@article {49773, title = {Capturing the most wanted taxa through cross-sample correlations}, journal = {The ISME Journal}, year = {2016}, month = {Apr-03-2016}, issn = {1751-7362}, doi = {10.1038/ismej.2016.35}, url = {http://www.nature.com/doifinder/10.1038/ismej.2016.35}, author = {Almeida, Mathieu and Pop, Mihai and Le Chatelier, Emmanuelle and Prifti, Edi and Pons, Nicolas and Ghozlane, Amine and Ehrlich, S Dusko} } @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 {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 {49794, title = {Transcriptome Remodeling in Trypanosoma cruzi and Human Cells during Intracellular Infection.}, journal = {PLoS Pathog}, volume = {12}, year = {2016}, month = {2016 Apr}, pages = {e1005511}, abstract = {

Intracellular colonization and persistent infection by the kinetoplastid protozoan parasite, Trypanosoma cruzi, underlie the pathogenesis of human Chagas disease. To obtain global insights into the T. cruzi infective process, transcriptome dynamics were simultaneously captured in the parasite and host cells in an infection time course of human fibroblasts. Extensive remodeling of the T. cruzi transcriptome was observed during the early establishment of intracellular infection, coincident with a major developmental transition in the parasite. Contrasting this early response, few additional changes in steady state mRNA levels were detected once mature T. cruzi amastigotes were formed. Our findings suggest that transcriptome remodeling is required to establish a modified template to guide developmental transitions in the parasite, whereas homeostatic functions are regulated independently of transcriptomic changes, similar to that reported in related trypanosomatids. Despite complex mechanisms for regulation of phenotypic expression in T. cruzi, transcriptomic signatures derived from distinct developmental stages mirror known or projected characteristics of T. cruzi biology. Focusing on energy metabolism, we were able to validate predictions forecast in the mRNA expression profiles. We demonstrate measurable differences in the bioenergetic properties of the different mammalian-infective stages of T. cruzi and present additional findings that underscore the importance of mitochondrial electron transport in T. cruzi amastigote growth and survival. Consequences of T. cruzi colonization for the host include dynamic expression of immune response genes and cell cycle regulators with upregulation of host cholesterol and lipid synthesis pathways, which may serve to fuel intracellular T. cruzi growth. Thus, in addition to the biological inferences gained from gene ontology and functional enrichment analysis of differentially expressed genes in parasite and host, our comprehensive, high resolution transcriptomic dataset provides a substantially more detailed interpretation of T. cruzi infection biology and offers a basis for future drug and vaccine discovery efforts.

}, issn = {1553-7374}, doi = {10.1371/journal.ppat.1005511}, author = {Li, Yuan and Shah-Simpson, Sheena and Okrah, Kwame and Belew, A Trey and Choi, Jungmin and Caradonna, Kacey L and Padmanabhan, Prasad and Ndegwa, David M and Temanni, M Ramzi and Corrada Bravo, Hector and El-Sayed, Najib M and Burleigh, Barbara A} } @article {49658, title = {Diversion of aspartate in ASS1-deficient tumours fosters de novo pyrimidine synthesis}, journal = {Nature}, volume = {527}, year = {2015}, month = {Nov-11-2015}, pages = {379 - 383}, issn = {0028-0836}, doi = {10.1038/nature15529}, url = {http://www.nature.com/doifinder/10.1038/nature15529}, author = {Rabinovich, Shiran and Adler, Lital and Yizhak, Keren and Sarver, Alona and Silberman, Alon and Agron, Shani and Stettner, Noa and Sun, Qin and Brandis, Alexander and Helbling, Daniel and Korman, Stanley and Itzkovitz, Shalev and Dimmock, David and Ulitsky, Igor and Nagamani, Sandesh C. S. and Ruppin, Eytan and Erez, Ayelet} } @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 {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 {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 {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 {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 {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 {49585, title = {Glycan Degradation (GlyDeR) Analysis Predicts Mammalian Gut Microbiota Abundance and Host Diet-Specific Adaptations}, volume = {5}, year = {2014}, month = {May-08-2016}, pages = {e01526-14 - e01526-14}, doi = {10.1128/mBio.01526-14}, url = {http://mbio.asm.org/cgi/doi/10.1128/mBio.01526-14}, author = {Eilam, O. and Zarecki, R. and Oberhardt, M. and Ursell, L. K. and Kupiec, M. and Knight, R. and Gophna, U. and Ruppin, E.} } @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} } @article {49535, title = {Genomic analysis of sequence-dependent DNA curvature in Leishmania.}, volume = {8}, year = {2013}, month = {2013}, pages = {e63068}, abstract = {

Leishmania major is a flagellated protozoan parasite of medical importance. Like other members of the Trypanosomatidae family, it possesses unique mechanisms of gene expression such as constitutive polycistronic transcription of directional gene clusters, gene amplification, mRNA trans-splicing, and extensive editing of mitochondrial transcripts. The molecular signals underlying most of these processes remain under investigation. In order to investigate the role of DNA secondary structure signals in gene expression, we carried out a genome-wide in silico analysis of the intrinsic DNA curvature. The L. major genome revealed a lower frequency of high intrinsic curvature regions as well as inter- and intra- chromosomal distribution heterogeneity, when compared to prokaryotic and eukaryotic organisms. Using a novel method aimed at detecting region-integrated intrinsic curvature (RIIC), high DNA curvature was found to be associated with regions implicated in transcription initiation. Those include divergent strand-switch regions between directional gene clusters and regions linked to markers of active transcription initiation such as acetylated H3 histone, TRF4 and SNAP50. These findings suggest a role for DNA curvature in transcription initiation in Leishmania supporting the relevance of DNA secondary structures signals.

}, keywords = {Chromosome mapping, Comparative Genomic Hybridization, Computational Biology, DNA, Protozoan, Genome, Protozoan, Genomics, HUMANS, Leishmania, Nucleic Acid Conformation}, issn = {1932-6203}, doi = {10.1371/journal.pone.0063068}, author = {Smircich, Pablo and Forteza, Diego and El-Sayed, Najib M and Garat, Beatriz} } @article {49653, title = {Functional genomics of trypanosomatids.}, journal = {Parasite Immunol}, volume = {34}, year = {2012}, month = {2012 Feb-Mar}, pages = {72-9}, abstract = {

The decoding of the Tritryp reference genomes nearly 7 years ago provided a first peek into the biology of pathogenic trypanosomatids and a blueprint that has paved the way for genome-wide studies. Although 60-70\% of the predicted protein coding genes in Trypanosoma brucei, Trypanosoma cruzi and Leishmania major remain unannotated, the functional genomics landscape is rapidly changing. Facilitated by the advent of next-generation sequencing technologies, improved structural and functional annotation and genes and their products are emerging. Information is also growing for the interactions between cellular components as transcriptomes, regulatory networks and metabolomes are characterized, ushering in a new era of systems biology. Simultaneously, the launch of comparative sequencing of multiple strains of kinetoplastids will finally lead to the investigation of a vast, yet to be explored, evolutionary and pathogenomic space.

}, keywords = {Animals, Genome, Protozoan, Genomics, HUMANS, Proteome, Protozoan Proteins, Transcriptome, Trypanosomatina}, issn = {1365-3024}, doi = {10.1111/j.1365-3024.2011.01347.x}, author = {Choi, J and El-Sayed, N M} } @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 {38471, title = {Role of Shrimp Chitin in the Ecology of Toxigenic Vibrio cholerae and Cholera Transmission}, journal = {Frontiers in MicrobiologyFront MicrobiolFrontiers in MicrobiologyFront Microbiol}, volume = {2}, year = {2012}, type = {10.3389/fmicb.2011.00260}, abstract = {Seasonal plankton blooms correlate with occurrence of cholera in Bangladesh, although the mechanism of how dormant Vibrio cholerae, enduring interepidemic period in biofilms and plankton, initiates seasonal cholera is not fully understood. In this study, laboratory microcosms prepared with estuarine Mathbaria water (MW) samples supported active growth of toxigenic V. cholerae O1 up to 7 weeks as opposed to 6 months when microcosms were supplemented with dehydrated shrimp chitin chips (CC) as the single source of nutrient. Bacterial counting and detection of wbe and ctxA genes were done employing culture, direct fluorescent antibody (DFA) assay, and multiplex-polymerase chain reaction methods. In MW microcosm, the aqueous phase became clear as the non-culturable cells settled, whereas the aqueous phase of the MW{\textendash}CC microcosm became turbid from bacterial growth stimulated by chitin. Bacterial chitin degradation and biofilm formation proceeded from an initial steady state to a gradually declining bacterial culturable count. V. cholerae within the microenvironments of chitin and chitin-associated biofilms remained metabolically active even in a high acidic environment without losing either viability or virulence. It is concluded that the abundance of chitin that occurs during blooms plays an important role in the aquatic life cycle of V. cholerae and, ultimately, in the seasonal transmission of cholera.}, isbn = {1664-302X}, author = {Nahar, Shamsun and Sultana, Marzia and Naser, M. Niamul and Nair, Gopinath B. and Watanabe, Haruo and Ohnishi, Makoto and Yamamoto, Shouji and Endtz, Hubert and Cravioto, Alejandro and Sack, R. Bradley and Hasan, Nur A. and Sadique, Abdus and Huq, Anwar and Rita R. Colwell and Alam, Munirul} } @article {38516, title = {Structure, function and diversity of the healthy human microbiome}, journal = {NatureNature}, volume = {486}, year = {2012}, author = {Huttenhower, C. and Gevers, D. and Knight, R. and Abubucker, S. and Badger, J. H. and Chinwalla, A. T. and Creasy, H. H. and Earl, A. M. and Fitzgerald, M. G. and Fulton, R. S. and others,} } @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 {49652, title = {The genome and its implications.}, journal = {Adv Parasitol}, volume = {75}, year = {2011}, month = {2011}, pages = {209-30}, abstract = {

Trypanosoma cruzi has a heterogeneous population composed of a pool of strains that circulate in the domestic and sylvatic cycles. Genome sequencing of the clone CL Brener revealed a highly repetitive genome of about 110Mb containing an estimated 22,570 genes. Because of its hybrid nature, sequences representing the two haplotypes have been generated. In addition, a repeat content close to 50\% made the assembly of the estimated 41 pairs of chromosomes quite challenging. Similar to other trypanosomatids, the organization of T. cruzi chromosomes was found to be very peculiar, with protein-coding genes organized in long polycistronic transcription units encoding 20 or more proteins in one strand separated by strand switch regions. Another remarkable feature of the T. cruzi genome is the massive expansion of surface protein gene families. Because of the high genetic diversity of the T. cruzi population, sequencing of additional strains and comparative genomic and transcriptome analyses are in progress. Five years after its publication, the genome data have proven to be an essential tool for the study of T. cruzi and increasing efforts to translate this knowledge into the development of new modes of intervention to control Chagas disease are underway.

}, keywords = {Animals, Antigens, Protozoan, Chagas Disease, Chromosomes, Comparative Genomic Hybridization, DNA, Protozoan, Gene Expression Regulation, Genetic Variation, Genome, Protozoan, Host-Parasite Interactions, HUMANS, Species Specificity, Synteny, Transcription, Genetic, Transfection, Trypanosoma cruzi}, issn = {0065-308X}, doi = {10.1016/B978-0-12-385863-4.00010-1}, author = {Teixeira, Santuza M and El-Sayed, Najib M and Ara{\'u}jo, Patr{\'\i}cia R} } @article {49651, title = {Identification of Schistosoma mansoni microRNAs.}, journal = {BMC Genomics}, volume = {12}, year = {2011}, month = {2011}, pages = {47}, abstract = {

BACKGROUND: MicroRNAs (miRNAs) constitute a class of single-stranded RNAs which play a crucial role in regulating development and controlling gene expression by targeting mRNAs and triggering either translation repression or messenger RNA (mRNA) degradation. miRNAs are widespread in eukaryotes and to date over 14,000 miRNAs have been identified by computational and experimental approaches. Several miRNAs are highly conserved across species. In Schistosoma, the full set of miRNAs and their expression patterns during development remain poorly understood. Here we report on the development and implementation of a homology-based detection strategy to search for miRNA genes in Schistosoma mansoni. In addition, we report results on the experimental detection of miRNAs by means of cDNA cloning and sequencing of size-fractionated RNA samples.

