TY - JOUR T1 - Capturing the most wanted taxa through cross-sample correlations JF - The ISME Journal Y1 - 2016 A1 - Almeida, Mathieu A1 - Pop, Mihai A1 - Le Chatelier, Emmanuelle A1 - Prifti, Edi A1 - Pons, Nicolas A1 - Ghozlane, Amine A1 - Ehrlich, S Dusko UR - http://www.nature.com/doifinder/10.1038/ismej.2016.35 J1 - ISME J M3 - 10.1038/ismej.2016.35 ER - TY - JOUR T1 - Dual Transcriptome Profiling of Leishmania-Infected Human Macrophages Reveals Distinct Reprogramming Signatures JF - mBio Y1 - 2016 A1 - Fernandes, Maria Cecilia A1 - Dillon, Laura A. L. A1 - Belew, Ashton Trey A1 - Bravo, Héctor Corrada A1 - Mosser, David M. A1 - El-Sayed, Najib M. VL - 7 UR - http://mbio.asm.org/lookup/doi/10.1128/mBio.00027-16https://syndication.highwire.org/content/doi/10.1128/mBio.00027-16 CP - 3 J1 - mBio M3 - 10.1128/mBio.00027-16 ER - TY - JOUR T1 - The fruRBA operon is necessary for Group A Streptococcal growth in fructose and for resistance to neutrophil killing during growth in whole human blood. JF - Infect Immun Y1 - 2016 A1 - Valdes, Kayla M A1 - Sundar, Ganesh S A1 - Vega, Luis A A1 - Belew, Ashton T A1 - Islam, Emrul A1 - Binet, Rachel A1 - El-Sayed, Najib M A1 - Le Breton, Yoann A1 - McIver, Kevin S AB -

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.

M3 - 10.1128/IAI.01296-15 ER - TY - JOUR T1 - Identification guide to the heterobranch sea slugs (Mollusca: Gastropoda) from Bocas del Toro, Panama JF - Marine Biodiversity Records Y1 - 2016 A1 - Goodheart, Jessica A1 - Ellingson, Ryan A. A1 - Vital, Xochitl G. A1 - ão Filho, Hilton C. A1 - McCarthy, Jennifer B. A1 - Medrano, Sabrina M. A1 - Bhave, Vishal J. A1 - ía-Méndez, Kimberly A1 - énez, Lina M. A1 - ópez, Gina A1 - Hoover, Craig A. A1 - Awbrey, Jaymes D. A1 - De Jesus, Jessika M. A1 - Gowacki, William A1 - Krug, Patrick J. A1 - és, Ángel VL - 96737453830254034557880541418411912544728739317415779780725696418782226404216145163412560451520488424050829677 UR - http://mbr.biomedcentral.com/articles/10.1186/s41200-016-0048-zhttp://link.springer.com/content/pdf/10.1186/s41200-016-0048-z CP - 12343–4 J1 - Mar Biodivers Rec M3 - 10.1186/s41200-016-0048-z ER - TY - JOUR T1 - The fruRBA Operon Is Necessary for Group A Streptococcal Growth in Fructose and for Resistance to Neutrophil Killing during Growth in Whole Human Blood JF - Infection and Immunity Y1 - 2016 A1 - Valdes, Kayla M. A1 - Sundar, Ganesh S. A1 - Vega, Luis A. A1 - Belew, Ashton T. A1 - Islam, Emrul A1 - Binet, Rachel A1 - El-Sayed, Najib M. A1 - Le Breton, Yoann A1 - McIver, Kevin S. ED - Camilli, A. VL - 84 UR - http://iai.asm.org/lookup/doi/10.1128/IAI.01296-15 CP - 4 J1 - Infect. Immun. M3 - 10.1128/IAI.01296-15 ER - TY - JOUR T1 - Transcriptome Remodeling in Trypanosoma cruzi and Human Cells during Intracellular Infection. JF - PLoS Pathog Y1 - 2016 A1 - Li, Yuan A1 - Shah-Simpson, Sheena A1 - Okrah, Kwame A1 - Belew, A Trey A1 - Choi, Jungmin A1 - Caradonna, Kacey L A1 - Padmanabhan, Prasad A1 - Ndegwa, David M A1 - Temanni, M Ramzi A1 - Corrada Bravo, Hector A1 - El-Sayed, Najib M A1 - Burleigh, Barbara A AB -

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.

