxin-Coregulated Pilus Pathogenicity Island}, journal = {Infection and ImmunityInfect. Immun.Infection and ImmunityInfect. Immun.}, volume = {71}, year = {2003}, type = {10.1128/IAI.71.2.1020-1025.2003}, abstract = {The major virulence factors of toxigenic Vibrio cholerae are cholera toxin (CT), which is encoded by a lysogenic bacteriophage (CTXΦ), and toxin-coregulated pilus (TCP), an essential colonization factor which is also the receptor for CTXΦ. The genes for the biosynthesis of TCP are part of a larger genetic element known as the TCP pathogenicity island. To assess their pathogenic potential, we analyzed environmental strains of V. cholerae carrying genetic variants of the TCP pathogenicity island for colonization of infant mice, susceptibility to CTXΦ, and diarrheagenicity in adult rabbits. Analysis of 14 environmental strains, including 3 strains carrying a new allele of the tcpA gene, 9 strains carrying a new allele of the toxT gene, and 2 strains carrying conventional tcpA and toxT genes, showed that all strains colonized infant mice with various efficiencies in competition with a control El Tor biotype strain of V. cholerae O1. Five of the 14 strains were susceptible to CTXΦ, and these transductants produced CT and caused diarrhea in adult rabbits. These results suggested that the new alleles of the tcpA and toxT genes found in environmental strains of V. cholerae encode biologically active gene products. Detection of functional homologs of the TCP island genes in environmental strains may have implications for understanding the origin and evolution of virulence genes of V. cholerae.}, isbn = {0019-9567, 1098-5522}, author = {Faruque, Shah M. and Kamruzzaman, M. and Meraj, Ismail M. and Chowdhury, Nityananda and Nair, G. Balakrish and Sack, R. Bradley and Rita R. Colwell and Sack, David A.} } @article {38458, title = {Reduction of Cholera in Bangladeshi Villages by Simple Filtration}, journal = {Proceedings of the National Academy of SciencesPNASProceedings of the National Academy of SciencesPNAS}, volume = {100}, year = {2003}, type = {10.1073/pnas.0237386100}, abstract = {Based on results of ecological studies demonstrating that Vibrio cholerae, the etiological agent of epidemic cholera, is commensal to zooplankton, notably copepods, a simple filtration procedure was developed whereby zooplankton, most phytoplankton, and particulates >20 μm were removed from water before use. Effective deployment of this filtration procedure, from September 1999 through July 2002 in 65 villages of rural Bangladesh, of which the total population for the entire study comprised ≈133,000 individuals, yielded a 48\% reduction in cholera (P < 0.005) compared with the control.}, isbn = {0027-8424, 1091-6490}, author = {Rita R. Colwell and Huq, Anwar and M. Sirajul Islam and K. M. A. Aziz and Yunus, M. and N. Huda Khan and A. Mahmud and Sack, R. Bradley and Nair, G. B. and J. Chakraborty and Sack, David A. and E. Russek-Cohen} } @article {38489, title = {The sequence and analysis of Trypanosoma brucei chromosome II}, journal = {Nucleic acids researchNucleic Acids Research}, volume = {31}, year = {2003}, author = {Najib M. El-Sayed and Ghedin, E. and Song, J. and MacLeod, A. and Bringaud, F. and Larkin, C. and Wanless, D. and Peterson, J. and Hou, L. and Taylor, S. and others,} } @article {49633, title = {The sequence and analysis of Trypanosoma brucei chromosome II.}, journal = {Nucleic Acids Res}, volume = {31}, year = {2003}, month = {2003 Aug 15}, pages = {4856-63}, abstract = {

We report here the sequence of chromosome II from Trypanosoma brucei, the causative agent of African sleeping sickness. The 1.2-Mb pairs encode about 470 predicted genes organised in 17 directional clusters on either strand, the largest cluster of which has 92 genes lined up over a 284-kb region. An analysis of the GC skew reveals strand compositional asymmetries that coincide with the distribution of protein-coding genes, suggesting these asymmetries may be the result of transcription-coupled repair on coding versus non-coding strand. A 5-cM genetic map of the chromosome reveals recombinational {\textquoteright}hot{\textquoteright} and {\textquoteright}cold{\textquoteright} regions, the latter of which is predicted to include the putative centromere. One end of the chromosome consists of a 250-kb region almost exclusively composed of RHS (pseudo)genes that belong to a newly characterised multigene family containing a hot spot of insertion for retroelements. Interspersed with the RHS genes are a few copies of truncated RNA polymerase pseudogenes as well as expression site associated (pseudo)genes (ESAGs) 3 and 4, and 76 bp repeats. These features are reminiscent of a vestigial variant surface glycoprotein (VSG) gene expression site. The other end of the chromosome contains a 30-kb array of VSG genes, the majority of which are pseudogenes, suggesting that this region may be a site for modular de novo construction of VSG gene diversity during transposition/gene conversion events.

}, keywords = {Animals, Antigens, Protozoan, Chromosome mapping, Chromosomes, DNA, Protozoan, Gene Duplication, Genes, Protozoan, Molecular Sequence Data, Pseudogenes, Recombination, Genetic, Sequence Analysis, DNA, Trypanosoma brucei brucei}, issn = {1362-4962}, author = {el-Sayed, Najib M A and Ghedin, Elodie and Song, Jinming and MacLeod, Annette and Bringaud, Frederic and Larkin, Christopher and Wanless, David and Peterson, Jeremy and Hou, Lihua and Taylor, Sonya and Tweedie, Alison and Biteau, Nicolas and Khalak, Hanif G and Lin, Xiaoying and Mason, Tanya and Hannick, Linda and Caler, Elisabet and Blandin, Ga{\"e}lle and Bartholomeu, Daniella and Simpson, Anjana J and Kaul, Samir and Zhao, Hong and Pai, Grace and Van Aken, Susan and Utterback, Teresa and Haas, Brian and Koo, Hean L and Umayam, Lowell and Suh, Bernard and Gerrard, Caroline and Leech, Vanessa and Qi, Rong and Zhou, Shiguo and Schwartz, David and Feldblyum, Tamara and Salzberg, Steven and Tait, Andrew and Turner, C Michael R and Ullu, Elisabetta and White, Owen and Melville, Sara and Adams, Mark D and Fraser, Claire M and Donelson, John E} } @article {49686, title = {Sex-lethal splicing autoregulation in vivo: interactions between SEX-LETHAL, the U1 snRNP and U2AF underlie male exon skipping.}, journal = {Development}, volume = {130}, year = {2003}, month = {2003 Feb}, pages = {463-71}, abstract = {

Alternative splicing of the Sex-lethal pre-mRNA has long served as a model example of a regulated splicing event, yet the mechanism by which the female-specific SEX-LETHAL RNA-binding protein prevents inclusion of the translation-terminating male exon is not understood. Thus far, the only general splicing factor for which there is in vivo evidence for a regulatory role in the pathway leading to male-exon skipping is sans-fille (snf), a protein component of the spliceosomal U1 and U2 snRNPs. Its role, however, has remained enigmatic because of questions about whether SNF acts as part of an intact snRNP or a free protein. We provide evidence that SEX-LETHAL interacts with SANS-FILLE in the context of the U1 snRNP, through the characterization of a point mutation that interferes with both assembly into the U1 snRNP and complex formation with SEX-LETHAL. Moreover, we find that SEX-LETHAL associates with other integral U1 snRNP components, and we provide genetic evidence to support the biological relevance of these physical interactions. Similar genetic and biochemical approaches also link SEX-LETHAL with the heterodimeric splicing factor, U2AF. These studies point specifically to a mechanism by which SEX-LETHAL represses splicing by interacting with these key splicing factors at both ends of the regulated male exon. Moreover, because U2AF and the U1 snRNP are only associated transiently with the pre-mRNA during the course of spliceosome assembly, our studies are difficult to reconcile with the current model that proposes that the SEX-LETHAL blocks splicing at the second catalytic step, and instead argue that the SEX-LETHAL protein acts after splice site recognition, but before catalysis begins.