RESULTS: Homology search using the high-throughput pipeline was performed with all known miRNAs in miRBase. A total of 6,211 mature miRNAs were used as reference sequences and 110 unique S. mansoni sequences were returned by BLASTn analysis. The existing mature miRNAs that produced these hits are reported, as well as the locations of the homologous sequences in the S. mansoni genome. All BLAST hits aligned with at least 95\% of the miRNA sequence, resulting in alignment lengths of 19-24 nt. Following several filtering steps, 15 potential miRNA candidates were identified using this approach. By sequencing small RNA cDNA libraries from adult worm pairs, we identified 211 novel miRNA candidates in the S. mansoni genome. Northern blot analysis was used to detect the expression of the 30 most frequent sequenced miRNAs and to compare the expression level of these miRNAs between the lung stage schistosomula and adult worm stages. Expression of 11 novel miRNAs was confirmed by northern blot analysis and some presented a stage-regulated expression pattern. Three miRNAs previously identified from S. japonicum were also present in S. mansoni.

CONCLUSION: Evidence for the presence of miRNAs in S. mansoni is presented. The number of miRNAs detected by homology-based computational methods in S. mansoni is limited due to the lack of close relatives in the miRNA repository. In spite of this, the computational approach described here can likely be applied to the identification of pre-miRNA hairpins in other organisms. Construction and analysis of a small RNA library led to the experimental identification of 14 novel miRNAs from S. mansoni through a combination of molecular cloning, DNA sequencing and expression studies. Our results significantly expand the set of known miRNAs in multicellular parasites and provide a basis for understanding the structural and functional evolution of miRNAs in these metazoan parasites.

}, keywords = {Animals, Computational Biology, Genome, Helminth, MicroRNAs, Schistosoma mansoni}, issn = {1471-2164}, doi = {10.1186/1471-2164-12-47}, author = {Sim{\~o}es, Mariana C and Lee, Jonathan and Djikeng, Appolinaire and Cerqueira, Gustavo C and Zerlotini, Adhemar and da Silva-Pereira, Rosiane A and Dalby, Andrew R and LoVerde, Philip and El-Sayed, Najib M and Oliveira, Guilherme} } @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 {38540, title = {Transcriptional Regulation Via TF-Modifying Enzymes: An Integrative Model-Based Analysis}, journal = {Nucleic Acids ResearchNucl. Acids Res.Nucleic Acids ResearchNucl. Acids Res.}, volume = {39}, year = {2011}, type = {10.1093/nar/gkr172}, abstract = {Transcription factor activity is largely regulated through post-translational modification. Here, we report the first integrative model of transcription that includes both interactions between transcription factors and promoters, and between transcription factors and modifying enzymes. Simulations indicate that our method is robust against noise. We validated our tool on a well-studied stress response network in yeast and on a STAT1-mediated regulatory network in human B cells. Our work represents a significant step toward a comprehensive model of gene transcription.}, isbn = {0305-1048, 1362-4962}, author = {Everett, Logan J. and Jensen, Shane T. and Sridhar Hannenhalli} } @article {49648, title = {The Alveolate Perkinsus marinus: biological insights from EST gene discovery.}, journal = {BMC Genomics}, volume = {11}, year = {2010}, month = {2010}, pages = {228}, abstract = {

BACKGROUND: Perkinsus marinus, a protozoan parasite of the eastern oyster Crassostrea virginica, has devastated natural and farmed oyster populations along the Atlantic and Gulf coasts of the United States. It is classified as a member of the Perkinsozoa, a recently established phylum considered close to the ancestor of ciliates, dinoflagellates, and apicomplexans, and a key taxon for understanding unique adaptations (e.g. parasitism) within the Alveolata. Despite intense parasite pressure, no disease-resistant oysters have been identified and no effective therapies have been developed to date.

RESULTS: To gain insight into the biological basis of the parasite{\textquoteright}s virulence and pathogenesis mechanisms, and to identify genes encoding potential targets for intervention, we generated>31,000 5{\textquoteright} expressed sequence tags (ESTs) derived from four trophozoite libraries generated from two P. marinus strains. Trimming and clustering of the sequence tags yielded 7,863 unique sequences, some of which carry a spliced leader. Similarity searches revealed that 55\% of these had hits in protein sequence databases, of which 1,729 had their best hit with proteins from the chromalveolates (E-value

CONCLUSIONS: Our transcriptome analysis of P. marinus, the first for any member of the Perkinsozoa, contributes new insight into its biology and taxonomic position. It provides a very informative, albeit preliminary, glimpse into the expression of genes encoding functionally relevant proteins as potential targets for chemotherapy, and evidence for the presence of a relict plastid. Further, although P. marinus sequences display significant similarity to those from both apicomplexans and dinoflagellates, the presence of trans-spliced transcripts confirms the previously established affinities with the latter. The EST analysis reported herein, together with the recently completed sequence of the P. marinus genome and the development of transfection methodology, should result in improved intervention strategies against dermo disease.