VL - 12 CP - 4 M3 - 10.1371/journal.ppat.1005511 ER - TY - JOUR T1 - Diversion of aspartate in ASS1-deficient tumours fosters de novo pyrimidine synthesis JF - Nature Y1 - 2015 A1 - Rabinovich, Shiran A1 - Adler, Lital A1 - Yizhak, Keren A1 - Sarver, Alona A1 - Silberman, Alon A1 - Agron, Shani A1 - Stettner, Noa A1 - Sun, Qin A1 - Brandis, Alexander A1 - Helbling, Daniel A1 - Korman, Stanley A1 - Itzkovitz, Shalev A1 - Dimmock, David A1 - Ulitsky, Igor A1 - Nagamani, Sandesh C. S. A1 - Ruppin, Eytan A1 - Erez, Ayelet VL - 527 UR - http://www.nature.com/doifinder/10.1038/nature15529 CP - 7578 J1 - Nature M3 - 10.1038/nature15529 ER - TY - JOUR T1 - Essential Genes in the Core Genome of the Human Pathogen Streptococcus pyogenes. JF - Sci Rep Y1 - 2015 A1 - Le Breton, Yoann A1 - Belew, Ashton T A1 - Valdes, Kayla M A1 - Islam, Emrul A1 - Curry, Patrick A1 - Tettelin, Hervé A1 - Shirtliff, Mark E A1 - El-Sayed, Najib M A1 - McIver, Kevin S AB -

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.

VL - 5 M3 - 10.1038/srep09838 ER - TY - Generic T1 - Fumarate induces redox-dependent senescence by modifying glutathione metabolism. Y1 - 2015 A1 - Zheng, Liang A1 - Cardaci, Simone A1 - Jerby, Livnat A1 - MacKenzie, Elaine D A1 - Sciacovelli, Marco A1 - Johnson, T Isaac A1 - Gaude, Edoardo A1 - King, Ayala A1 - Leach, Joshua D G A1 - Edrada-Ebel, RuAngelie A1 - Hedley, Ann A1 - Morrice, Nicholas A A1 - Kalna, Gabriela A1 - Blyth, Karen A1 - Ruppin, Eytan A1 - Frezza, Christian A1 - Gottlieb, Eyal AB -

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.

JA - Nat Commun VL - 6 M3 - 10.1038/ncomms7001 ER - TY - Generic T1 - The generation of macrophages with anti-inflammatory activity in the absence of STAT6 signaling. Y1 - 2015 A1 - Fleming, Bryan D A1 - Chandrasekaran, Prabha A1 - Dillon, Laura A L A1 - Dalby, Elizabeth A1 - Suresh, Rahul A1 - Sarkar, Arup A1 - El-Sayed, Najib M A1 - Mosser, David M AB -

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.

JA - J Leukoc Biol VL - 98 CP - 3 M3 - 10.1189/jlb.2A1114-560R ER - TY - Generic T1 - Proteomics-based metabolic modeling reveals that fatty acid oxidation (FAO) controls endothelial cell (EC) permeability. Y1 - 2015 A1 - Patella, Francesca A1 - Schug, Zachary T A1 - Persi, Erez A1 - Neilson, Lisa J A1 - Erami, Zahra A1 - Avanzato, Daniele A1 - Maione, Federica A1 - Hernandez-Fernaud, Juan R A1 - Mackay, Gillian A1 - Zheng, Liang A1 - Reid, Steven A1 - Frezza, Christian A1 - Giraudo, Enrico A1 - Fiorio Pla, Alessandra A1 - Anderson, Kurt A1 - Ruppin, Eytan A1 - Gottlieb, Eyal A1 - Zanivan, Sara AB -

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.