}, keywords = {Alternative Splicing, Amino Acid Sequence, Animals, Animals, Genetically Modified, Drosophila melanogaster, Drosophila Proteins, Exons, Female, Gene Expression Regulation, Developmental, Genes, Insect, Homeostasis, Male, Models, Genetic, Molecular Sequence Data, Nuclear Proteins, Point Mutation, Ribonucleoprotein, U1 Small Nuclear, Ribonucleoproteins, RNA Splicing, RNA-Binding Proteins, Sequence Homology, Amino Acid, Sex Differentiation}, issn = {0950-1991}, author = {Nagengast, Alexis A and Stitzinger, Shane M and Tseng, Chin-Hsiu and Mount, Stephen M and Salz, Helen K} } @article {38536, title = {The transcription factor Eyes absent is a protein tyrosine phosphatase}, journal = {NatureNature}, volume = {426}, year = {2003}, note = {http://www.ncbi.nlm.nih.gov/pubmed/14628053?dopt=Abstract}, type = {10.1038/nature02097}, abstract = {Post-translational modifications provide sensitive and flexible mechanisms to dynamically modulate protein function in response to specific signalling inputs. In the case of transcription factors, changes in phosphorylation state can influence protein stability, conformation, subcellular localization, cofactor interactions, transactivation potential and transcriptional output. Here we show that the evolutionarily conserved transcription factor Eyes absent (Eya) belongs to the phosphatase subgroup of the haloacid dehalogenase (HAD) superfamily, and propose a function for it as a non-thiol-based protein tyrosine phosphatase. Experiments performed in cultured Drosophila cells and in vitro indicate that Eyes absent has intrinsic protein tyrosine phosphatase activity and can autocatalytically dephosphorylate itself. Confirming the biological significance of this function, mutations that disrupt the phosphatase active site severely compromise the ability of Eyes absent to promote eye specification and development in Drosophila. Given the functional importance of phosphorylation-dependent modulation of transcription factor activity, this evidence for a nuclear transcriptional coactivator with intrinsic phosphatase activity suggests an unanticipated method of fine-tuning transcriptional regulation.}, keywords = {Amino Acid Motifs, Amino Acid Sequence, Animals, Antibodies, Phospho-Specific, Drosophila melanogaster, Drosophila Proteins, Embryonic Induction, eye, Eye Proteins, Gene Expression Regulation, Kinetics, Mice, Models, Molecular, Molecular Sequence Data, Mutation, Phosphorylation, Protein Conformation, Protein Tyrosine Phosphatases, Substrate Specificity, Transcription Factors}, author = {Tootle, Tina L. and Silver, Serena J. and Davies, Erin L. and Newman, Victoria and Latek, Robert R. and Mills, Ishara A. and J. Selengut and Parlikar, Beth E. W. and Rebay, Ilaria} } @article {38148, title = {Characterization of Pseudoalteromonas citrea and P. nigrifaciens Isolated from Different Ecological Habitats Based on REP-PCR Genomic Fingerprints}, journal = {Systematic and Applied MicrobiologySystematic and Applied Microbiology}, volume = {25}, year = {2002}, type = {10.1078/0723-2020-00103}, abstract = {SummaryDNA primers corresponding to conserved repetitive interspersed genomic motifs and PCR were used to show that REP, ERIC and BOX-like DNA sequences are present in marine, oxidative, Gram-negative Pseudoalteromonas strains. REP, ERIC and BOX-PCR were used for rapid molecular characterization of both the type species of the genus and environmental strains isolated from samples collected in different geographical areas. PCR-generated genomic fingerprint patterns were found to be both complex and strain specific. Analysis of the genotypic structure of phenotypically diverse P. citrea revealed a geographic clustering of Far Eastern brown-pigmented, agar-digesting strains of this species. Marine isolates of P. nigrifaciens with 67{\textendash}70\% DNA relatedness generated genomic patterns different from those of the type strain and formed a separate cluster. It is concluded that REP, ERIC and BOX-PCR are effective in generating strain specific patterns that can be used to elucidate geographic distribution, with these genomic patterns providing a valuable biogeographic criterion.}, keywords = {biogeography, BOX-PCR, ERIC, Pseudoalteromonas, REP}, isbn = {0723-2020}, author = {Ivanova, Elena P. and Matte, Glavur R. and Matte, Maria H. and Coenye, Tom and Huq, Anwarul and Rita R. Colwell} } @inbook {38153, title = {Combinatorial Algorithms for Design of DNA Arrays}, booktitle = {Chip TechnologyChip Technology}, series = {Advances in Biochemical Engineering/Biotechnology}, volume = {77}, year = {2002}, publisher = {Springer Berlin / Heidelberg}, organization = {Springer Berlin / Heidelberg}, abstract = {Optimal design of DNA arrays requires the development of algorithms with two-fold goals: reducing the effects caused by unintended illumination ( border length minimization problem ) and reducing the complexity of masks ( mask decomposition problem ). We describe algorithms that reduce the number of rectangles in mask decomposition by 20{\textendash}30\% as compared to a standard array design under the assumption that the arrangement of oligonucleotides on the array is fixed. This algorithm produces provably optimal solution for all studied real instances of array design. We also address the difficult problem of finding an arrangement which minimizes the border length and come up with a new idea of threading that significantly reduces the border length as compared to standard designs.}, isbn = {978-3-540-43215-9}, author = {Sridhar Hannenhalli and Hubbell, Earl and Lipshutz, Robert and Pevzner, Pavel}, editor = {Hoheisel, J{\"o}rg and Brazma, A. and B{\"u}ssow, K. and Cantor, C. and Christians, F. and Chui, G. and Diaz, R. and Drmanac, R. and Drmanac, S. and Eickhoff, H. and Fellenberg, K. and Sridhar Hannenhalli and Hoheisel, J. and Hou, A. and Hubbell, E. and Jin, H. and Jin, P. and Jurinke, C. and Konthur, Z. and K{\"o}ster, H. and Kwon, S. and Lacy, S. and Lehrach, H. and Lipshutz, R. and Little, D. and Lueking, A. and McGall, G. and Moeur, B. and Nordhoff, E. and Nyarsik, L. and Pevzner, P. and Robinson, A. and Sarkans, U. and Shafto, J. and Sohail, M. and Southern, E. and Swanson, D. and Ukrainczyk, T. and van den Boom, D. and Vilo, J. and Vingron, M. and Walter, G. and Xu, C.} } @article {49687, title = {The draft genome of Ciona intestinalis: insights into chordate and vertebrate origins.}, journal = {Science}, volume = {298}, year = {2002}, month = {2002 Dec 13}, pages = {2157-67}, abstract = {

The first chordates appear in the fossil record at the time of the Cambrian explosion, nearly 550 million years ago. The modern ascidian tadpole represents a plausible approximation to these ancestral chordates. To illuminate the origins of chordate and vertebrates, we generated a draft of the protein-coding portion of the genome of the most studied ascidian, Ciona intestinalis. The Ciona genome contains approximately 16,000 protein-coding genes, similar to the number in other invertebrates, but only half that found in vertebrates. Vertebrate gene families are typically found in simplified form in Ciona, suggesting that ascidians contain the basic ancestral complement of genes involved in cell signaling and development. The ascidian genome has also acquired a number of lineage-specific innovations, including a group of genes engaged in cellulose metabolism that are related to those in bacteria and fungi.

}, keywords = {Alleles, Animals, Apoptosis, Base Sequence, Cellulose, Central Nervous System, Ciona intestinalis, Computational Biology, Endocrine System, Gene Dosage, Gene Duplication, genes, Genes, Homeobox, Genome, Heart, Immunity, Molecular Sequence Data, Multigene Family, Muscle Proteins, Organizers, Embryonic, Phylogeny, Polymorphism, Genetic, Proteins, Sequence Analysis, DNA, Sequence Homology, Nucleic Acid, Species Specificity, Thyroid Gland, Urochordata, Vertebrates}, issn = {1095-9203}, doi = {10.1126/science.1080049}, author = {Dehal, Paramvir and Satou, Yutaka and Campbell, Robert K and Chapman, Jarrod and Degnan, Bernard and De Tomaso, Anthony and Davidson, Brad and Di Gregorio, Anna and Gelpke, Maarten and Goodstein, David M and Harafuji, Naoe and Hastings, Kenneth E M and Ho, Isaac and Hotta, Kohji and Huang, Wayne and Kawashima, Takeshi and Lemaire, Patrick and Martinez, Diego and Meinertzhagen, Ian A and Necula, Simona and Nonaka, Masaru and Putnam, Nik and Rash, Sam and Saiga, Hidetoshi and Satake, Masanobu and Terry, Astrid and Yamada, Lixy and Wang, Hong-Gang and Awazu, Satoko and Azumi, Kaoru and Boore, Jeffrey and Branno, Margherita and Chin-Bow, Stephen and DeSantis, Rosaria and Doyle, Sharon and Francino, Pilar and Keys, David N and Haga, Shinobu and Hayashi, Hiroko and Hino, Kyosuke and Imai, Kaoru S and Inaba, Kazuo and Kano, Shungo and Kobayashi, Kenji and Kobayashi, Mari and Lee, Byung-In and Makabe, Kazuhiro W and Manohar, Chitra and Matassi, Giorgio and Medina, Monica and Mochizuki, Yasuaki and Mount, Steve and Morishita, Tomomi and Miura, Sachiko and Nakayama, Akie and Nishizaka, Satoko and Nomoto, Hisayo and Ohta, Fumiko and Oishi, Kazuko and Rigoutsos, Isidore and Sano, Masako and Sasaki, Akane and Sasakura, Yasunori and Shoguchi, Eiichi and Shin-i, Tadasu and Spagnuolo, Antoinetta and Stainier, Didier and Suzuki, Miho M and Tassy, Olivier and Takatori, Naohito and Tokuoka, Miki and Yagi, Kasumi and Yoshizaki, Fumiko and Wada, Shuichi and Zhang, Cindy and Hyatt, P Douglas and Larimer, Frank and Detter, Chris and Doggett, Norman and Glavina, Tijana and Hawkins, Trevor and Richardson, Paul and Lucas, Susan and Kohara, Yuji and Levine, Michael and Satoh, Nori and Rokhsar, Daniel S} } @article {49688, title = {Evidence for a plastid origin of plant ethylene receptor genes.}, journal = {Plant Physiol}, volume = {130}, year = {2002}, month = {2002 Sep}, pages = {10-4}, keywords = {Amino Acid Sequence, Anabaena, Arabidopsis, Cyanobacteria, Molecular Sequence Data, Plant Proteins, Plastids, Protein Kinases, Receptors, Cell Surface, Sequence Homology, Amino Acid}, issn = {0032-0889}, doi = {10.1104/pp.005397}, author = {Mount, Stephen M and Chang, Caren} } @article {38304, title = {Genome sequence of the human malaria parasite Plasmodium falciparum}, journal = {NatureNature}, volume = {419}, year = {2002}, note = {http://www.ncbi.nlm.nih.gov/pubmed/12368864?dopt=Abstract}, type = {10.1038/nature01097}, abstract = {The parasite Plasmodium falciparum is responsible for hundreds of millions of cases of malaria, and kills more than one million African children annually. Here we report an analysis of the genome sequence of P. falciparum clone 3D7. The 23-megabase nuclear genome consists of 14 chromosomes, encodes about 5,300 genes, and is the most (A + T)-rich genome sequenced to date. Genes involved in antigenic variation are concentrated in the subtelomeric regions of the chromosomes. Compared to the genomes of free-living eukaryotic microbes, the genome of this intracellular parasite encodes fewer enzymes and transporters, but a large proportion of genes are devoted to immune evasion and host-parasite interactions. Many nuclear-encoded proteins are targeted to the apicoplast, an organelle involved in fatty-acid and isoprenoid metabolism. The genome sequence provides the foundation for future studies of this organism, and is being exploited in the search for new drugs and vaccines to fight malaria.}, keywords = {Animals, Chromosome Structures, DNA Repair, DNA Replication, DNA, Protozoan, Evolution, Molecular, Genome, Protozoan, HUMANS, Malaria Vaccines, Malaria, Falciparum, Membrane Transport Proteins, Molecular Sequence Data, Plasmodium falciparum, Plastids, Proteome, Protozoan Proteins, Recombination, Genetic, Sequence Analysis, DNA}, author = {Gardner, Malcolm J. and Hall, Neil and Fung, Eula and White, Owen and Berriman, Matthew and Hyman, Richard W. and Carlton, Jane M. and Pain, Arnab and Nelson, Karen E. and Bowman, Sharen and Paulsen, Ian T. and James, Keith and Eisen, Jonathan A. and Rutherford, Kim and Salzberg, Steven L. and Craig, Alister and Kyes, Sue and Chan, Man-Suen and Nene, Vishvanath and Shallom, Shamira J. and Suh, Bernard and Peterson, Jeremy and Angiuoli, Sam and Pertea, Mihaela and Allen, Jonathan and J. Selengut and Haft, Daniel and Mather, Michael W. and Vaidya, Akhil B. and Martin, David M. A. and Fairlamb, Alan H. and Fraunholz, Martin J. and Roos, David S. and Ralph, Stuart A. and McFadden, Geoffrey I. and Cummings, Leda M. and Subramanian, G. Mani and Mungall, Chris and Venter, J. Craig and Carucci, Daniel J. and Hoffman, Stephen L. and Newbold, Chris and Davis, Ronald W. and Fraser, Claire M. and Barrell, Bart} } @article {38406, title = {A new, expressed multigene family containing a hot spot for insertion of retroelements is associated with polymorphic subtelomeric regions of Trypanosoma brucei}, journal = {Eukaryotic cellEukaryotic Cell}, volume = {1}, year = {2002}, author = {Bringaud, F. and Biteau, N. and Melville, S. E. and Hez, S. and Najib M. El-Sayed and Leech, V. and Berriman, M. and Hall, N. and Donelson, J. E. and Baltz, T.} } @article {49631, title = {A new, expressed multigene family containing a hot spot for insertion of retroelements is associated with polymorphic subtelomeric regions of Trypanosoma brucei.}, journal = {Eukaryot Cell}, volume = {1}, year = {2002}, month = {2002 Feb}, pages = {137-51}, abstract = {