}, keywords = {Alveolata, Animals, Expressed Sequence Tags, Ostreidae, Phylogeny}, issn = {1471-2164}, doi = {10.1186/1471-2164-11-228}, author = {Joseph, Sandeep J and Fern{\'a}ndez-Robledo, Jos{\'e} A and Gardner, Malcolm J and El-Sayed, Najib M and Kuo, Chih-Horng and Schott, Eric J and Wang, Haiming and Kissinger, Jessica C and Vasta, Gerardo R} } @inbook {49666, title = {Genetics of Trypanosoma cruzi in American Trypanosomiasis: Chagas Disease One hundred Years of Research }, year = {2010}, publisher = {Elsevier Press}, organization = {Elsevier Press}, address = {Burlington}, author = {Bartholomeu, D. and Buck, G. and Teixeira, S. and El-Sayed, N.M.} } @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 {38331, title = {Hopx and Hdac2 Interact to Modulate Gata4 Acetylation and Embryonic Cardiac Myocyte Proliferation}, journal = {Developmental CellDevelopmental Cell}, volume = {19}, year = {2010}, type = {10.1016/j.devcel.2010.08.012}, abstract = {SummaryRegulation of chromatin structure via histone modification has recently received intense attention. Here,~we demonstrate that the chromatin-modifying enzyme histone deacetylase 2 (Hdac2) functions with a small homeodomain factor, Hopx, to mediate deacetylation of Gata4, which is expressed by cardiac progenitor cells and plays critical roles in the regulation of cardiogenesis. In the absence of Hopx and Hdac2 in mouse embryos, Gata4 hyperacetylation is associated with a marked increase in~cardiac myocyte proliferation, upregulation of Gata4 target genes, and perinatal lethality. Hdac2 physically interacts with Gata4, and this interaction is stabilized by Hopx. The ability of Gata4 to transactivate cell cycle genes is impaired by Hopx/Hdac2-mediated deacetylation, and this effect is abrogated by loss of Hdac2-Gata4 interaction. These results suggest that Gata4 is a nonhistone target of Hdac2-mediated deacetylation and that Hdac2, Hopx, and Gata4 coordinately regulate cardiac myocyte proliferation during embryonic development.}, isbn = {1534-5807}, author = {Trivedi, Chinmay M. and Zhu, Wenting and Wang, Qiaohong and Jia, Cheng and Kee, Hae Jin and Li, Li and Sridhar Hannenhalli and Epstein, Jonathan A.} } @article {38381, title = {Mimosa: Mixture model of co-expression to detect modulators of regulatory interaction}, journal = {Algorithms for Molecular BiologyAlgorithms for Molecular Biology}, volume = {5}, year = {2010}, type = {10.1186/1748-7188-5-4}, abstract = {Functionally related genes tend to be correlated in their expression patterns across multiple conditions and/or tissue-types. Thus co-expression networks are often used to investigate functional groups of genes. In particular, when one of the genes is a transcription factor (TF), the co-expression-based interaction is interpreted, with caution, as a direct regulatory interaction. However, any particular TF, and more importantly, any particular regulatory interaction, is likely to be active only in a subset of experimental conditions. Moreover, the subset of expression samples where the regulatory interaction holds may be marked by presence or absence of a modifier gene, such as an enzyme that post-translationally modifies the TF. Such subtlety of regulatory interactions is overlooked when one computes an overall expression correlation.}, isbn = {1748-7188}, author = {Hansen, Matthew and Everett, Logan and Singh, Larry and Sridhar Hannenhalli} } @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 {38459, title = {Regulating the regulators: modulators of transcription factor activity}, journal = {Methods Mol. BiolMethods Mol. Biol}, volume = {674}, year = {2010}, publisher = {Springer}, author = {Everett, L. and Hansen, M. and Sridhar Hannenhalli} } @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 {38190, title = {CTCF binding site classes exhibit distinct evolutionary, genomic, epigenomic and transcriptomic features}, journal = {Genome BiologyGenome Biology}, volume = {10}, year = {2009}, type = {10.1186/gb-2009-10-11-r131}, abstract = {CTCF (CCCTC-binding factor) is an evolutionarily conserved zinc finger protein involved in diverse functions ranging from negative regulation of MYC, to chromatin insulation of the beta-globin gene cluster, to imprinting of the Igf2 locus. The 11 zinc fingers of CTCF are known to differentially contribute to the CTCF-DNA interaction at different binding sites. It is possible that the differences in CTCF-DNA conformation at different binding sites underlie CTCF{\textquoteright}s functional diversity. If so, the CTCF binding sites may belong to distinct classes, each compatible with a specific functional role.}, isbn = {1465-6906}, author = {Essien, Kobby and Vigneau, Sebastien and Apreleva, Sofia and Singh, Larry N. and Bartolomei, Marisa S. and Sridhar Hannenhalli} } @article {49836, title = {Estimating Tree-Structured Covariance Matrices via Mixed-Integer Programming}, journal = {J Mach Learn Res}, volume = {5}, year = {2009}, pages = {41-48}, chapter = {41}, author = {Corrada Bravo, Hector and Wright, Stephen and Eng, Kevin H. and Keles, S{\"u}nd{\"u}z and Wahba, Grace} } @article {38256, title = {Extreme polymorphism in a vaccine antigen and risk of clinical malaria: implications for vaccine development}, journal = {Sci Transl MedSci Transl Med}, volume = {1}, year = {2009}, type = {10.1126/scitranslmed.3000257}, abstract = {Vaccines directed against the blood stages of Plasmodium falciparum malaria are intended to prevent the parasite from invading and replicating within host cells. No blood-stage malaria vaccine has shown clinical efficacy in humans. Most malaria vaccine antigens are parasite surface proteins that have evolved extensive genetic diversity, and this diversity could allow malaria parasites to escape vaccine-induced immunity. We examined the extent and within-host dynamics of genetic diversity in the blood-stage malaria vaccine antigen apical membrane antigen-1 in a longitudinal study in Mali. Two hundred and fourteen unique apical membrane antigen-1 haplotypes were identified among 506 human infections, and amino acid changes near a putative invasion machinery binding site were strongly associated with the development of clinical symptoms, suggesting that these residues may be important to consider in designing polyvalent apical membrane antigen-1 vaccines and in assessing vaccine efficacy in field trials. This extreme diversity may pose a serious obstacle to an effective polyvalent recombinant subunit apical membrane antigen-1 vaccine.}, author = {Takala, S. L. and Coulibaly, D. and Thera, M. A. and Batchelor, A. H. and Michael P. Cummings and Escalante, A. A. and Ouattara, A. and Traor{\'e}, K. and Niangaly, A. and Djimd{\'e}, A. A. and Doumbo, O. K. and Plowe, C. V.} } @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 {38380, title = {Mimosa: mixture model of co-expression to detect modulators of regulatory interaction}, journal = {Algorithms in BioinformaticsAlgorithms in Bioinformatics}, year = {2009}, publisher = {Springer Berlin/Heidelberg}, author = {Hansen, M. and Everett, L. and Singh, L. and Sridhar Hannenhalli} } @article {38432, title = {A phylogenetic mixture model for the evolution of gene expression}, journal = {Molecular biology and evolutionMolecular biology and evolution}, volume = {26}, year = {2009}, author = {Eng, K. H. and H{\'e}ctor Corrada Bravo and Keles, S.} } @article {38453, title = {PTM-Switchboard{\textemdash}a database of posttranslational modifications of transcription factors, the mediating enzymes and target genes}, journal = {Nucleic acids researchNucleic Acids Research}, volume = {37}, year = {2009}, publisher = {Oxford Univ Press}, author = {Everett, L. and Vo, A. and Sridhar Hannenhalli} } @inbook {38475, title = {Salient Frame Detection for Molecular Dynamics Simulations}, booktitle = {Scientific VisualizationScientific Visualization}, year = {2009}, publisher = {Dagstuhl Seminar Proceedings 09251}, organization = {Dagstuhl Seminar Proceedings 09251}, author = {Kim, Youngmin and Patro, Robert and Ip, Cheuk Yiu and O{\textquoteright}Leary, Dianne P. and Anishkin, Andriy and Sukharev, Sergei and Varshney, Amitabh}, editor = {Ebert, D. S. and Gr, and x6f, and x, and ller, E. and Hagen, H. and Kaufman, A.} } @article {38498, title = {Serogroup, Virulence, and Genetic Traits of Vibrio Parahaemolyticus in the Estuarine Ecosystem of Bangladesh}, journal = {Applied and Environmental MicrobiologyAppl. Environ. Microbiol.Applied and Environmental MicrobiologyAppl. Environ. Microbiol.}, volume = {75}, year = {2009}, type = {10.1128/AEM.00266-09}, abstract = {Forty-two strains of Vibrio parahaemolyticus were isolated from Bay of Bengal estuaries and, with two clinical strains, analyzed for virulence, phenotypic, and molecular traits. Serological analysis indicated O8, O3, O1, and K21 to be the major O and K serogroups, respectively, and O8:K21, O1:KUT, and O3:KUT to be predominant. The K antigen(s) was untypeable, and pandemic serogroup O3:K6 was not detected. The presence of genes toxR and tlh were confirmed by PCR in all but two strains, which also lacked toxR. A total of 18 (41\%) strains possessed the virulence gene encoding thermostable direct hemolysin (TDH), and one had the TDH-related hemolysin (trh) gene, but not tdh. Ten (23\%) strains exhibited Kanagawa phenomenon that surrogates virulence, of which six, including the two clinical strains, possessed tdh. Of the 18 tdh-positive strains, 17 (94\%), including the two clinical strains, had the seromarker O8:K21, one was O9:KUT, and the single trh-positive strain was O1:KUT. None had the group-specific or ORF8 pandemic marker gene. DNA fingerprinting employing pulsed-field gel electrophoresis (PFGE) of SfiI-digested DNA and cluster analysis showed divergence among the strains. Dendrograms constructed using PFGE (SfiI) images from a soft database, including those of pandemic and nonpandemic strains of diverse geographic origin, however, showed that local strains formed a cluster, i.e., {\textquotedblleft}clonal cluster,{\textquotedblright} as did pandemic strains of diverse origin. The demonstrated prevalence of tdh-positive and diarrheagenic serogroup O8:K21 strains in coastal villages of Bangladesh indicates a significant human health risk for inhabitants.}, isbn = {0099-2240, 1098-5336}, author = {Alam, Munirul and Chowdhury, Wasimul B. and Bhuiyan, N. A. and Islam, Atiqul and Hasan, Nur A. and Nair, G. Balakrish and Watanabe, H. and Siddique, A. K. and Huq, Anwar and Sack, R. Bradley and Akhter, M. Z. and Grim, Christopher J. and Kam, K. M. and Luey, C. K. Y. and Endtz, Hubert P. and Cravioto, Alejandro and Rita R. Colwell} } @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 {38170, title = {Computational Analysis of Constraints on Noncoding Regions, Coding Regions and Gene Expression in Relation to Plasmodium Phenotypic Diversity}, journal = {PLoS ONEPLoS ONEPLoS ONEPLoS ONE}, volume = {3}, year = {2008}, type = {10.1371/journal.pone.0003122}, abstract = {Malaria-causing Plasmodium species exhibit marked differences including host choice and preference for invading particular cell types. The genetic bases of phenotypic differences between parasites can be understood, in part, by investigating constraints on gene expression and genic sequences, both coding and regulatory.We investigated the evolutionary constraints on sequence and expression of parasitic genes by applying comparative genomics approaches to 6 Plasmodium genomes and 2 genome-wide expression studies. We found that the coding regions of Plasmodium transcription factor and sexual development genes are relatively less constrained, as are those of genes encoding CCCH zinc fingers and invasion proteins, which all play important roles in these parasites. Transcription factors and genes with stage-restricted expression have conserved upstream regions and so do several gene classes critical to the parasite{\textquoteright}s lifestyle, namely, ion transport, invasion, chromatin assembly and CCCH zinc fingers. Additionally, a cross-species comparison of expression patterns revealed that Plasmodium-specific genes exhibit significant expression divergence. Overall, constraints on Plasmodium{\textquoteright}s protein coding regions confirm observations from other eukaryotes in that transcription factors are under relatively lower constraint. Proteins relevant to the parasite{\textquoteright}s unique lifestyle also have lower constraint on their coding regions. Greater conservation between Plasmodium species in terms of promoter motifs suggests tight regulatory control of lifestyle genes. However, an interspecies divergence in expression patterns of these genes suggests that either expression is controlled via genomic or epigenomic features not encoded in the proximal promoter sequence, or alternatively, the combinatorial interactions between motifs confer species-specific expression patterns.}, author = {Essien, Kobby and Sridhar Hannenhalli and Stoeckert, Christian J.} } @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 {38236, title = {Estimating Tree-Structured Covariance Matrices via Mixed-Integer Programming with an Application to Phylogenetic Analysis of Gene Expression}, volume = {1142}, year = {2008}, institution = {Department of Statistics, University of Wisconsin}, abstract = {We present a novel method for estimating tree-structured covariance matrices directly fromobserved continuous data. A representation of these classes of matrices as linear combinations of rank-one matrices indicating object partitions is used to formulate estimation as instances of well-studied numerical optimization problems. In particular, we present estimation based on projection where the covariance estimate is the nearest tree-structured covariance matrix to an observed sample covariance matrix. The problem is posed as a linear or quadratic mixed-integer program (MIP) where a setting of the integer variables in the MIP specifies a set of tree topologies of the structured covariance matrix. We solve these problems to optimality using efficient and robust existing MIP solvers. We also show that the least squares distance method of Fitch and Margoliash (1967) can be formulated as a quadratic MIP and thus solved exactly using existing, robust branch-and-bound MIP solvers. Our motivation for this method is the discovery of phylogenetic structure directly from gene expression data. Recent studies have adapted traditional phylogenetic comparative anal- ysis methods to expression data. Typically, these methods first estimate a phylogenetic tree from genomic sequence data and subsequently analyze expression data. A covariance matrix constructed from the sequence-derived tree is used to correct for the lack of independence in phy- logenetically related taxa. However, recent results have shown that the hierarchical structure of sequence-derived tree estimates are highly sensitive to the genomic region chosen to build them. To circumvent this difficulty, we propose a stable method for deriving tree-structured covariance matrices directly from gene expression as an exploratory step that can guide investigators in their modelling choices for these types of comparative analysis. We present a case study in phylogenetic analysis of expression in yeast gene families. Our method is able to corroborate the presence of phylogenetic structure in the response of expression in a subset of the gene families under particular experimental conditions. Additionally, when used in conjunction with transcription factor occupancy data, our methods show that alternative modelling choices should be considered when creating sequence-derived trees for this comparative analysis.}, author = {H{\'e}ctor Corrada Bravo and Eng, K. H. and Keles, S. and Wahba, G. and Wright, 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 {38472, title = {Role of transposable elements in trypanosomatids}, journal = {Microbes and InfectionMicrobes and Infection}, volume = {10}, year = {2008}, type = {16/j.micinf.2008.02.009}, abstract = {Transposable elements constitute 2-5\% of the genome content in trypanosomatid parasites. Some of them are involved in critical cellular functions, such as the regulation of gene expression in Leishmania spp. In this review, we highlight the remarkable role extinct transposable elements can play as the source of potential new functions.}, keywords = {Cellular function, Domestication, Evolution, Gene expression, Leishmania, Regulation of mRNA stability, Retroposon, Transposable element, Trypanosoma}, isbn = {1286-4579}, author = {Bringaud, Frederic and Ghedin, Elodie and Najib M. El-Sayed and Papadopoulou, Barbara} } @article {49643, title = {Schistosoma mansoni: Microarray analysis of gene expression induced by host sex.}, journal = {Exp Parasitol}, volume = {120}, year = {2008}, month = {2008 Dec}, pages = {357-63}, abstract = {

Schistosoma mansoni is a digenetic trematode and a human parasite responsible for high social and economic impact. Although some authors have studied the effect of host hormones on parasites, not much is known about the effects of host sex on gene expression in Schistosomes. In order to study gene transcripts associated with the host sex, we compared the gene expression profiles of both male and female unisexual adult S. mansoni parasites raised on either male or female hosts, using DNA microarrays. Our results show that host sex caused differential expression of at least 11 genes in female parasites and of 134 in male parasites. Of the differentially expressed genes in female worms, 10 were preferentially expressed in female worms from male mice, while of the 134 differentially expressed genes in male parasites, 79 (59\%) were preferentially expressed in worms from female mice. Further investigation of the role of each of those genes will help understand better their importance in the pathogenesis of Schistosomiasis.

}, keywords = {Animals, Biomphalaria, Female, Gene expression, Host-Parasite Interactions, Male, Mice, Oligonucleotide Array Sequence Analysis, Reverse Transcriptase Polymerase Chain Reaction, RNA, Helminth, Schistosoma mansoni, Schistosomiasis mansoni, Sex Factors}, issn = {1090-2449}, doi = {10.1016/j.exppara.2008.09.005}, author = {Waisberg, M and Lobo, F P and Cerqueira, G C and Passos, L K J and Carvalho, O S and El-Sayed, N M and Franco, G R} } @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 {38152, title = {Cofactor-independent phosphoglycerate mutase is an essential gene in procyclic form Trypanosoma brucei}, journal = {Parasitology researchParasitology research}, volume = {100}, year = {2007}, author = {Djikeng, A. and Raverdy, S. and Foster, Jeffrey S. and Bartholomeu, D. and Zhang, Y. and Najib M. El-Sayed and Carlow, C.} } @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 {38254, title = {The Expression of a Plant-type Ferredoxin Redox System provides Molecular Evidence for a Plastid in the Early Dinoflagellate Perkinsus marinus}, journal = {ProtistProtist}, volume = {158}, year = {2007}, type = {16/j.protis.2006.09.003}, abstract = {Perkinsus marinus is a parasitic protozoan with a phylogenetic positioning between Apicomplexa and dinoflagellates. It is thus of interest for reconstructing the early evolution of eukaryotes, especially with regard to the acquisition of secondary plastids in these organisms. It is also an important pathogen of oysters, and the definition of parasite-specific metabolic pathways would be beneficial for the identification of efficient treatments for infected mollusks. Although these different scientific interests have resulted in the start of a genome project for this organism, it is still unknown whether P. marinus contains a plastid or plastid-like organelle like the related dinoflagellates and Apicomplexa. Here, we show that in vitro-cultivated parasites contain transcripts of the plant-type ferredoxin and its associated reductase. Both proteins are nuclear-encoded and possess N-terminal targeting sequences similar to those characterized in dinoflagellates. Since this redox pair is exclusively found in cyanobacteria and plastid-harboring organisms its presence also in P. marinus is highly indicative of a plastid. We also provide additional evidence for such an organelle by demonstrating pharmacological sensitivity to inhibitors of plastid-localized enzymes involved in fatty acid biosynthesis (e.g. acetyl-CoA carboxylase) and by detection of genes for three enzymes of plastid-localized isoprenoid biosynthesis (1-deoxy-D-xylulose 5-phosphate reductoisomerase, (E)-4-hydroxy-3-methyl-but-2-enyl diphosphate reductase, and (E)-4-hydroxy-3-methyl-but-2-enyl diphosphate synthase).}, keywords = {Apicomplexa, ferredoxin, Perkinsozoa, plastid, transit peptide}, isbn = {1434-4610}, author = {Stelter, Kathrin and Najib M. El-Sayed and Seeber, Frank} } @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} } @article {38377, title = {Microarray analysis of gene expression induced by sexual contact in Schistosoma mansoni}, journal = {BMC GenomicsBMC Genomics}, volume = {8}, year = {2007}, type = {10.1186/1471-2164-8-181}, abstract = {BACKGROUND:The parasitic trematode Schistosoma mansoni is one of the major causative agents of Schistosomiasis, a disease that affects approximately 200 million people, mostly in developing countries. Since much of the pathology is associated with eggs laid by the female worm, understanding the mechanisms involved in oogenesis and sexual maturation is an important step towards the discovery of new targets for effective drug therapy. It is known that the adult female worm only develops fully in the presence of a male worm and that the rates of oviposition and maturation of eggs are significantly increased by mating. In order to study gene transcripts associated with sexual maturation and oviposition, we compared the gene expression profiles of sexually mature and immature parasites using DNA microarrays.RESULTS:For each experiment, three amplified RNA microarray hybridizations and their dye swaps were analyzed. Our results show that 265 transcripts are differentially expressed in adult females and 53 in adult males when mature and immature worms are compared. Of the genes differentially expressed, 55\% are expressed at higher levels in paired females while the remaining 45\% are more expressed in unpaired ones and 56.6\% are expressed at higher levels in paired male worms while the remaining 43.4\% are more expressed in immature parasites. Real-time RT-PCR analysis validated the microarray results. Several new maturation associated transcripts were identified. Genes that were up-regulated in single-sex females were mostly related to energy generation (i.e. carbohydrate and protein metabolism, generation of precursor metabolites and energy, cellular catabolism, and organelle organization and biogenesis) while genes that were down-regulated related to RNA metabolism, reactive oxygen species metabolism, electron transport, organelle organization and biogenesis and protein biosynthesis.CONCLUSION:Our results confirm previous observations related to gene expression induced by sexual maturation in female schistosome worms. They also increase the list of S. mansoni maturation associated transcripts considerably, therefore opening new and exciting avenues for the study of the conjugal biology and development of new drugs against schistosomes.}, isbn = {1471-2164}, author = {Waisberg, Michael and Lobo, Francisco and Cerqueira, Gustavo and Passos, Liana and Carvalho, Omar and Franco, Gloria and Najib M. El-Sayed} } @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 {38481, title = {Schistosoma mansoni genome: Closing in on a final gene set}, journal = {Experimental ParasitologyExperimental Parasitology}, volume = {117}, year = {2007}, type = {16/j.exppara.2007.06.005}, abstract = {The Schistosoma mansoni genome sequencing consortium has recently released the latest versions of the genome assembly as well as an automated preliminary gene structure annotation. The combined datasets constitute a vast resource for researchers to exploit in a variety of post-genomic studies with an emphasis of transcriptomic and proteomic tools. Here we present an innovative method used for combining diverse sources of evidence including ab initio gene predictions, protein and transcript sequence homologies, and cross-genome sequence homologies between S. mansoni and Schistosoma japonicum to define a comprehensive list of protein-coding genes.}, keywords = {Annotation, Gene finding, Genome, Schistosoma mansoni}, isbn = {0014-4894}, author = {Haas, Brian J. and Berriman, Matthew and Hirai, Hirohisa and Cerqueira, Gustavo G. and LoVerde, Philip T. and Najib M. El-Sayed} } @article {49641, title = {Analysis of fat body transcriptome from the adult tsetse fly, Glossina morsitans morsitans.}, journal = {Insect Mol Biol}, volume = {15}, year = {2006}, month = {2006 Aug}, pages = {411-24}, abstract = {

Tsetse flies (Diptera: Glossinidia) are vectors of pathogenic African trypanosomes. To develop a foundation for tsetse physiology, a normalized expressed sequence tag (EST) library was constructed from fat body tissue of immune-stimulated Glossina morsitans morsitans. Analysis of 20,257 high-quality ESTs yielded 6372 unique genes comprised of 3059 tentative consensus (TC) sequences and 3313 singletons (available at http://aksoylab.yale.edu). We analysed the putative fat body transcriptome based on homology to other gene products with known functions available in the public domain. In particular, we describe the immune-related products, reproductive function related yolk proteins and milk-gland protein, iron metabolism regulating ferritins and transferrin, and tsetse{\textquoteright}s major energy source proline biosynthesis. Expression analysis of the three yolk proteins indicates that all are detected in females, while only the yolk protein with similarity to lipases, is expressed in males. Milk gland protein, apparently important for larval nutrition, however, is primarily synthesized by accessory milk gland tissue.

}, keywords = {Adipose Tissue, Animals, Base Sequence, Computational Biology, DNA Primers, Egg Proteins, Expressed Sequence Tags, Female, Gene Expression Profiling, Insect Vectors, Male, Molecular Sequence Data, Reverse Transcriptase Polymerase Chain Reaction, Sequence Analysis, DNA, Sex Factors, Tsetse Flies}, issn = {0962-1075}, doi = {10.1111/j.1365-2583.2006.00649.x}, author = {Attardo, G M and Strickler-Dinglasan, P and Perkin, S A H and Caler, E and Bonaldo, M F and Soares, M B and El-Sayeed, N and Aksoy, S} } @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}} } @inbook {38177, title = {Conservation Patterns in cis-Elements Reveal Compensatory Mutations}, booktitle = {Comparative GenomicsComparative Genomics}, series = {Lecture Notes in Computer Science}, volume = {4205}, year = {2006}, publisher = {Springer Berlin / Heidelberg}, organization = {Springer Berlin / Heidelberg}, abstract = {Transcriptional regulation critically depends on proper interactions between transcription factors (TF) and their cognate DNA binding sites or cis elements. A better understanding and modelling of the TF-DNA interaction is an important area of research. The Positional Weight Matrix (PWM) is the most common model of TF-DNA binding and it presumes that the nucleotide preferences at individual positions within the binding site are independent. However, studies have shown that this independence assumption does not always hold. If the nucleotide preference at one position depends on the nucleotide at another position, a chance mutation at one position should exert selection pressures at the other position. By comparing the patterns of evolutionary conservation at individual positions within cis elements, here we show that positional dependence within binding sites is highly prevalent. We also show that dependent positions are more likely to be functional, as evidenced by a higher information content and higher conservation. We discuss two examples{\textemdash}Elk-1 and SAP-1 where the inferred compensatory mutation is consistent with known TF-DNA crystal structure.}, isbn = {978-3-540-44529-6}, author = {Evans, Perry and Donahue, Greg and Sridhar Hannenhalli}, editor = {Bourque, Guillaume and El-Mabrouk, Nadia} } @article {38196, title = {Dense Subgraph Computation Via Stochastic Search: Application to Detect Transcriptional Modules}, journal = {BioinformaticsBioinformaticsBioinformaticsBioinformatics}, volume = {22}, year = {2006}, type = {10.1093/bioinformatics/btl260}, abstract = {Motivation: In a tri-partite biological network of transcription factors, their putative target genes, and the tissues in which the target genes are differentially expressed, a tightly inter-connected (dense) subgraph may reveal knowledge about tissue specific transcription regulation mediated by a specific set of transcription factors{\textemdash}a tissue-specific transcriptional module. This is just one context in which an efficient computation of dense subgraphs in a multi-partite graph is needed.Result: Here we report a generic stochastic search based method to compute dense subgraphs in a graph with an arbitrary number of partitions and an arbitrary connectivity among the partitions. We then use the tool to explore tissue-specific transcriptional regulation in the human genome. We validate our findings in Skeletal muscle based on literature. We could accurately deduce biological processes for transcription factors via the tri-partite clusters of transcription factors, genes, and the functional annotation of genes. Additionally, we propose a few previously unknown TF-pathway associations and tissue-specific roles for certain pathways. Finally, our combined analysis of Cardiac, Skeletal, and Smooth muscle data recapitulates the evolutionary relationship among the three tissues. Contact:sridharh@pcbi.upenn.edu}, isbn = {1367-4803, 1460-2059}, author = {Everett, Logan and Wang, Li-San and Sridhar Hannenhalli} } @article {38243, title = {Evolution of non-LTR retrotransposons in the trypanosomatid genomes: Leishmania major has lost the active elements}, journal = {Molecular and Biochemical ParasitologyMolecular and Biochemical Parasitology}, volume = {145}, year = {2006}, type = {16/j.molbiopara.2005.09.017}, abstract = {The ingi and L1Tc non-LTR retrotransposons - which constitute the ingi clade - are abundant in the genome of the trypanosomatid species Trypanosoma brucei and Trypanosoma cruzi, respectively. The corresponding retroelements, however, are not present in the genome of a closely related trypanosomatid, Leishmania major. To study the evolution of non-LTR retrotransposons in trypanosomatids, we have analyzed all ingi/L1Tc elements and highly degenerate ingi/L1Tc-related sequences identified in the recently completed T. brucei, T. cruzi and L. major genomes. The coding sequences of 242 degenerate ingi/L1Tc-related elements (DIREs) in all three genomes were reconstituted by removing the numerous frame shifts. Three independent phylogenetic analyses conducted on the conserved domains encoded by these elements show that all DIREs, including the 52 L. major DIREs, form a monophyletic group belonging to the ingi clade. This indicates that the trypanosomatid ancestor contained active mobile elements that have been retained in the Trypanosoma species, but were lost from L. major genome, where only remnants (DIRE) are detectable. All 242 DIREs analyzed group together according to their species origin with the exception of 11 T. cruzi DIREs which are close to the T. brucei ingi/DIRE families. Considering the absence of known horizontal transfer between the African T. brucei and the South-American T. cruzi, this suggests that this group of elements evolved at a lower rate when compared to the other trypanosomatid elements. Interestingly, the only nucleotide sequence conserved between ingi and L1Tc (the first 79 residues) is also present at the 5{\textquoteright}-extremity of all the full length DIREs and suggests a possible role for this conserved motif, as well as for DIREs.}, keywords = {Degenerate retroelement, Evolution, Ingi, L1Tc, Leishmania major, Non-LTR retrotransposon, Retroposon, Trypanosoma brucei, Trypanosoma cruzi}, isbn = {0166-6851}, author = {Bringaud, Frederic and Ghedin, Elodie and Blandin, Ga{\"e}lle and Bartholomeu, Daniella C. and Caler, Elisabet and Levin, Mariano J. and Baltz, Th{\'e}o and Najib M. El-Sayed} } @article {38371, title = {Metagenomic Analysis of the Human Distal Gut Microbiome}, journal = {ScienceScienceScienceScience}, volume = {312}, year = {2006}, type = {10.1126/science.1124234}, abstract = {The human intestinal microbiota is composed of 1013 to 1014 microorganisms whose collective genome ({\textquotedblleft}microbiome{\textquotedblright}) contains at least 100 times as many genes as our own genome. We analyzed \~{}78 million base pairs of unique DNA sequence and 2062 polymerase chain reaction{\textendash}amplified 16S ribosomal DNA sequences obtained from the fecal DNAs of two healthy adults. Using metabolic function analyses of identified genes, we compared our human genome with the average content of previously sequenced microbial genomes. Our microbiome has significantly enriched metabolism of glycans, amino acids, and xenobiotics; methanogenesis; and 2-methyl-d-erythritol 4-phosphate pathway{\textendash}mediated biosynthesis of vitamins and isoprenoids. Thus, humans are superorganisms whose metabolism represents an amalgamation of microbial and human attributes.}, isbn = {0036-8075, 1095-9203}, author = {Gill, Steven R. and M. Pop and DeBoy, Robert T. and Eckburg, Paul B. and Turnbaugh, Peter J. and Samuel, Buck S. and Gordon, Jeffrey I. and Relman, David A. and Fraser-Liggett, Claire M. and Nelson, Karen E.} } @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 {38479, title = {Schistosoma mansoni (Platyhelminthes, Trematoda) nuclear receptors: Sixteen new members and a novel subfamily}, journal = {GeneGene}, volume = {366}, year = {2006}, type = {16/j.gene.2005.09.013}, abstract = {Nuclear receptors (NRs) are important transcriptional modulators in metazoans. Sixteen new NRs were identified in the Platyhelminth trematode, Schistosoma mansoni. Three were found to possess novel tandem DNA-binding domains that identify a new subfamily of NR. Two NRs are homologues of the thyroid hormone receptor that previously were thought to be restricted to chordates. This study brings the total number of identified NR in S. mansoni to 21. Phylogenetic and comparative genomic analyses demonstrate that S. mansoni NRs share an evolutionary lineage with that of arthropods and vertebrates. Phylogenic analysis shows that more than half of the S. mansoni nuclear receptors evolved from a second gene duplication. As the second gene duplication of NRs was thought to be specific to vertebrates, our data challenge the current theory of NR evolution.}, keywords = {Nuclear receptors, Schistosoma mansoni}, isbn = {0378-1119}, author = {Wu, Wenjie and Niles, Edward G. and Najib M. El-Sayed and Berriman, Matthew and LoVerde, Philip T.} } @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 {38549, title = {The Trypanosoma cruzi L1Tc and NARTc non-LTR retrotransposons show relative site specificity for insertion}, journal = {Molecular biology and evolutionMolecular biology and evolution}, volume = {23}, year = {2006}, author = {Bringaud, F. and Bartholomeu, D. C. and Blandin, G. and Delcher, A. and Baltz, T. and Najib M. El-Sayed and Ghedin, E.} } @article {49639, title = {The Trypanosoma cruzi L1Tc and NARTc non-LTR retrotransposons show relative site specificity for insertion.}, journal = {Mol Biol Evol}, volume = {23}, year = {2006}, month = {2006 Feb}, pages = {411-20}, abstract = {