We describe a novel gene family that forms clusters in subtelomeric regions of Trypanosoma brucei chromosomes and partially accounts for the observed clustering of retrotransposons. The ingi and ribosomal inserted mobile element (RIME) non-LTR retrotransposons share 250 bp at both extremities and are the most abundant putatively mobile elements, with about 500 copies per haploid genome. From cDNA clones and subsequently in the T. brucei genomic DNA databases, we identified 52 homologous gene and pseudogene sequences, 16 of which contain a RIME and/or ingi retrotransposon inserted at exactly the same relative position. Here these genes are called the RHS family, for retrotransposon hot spot. Comparison of the protein sequences encoded by RHS genes (21 copies) and pseudogenes (24 copies) revealed a conserved central region containing an ATP/GTP-binding motif and the RIME/ingi insertion site. The RHS proteins share between 13 and 96\% identity, and six subfamilies, RHS1 to RHS6, can be defined on the basis of their divergent C-terminal domains. Immunofluorescence and Western blot analyses using RHS subfamily-specific immune sera show that RHS proteins are constitutively expressed and occur mainly in the nucleus. Analysis of Genome Survey Sequence databases indicated that the Trypanosoma brucei diploid genome contains about 280 RHS (pseudo)genes. Among the 52 identified RHS (pseudo)genes, 48 copies are in three RHS clusters located in subtelomeric regions of chromosomes Ia and II and adjacent to the active bloodstream form expression site in T. brucei strain TREU927/4 GUTat10.1. RHS genes comprise the remaining sequence of the size-polymorphic "repetitive region" described for T. brucei chromosome I, and a homologous gene family is present in the Trypanosoma cruzi genome.

}, keywords = {Amino Acid Sequence, Animals, Base Sequence, Cloning, Molecular, DNA Primers, DNA, Protozoan, Escherichia coli, Genes, Protozoan, Molecular Sequence Data, Multigene Family, Mutagenesis, Insertional, Phylogeny, Polymorphism, Genetic, Protozoan Proteins, Pseudogenes, Retroelements, sequence alignment, Sequence Homology, Amino Acid, Telomere, Trypanosoma brucei brucei, Trypanosoma cruzi}, issn = {1535-9778}, author = {Bringaud, Frederic and Biteau, Nicolas and Melville, Sara E and Hez, St{\'e}phanie and El-Sayed, Najib M and Leech, Vanessa and Berriman, Matthew and Hall, Neil and Donelson, John E and Baltz, Th{\'e}o} } @article {38449, title = {Proceedings of the sixth annual international conference on Computational biology}, year = {2002}, publisher = {ACM}, author = {Myers, G. and Sridhar Hannenhalli and Sankoff, D. and Istrail, S. and Pevzner, P. and Waterman, M.} } @article {38492, title = {Sequence of Plasmodium falciparum chromosomes 2, 10, 11 and 14}, journal = {NatureNature}, volume = {419}, year = {2002}, note = {http://www.ncbi.nlm.nih.gov/pubmed/12368868?dopt=Abstract}, type = {10.1038/nature01094}, abstract = {The mosquito-borne malaria parasite Plasmodium falciparum kills an estimated 0.7-2.7 million people every year, primarily children in sub-Saharan Africa. Without effective interventions, a variety of factors-including the spread of parasites resistant to antimalarial drugs and the increasing insecticide resistance of mosquitoes-may cause the number of malaria cases to double over the next two decades. To stimulate basic research and facilitate the development of new drugs and vaccines, the genome of Plasmodium falciparum clone 3D7 has been sequenced using a chromosome-by-chromosome shotgun strategy. We report here the nucleotide sequences of chromosomes 10, 11 and 14, and a re-analysis of the chromosome 2 sequence. These chromosomes represent about 35\% of the 23-megabase P. falciparum genome.}, keywords = {Animals, Chromosomes, DNA, Protozoan, Genome, Protozoan, Plasmodium falciparum, Proteome, Protozoan Proteins, Sequence Analysis, DNA}, author = {Gardner, Malcolm J. and Shallom, Shamira J. and Carlton, Jane M. and Salzberg, Steven L. and Nene, Vishvanath and Shoaibi, Azadeh and Ciecko, Anne and Lynn, Jeffery and Rizzo, Michael and Weaver, Bruce and Jarrahi, Behnam and Brenner, Michael and Parvizi, Babak and Tallon, Luke and Moazzez, Azita and Granger, David and Fujii, Claire and Hansen, Cheryl and Pederson, James and Feldblyum, Tamara and Peterson, Jeremy and Suh, Bernard and Angiuoli, Sam and Pertea, Mihaela and Allen, Jonathan and J. Selengut and White, Owen and Cummings, Leda M. and Smith, Hamilton O. and Adams, Mark D. and Venter, J. Craig and Carucci, Daniel J. and Hoffman, Stephen L. and Fraser, Claire M.} } @article {38105, title = {The African trypanosome genome}, journal = {International Journal for ParasitologyInternational Journal for Parasitology}, volume = {30}, year = {2000}, type = {16/S0020-7519(00)00015-1}, abstract = {The haploid nuclear genome of the African trypanosome, Trypanosoma brucei, is about 35 Mb and varies in size among different trypanosome isolates by as much as 25\%. The nuclear DNA of this diploid organism is distributed among three size classes of chromosomes: the megabase chromosomes of which there are at least 11 pairs ranging from 1 Mb to more than 6 Mb (numbered I-XI from smallest to largest); several intermediate chromosomes of 200-900 kb and uncertain ploidy; and about 100 linear minichromosomes of 50-150 kb. Size differences of as much as four-fold can occur, both between the two homologues of a megabase chromosome pair in a specific trypanosome isolate and among chromosome pairs in different isolates. The genomic DNA sequences determined to date indicated that about 50\% of the genome is coding sequence. The chromosomal telomeres possess TTAGGG repeats and many, if not all, of the telomeres of the megabase and intermediate chromosomes are linked to expression sites for genes encoding variant surface glycoproteins (VSGs). The minichromosomes serve as repositories for VSG genes since some but not all of their telomeres are linked to unexpressed VSG genes. A gene discovery program, based on sequencing the ends of cloned genomic DNA fragments, has generated more than 20 Mb of discontinuous single-pass genomic sequence data during the past year, and the complete sequences of chromosomes I and II (about 1 Mb each) in T. brucei GUTat 10.1 are currently being determined. It is anticipated that the entire genomic sequence of this organism will be known in a few years. Analysis of a test microarray of 400 cDNAs and small random genomic DNA fragments probed with RNAs from two developmental stages of T. brucei demonstrates that the microarray technology can be used to identify batteries of genes differentially expressed during the various life cycle stages of this parasite.}, isbn = {0020-7519}, author = {Najib M. El-Sayed and Hegde, Priti and Quackenbush, John and Melville, Sara E. and Donelson, John E.} } @article {49691, title = {Expanding the definition of informational suppression.}, journal = {Trends Genet}, volume = {16}, year = {2000}, month = {2000 Apr}, pages = {157}, keywords = {Animals, DNA-Binding Proteins, Drosophila Proteins, Nuclear Proteins, Recombinant Proteins, Repressor Proteins, Suppression, Genetic, Transcription Factors}, issn = {0168-9525}, author = {Mount, S M and Anderson, P} } @article {49692, title = {The genome sequence of Drosophila melanogaster.}, journal = {Science}, volume = {287}, year = {2000}, month = {2000 Mar 24}, pages = {2185-95}, abstract = {

The fly Drosophila melanogaster is one of the most intensively studied organisms in biology and serves as a model system for the investigation of many developmental and cellular processes common to higher eukaryotes, including humans. We have determined the nucleotide sequence of nearly all of the approximately 120-megabase euchromatic portion of the Drosophila genome using a whole-genome shotgun sequencing strategy supported by extensive clone-based sequence and a high-quality bacterial artificial chromosome physical map. Efforts are under way to close the remaining gaps; however, the sequence is of sufficient accuracy and contiguity to be declared substantially complete and to support an initial analysis of genome structure and preliminary gene annotation and interpretation. The genome encodes approximately 13,600 genes, somewhat fewer than the smaller Caenorhabditis elegans genome, but with comparable functional diversity.