The trypanosomatid protozoan Trypanosoma cruzi contains long autonomous (L1Tc) and short nonautonomous (NARTc) non-long terminal repeat retrotransposons. NARTc (0.25 kb) probably derived from L1Tc (4.9 kb) by 3{\textquoteright}-deletion. It has been proposed that their apparent random distribution in the genome is related to the L1Tc-encoded apurinic/apyrimidinic endonuclease (APE) activity, which repairs modified residues. To address this question we used the T. cruzi (CL-Brener strain) genome data to analyze the distribution of all the L1Tc/NARTc elements present in contigs larger than 10 kb. This data set, which represents 0.91x sequence coverage of the haploid nuclear genome ( approximately 55 Mb), contains 419 elements, including 112 full-length L1Tc elements (14 of which are potentially functional) and 84 full-length NARTc. Approximately half of the full-length elements are flanked by a target site duplication, most of them (87\%) are 12 bp long. Statistical analyses of sequences flanking the full-length elements show the same highly conserved pattern upstream of both the L1Tc and NARTc retrotransposons. The two most conserved residues are a guanine and an adenine, which flank the site where first-strand cleavage is performed by the element-encoded endonuclease activity. This analysis clearly indicates that the L1Tc and NARTc elements display relative site specificity for insertion, which suggests that the APE activity is not responsible for first-strand cleavage of the target site.

}, keywords = {Animals, DNA, Protozoan, DNA-(Apurinic or Apyrimidinic Site) Lyase, Mutagenesis, Insertional, Retroelements, Sequence Deletion, Trypanosoma cruzi}, issn = {0737-4038}, doi = {10.1093/molbev/msj046}, author = {Bringaud, Frederic and Bartholomeu, Daniella C and Blandin, Ga{\"e}lle and Delcher, Arthur and Baltz, Th{\'e}o and el-Sayed, Najib M A and Ghedin, Elodie} } @article {49640, title = {Trypanosoma cruzi mitochondrial maxicircles display species- and strain-specific variation and a conserved element in the non-coding region.}, journal = {BMC Genomics}, volume = {7}, year = {2006}, month = {2006}, pages = {60}, abstract = {

BACKGROUND: The mitochondrial DNA of kinetoplastid flagellates is distinctive in the eukaryotic world due to its massive size, complex form and large sequence content. Comprised of catenated maxicircles that contain rRNA and protein-coding genes and thousands of heterogeneous minicircles encoding small guide RNAs, the kinetoplast network has evolved along with an extreme form of mRNA processing in the form of uridine insertion and deletion RNA editing. Many maxicircle-encoded mRNAs cannot be translated without this post-transcriptional sequence modification.

RESULTS: We present the complete sequence and annotation of the Trypanosoma cruzi maxicircles for the CL Brener and Esmeraldo strains. Gene order is syntenic with Trypanosoma brucei and Leishmania tarentolae maxicircles. The non-coding components have strain-specific repetitive regions and a variable region that is unique for each strain with the exception of a conserved sequence element that may serve as an origin of replication, but shows no sequence identity with L. tarentolae or T. brucei. Alternative assemblies of the variable region demonstrate intra-strain heterogeneity of the maxicircle population. The extent of mRNA editing required for particular genes approximates that seen in T. brucei. Extensively edited genes were more divergent among the genera than non-edited and rRNA genes. Esmeraldo contains a unique 236-bp deletion that removes the 5{\textquoteright}-ends of ND4 and CR4 and the intergenic region. Esmeraldo shows additional insertions and deletions outside of areas edited in other species in ND5, MURF1, and MURF2, while CL Brener has a distinct insertion in MURF2.

CONCLUSION: The CL Brener and Esmeraldo maxicircles represent two of three previously defined maxicircle clades and promise utility as taxonomic markers. Restoration of the disrupted reading frames might be accomplished by strain-specific RNA editing. Elements in the non-coding region may be important for replication, transcription, and anchoring of the maxicircle within the kinetoplast network.

}, keywords = {Amino Acid Sequence, Animals, Animals, Inbred Strains, Base Composition, Conserved Sequence, DNA, Kinetoplast, Frameshifting, Ribosomal, Gene Deletion, Gene Order, Genetic Variation, Leishmania, Models, Biological, Molecular Sequence Data, Muscle Proteins, NADH Dehydrogenase, Open Reading Frames, Regulatory Elements, Transcriptional, RNA Editing, Sequence Homology, Amino Acid, Species Specificity, Trypanosoma brucei brucei, Trypanosoma cruzi, Ubiquitin-Protein Ligases, Untranslated Regions}, issn = {1471-2164}, doi = {10.1186/1471-2164-7-60}, author = {Westenberger, Scott J and Cerqueira, Gustavo C and El-Sayed, Najib M and Zingales, Bianca and Campbell, David A and Sturm, Nancy R} } @article {38550, title = {Trypanosoma cruzi mitochondrial maxicircles display species- and strain-specific variation and a conserved element in the non-coding region}, journal = {BMC GenomicsBMC Genomics}, volume = {7}, year = {2006}, type = {10.1186/1471-2164-7-60}, abstract = {BACKGROUND:The mitochondrial DNA of kinetoplastid flagellates is distinctive in the eukaryotic world due to its massive size, complex form and large sequence content. Comprised of catenated maxicircles that contain rRNA and protein-coding genes and thousands of heterogeneous minicircles encoding small guide RNAs, the kinetoplast network has evolved along with an extreme form of mRNA processing in the form of uridine insertion and deletion RNA editing. Many maxicircle-encoded mRNAs cannot be translated without this post-transcriptional sequence modification.RESULTS:We present the complete sequence and annotation of the Trypanosoma cruzi maxicircles for the CL Brener and Esmeraldo strains. Gene order is syntenic with Trypanosoma brucei and Leishmania tarentolae maxicircles. The non-coding components have strain-specific repetitive regions and a variable region that is unique for each strain with the exception of a conserved sequence element that may serve as an origin of replication, but shows no sequence identity with L. tarentolae or T. brucei. Alternative assemblies of the variable region demonstrate intra-strain heterogeneity of the maxicircle population. The extent of mRNA editing required for particular genes approximates that seen in T. brucei. Extensively edited genes were more divergent among the genera than non-edited and rRNA genes. Esmeraldo contains a unique 236-bp deletion that removes the 5{\textquoteright}-ends of ND4 and CR4 and the intergenic region. Esmeraldo shows additional insertions and deletions outside of areas edited in other species in ND5, MURF1, and MURF2, while CL Brener has a distinct insertion in MURF2.CONCLUSION:The CL Brener and Esmeraldo maxicircles represent two of three previously defined maxicircle clades and promise utility as taxonomic markers. Restoration of the disrupted reading frames might be accomplished by strain-specific RNA editing. Elements in the non-coding region may be important for replication, transcription, and anchoring of the maxicircle within the kinetoplast network.}, isbn = {1471-2164}, author = {Westenberger, Scott and Cerqueira, Gustavo and Najib M. El-Sayed and Zingales, Bianca and Campbell, David and Sturm, Nancy} } @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 {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 {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 {38307, title = {Genome-Wide Analysis of Chromosomal Features Repressing Human Immunodeficiency Virus Transcription}, journal = {Journal of VirologyJ. Virol.Journal of VirologyJ. Virol.}, volume = {79}, year = {2005}, type = {10.1128/JVI.79.11.6610-6619.2005}, abstract = {We have investigated regulatory sequences in noncoding human DNA that are associated with repression of an integrated human immunodeficiency virus type 1 (HIV-1) promoter. HIV-1 integration results in the formation of precise and homogeneous junctions between viral and host DNA, but integration takes place at many locations. Thus, the variation in HIV-1 gene expression at different integration sites reports the activity of regulatory sequences at nearby chromosomal positions. Negative regulation of HIV transcription is of particular interest because of its association with maintaining HIV in a latent state in cells from infected patients. To identify chromosomal regulators of HIV transcription, we infected Jurkat T cells with an HIV-based vector transducing green fluorescent protein (GFP) and separated cells into populations containing well-expressed (GFP-positive) or poorly expressed (GFP-negative) proviruses. We then determined the chromosomal locations of the two classes by sequencing 971 junctions between viral and cellular DNA. Possible effects of endogenous cellular transcription were characterized by transcriptional profiling. Low-level GFP expression correlated with integration in (i) gene deserts, (ii) centromeric heterochromatin, and (iii) very highly expressed cellular genes. These data provide a genome-wide picture of chromosomal features that repress transcription and suggest models for transcriptional latency in cells from HIV-infected patients.}, isbn = {0022-538X, 1098-5514}, author = {Lewinski, M. K. and Bisgrove, D. and Shinn, P. and Chen, H. and Hoffmann, C. and Sridhar Hannenhalli and Verdin, E. and Berry, C. C. and Ecker, J. R. and Bushman, F. D.} } @article {38450, title = {Promoter architecture and response to a positive regulator of archaeal transcription}, journal = {Molecular MicrobiologyMolecular Microbiology}, volume = {56}, year = {2005}, type = {10.1111/j.1365-2958.2005.04563.x}, abstract = {The archaeal transcription apparatus is chimeric: its core components (RNA polymerase and basal factors) closely resemble those of eukaryotic RNA polymerase II, but the putative archaeal transcriptional regulators are overwhelmingly of bacterial type. Particular interest attaches to how these bacterial-type effectors, especially activators, regulate a eukaryote-like transcription system. The hyperthermophilic archaeon Methanocaldococcus jannaschii encodes a potent transcriptional activator, Ptr2, related to the Lrp/AsnC family of bacterial regulators. Ptr2 activates rubredoxin 2 (rb2) transcription through a bipartite upstream activating site (UAS), and conveys its stimulatory effects on its cognate transcription machinery through direct recruitment of the TATA binding protein (TBP). A functional dissection of the highly constrained architecture of the rb2 promoter shows that a {\textquoteleft}one-site{\textquoteright} minimal UAS suffices for activation by Ptr2, and specifies the required placement of this site. The presence of such a simplified UAS upstream of the natural rubrerythrin (rbr) promoter also suffices for positive regulation by Ptr2 in vitro, and TBP recruitment remains the primary means of transcriptional activation at this promoter.}, isbn = {1365-2958}, author = {Ouhammouch, Mohamed and Langham, Geoffrey E. and Hausner, Winfried and Simpson, Anjana J. and Najib M. El-Sayed and Geiduschek, E. Peter} } @article {38496, title = {Serendipitous discovery of Wolbachia genomes in multiple Drosophila species}, journal = {Genome BiologyGenome Biology}, volume = {6}, year = {2005}, type = {10.1186/gb-2005-6-3-r23}, abstract = {The Trace Archive is a repository for the raw, unanalyzed data generated by large-scale genome sequencing projects. The existence of this data offers scientists the possibility of discovering additional genomic sequences beyond those originally sequenced. In particular, if the source DNA for a sequencing project came from a species that was colonized by another organism, then the project may yield substantial amounts of genomic DNA, including near-complete genomes, from the symbiotic or parasitic organism.}, isbn = {1465-6906}, author = {Salzberg, Steven L. and Hotopp, Julie C. D. and Delcher, Arthur L. and M. Pop and Smith, Douglas R. and Eisen, Michael B. and Nelson, William C.} } @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 {49637, title = {Transcriptional profiling of the hyperthermophilic methanarchaeon Methanococcus jannaschii in response to lethal heat and non-lethal cold shock.}, journal = {Environ Microbiol}, volume = {7}, year = {2005}, month = {2005 Jun}, pages = {789-97}, abstract = {

Temperature shock of the hyperthermophilic methanarchaeon Methanococcus jannaschii from its optimal growth temperature of 85 degrees C to 65 degrees C and 95 degrees C resulted in different transcriptional responses characteristic of both the direction of shock (heat or cold shock) and whether the shock was lethal. Specific outcomes of lethal heat shock to 95 degrees C included upregulation of genes encoding chaperones, and downregulation of genes encoding subunits of the H+ transporting ATP synthase. A gene encoding an alpha subunit of a putative prefoldin was also upregulated, which may comprise a novel element in the protein processing pathway in M. jannaschii. Very different responses were observed upon cold shock to 65 degrees C. These included upregulation of a gene encoding an RNA helicase and other genes involved in transcription and translation, and upregulation of genes coding for proteases and transport proteins. Also upregulated was a gene that codes for an 18 kDa FKBP-type PPIase, which may facilitate protein folding at low temperatures. Transcriptional profiling also revealed several hypothetical proteins that respond to temperature stress conditions.

}, keywords = {Adaptation, Physiological, Archaeal Proteins, Cold Temperature, Gene Expression Profiling, Gene Expression Regulation, Archaeal, Heat-Shock Proteins, Hot Temperature, Methanococcus, Temperature, Transcription, Genetic}, issn = {1462-2912}, doi = {10.1111/j.1462-2920.2005.00751.x}, author = {Boonyaratanakornkit, Boonchai B and Simpson, Anjana J and Whitehead, Timothy A and Fraser, Claire M and el-Sayed, Najib M A and Clark, Douglas S} } @article {38538, title = {Transcriptional profiling of the hyperthermophilic methanarchaeon Methanococcus jannaschii in response to lethal heat and non-lethal cold shock}, journal = {Environmental MicrobiologyEnvironmental Microbiology}, volume = {7}, year = {2005}, type = {10.1111/j.1462-2920.2005.00751.x}, abstract = {Temperature shock of the hyperthermophilic methanarchaeon Methanococcus jannaschii from its optimal growth temperature of 85{\textdegree}C to 65{\textdegree}C and 95{\textdegree}C resulted in different transcriptional responses characteristic of both the direction of shock (heat or cold shock) and whether the shock was lethal. Specific outcomes of lethal heat shock to 95{\textdegree}C included upregulation of genes encoding chaperones, and downregulation of genes encoding subunits of the H+ transporting ATP synthase. A gene encoding an α subunit of a putative prefoldin was also upregulated, which may comprise a novel element in the protein processing pathway in M. jannaschii. Very different responses were observed upon cold shock to 65{\textdegree}C. These included upregulation of a gene encoding an RNA helicase and other genes involved in transcription and translation, and upregulation of genes coding for proteases and transport proteins. Also upregulated was a gene that codes for an 18~kDa FKBP-type PPIase, which may facilitate protein folding at low temperatures. Transcriptional profiling also revealed several hypothetical proteins that respond to temperature stress conditions.}, isbn = {1462-2920}, author = {Boonyaratanakornkit, Boonchai B. and Simpson, Anjana J. and Whitehead, Timothy A. and Fraser, Claire M. and Najib M. El-Sayed and Clark, Douglas S.} } @conference {49565, title = {What Are the Ants Doing? Vision-Based Tracking and Reconstruction of Control Programs}, booktitle = {2005 IEEE International Conference on Robotics and AutomationProceedings of the 2005 IEEE International Conference on Robotics and Automation}, year = {2005}, publisher = {IEEE}, organization = {IEEE}, address = {Barcelona, Spain}, doi = {10.1109/ROBOT.2005.1570762}, url = {http://ieeexplore.ieee.org/lpdocs/epic03/wrapper.htm?arnumber=1570762}, author = {Egerstedt, M. and Balch, T. and Dellaert, F. and Delmotte, F. and Khan, Z.} } @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 {38104, title = {Advances in schistosome genomics}, journal = {Trends in ParasitologyTrends in Parasitology}, volume = {20}, year = {2004}, type = {16/j.pt.2004.02.002}, abstract = {In Spring 2004, the first draft of the 270~Mb genome of Schistosoma mansoni will be released. This sequence is based on the assembly and annotation of a >7.5-fold coverage, shotgun sequencing project. The key stages involved in the international collaborative efforts that have led to the generation of these sequencing data for the parasite S. mansoni are discussed here.}, isbn = {1471-4922}, author = {Najib M. El-Sayed and Bartholomeu, Daniella and Ivens, Alasdair and Johnston, David A. and LoVerde, Philip T.} } @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 {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} } @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 {38437, title = {Polylysogeny and prophage induction by secondary infection in Vibrio cholerae}, journal = {Environmental MicrobiologyEnvironmental Microbiology}, volume = {6}, year = {2004}, type = {10.1111/j.1462-2920.2004.00603.x}, abstract = {Strains of Vibrio cholerae O1, biotypes El Tor and classical, were infected with a known temperate phage (ΦP15) and monitored over a 15-day period for prophage induction. Over the course of the experiment two morphologically and three genomically distinct virus-like particles were observed from the phage-infected El Tor strain by transmission electron microscopy and field inversion gel electrophoresis, respectively, whereas only one phage, ΦP15, was observed from the infected classical strain. In the uninfected El Tor culture one prophage was spontaneously induced after 6~days. No induction in either strain was observed after treatment with mitomycin C. Data indicate that El Tor biotypes of V. cholerae may be polylysogenic and that secondary infection can promote multiple prophage induction. These traits may be important in the transfer of genetic material among V. cholerae by providing an environmentally relevant route for multiple prophage propagation and transmission.}, isbn = {1462-2920}, author = {Espeland, Eric M. and Lipp, Erin K. and Huq, Anwar and Rita R. Colwell} } @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 {49664, title = {Sequencing strategies for parasite genomes.}, journal = {Methods Mol Biol}, volume = {270}, year = {2004}, month = {2004}, pages = {1-16}, abstract = {

Recent advances in the field of sequencing have enabled the determination of the complete nucleotide sequence of a large number of complex genomes. The complete genome sequence of the parasite Plasmodium falciparum has been published recently, and many other parasite genome initiatives are underway. Parasite genomes vary in size, nucleotide composition, polymorphism level, content, and distribution of repetitive elements. These genomic features affect the performance of sequencing strategies. As a consequence, each of the ongoing parasite genome projects has adopted distinct sequencing approaches. The degree of completeness and accuracy desired as well as available funds should be considered carefully when choosing the most appropriate sequencing strategy.

}, keywords = {Animals, Chromosome Walking, Chromosomes, Artificial, Bacterial, Genetic Markers, Genome, Protozoan, Plasmodium falciparum}, issn = {1064-3745}, doi = {10.1385/1-59259-793-9:001}, author = {Bartholomeu, Daniella and El-Sayed, Najib M} } @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 {38206, title = {Direct Detection of Vibrio Cholerae and ctxA in Peruvian Coastal Water and Plankton by PCR}, journal = {Applied and Environmental MicrobiologyAppl. Environ. Microbiol.Applied and Environmental MicrobiologyAppl. Environ. Microbiol.}, volume = {69}, year = {2003}, type = {10.1128/AEM.69.6.3676-3680.2003}, abstract = {Seawater and plankton samples were collected over a period of 17 months from November 1998 to March 2000 along the coast of Peru. Total DNA was extracted from water and from plankton grouped by size into two fractions (64 μm to 202 μm and >202 μm). All samples were assayed for Vibrio cholerae, V. cholerae O1, V. cholerae O139, and ctxA by PCR. Of 50 samples collected and tested, 33 (66.0\%) were positive for V. cholerae in at least one of the three fractions. Of these, 62.5\% (n = 32) contained V. cholerae O1; ctxA was detected in 25\% (n = 20) of the V. cholerae O1-positive samples. None were positive for V. cholerae O139. Thus, PCR was successfully employed in detecting toxigenic V. cholerae directly in seawater and plankton samples and provides evidence for an environmental reservoir for this pathogen in Peruvian coastal waters.}, isbn = {0099-2240, 1098-5336}, author = {Lipp, Erin K. and Rivera, Irma N. G. and Gil, Ana I. and Espeland, Eric M. and Choopun, Nipa and Louis, Val{\'e}rie R. and Russek-Cohen, Estelle and Huq, Anwar and Rita R. Colwell} } @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 {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 {49629, title = {Analysis of stage-specific gene expression in the bloodstream and the procyclic form of Trypanosoma brucei using a genomic DNA-microarray.}, journal = {Mol Biochem Parasitol}, volume = {123}, year = {2002}, month = {2002 Aug 28}, pages = {115-23}, abstract = {

A microarray comprising 21,024 different PCR products spotted on glass slides was constructed for gene expression studies on Trypanosoma brucei. The arrayed fragments were generated from a T. brucei shotgun clone library, which had been prepared from randomly sheared and size-fractionated genomic DNA. For the identification of stage-specific gene activity, total RNA from in vitro cultures of the human, long slender form and the insect, procyclic form of the parasite was labelled and hybridised to the microarray. Approximately 75\% of the genomic fragments produced a signal and about 2\% exhibited significant differences between the transcript levels in the bloodstream and procyclic forms. A few results were confirmed by Northern blot analysis or reverse-transcription and PCR. Three hundred differentially regulated clones have been selected for sequencing. So far, of 33 clones that showed about 2-fold or more over-expression in bloodstream forms, 15 contained sequences similar to those of VSG expression sites and at least six others appeared non-protein-coding. Of 29 procyclic-specific clones, at least eight appeared not to be protein-coding. A surprisingly large proportion of known regulated genes was already identified in this small sample, and some new ones were found, illustrating the utility of genomic arrays.