}, keywords = {Animals, Biological Transport, Chromatin, Cloning, Molecular, Computational Biology, Contig Mapping, Cytochrome P-450 Enzyme System, DNA Repair, DNA Replication, Drosophila melanogaster, Euchromatin, Gene Library, Genes, Insect, Genome, Heterochromatin, Insect Proteins, Nuclear Proteins, Protein Biosynthesis, Sequence Analysis, DNA, Transcription, Genetic}, issn = {0036-8075}, author = {Adams, M D and Celniker, S E and Holt, R A and Evans, C A and Gocayne, J D and Amanatides, P G and Scherer, S E and Li, P W and Hoskins, R A and Galle, R F and George, R A and Lewis, S E and Richards, S and Ashburner, M and Henderson, S N and Sutton, G G and Wortman, J R and Yandell, M D and Zhang, Q and Chen, L X and Brandon, R C and Rogers, Y H and Blazej, R G and Champe, M and Pfeiffer, B D and Wan, K H and Doyle, C and Baxter, E G and Helt, G and Nelson, C R and Gabor, G L and Abril, J F and Agbayani, A and An, H J and Andrews-Pfannkoch, C and Baldwin, D and Ballew, R M and Basu, A and Baxendale, J and Bayraktaroglu, L and Beasley, E M and Beeson, K Y and Benos, P V and Berman, B P and Bhandari, D and Bolshakov, S and Borkova, D and Botchan, M R and Bouck, J and Brokstein, P and Brottier, P and Burtis, K C and Busam, D A and Butler, H and Cadieu, E and Center, A and Chandra, I and Cherry, J M and Cawley, S and Dahlke, C and Davenport, L B and Davies, P and de Pablos, B and Delcher, A and Deng, Z and Mays, A D and Dew, I and Dietz, S M and Dodson, K and Doup, L E and Downes, M and Dugan-Rocha, S and Dunkov, B C and Dunn, P and Durbin, K J and Evangelista, C C and Ferraz, C and Ferriera, S and Fleischmann, W and Fosler, C and Gabrielian, A E and Garg, N S and Gelbart, W M and Glasser, K and Glodek, A and Gong, F and Gorrell, J H and Gu, Z and Guan, P and Harris, M and Harris, N L and Harvey, D and Heiman, T J and Hernandez, J R and Houck, J and Hostin, D and Houston, K A and Howland, T J and Wei, M H and Ibegwam, C and Jalali, M and Kalush, F and Karpen, G H and Ke, Z and Kennison, J A and Ketchum, K A and Kimmel, B E and Kodira, C D and Kraft, C and Kravitz, S and Kulp, D and Lai, Z and Lasko, P and Lei, Y and Levitsky, A A and Li, J and Li, Z and Liang, Y and Lin, X and Liu, X and Mattei, B and McIntosh, T C and McLeod, M P and McPherson, D and Merkulov, G and Milshina, N V and Mobarry, C and Morris, J and Moshrefi, A and Mount, S M and Moy, M and Murphy, B and Murphy, L and Muzny, D M and Nelson, D L and Nelson, D R and Nelson, K A and Nixon, K and Nusskern, D R and Pacleb, J M and Palazzolo, M and Pittman, G S and Pan, S and Pollard, J and Puri, V and Reese, M G and Reinert, K and Remington, K and Saunders, R D and Scheeler, F and Shen, H and Shue, B C and Sid{\'e}n-Kiamos, I and Simpson, M and Skupski, M P and Smith, T and Spier, E and Spradling, A C and Stapleton, M and Strong, R and Sun, E and Svirskas, R and Tector, C and Turner, R and Venter, E and Wang, A H and Wang, X and Wang, Z Y and Wassarman, D A and Weinstock, G M and Weissenbach, J and Williams, S M and Worley, K C and Wu, D and Yang, S and Yao, Q A and Ye, J and Yeh, R F and Zaveri, J S and Zhan, M and Zhang, G and Zhao, Q and Zheng, L and Zheng, X H and Zhong, F N and Zhong, W and Zhou, X and Zhu, S and Zhu, X and Smith, H O and Gibbs, R A and Myers, E W and Rubin, G M and Venter, J C} } @article {49689, title = {Genomic sequence, splicing, and gene annotation.}, journal = {Am J Hum Genet}, volume = {67}, year = {2000}, month = {2000 Oct}, pages = {788-92}, keywords = {Animals, Consensus Sequence, Exons, genes, Genome, Genomics, HUMANS, Nucleotides, Regulatory Sequences, Nucleic Acid, RNA Splice Sites, RNA Splicing, Untranslated Regions}, issn = {0002-9297}, doi = {10.1086/303098}, author = {Mount, S M} } @article {49690, title = {Pre-messenger RNA processing factors in the Drosophila genome.}, journal = {J Cell Biol}, volume = {150}, year = {2000}, month = {2000 Jul 24}, pages = {F37-44}, keywords = {Animals, Drosophila melanogaster, Genome, Genomic Library, HUMANS, RNA Precursors, RNA, Messenger}, issn = {0021-9525}, author = {Mount, S M and Salz, H K} } @article {38548, title = {Trends in the early careers of life scientists - Preface and executive summary}, journal = {Mol Biol CellMol Biol Cell}, volume = {9}, year = {1998}, author = {Tilghman, S. and Astin, H. S. and Brinkley, W. and Chilton, M. D. and Michael P. Cummings and Ehrenberg, R. G. and Fox, M. F. and Glenn, K. and Green, P. J. and Hans, S. and Kelman, A. and LaPidus, J. and Levin, B. and McIntosh, J. R. and Riecken, H. and Stephen, P. E.} } @article {49693, title = {Genetic depletion reveals an essential role for an SR protein splicing factor in vertebrate cells.}, journal = {Bioessays}, volume = {19}, year = {1997}, month = {1997 Mar}, pages = {189-92}, abstract = {

SR proteins are essential for the splicing of messenger RNA precursors in vitro, where they also alter splice site selection in a concentration-dependent manner. Although experiments involving overexpression or dominant mutations have confirmed that these proteins can influence RNA processing decisions in vivo, similar results with loss-of-function mutations have been lacking. Now, a system for genetic depletion of the chicken B cell line DT40 has revealed that the SR protein ASF/SF2 (alternative splicing factor/splicing factor 2) is essential for viability in these cells(1). This study opens the way for a complete functional dissection of this protein, and other SR proteins, in vivo.