}, keywords = {Animals, Blotting, Northern, Escherichia coli, Gene expression, Gene Expression Profiling, Genes, Protozoan, HUMANS, Life Cycle Stages, Molecular Sequence Data, Oligonucleotide Array Sequence Analysis, Polymerase Chain Reaction, Transcription, Genetic, Trypanosoma brucei brucei}, issn = {0166-6851}, author = {Diehl, Susanne and Diehl, Frank and El-Sayed, Najib M and Clayton, Christine and Hoheisel, J{\"o}rg D} } @article {38115, title = {Analysis of stage-specific gene expression in the bloodstream and the procyclic form of Trypanosoma brucei using a genomic DNA-microarray}, journal = {Molecular and Biochemical ParasitologyMolecular and Biochemical Parasitology}, volume = {123}, year = {2002}, type = {16/S0166-6851(02)00138-X}, abstract = {A microarray comprising 21[punctuation space]024 different PCR products spotted on glass slides was constructed for gene expression studies on Trypanosoma brucei. The arrayed fragments were generated from a T. brucei shotgun clone library, which had been prepared from randomly sheared and size-fractionated genomic DNA. For the identification of stage-specific gene activity, total RNA from in vitro cultures of the human, long slender form and the insect, procyclic form of the parasite was labelled and hybridised to the microarray. Approximately 75\% of the genomic fragments produced a signal and about 2\% exhibited significant differences between the transcript levels in the bloodstream and procyclic forms. A few results were confirmed by Northern blot analysis or reverse-transcription and PCR. Three hundred differentially regulated clones have been selected for sequencing. So far, of 33 clones that showed about 2-fold or more over-expression in bloodstream forms, 15 contained sequences similar to those of VSG expression sites and at least six others appeared non-protein-coding. Of 29 procyclic-specific clones, at least eight appeared not to be protein-coding. A surprisingly large proportion of known regulated genes was already identified in this small sample, and some new ones were found, illustrating the utility of genomic arrays.}, keywords = {Expression, Gene, Microarray, Regulation, Trypanosoma brucei}, isbn = {0166-6851}, author = {Diehl, Susanne and Diehl, Frank and Najib M. El-Sayed and Clayton, Christine and Hoheisel, J{\"o}rg D.} } @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 {38295, title = {Genome sequence and comparative analysis of the model rodent malaria parasite Plasmodium yoelii yoelii}, journal = {NatureNature}, volume = {419}, year = {2002}, type = {10.1038/nature01099}, abstract = {Species of malaria parasite that infect rodents have long been used as models for malaria disease research. Here we report the whole-genome shotgun sequence of one species, Plasmodium yoelii yoelii, and comparative studies with the genome of the human malaria parasite Plasmodium falciparum clone 3D7. A synteny map of 2,212 P. y. yoelii contiguous DNA sequences (contigs) aligned to 14 P. falciparum chromosomes reveals marked conservation of gene synteny within the body of each chromosome. Of about 5,300 P. falciparum genes, more than 3,300 P. y. yoelii orthologues of predominantly metabolic function were identified. Over 800 copies of a variant antigen gene located in subtelomeric regions were found. This is the first genome sequence of a model eukaryotic parasite, and it provides insight into the use of such systems in the modelling of Plasmodium biology and disease.}, isbn = {0028-0836}, author = {Carlton, Jane M. and Angiuoli, Samuel V. and Suh, Bernard B. and Kooij, Taco W. and Pertea, Mihaela and Silva, Joana C. and Ermolaeva, Maria D. and Allen, Jonathan E. and J. Selengut and Koo, Hean L. and Peterson, Jeremy D. and M. Pop and Kosack, Daniel S. and Shumway, Martin F. and Bidwell, Shelby L. and Shallom, Shamira J. and Aken, Susan E. van and Riedmuller, Steven B. and Feldblyum, Tamara V. and Cho, Jennifer K. and Quackenbush, John and Sedegah, Martha and Shoaibi, Azadeh and Cummings, Leda M. and Florens, Laurence and Yates, John R. and Raine, J. Dale and Sinden, Robert E. and Harris, Michael A. and Cunningham, Deirdre A. and Preiser, Peter R. and Bergman, Lawrence W. and Vaidya, Akhil B. and Lin, Leo H. van and Janse, Chris J. and Waters, Andrew P. and Smith, Hamilton O. and White, Owen R. and Salzberg, Steven L. and Venter, J. Craig and Fraser, Claire M. and Hoffman, Stephen L. and Gardner, Malcolm J. and Carucci, Daniel J.} } @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 {38334, title = {Identification of non-autonomous non-LTR retrotransposons in the genome of Trypanosoma cruzi}, journal = {Molecular and Biochemical ParasitologyMolecular and Biochemical Parasitology}, volume = {124}, year = {2002}, type = {16/S0166-6851(02)00167-6}, abstract = {As observed for most eukaryotic cells, trypanosomatids contains non-LTR retrotransposons randomly inserted in the nuclear genome. Autonomous retroelements which, code for their own transposition, have been characterized in Trypanosoma brucei (ingi) and Trypanosoma cruzi (L1Tc), whereas non-autonomous retroelements have only been characterized in T. brucei (RIME). Here, we have characterized in the genome of Trypanosoma cruzi four complete copies of a non-autonomous non-LTR retrotransposon, called NARTc. This 0.26 kb NARTc element has the characteristics of non-LTR retrotransposons: the presence a poly(dA) tail and of a short flanking duplicated motif. Analysis of the Genome Survey Sequence databases indicated that the Trypanosoma cruzi haploid genome contains about 140 NARTc copies and about twice as many L1Tc copies. Interestingly, the NARTc and L1Tc retroelements share, with the Trypanosoma brucei ingi and RIME retrotransposons, a common sequence (the first 45 bp with 91\% identity), whereas the remaining sequences are very divergent. This suggests that these four trypanosome non-LTR retrotransposons were derived from the same common ancester and the sequence of their 5{\textquoteright}-extremity may have a functional role. In addition, the genome of Leishmania major contains the same conserved motif present in the trypanosome retroelements, whicle no transposable elements have been detected so far in Leishmania sp.}, keywords = {Ingi, L1Tc, Non-LTR retrotransposon, RIME, Trypanosoma brucei, Trypanosoma cruzi}, isbn = {0166-6851}, author = {Bringaud, Frederic and Garc{\'\i}a-P{\'e}rez, Jos{\'e} Luis and Heras, Sara R. and Ghedin, Elodie and Najib M. El-Sayed and Andersson, Bj{\"o}rn and Baltz, Th{\'e}o and Lopez, Manuel C.} } @article {49630, title = {Identification of non-autonomous non-LTR retrotransposons in the genome of Trypanosoma cruzi.}, journal = {Mol Biochem Parasitol}, volume = {124}, year = {2002}, month = {2002 Sep-Oct}, pages = {73-8}, abstract = {

As observed for most eukaryotic cells, trypanosomatids contains non-LTR retrotransposons randomly inserted in the nuclear genome. Autonomous retroelements which, code for their own transposition, have been characterized in Trypanosoma brucei (ingi) and Trypanosoma cruzi (L1Tc), whereas non-autonomous retroelements have only been characterized in T. brucei (RIME). Here, we have characterized in the genome of Trypanosoma cruzi four complete copies of a non-autonomous non-LTR retrotransposon, called NARTc. This 0.26 kb NARTc element has the characteristics of non-LTR retrotransposons: the presence a poly(dA) tail and of a short flanking duplicated motif. Analysis of the Genome Survey Sequence databases indicated that the Trypanosoma cruzi haploid genome contains about 140 NARTc copies and about twice as many L1Tc copies. Interestingly, the NARTc and L1Tc retroelements share, with the Trypanosoma brucei ingi and RIME retrotransposons, a common sequence (the first 45 bp with 91\% identity), whereas the remaining sequences are very divergent. This suggests that these four trypanosome non-LTR retrotransposons were derived from the same common ancester and the sequence of their 5{\textquoteright}-extremity may have a functional role. In addition, the genome of Leishmania major contains the same conserved motif present in the trypanosome retroelements, whicle no transposable elements have been detected so far in Leishmania sp.

}, keywords = {Animals, Base Sequence, Computational Biology, Genome, Protozoan, Long Interspersed Nucleotide Elements, Molecular Sequence Data, Retroelements, Short Interspersed Nucleotide Elements, Trypanosoma cruzi}, issn = {0166-6851}, author = {Bringaud, Frederic and Garc{\'\i}a-P{\'e}rez, Jos{\'e} Luis and Heras, Sara R and Ghedin, Elodie and El-Sayed, Najib M and Andersson, Bj{\"o}rn and Baltz, Th{\'e}o and Lopez, Manuel C} } @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 {38551, title = {Trypanosoma cruzi: RNA structure and post-transcriptional control of tubulin gene expression}, journal = {Experimental ParasitologyExperimental Parasitology}, volume = {102}, year = {2002}, type = {16/S0014-4894(03)00034-1}, abstract = {Changes in tubulin expression are among the biochemical and morphological adaptations that occur during the life cycle of Trypanosomatids. To investigate the mechanism responsible for the differential accumulation of tubulin mRNAs in Trypanosoma cruzi, we determine the sequences of [alpha]- and [beta]-tubulin transcripts and analyzed their expression during the life cycle of the parasite. Two [beta]-tubulin mRNAs of 1.9 and 2.3~kb were found to differ mainly by an additional 369 nucleotides at the end of the 3{\textquoteright} untranslated region (UTR). Although their transcription rates are similar in epimastigotes and amastigotes, [alpha]- and [beta]-tubulin transcripts are 3- to 6-fold more abundant in epimastigotes than in trypomastigotes and amastigotes. Accordingly, the half-lives of [alpha]- and [beta]-tubulin mRNAs are significantly higher in epimastigotes than in amastigotes. Transient transfection experiments indicated that positive regulatory elements occur in the 3{\textquoteright} UTR plus downstream intergenic region of the [alpha]-tubulin gene and that both positive and negative elements occur in the equivalent regions of the [beta]-tubulin gene.Index Descriptions and Abbreviations: Kinetoplastida; Trypanosoma cruzi; tubulin; gene regulation; PCR, polymerase chain reaction; UTR, untranslated region; IR, intergenic region; SL, spliced leader; BAC, bacterial artificial chromosome.}, isbn = {0014-4894}, author = {Bartholomeu, Daniella C. and Silva, Rosiane A. and Galv{\~a}o, Lucia M. C. and Najib M. El-Sayed and Donelson, John E. and Teixeira, Santuza M. R.} } @article {49632, title = {Trypanosoma cruzi: RNA structure and post-transcriptional control of tubulin gene expression.}, journal = {Exp Parasitol}, volume = {102}, year = {2002}, month = {2002 Nov-Dec}, pages = {123-33}, abstract = {

Changes in tubulin expression are among the biochemical and morphological adaptations that occur during the life cycle of Trypanosomatids. To investigate the mechanism responsible for the differential accumulation of tubulin mRNAs in Trypanosoma cruzi, we determine the sequences of alpha- and beta-tubulin transcripts and analyzed their expression during the life cycle of the parasite. Two beta-tubulin mRNAs of 1.9 and 2.3 kb were found to differ mainly by an additional 369 nucleotides at the end of the 3{\textquoteright} untranslated region (UTR). Although their transcription rates are similar in epimastigotes and amastigotes, alpha- and beta-tubulin transcripts are 3- to 6-fold more abundant in epimastigotes than in trypomastigotes and amastigotes. Accordingly, the half-lives of alpha- and beta-tubulin mRNAs are significantly higher in epimastigotes than in amastigotes. Transient transfection experiments indicated that positive regulatory elements occur in the 3{\textquoteright} UTR plus downstream intergenic region of the alpha-tubulin gene and that both positive and negative elements occur in the equivalent regions of the beta-tubulin gene.