}, keywords = {Amino Acid Sequence, Animals, Molecular Sequence Data, Nuclear Proteins, RNA Splicing, RNA-Binding Proteins, Serine-Arginine Splicing Factors, Vertebrates}, issn = {0265-9247}, doi = {10.1002/bies.950190302}, author = {Mount, S M} } @article {38326, title = {Hardness of flip-cut problems from optical mapping}, journal = {Journal of Computational BiologyJournal of Computational Biology}, volume = {4}, year = {1997}, author = {Dan{\v C}{\'I}K, V. and Sridhar Hannenhalli and Muthukrishnan, S.} } @article {38361, title = {Local rules for protein folding on a triangular lattice and generalized hydrophobicity in the HP model}, journal = {Journal of Computational BiologyJournal of Computational Biology}, volume = {4}, year = {1997}, author = {Agarwala, R. and Batzoglou, S. and Dan{\v C}{\'I}K, V. and Decatur, S. E. and Sridhar Hannenhalli and Farach, M. and Muthukrishnan, S. and Skiena, S.} } @article {38527, title = {Testing simple polygons}, journal = {Computational GeometryComputational Geometry}, volume = {8}, year = {1997}, type = {10.1016/S0925-7721(96)00015-6}, abstract = {We consider the problem of verifying a simple polygon in the plane using {\textquotedblleft}test points{\textquotedblright}. A test point is a geometric probe that takes as input a point in Euclidean space, and returns {\textquotedblleft}+{\textquotedblright} if the point is inside the object being probed or {\textquotedblleft}-{\textquotedblright} if it is outside. A verification procedure takes as input a description of a target object, including its location and orientation, and it produces a set of test points that are used to verify whether a test object matches the description. We give a procedure for verifying an n-sided, non-degenerate, simple target polygon using 5n test points. This testing strategy works even if the test polygon has n + 1 vertices, and we show a lower bound of 3n + 1 test points for this case. We also give algorithms using O(n) test points for simple polygons that may be degenerate and for test polygons that may have up to n + 2 vertices. All of these algorithms work for polygons with holes. We also discuss extensions of our results to higher dimensions.}, keywords = {probing, Testing, Verifying}, isbn = {0925-7721}, author = {Arkin, Esther M. and Belleville, Patrice and Mitchell, Joseph S. B. and Mount, Dave and Romanik, Kathleen and Salzberg, Steven and Souvaine, Diane} } @article {49695, title = {AT-AC introns: an ATtACk on dogma.}, journal = {Science}, volume = {271}, year = {1996}, month = {1996 Mar 22}, pages = {1690-2}, keywords = {Animals, Base Composition, Base Sequence, Consensus Sequence, HUMANS, Introns, Molecular Sequence Data, Mutation, RNA Precursors, RNA Splicing, RNA, Small Nuclear, Spliceosomes}, issn = {0036-8075}, author = {Mount, S M} } @article {38204, title = {Differential expression of the expression site-associated gene I family in African trypanosomes}, journal = {Journal of Biological ChemistryJournal of Biological Chemistry}, volume = {271}, year = {1996}, author = {Morgan, R. W. and Najib M. El-Sayed and Kepa, J. K. and Pedram, M. and Donelson, J. E.} } @article {38212, title = {DNA sequence variation in the ribosomal internal transcribed spacer region of freshwater {\i}t Cladophora species (Chlorophyta)}, journal = {J PhycolJ Phycol}, volume = {32}, year = {1996}, abstract = {Freshwater species of Cladophora (Chlorophyta) are globally distributed and occupy an unusually wide range of ecological habitats. Delineating species is difficult because most easily observed morphological traits are highly variable and because sexual reproduction has not been clearly documented. Synthesizing ecological data on freshwater Cladophora species is problematic because it is unclear whether freshwater Cladophora species comprise many genetically distinct species or a few ecologically and morphologically variable and / or plastic species. We determined nucleotide sequences of the internal transcribed spacer (ITS) region of the nuclear ribosomal cistron of freshwater Cladophora species from a wide range of habitats and geographic locations. We compared these sequences to those derived from culture collections of C. fracta and C. glomerata, the two most commonly reported freshwater Cladophora species. Cladophora fracta and C. glomerata had very similar ITS sequences (95.3\%). All other sequences were identical to those from the C. fracta or C. glomerata culture collections with the exception of one California sample that was similar to both C. fracta (95.6\%) and C. glomerata (92.4\%). ITS genotypes did not correlate with morphology or geography. This analysis shows that common freshwater Cladophora species comprise very few (possibly one) ecologically and morphologically variable species.}, keywords = {algae, Chlorophyta, Cladophora, diversity, freshwater, genetic, internal, spacer, transcribed}, author = {Marks, J. C. and Michael P. Cummings} } @inbook {38257, title = {Fast sorting by reversal}, booktitle = {Combinatorial Pattern MatchingCombinatorial Pattern Matching}, series = {Lecture Notes in Computer Science}, volume = {1075}, year = {1996}, publisher = {Springer Berlin / Heidelberg}, organization = {Springer Berlin / Heidelberg}, abstract = {Analysis of genomes evolving by inversions leads to a combinatorial problem of sorting by reversals studied in detail recently. Following a series of work recently, Hannenhalli and Pevzner developed the first polynomial algorithm for the problem of sorting signed permutations by reversals and proposed an O(n 4 ) implementation of the algorithm. In this paper we exploit a few combinatorial properties of the cycle graph of a permutation and propose an O(n 2 (n)) implementation of the algorithm where is the inverse Ackerman function. Besides making this algorithm practical, our technique improves implementations of the other rearrangement distance problems.}, isbn = {978-3-540-61258-2}, author = {Berman, Piotr and Sridhar Hannenhalli}, editor = {Hirschberg, Dan and Myers, Gene} } @article {49694, title = {Ribosomal RNA: small nucleolar RNAs make their mark.}, journal = {Curr Biol}, volume = {6}, year = {1996}, month = {1996 Nov 1}, pages = {1413-5}, abstract = {

Small nucleolar RNAs direct the location of certain methylations in ribosomal RNA by direct base pairing; although evolutionarily conserved, the physiological significance of these modifications remains unclear.

}, keywords = {Animals, Methylation, Ribonucleoproteins, Small Nuclear, RNA, Ribosomal}, issn = {0960-9822}, author = {Peculis, B A and Mount, S M} } @article {49696, title = {Genetic enhancement of RNA-processing defects by a dominant mutation in B52, the Drosophila gene for an SR protein splicing factor.}, journal = {Mol Cell Biol}, volume = {15}, year = {1995}, month = {1995 Nov}, pages = {6273-82}, abstract = {

SR proteins are essential for pre-mRNA splicing in vitro, act early in the splicing pathway, and can influence alternative splice site choice. Here we describe the isolation of both dominant and loss-of-function alleles of B52, the gene for a Drosophila SR protein. The allele B52ED was identified as a dominant second-site enhancer of white-apricot (wa), a retrotransposon insertion in the second intron of the eye pigmentation gene white with a complex RNA-processing defect. B52ED also exaggerates the mutant phenotype of a distinct white allele carrying a 5{\textquoteright} splice site mutation (wDR18), and alters the pattern of sex-specific splicing at doublesex under sensitized conditions, so that the male-specific splice is favored. In addition to being a dominant enhancer of these RNA-processing defects, B52ED is a recessive lethal allele that fails to complement other lethal alleles of B52. Comparison of B52ED with the B52+ allele from which it was derived revealed a single change in a conserved amino acid in the beta 4 strand of the first RNA-binding domain of B52, which suggests that altered RNA binding is responsible for the dominant phenotype. Reversion of the B52ED dominant allele with X rays led to the isolation of a B52 null allele. Together, these results indicate a critical role for the SR protein B52 in pre-mRNA splicing in vivo.

}, keywords = {Alleles, Amino Acid Sequence, Animals, Base Sequence, DNA Primers, Drosophila melanogaster, Drosophila Proteins, Frameshift Mutation, Genes, Dominant, Genes, Insect, Molecular Sequence Data, Nuclear Proteins, Phosphoproteins, Point Mutation, Protein Structure, Tertiary, Proteins, RNA Splicing, RNA-Binding Proteins, Sequence Deletion, Sex Determination Analysis}, issn = {0270-7306}, author = {Peng, X and Mount, S M} } @article {49697, title = {Localization of sequences required for size-specific splicing of a small Drosophila intron in vitro.}, journal = {J Mol Biol}, volume = {253}, year = {1995}, month = {1995 Oct 27}, pages = {426-37}, abstract = {

Many introns in Drosophila and other invertebrates are less than 80 nucleotides in length, too small to be recognized by the vertebrate splicing machinery. Comparison of nuclear splicing extracts from human HeLa and Drosophila Kc cells has revealed species-specificity, consistent with the observed size differences. Here we present additional results with the 68 nucleotide fifth intron of the Drosophila myosin heavy chain gene. As observed with the 74 nucleotide second intron of the Drosophila white gene, the wild-type myosin intron is accurately spliced in a homologous extract, and increasing the size by 16 nucleotides both eliminates splicing in the Drosophila extract and allows accurate splicing in the human extract. In contrast to previous results, however, an upstream cryptic 5{\textquoteright} splice site is activated when the wild-type myosin intron is tested in a human HeLa cell nuclear extract, resulting in the removal of a 98 nucleotide intron. The size dependence of splicing in Drosophila extracts is also intron-specific; we noted that a naturally larger (150 nucleotide) intron from the ftz gene is efficiently spliced in Kc cell extracts that do not splice enlarged introns (of 84, 90, 150 or 350 nucleotides) derived from the 74 nucleotide white intron. Here, we have exploited that observation, using a series of hybrid introns to show that a region of 46 nucleotides at the 3{\textquoteright} end of the white intron is sufficient to confer the species-specific size effect. At least two sequence elements within this region, yet distinct from previously described branchpoint and pyrimidine tract signals, are required for efficient splicing of small hybrid introns in vitro.

}, keywords = {Animals, Base Sequence, Cell Line, DNA, Drosophila, Genes, Insect, HeLa Cells, HUMANS, Introns, Molecular Sequence Data, Myosin Heavy Chains, RNA Splicing, Species Specificity}, issn = {0022-2836}, doi = {10.1006/jmbi.1995.0564}, author = {Guo, M and Mount, S M} } @article {49699, title = {P element-mediated in vivo deletion analysis of white-apricot: deletions between direct repeats are strongly favored.}, journal = {Genetics}, volume = {136}, year = {1994}, month = {1994 Mar}, pages = {1001-11}, abstract = {

We have isolated and characterized deletions arising within a P transposon, P[hswa], in the presence of P transposase. P[hswa] carries white-apricot (wa) sequences, including a complete copia element, under the control of an hsp70 promoter, and resembles the original wa allele in eye color phenotype. In the presence of P transposase, P[hswa] shows a high overall rate (approximately 3\%) of germline mutations that result in increased eye pigmentation. Of 234 derivatives of P[hswa] with greatly increased eye pigmentation, at least 205 carried deletions within copia. Of these, 201 were precise deletions between the directly repeated 276-nucleotide copia long terminal repeats (LTRs), and four were unique deletions. High rates of transposase-induced precise deletion were observed within another P transposon carrying unrelated 599 nucleotide repeats (yeast 2 mu FLP; recombinase target sites) separated by 5.7 kb. Our observation that P element-mediated deletion formation occurs preferentially between direct repeats suggests general methods for controlling deletion formation.

}, keywords = {Alleles, Animals, Animals, Genetically Modified, Base Sequence, Crosses, Genetic, DNA, DNA Transposable Elements, Drosophila, Eye Color, Female, Genes, Insect, Male, Molecular Sequence Data, Nucleotidyltransferases, PHENOTYPE, Recombination, Genetic, Repetitive Sequences, Nucleic Acid, Sequence Deletion, Transformation, Genetic, Transposases}, issn = {0016-6731}, author = {Kurkulos, M and Weinberg, J M and Roy, D and Mount, S M} } @article {49698, title = {Suppressor U1 snRNAs in Drosophila.}, journal = {Genetics}, volume = {138}, year = {1994}, month = {1994 Oct}, pages = {365-78}, abstract = {

Although the role of U1 small nuclear RNAs (snRNAs) in 5{\textquoteright} splice site recognition is well established, suppressor U1 snRNAs active in intact multicellular animals have been lacking. Here we describe suppression of a 5{\textquoteright} splice site mutation in the Drosophila melanogaster white gene (wDR18) by compensatory changes in U1 snRNA. Mutation of positions -1 and +6 of the 5{\textquoteright} splice site of the second intron (ACG[GTGAGT to ACC]GTGAGC) results in the accumulation of RNA retaining this 74-nucleotide intron in both transfected cells and transgenic flies. U1-3G, a suppressor U1 snRNA which restores base-pairing at position +6 of the mutant intron, increases the ratio of spliced to unspliced wDR18 RNA up to fivefold in transfected Schneider cells and increases eye pigmentation in wDR18 flies. U1-9G, which targets position -1, suppresses wDR18 in transfected cells less well. U1-3G,9G has the same effect as U1-3G although it accumulates to lower levels. Suppression of wDR18 has revealed that the U1b embryonic variant (G134 to U) is active in Schneider cells and pupal eye discs. However, the combination of 9G with 134U leads to reduced accumulation of both U1b-9G and U1b-3G,9G, possibly because nucleotides 9 and 134 both participate in a potential long-range intramolecular base-pairing interaction. High levels of functional U1-3G suppressor reduce both viability and fertility in transformed flies. These results show that, despite the difficulties inherent in stably altering splice site selection in multicellular organisms, it is possible to obtain suppressor U1 snRNAs in flies.

}, keywords = {Alternative Splicing, Animals, Base Sequence, Cell Line, Cell Nucleus, DNA Primers, Drosophila melanogaster, Female, Genes, Suppressor, Genetic Variation, GENOTYPE, Introns, Male, Molecular Sequence Data, Mutagenesis, Site-Directed, Nucleic Acid Conformation, Oligodeoxyribonucleotides, PHENOTYPE, Recombinant Proteins, Ribonucleoprotein, U1 Small Nuclear, RNA, Small Nuclear, Transfection, Transformation, Genetic}, issn = {0016-6731}, author = {Lo, P C and Roy, D and Mount, S M} } @article {49700, title = {Gene organization: nested genes take flight.}, journal = {Curr Biol}, volume = {3}, year = {1993}, month = {1993 Jun 1}, pages = {372-4}, issn = {0960-9822}, author = {Mount, S and Henikoff, S} } @article {49701, title = {Species-specific signals for the splicing of a short Drosophila intron in vitro.}, journal = {Mol Cell Biol}, volume = {13}, year = {1993}, month = {1993 Feb}, pages = {1104-18}, abstract = {

The effects of branchpoint sequence, the pyrimidine stretch, and intron size on the splicing efficiency of the Drosophila white gene second intron were examined in nuclear extracts from Drosophila and human cells. This 74-nucleotide intron is typical of many Drosophila introns in that it lacks a significant pyrimidine stretch and is below the minimum size required for splicing in human nuclear extracts. Alteration of sequences of adjacent to the 3{\textquoteright} splice site to create a pyrimidine stretch was necessary for splicing in human, but not Drosophila, extracts. Increasing the size of this intron with insertions between the 5{\textquoteright} splice site and the branchpoint greatly reduced the efficiency of splicing of introns longer than 79 nucleotides in Drosophila extracts but had an opposite effect in human extracts, in which introns longer than 78 nucleotides were spliced with much greater efficiency. The white-apricot copia insertion is immediately adjacent to the branchpoint normally used in the splicing of this intron, and a copia long terminal repeat insertion prevents splicing in Drosophila, but not human, extracts. However, a consensus branchpoint does not restore the splicing of introns containing the copia long terminal repeat, and alteration of the wild-type branchpoint sequence alone does not eliminate splicing. These results demonstrate species specificity of splicing signals, particularly pyrimidine stretch and size requirements, and raise the possibility that variant mechanisms not found in mammals may operate in the splicing of small introns in Drosophila and possibly other species.

}, keywords = {Animals, Base Sequence, Cell Nucleus, Consensus Sequence, DNA, DNA Transposable Elements, Drosophila, Drosophila Proteins, Electrophoresis, Polyacrylamide Gel, HeLa Cells, HUMANS, Introns, Molecular Sequence Data, Mutation, Peptide Hydrolases, Proteins, Regulatory Sequences, Nucleic Acid, Retroelements, RNA Splicing, Species Specificity}, issn = {0270-7306}, author = {Guo, M and Lo, P C and Mount, S M} } @article {49702, title = {Splicing signals in Drosophila: intron size, information content, and consensus sequences.}, journal = {Nucleic Acids Res}, volume = {20}, year = {1992}, month = {1992 Aug 25}, pages = {4255-62}, abstract = {

A database of 209 Drosophila introns was extracted from Genbank (release number 64.0) and examined by a number of methods in order to characterize features that might serve as signals for messenger RNA splicing. A tight distribution of sizes was observed: while the smallest introns in the database are 51 nucleotides, more than half are less than 80 nucleotides in length, and most of these have lengths in the range of 59-67 nucleotides. Drosophila splice sites found in large and small introns differ in only minor ways from each other and from those found in vertebrate introns. However, larger introns have greater pyrimidine-richness in the region between 11 and 21 nucleotides upstream of 3{\textquoteright} splice sites. The Drosophila branchpoint consensus matrix resembles C T A A T (in which branch formation occurs at the underlined A), and differs from the corresponding mammalian signal in the absence of G at the position immediately preceding the branchpoint. The distribution of occurrences of this sequence suggests a minimum distance between 5{\textquoteright} splice sites and branchpoints of about 38 nucleotides, and a minimum distance between 3{\textquoteright} splice sites and branchpoints of 15 nucleotides. The methods we have used detect no information in exon sequences other than in the few nucleotides immediately adjacent to the splice sites. However, Drosophila resembles many other species in that there is a discontinuity in A + T content between exons and introns, which are A + T rich.

}, keywords = {Animals, Base Sequence, Consensus Sequence, Databases, Factual, Drosophila, Introns, Molecular Sequence Data, RNA Splicing, RNA, Messenger, software}, issn = {0305-1048}, author = {Mount, S M and Burks, C and Hertz, G and Stormo, G D and White, O and Fields, C} } @article {49703, title = {Polyadenylylation in copia requires unusually distant upstream sequences.}, journal = {Proc Natl Acad Sci U S A}, volume = {88}, year = {1991}, month = {1991 Apr 15}, pages = {3038-42}, abstract = {

Retroviruses and related genetic elements generate terminally redundant RNA products by differential polyadenylylation within a long terminal repeat. Expression of the white-apricot (wa) allele of Drosophila melanogaster, which carries an insertion of the 5.1-kilobase retrovirus-like transposable element copia in a small intron, is influenced by signals within copia. By using this indicator, we have isolated a 518-base-pair deletion, 312 base pairs upstream of the copia polyadenylylation site, that is phenotypically like much larger deletions and eliminates RNA species polyadenylylated in copia. This requirement of distant upstream sequences for copia polyadenylylation has implications for the expression of many genetic elements bearing long terminal repeats.

}, keywords = {Animals, Base Sequence, Blotting, Northern, DNA Transposable Elements, Drosophila melanogaster, Eye Color, Molecular Sequence Data, Oligonucleotides, Polymerase Chain Reaction, Regulatory Sequences, Nucleic Acid, Repetitive Sequences, Nucleic Acid, RNA Processing, Post-Transcriptional, RNA, Messenger}, issn = {0027-8424}, author = {Kurkulos, M and Weinberg, J M and Pepling, M E and Mount, S M} } @article {49705, title = {Characterization of enhancer-of-white-apricot in Drosophila melanogaster.}, journal = {Genetics}, volume = {126}, year = {1990}, month = {1990 Dec}, pages = {1061-9}, abstract = {

The white-apricot (wa) allele differs from the wild-type white gene by the presence of the retrovirus-like transposable element copia within the transcription unit. Most RNAs derived from wa have 3{\textquoteright} termini within this insertion, and only small amounts of structurally normal RNA are produced. The activity of wa is reduced in trans by a semidominant mutation in the gene Enhancer-of-white-apricot (E(wa). Flies that are wa and heterozygous for the enhancer have eyes which are much lighter than the orange-yellow of wa alone while E(wa) homozygotes have white eyes. This semidominant effect on pigmentation is correlated with a corresponding decrease in white RNA having wild type structure, and flies homozygous for E(wa) have increased levels of aberrant RNAs. Three reverant alleles of E(wa) generated by reversion of the dominant enhancer phenotype with gamma radiation are noncomplementing recessive lethals, with death occurring during the larval stage. The effects on wa eye pigmentation of varying doses of the original E(wa) allele, the wild type allele, and the revertant alleles suggest that the original E(wa) allele produces a product that interferes with the activity of the wild type gene and that the revertants are null alleles. We propose that the E(wa) gene product influences the activity of the downstream copia long terminal repeat in 3{\textquoteright} end formation.