}, keywords = {Animals, Base Sequence, Blotting, Northern, DNA, Complementary, DNA, Protozoan, Gene Expression Regulation, Half-Life, Life Cycle Stages, Molecular Sequence Data, RNA Processing, Post-Transcriptional, RNA, Messenger, RNA, Protozoan, Transcription, Genetic, Transfection, Trypanosoma cruzi, Tubulin}, issn = {0014-4894}, author = {Bartholomeu, Daniella C and Silva, Rosiane A and Galv{\~a}o, Lucia M C and el-Sayed, Najib M A and Donelson, John E and Teixeira, Santuza M R} } @article {38113, title = {Analysis of a donor gene region for a variant surface glycoprotein and its expression site in African trypanosomes}, journal = {Nucleic acids researchNucleic Acids Research}, volume = {29}, year = {2001}, author = {LaCount, D. J. and Najib M. El-Sayed and Kaul, S. and Wanless, D. and Turner, C. M. R. and Donelson, J. E.} } @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 {38144, title = {A Case for Evolutionary Genomics and the Comprehensive Examination of Sequence Biodiversity}, journal = {Molecular Biology and EvolutionMol Biol EvolMolecular Biology and EvolutionMol Biol Evol}, volume = {17}, year = {2000}, abstract = {Comparative analysis is one of the most powerful methods available for understanding the diverse and complex systems found in biology, but it is often limited by a lack of comprehensive taxonomic sampling. Despite the recent development of powerful genome technologies capable of producing sequence data in large quantities (witness the recently completed first draft of the human genome), there has been relatively little change in how evolutionary studies are conducted. The application of genomic methods to evolutionary biology is a challenge, in part because gene segments from different organisms are manipulated separately, requiring individual purification, cloning, and sequencing. We suggest that a feasible approach to collecting genome-scale data sets for evolutionary biology (i.e., evolutionary genomics) may consist of combination of DNA samples prior to cloning and sequencing, followed by computational reconstruction of the original sequences. This approach will allow the full benefit of automated protocols developed by genome projects to be realized; taxon sampling levels can easily increase to thousands for targeted genomes and genomic regions. Sequence diversity at this level will dramatically improve the quality and accuracy of phylogenetic inference, as well as the accuracy and resolution of comparative evolutionary studies. In particular, it will be possible to make accurate estimates of normal evolution in the context of constant structural and functional constraints (i.e., site-specific substitution probabilities), along with accurate estimates of changes in evolutionary patterns, including pairwise coevolution between sites, adaptive bursts, and changes in selective constraints. These estimates can then be used to understand and predict the effects of protein structure and function on sequence evolution and to predict unknown details of protein structure, function, and functional divergence. In order to demonstrate the practicality of these ideas and the potential benefit for functional genomic analysis, we describe a pilot project we are conducting to simultaneously sequence large numbers of vertebrate mitochondrial genomes.}, isbn = {0737-4038, 1537-1719}, author = {Pollock, David D. and Eisen, Jonathan A. and Doggett, Norman A. and Michael P. Cummings} } @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 {38390, title = {More surprises from Kinetoplastida}, 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 = {96}, year = {1999}, author = {Donelson, J. E. and Gardner, M. J. and Najib M. El-Sayed} } @inbook {49665, title = {Multiple mechanisms of immune evasion by African trypanosomes}, booktitle = {The Trypanosome Surface }, year = {1999}, pages = {71-91}, publisher = {De Boeck \& Larcier s.a.}, organization = {De Boeck \& Larcier s.a.}, address = {Brussels}, author = {Donelson, J.E. and Hill, K.L. and El-Sayed, N.M.A.} } @article {49627, title = {Genetic nomenclature for Trypanosoma and Leishmania.}, journal = {Mol Biochem Parasitol}, volume = {97}, year = {1998}, month = {1998 Nov 30}, pages = {221-4}, keywords = {Animals, Leishmania, Terminology as Topic, Trypanosoma}, issn = {0166-6851}, author = {Clayton, C and Adams, M and Almeida, R and Baltz, T and Barrett, M and Bastien, P and Belli, S and Beverley, S and Biteau, N and Blackwell, J and Blaineau, C and Boshart, M and Bringaud, F and Cross, G and Cruz, A and Degrave, W and Donelson, J and El-Sayed, N and Fu, G and Ersfeld, K and Gibson, W and Gull, K and Ivens, A and Kelly, J and Vanhamme, L} } @article {38392, title = {Multiple mechanisms of immune evasion by African trypanosomes}, journal = {Molecular and Biochemical ParasitologyMolecular and Biochemical Parasitology}, volume = {91}, year = {1998}, type = {16/S0166-6851(97)00209-0}, abstract = {During infection of a mammalian host, African trypanosomes are in constant contact with the host{\textquoteright}s immune system. These protozoan parasites are infamous for their ability to evade the immune responses by periodically switching their major variant surface glycoprotein (VSG), a phenomenon called antigenic variation. Antigenic variation, however, is likely to be only one of several mechanisms enabling these organisms to thrive in the face of the immune defenses. The ability to grow in high levels of interferon-gamma (IFN-[gamma]) and to avoid complement-mediated destruction may also facilitate the parasite{\textquoteright}s survival. In this review we summarize (i) the activation of trypanosome genes for three different VSGs during antigenic variation, (ii) the secretion of a trypanosome protein that induces host CD8+ T cells to produce IFN-[gamma], and (iii) the evidence for trypansome protein similar to a surface protease of Leishmania that plays a role in resistance to complement-mediated lysis.}, keywords = {Leishmania, Recombinant cloning, T cell, Trypanosomes, VSG genes}, isbn = {0166-6851}, author = {Donelson, John E. and Hill, Kent L. and Najib M. El-Sayed} } @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 {38106, title = {African trypanosomes have differentially expressed genes encoding homologues of the Leishmania GP63 surface protease}, journal = {Journal of Biological ChemistryJournal of Biological Chemistry}, volume = {272}, year = {1997}, author = {Najib M. El-Sayed and Donelson, J. E.} } @inbook {49663, title = {Sequencing and mapping the African trypanosome genome}, booktitle = {Trypanosomiasis and Leishmaniasis: Biology and Control }, year = {1997}, pages = {51-63}, publisher = {CAB International and the British Society for Parasitology pubs}, organization = {CAB International and the British Society for Parasitology pubs}, author = {El-Sayed, N.M.A and Donelson, J.E.} } @article {38520, title = {A survey of the Trypanosoma brucei rhodesiense genome using shotgun sequencing}, journal = {Molecular and Biochemical ParasitologyMolecular and Biochemical Parasitology}, volume = {84}, year = {1997}, type = {16/S0166-6851(96)02792-2}, abstract = {A comparison of the efficiency of sequencing random genomic DNA fragments versus random cDNAs for the discovery of new genes in African trypanosomes was undertaken. Trypanosome DNA was sheared to a 1.5-2.5 kb size distribution, cloned into a plasmid and the sequences at both ends of 183 cloned fragments determined. Sequences of both kinetoplast and nuclear DNA were identified. New coding regions were discovered for a variety of proteins, including cell division proteins, an RNA-binding protein and a homologue of the Leishmania surface protease GP63. In some cases, each end of a fragment was found to contain a different gene, demonstrating the proximity of those genes and suggesting that the density of genes in the African trypanosome genome is quite high. Repetitive sequence elements found included telomeric hexamer repeats, 76 bp repeats associated with VSG gene expression sites, 177 bp satellite repeats in minichromosomes and the Ingi transposon-like elements. In contrast to cDNA sequencing, no ribosomal protein genes were detected. For the sake of comparison, the sequences of 190 expressed sequence tags (ESTs) were also determined, and a similar number of new trypanosomal homologues were found including homologues of another putative surface protein and a human leucine-rich repeat-containing protein. We conclude from this analysis and our previous work that sequencing random DNA fragments in African trypanosomes is as efficient for gene discovery as is sequencing random cDNA clones.}, keywords = {Expressed sequence tag, Genome survey sequence, Trypanosoma brucei rhodesiense}, isbn = {0166-6851}, author = {Najib M. El-Sayed and Donelson, John E.} } @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 {38145, title = {cDNA expressed sequence tags of Trypanosoma brucei rhodesiense provide new insights into the biology of the parasite}, journal = {Molecular and Biochemical ParasitologyMolecular and Biochemical Parasitology}, volume = {73}, year = {1995}, type = {16/0166-6851(95)00098-L}, abstract = {A total of 518 expressed sequence tags (ESTs) have been generated from clones randomly selected from a cDNA library and a spliced leader sub-library of a Trypanosoma brucei rhodesiense bloodstream clone. 205 (39\%) of the clones were identified based on matches to 113 unique genes in the public databases. Of these, 71 cDNAs display significant similarities to genes in unrelated organisms encoding metabolic enzymes, signal transduction proteins, transcription factors, ribosomal proteins, histones, a proliferation-associated protein and thimet oligopeptidase, among others. 313 of the cDNAs are not related to any other sequences in the databases. These cDNA ESTs provide new avenues of research for exploring both the novel trypanosome-specific genes and the genome organization of this parasite, as well as a resource for identifying trypanosome homologs to genes expressed in other organisms.}, keywords = {cDNA, Expressed sequence tag, Trypanosoma brucei rhodesiense}, isbn = {0166-6851}, author = {Najib M. El-Sayed and Alarcon, Clara M. and Beck, John C. and Sheffield, Val C. and Donelson, John E.} } @article {38189, title = {Crystallization and preliminary X-ray investigation of the recombinant Trypanosoma brucei rhodesiense calmodulin}, journal = {Proteins: Structure, Function, and BioinformaticsProteins: Structure, Function, and Bioinformatics}, volume = {21}, year = {1995}, author = {Najib M. El-Sayed and Patton, C. L. and Harkins, P. C. and Fox, R. O. and Anderson, K.} } @article {49628, title = {Detection of alloantigens during preimplantation development and early trophoblast differentiation in the mouse by immunoperoxidase labeling.}, journal = {J Exp Med}, volume = {143}, year = {1976}, month = {1976 Feb 1}, pages = {348-59}, abstract = {

An immunoperoxidase-labeling technique allowing visualization of antibody binding to the cell surface at the electron microscopical level has been employed an an analysis of H-2 and non-H-2 alloantigen expression on the early mouse embryo. The presence of non-H-2 antigenic determinants has been confirmed on eight-cell, morula, and blastocyst stages of development. Contrary to previous reports, however, low levels of H-2 antigen have also been detected on the blastocyst. This is the earliest stage at which H-2 has been shown to be expressed on the fertilized mouse egg and may reflect the greater resolution of the immunoperoxidase technique. Using two different models to study the critical peri-implantation stages, those of experimentally induced blastocyst activation and blastocyst outgrowth in vitro, it has been demonstrated that antigen loss occurs on the trophectoderm at the time of implantation, and that this is not necessarily dependent upon maternal influence. It is suggested that the loss may be an important factor in the prevention of maternal immune rejection during the establishment of the fetal allograft. The two major components of the early postimplantation conceptus display a striking differential in antigenic status. The embryonic sac shows a high degree of peroxidase labeling, while the ectoplacental cone trophoblast is unlabeled. These findings add support to the concept of antigenic neutrality of the early trophoblast and its role in the maintenance of a normal fetomaternal immunological equilibrium.

}, keywords = {Animals, Binding Sites, Antibody, Blastocyst, Cell Differentiation, Cell Membrane, Embryo Implantation, Embryonic Development, Epitopes, Female, Histocompatibility Antigens, HLA Antigens, Horseradish Peroxidase, Mice, Mice, Inbred Strains, Pregnancy, Pregnancy, Animal, Trophoblasts}, issn = {0022-1007}, author = {Searle, R F and Sellens, M H and Elson, J and Jenkinson, E J and Billington, W D} }