}, keywords = {Alleles, Animals, Blotting, Northern, DNA Transposable Elements, Drosophila melanogaster, Eye Color, Female, Heterozygote, Homozygote, Male, Nucleic Acid Hybridization, PHENOTYPE, Poly A, Reproduction, RNA, RNA, Messenger, Transcription, Genetic}, issn = {0016-6731}, author = {Peng, X B and Mount, S M} } @article {49704, title = {Drosophila melanogaster genes for U1 snRNA variants and their expression during development.}, journal = {Nucleic Acids Res}, volume = {18}, year = {1990}, month = {1990 Dec 11}, pages = {6971-9}, abstract = {

We have cloned and characterized a complete set of seven U1-related sequences from Drosophila melanogaster. These sequences are located at the three cytogenetic loci 21D, 82E, and 95C. Three of these sequences have been previously studied: one U1 gene at 21D which encodes the prototype U1 sequence (U1a), one U1 gene at 82E which encodes a U1 variant with a single nucleotide substitution (U1b), and a pseudogene at 82E. The four previously uncharacterized genes are another U1b gene at 82E, two additional U1a genes at 95C, and a U1 gene at 95C which encodes a new variant (U1c) with a distinct single nucleotide change relative to U1a. Three blocks of 5{\textquoteright} flanking sequence similarity are common to all six full length genes. Using specific primer extension assays, we have observed that the U1b RNA is expressed in Drosophila Kc cells and is associated with snRNP proteins, suggesting that the U1b-containing snRNP particles are able to participate in the process of pre-mRNA splicing. We have also examined the expression throughout Drosophila development of the two U1 variants relative to the prototype sequence. The U1c variant is undetectable by our methods, while the U1b variant exhibits a primarily embryonic pattern reminiscent of the expression of certain U1 variants in sea urchin, Xenopus, and mouse.

}, keywords = {Animals, Base Sequence, Blotting, Southern, Cloning, Molecular, Drosophila melanogaster, Gene Expression Regulation, genes, Genetic Variation, Molecular Sequence Data, Nucleic Acid Conformation, Pseudogenes, Restriction Mapping, RNA, Small Nuclear}, issn = {0305-1048}, author = {Lo, P C and Mount, S M} } @article {49707, title = {Sequence of a cDNA from the Drosophila melanogaster white gene.}, journal = {Nucleic Acids Res}, volume = {18}, year = {1990}, month = {1990 Mar 25}, pages = {1633}, keywords = {Amino Acid Sequence, Animals, Base Sequence, DNA, Drosophila melanogaster, Eye Color, genes, Molecular Sequence Data}, issn = {0305-1048}, author = {Pepling, M and Mount, S M} } @article {49706, title = {Structure and expression of the Drosophila melanogaster gene for the U1 small nuclear ribonucleoprotein particle 70K protein.}, journal = {Mol Cell Biol}, volume = {10}, year = {1990}, month = {1990 Jun}, pages = {2492-502}, abstract = {

A genomic clone encoding the Drosophila U1 small nuclear ribonucleoprotein particle 70K protein was isolated by hybridization with a human U1 small nuclear ribonucleoprotein particle 70K protein cDNA. Southern blot and in situ hybridizations showed that this U1 70K gene is unique in the Drosophila genome, residing at cytological position 27D1,2. Polyadenylated transcripts of 1.9 and 3.1 kilobases were observed. While the 1.9-kilobase mRNA is always more abundant, the ratio of these two transcripts is developmentally regulated. Analysis of cDNA and genomic sequences indicated that these two RNAs encode an identical protein with a predicted molecular weight of 52,879. Comparison of the U1 70K proteins predicted from Drosophila, human, and Xenopus cDNAs revealed 68\% amino acid identity in the most amino-terminal 214 amino acids, which include a sequence motif common to many proteins which bind RNA. The carboxy-terminal half is less well conserved but is highly charged and contains distinctive arginine-rich regions in all three species. These arginine-rich regions contain stretches of arginine-serine dipeptides like those found in transformer, transformer-2, and suppressor-of-white-apricot proteins, all of which have been identified as regulators of mRNA splicing in Drosophila melanogaster.

}, keywords = {Amino Acid Sequence, Animals, Base Sequence, Blotting, Northern, Blotting, Southern, Cloning, Molecular, DNA, Drosophila melanogaster, Gene expression, Gene Library, genes, HUMANS, Molecular Sequence Data, Molecular Weight, Oligonucleotide Probes, Poly A, Ribonucleoproteins, Ribonucleoproteins, Small Nuclear, RNA, RNA, Messenger, Sequence Homology, Nucleic Acid, Xenopus}, issn = {0270-7306}, author = {Mancebo, R and Lo, P C and Mount, S M} } @article {49708, title = {Partial revertants of the transposable element-associated suppressible allele white-apricot in Drosophila melanogaster: structures and responsiveness to genetic modifiers.}, journal = {Genetics}, volume = {118}, year = {1988}, month = {1988 Feb}, pages = {221-34}, abstract = {

The eye color phenotype of white-apricot (wa), a mutant allele of the white locus caused by the insertion of the transposable element copia into a small intron, is suppressed by the extragenic suppressor suppressor-of-white-apricot (su(wa] and enhanced by the extragenic enhancers suppressor-of-forked su(f] and Enhancer-of-white-apricot (E(wa]. Derivatives of wa have been analyzed molecularly and genetically in order to correlate the structure of these derivatives with their response to modifiers. Derivatives in which the copia element is replaced precisely by a solo long terminal repeat (sLTR) were generated in vitro and returned to the germline by P-element mediated transformation; flies carrying this allele within a P transposon show a nearly wild-type phenotype and no response to either su(f) or su(wa). In addition, eleven partial phenotypic revertants of wa were analyzed. Of these, one appears to be a duplication of a large region which includes wa, three are new alleles of su(wa), two are sLTR derivatives whose properties confirm results obtained using transformation, and five are secondary insertions into the copia element within wa. One of these, waR84h, differs from wa by the insertion of the most 3{\textquoteright} 83 nucleotides of the I factor. The five insertion derivatives show a variety of phenotypes and modes of interaction with su[f) and su(wa). The eye pigmentation of waR84h is affected by su(f) and E(wa), but not su(wa). These results demonstrate that copia (as opposed to the interruption of white sequences) is essential for the wa phenotype and its response to genetic modifiers, and that there are multiple mechanisms for the alteration of the wa phenotype by modifiers.

}, keywords = {Alleles, Animals, Base Sequence, DNA Transposable Elements, Drosophila melanogaster, Enhancer Elements, Genetic, GENOTYPE, Molecular Sequence Data, Mutation, Suppression, Genetic}, issn = {0016-6731}, author = {Mount, S M and Green, M M and Rubin, G M} } @article {49709, title = {Sequence similarity.}, journal = {Nature}, volume = {325}, year = {1987}, month = {1987 Feb 5-11}, pages = {487}, keywords = {Adenosine Triphosphate, Amino Acid Sequence, Animals, Bacterial Proteins, Biological Transport, Active, Carrier Proteins, Drosophila melanogaster, genes, HUMANS, Pigments, Biological, Sequence Homology, Nucleic Acid}, issn = {0028-0836}, doi = {10.1038/325487c0}, author = {Mount, S M} } @article {49710, title = {Complete nucleotide sequence of the Drosophila transposable element copia: homology between copia and retroviral proteins.}, journal = {Mol Cell Biol}, volume = {5}, year = {1985}, month = {1985 Jul}, pages = {1630-8}, abstract = {

We have determined the complete nucleotide sequence of the copia element present at the white-apricot allele of the white locus in Drosophila melanogaster. This transposable element is 5,146 nucleotides long and contains a single long open reading frame of 4,227 nucleotides. Analysis of the coding potential of the large open reading frame, which appears to encode a polyprotein, revealed weak homology to a number of retroviral proteins, including a protease, nucleic acid-binding protein, and reverse transcriptase. Better homology existed between another part of the copia open reading frame and a region of the retroviral pol gene recently shown to be distinct from reverse transcriptase and required for the integration of circular DNA forms of the retroviral genome to form proviruses. Comparison of the copia sequence with those of the Saccharomyces cerevisiae transposable element Ty, several vertebrate retroviruses, and the D. melanogaster copia-like element 17.6 showed that Ty was most similar to copia, sharing amino acid sequence homology and organizational features not found in the other genetic elements.

}, keywords = {Amino Acid Sequence, Animals, Base Sequence, Codon, DNA Helicases, DNA Transposable Elements, Drosophila melanogaster, Gene Expression Regulation, Gene Products, gag, Integrases, Repetitive Sequences, Nucleic Acid, Retroviridae, RNA-Directed DNA Polymerase, Viral Envelope Proteins, Viral Proteins}, issn = {0270-7306}, author = {Mount, S M and Rubin, G M} } @article {49713, title = {Lessons from mutant globins.}, journal = {Nature}, volume = {303}, year = {1983}, month = {1983 Jun 2-8}, pages = {380-1}, keywords = {Globins, HUMANS, Mutation, RNA, Messenger, Thalassemia, Transcription, Genetic}, issn = {0028-0836}, author = {Mount, S and Steitz, J} } @article {49715, title = {Pseudogenes for human small nuclear RNA U3 appear to arise by integration of self-primed reverse transcripts of the RNA into new chromosomal sites.}, journal = {Cell}, volume = {32}, year = {1983}, month = {1983 Feb}, pages = {461-72}, abstract = {

We find that both human and rat U3 snRNA can function as self-priming templates for AMV reverse transcriptase in vitro. The 74 base cDNA is primed by the 3{\textquoteright} end of intact U3 snRNA, and spans the characteristically truncated 69 or 70 base U3 sequence found in four different human U3 pseudogenes. The ability of human and rat U3 snRNA to self-prime is consistent with a U3 secondary structure model derived by a comparison between rat U3 snRNA and the homologous D2 snRNA from Dictyostelium discoideum. We propose that U3 pseudogenes are generated in vivo by integration of a self-primed cDNA copy of U3 snRNA at new chromosomal sites. We also consider the possibility that the same cDNA mediates gene conversion at the 5{\textquoteright} end of bona fide U3 genes where, over the entire region spanned by the U3 cDNA, the two rat U3 sequence variants U3A and U3B are identical.

}, keywords = {Animals, Base Sequence, DNA, genes, HUMANS, Nucleic Acid Conformation, Rats, Recombination, Genetic, Repetitive Sequences, Nucleic Acid, RNA, RNA, Small Nuclear, RNA-Directed DNA Polymerase, Templates, Genetic, Transcription, Genetic}, issn = {0092-8674}, author = {Bernstein, L B and Mount, S M and Weiner, A M} } @article {49712, title = {RNA processing. Sequences that signal where to splice.}, journal = {Nature}, volume = {304}, year = {1983}, pages = {309-10}, keywords = {Base Sequence, RNA Splicing, Saccharomyces cerevisiae}, issn = {0028-0836}, author = {Mount, S M} } @article {49716, title = {Small ribonucleoproteins from eukaryotes: structures and roles in RNA biogenesis.}, journal = {Cold Spring Harb Symp Quant Biol}, volume = {47 Pt 2}, year = {1983}, month = {1983}, pages = {893-900}, keywords = {Animals, Base Sequence, HeLa Cells, HUMANS, Mice, Molecular Weight, Nucleic Acid Conformation, Nucleic Acid Hybridization, Nucleoproteins, Ribonucleoproteins, Ribonucleoproteins, Small Nuclear, RNA Polymerase III, Transcription, Genetic}, issn = {0091-7451}, author = {Steitz, J A and Wolin, S L and Rinke, J and Pettersson, I and Mount, S M and Lerner, E A and Hinterberger, M and Gottlieb, E} } @article {49711, title = {Splicing of messenger RNA precursors is inhibited by antisera to small nuclear ribonucleoprotein.}, journal = {Cell}, volume = {35}, year = {1983}, month = {1983 Nov}, pages = {101-7}, abstract = {

A mouse monoclonal antibody and human autoimmune sera directed against various classes of small ribonucleoprotein particles have been tested for inhibition of mRNA splicing in a soluble in vitro system. The splicing of the first and second leader exons of adenovirus late RNA was inhibited only by those sera that reacted with U1 RNP. Both U1 RNP-specific human autoimmune serum and sera directed against the Sm class of small nuclear RNPs, including a mouse monoclonal antibody, specifically inhibited splicing. Antisera specific for U2 RNP had no effect on splicing nor did antisera specific for the La or Ro class of small RNPs. These results suggest that U1 RNP is essential for the splicing of mRNA precursors.

}, keywords = {Adenoviruses, Human, Antigens, Autoantigens, Base Sequence, Cell Extracts, HeLa Cells, HUMANS, Immune Sera, Nucleic Acid Precursors, Ribonucleoproteins, Ribonucleoproteins, Small Nuclear, RNA, RNA Precursors, RNA Splicing, RNA, Messenger, RNA, Small Cytoplasmic, RNA, Viral, Transcription, Genetic}, issn = {0092-8674}, author = {Padgett, R A and Mount, S M and Steitz, J A and Sharp, P A} } @article {49714, title = {The U1 small nuclear RNA-protein complex selectively binds a 5{\textquoteright} splice site in vitro.}, journal = {Cell}, volume = {33}, year = {1983}, month = {1983 Jun}, pages = {509-18}, abstract = {

The ability of purified U1 small nuclear RNA-protein complexes (U1 snRNPs) to bind in vitro to two RNAs transcribed from recombinant DNA clones by bacteriophage T7 RNA polymerase has been studied. A transcript which contains sequences corresponding to the small intron and flanking exons of the major mouse beta-globin gene is bound in marked preference to an RNA devoid of splice site sequences. The site of U1 snRNP binding to the globin RNA has been defined by T1 ribonuclease digestion of the RNA-U1 snRNP complex. A 15-17-nucleotide region, including the 5{\textquoteright} splice site, remains undigested and complexed with the snRNP such that it can be co-precipitated by antibodies directed against the U1 snRNP. Partial proteinase K digestion of the U1 snRNP abolishes interaction with the globin RNA, indicating that the snRNP proteins contribute significantly to RNA binding. No RNA cleavage, splicing, or recognition of the 3{\textquoteright} splice site by U1 snRNPs has been detected. Our results are discussed in terms of the probable role of U1 snRNPs in the messenger RNA splicing of eucaryotic cell nuclei.

}, keywords = {Base Sequence, DNA-Directed RNA Polymerases, HUMANS, Nucleoproteins, Ribonuclease T1, Ribonucleoproteins, Ribonucleoproteins, Small Nuclear, RNA, RNA Splicing, T-Phages}, issn = {0092-8674}, author = {Mount, S M and Pettersson, I and Hinterberger, M and Karmas, A and Steitz, J A} } @article {49717, title = {A catalogue of splice junction sequences.}, journal = {Nucleic Acids Res}, volume = {10}, year = {1982}, month = {1982 Jan 22}, pages = {459-72}, abstract = {

Splice junction sequences from a large number of nuclear and viral genes encoding protein have been collected. The sequence CAAG/GTAGAGT was found to be a consensus of 139 exon-intron boundaries (or donor sequences) and (TC)nNCTAG/G was found to be a consensus of 130 intron-exon boundaries (or acceptor sequences). The possible role of splice junction sequences as signals for processing is discussed.

}, keywords = {Animals, Base Sequence, genes, Genes, Viral, HUMANS, Repetitive Sequences, Nucleic Acid, RNA Splicing, Species Specificity}, issn = {0305-1048}, author = {Mount, S M} } @article {49718, title = {Structure and function of small ribonucleoproteins from eukaryotic cells.}, journal = {Princess Takamatsu Symp}, volume = {12}, year = {1982}, month = {1982}, pages = {101-7}, abstract = {

Autoantibodies from patients with systemic lupus erythematosus and other related diseases have been used to identify and study small RNA-protein complexes from mammalian cells. Properties of three previously described and several new classes of small ribonucleoproteins (RNPs) are reviewed. The sequence of Drosophila U1 RNA reveals that the region proposed to pair with 5{\textquoteright} splice junctions is conserved, while that proposed to interact with 3{\textquoteright} junctions diverges; this forces some revision of the model for U1 small nuclear (sn)RNP participation in hnRNA splicing. Further characterization of the Ro and La small RNPs has shown that the Ro small cytoplasmic (sc)RNPs are a subclass of La RNPs. Both tRNA and 5S rRNA precursors are at least transiently associated with the La protein. This raises the possibility that the La protein may be an RNA polymerase III transcription factor.

}, keywords = {Antigen-Antibody Complex, Autoantibodies, HUMANS, Lupus Erythematosus, Systemic, Nucleoproteins, Ribonucleoproteins, RNA Polymerase III, Transcription, Genetic}, author = {Steitz, J A and Berg, C and Gottlieb, E and Hardin, J A and Hashimoto, C and Hendrick, J P and Hinterberger, M and Krikeles, M and Lerner, M R and Mount, S M} } @article {49719, title = {Sequence of U1 RNA from Drosophila melanogaster: implications for U1 secondary structure and possible involvement in splicing.}, journal = {Nucleic Acids Res}, volume = {9}, year = {1981}, month = {1981 Dec 11}, pages = {6351-68}, abstract = {

U1 RNA from cultured Drosophila melanogaster cells (Kc) was identified by its ability to be recognized, as an RNP, by anti-(U1)RNP antibodies from human lupus patients. Its sequence was deduced largely from direct analysis of the RNA molecule and then confirmed by DNA sequence determinations on a genomic clone isolated by hybridization to Drosophila U1 RNA. The Drosophila U1 RNA sequence exhibits 72\% agreement with human U1 RNA. Nucleotides 3-11, which are complementary to the entire consensus sequence for donor (5{\textquoteright}) splice junctions in hnRNA, and to part of the acceptor (3{\textquoteright}) consensus, are exactly conserved. However, nucleotides 14-21, postulated to interact only with acceptor junctions, differ. Comparison of the Drosophila U1 sequence with vertebrate U1 sequences allows a particular secondary structure model to be preferred over others. These results are consistent with the hypothesis that U1 snRNPs are involved in splicing, but suggest specific modifications of the model detailing molecular interactions between U1 RNA and hnRNA during the splicing reaction.

}, keywords = {Animals, Antibodies, Autoimmune Diseases, Base Sequence, Cells, Cultured, Cloning, Molecular, Drosophila melanogaster, HUMANS, Lupus Erythematosus, Systemic, Nucleic Acid Conformation, Nucleic Acid Hybridization, Ribonuclease T1, Ribonucleoproteins, RNA, RNA, Small Nuclear}, issn = {0305-1048}, author = {Mount, S M and Steitz, J A} } @article {49720, title = {Transcription of cloned tRNA and 5S RNA genes in a Drosophila cell free extract.}, journal = {Nucleic Acids Res}, volume = {9}, year = {1981}, month = {1981 Aug 25}, pages = {3907-18}, abstract = {

We describe the preparation of a cell-free extract from Drosophila Kc cells which allows transcription of a variety of cloned eukaryotic RNA polymerase III genes. The extract has low RNA-processing nuclease activity and thus the major products obtained are primary transcripts.

}, keywords = {Animals, Cell-Free System, Cloning, Molecular, Drosophila, In Vitro Techniques, RNA, RNA Polymerase III, RNA, Transfer, Transcription, Genetic, Xenopus laevis}, issn = {0305-1048}, author = {Dingermann, T and Sharp, S and Appel, B and DeFranco, D and Mount, S and Heiermann, R and Pongs, O and S{\"o}ll, D} } @article {49721, title = {Are snRNPs involved in splicing?}, journal = {Nature}, volume = {283}, year = {1980}, month = {1980 Jan 10}, pages = {220-4}, keywords = {Animals, Base Sequence, Cell Line, Chickens, Erythrocytes, HUMANS, Liver, Lupus Erythematosus, Systemic, Molecular Weight, Nucleic Acid Precursors, Nucleoproteins, Ribonucleoproteins, RNA, Heterogeneous Nuclear, Species Specificity}, issn = {0028-0836}, author = {Lerner, M R and Boyle, J A and Mount, S M and Wolin, S L and Steitz, J A} }