JA - Mol Cell Proteomics VL - 14 CP - 3 M3 - 10.1074/mcp.M114.045575 ER - TY - JOUR T1 - Simultaneous transcriptional profiling of Leishmania major and its murine macrophage host cell reveals insights into host-pathogen interactions. JF - BMC Genomics Y1 - 2015 A1 - Dillon, Laura A L A1 - Suresh, Rahul A1 - Okrah, Kwame A1 - Corrada Bravo, Hector A1 - Mosser, David M A1 - El-Sayed, Najib M AB -

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'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.

VL - 16 CP - 1 M3 - 10.1186/s12864-015-2237-2 ER - TY - Generic T1 - Transcriptomic profiling of gene expression and RNA processing during Leishmania major differentiation. Y1 - 2015 A1 - Dillon, Laura A L A1 - Okrah, Kwame A1 - Hughitt, V Keith A1 - Suresh, Rahul A1 - Li, Yuan A1 - Fernandes, Maria Cecilia A1 - Belew, A Trey A1 - Corrada Bravo, Hector A1 - Mosser, David M A1 - El-Sayed, Najib M AB -

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' and 3' 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.

JA - Nucleic Acids Res VL - 43 CP - 14 M3 - 10.1093/nar/gkv656 ER - TY - JOUR T1 - Complete genome sequence of the quality control strain Staphylococcus aureus subsp. aureus ATCC 25923 JF - Genome announcements Y1 - 2014 A1 - Treangen, Todd J A1 - Maybank, Rosslyn A A1 - Enke, Sana A1 - Friss, Mary Beth A1 - Diviak, Lynn F A1 - Karaolis, David KR A1 - Koren, Sergey A1 - Ondov, Brian A1 - Phillippy, Adam M A1 - Bergman, Nicholas H VL - 2 ER - TY - JOUR T1 - Construction of a dairy microbial genome catalog opens new perspectives for the metagenomic analysis of dairy fermented products JF - BMC GenomicsBMC Genomics Y1 - 2014 A1 - Almeida, Mathieu A1 - Hebert, Agnes A1 - Abraham, Anne-Laure A1 - Rasmussen, Simon A1 - Monnet, Christophe A1 - Pons, Nicolas A1 - Delbes, Celine A1 - Loux, Valentin A1 - Batto, Jean-Michel A1 - Leonard, Pierre A1 - Kennedy, Sean A1 - Ehrlich, Stanislas A1 - Pop, Mihai A1 - Montel, Marie-Christine A1 - Irlinger, Francoise A1 - Renault, Pierre AB - 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. VL - 15 SN - 1471-2164 ER - TY - JOUR T1 - CTCF binding site sequence differences are associated with unique regulatory and functional trends during embryonic stem cell differentiation JF - Nucleic Acids ResNucleic Acids ResNucleic Acids Res Y1 - 2014 A1 - Plasschaert, R. N. A1 - Vigneau, S. A1 - Tempera, I. A1 - Gupta, R. A1 - Maksimoska, J. A1 - Everett, L. A1 - Davuluri, R. A1 - Mamorstein, R. A1 - Lieberman, P. M. A1 - Schultz, D. A1 - Sridhar Hannenhalli A1 - Bartolomei, M. S. KW - *Gene Expression Regulation KW - *Regulatory Elements, Transcriptional KW - Animals KW - Binding Sites KW - Cell Differentiation/*genetics KW - Cells, Cultured KW - Embryonic Stem Cells/cytology/*metabolism KW - Mice KW - Nucleotide Motifs KW - Protein Binding KW - Repressor Proteins/*metabolism AB - 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'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. VL - 42 SN - 1362-4962 (Electronic)
0305-1048 (Linking) N1 - 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'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. U2 - 3902912 J1 - Nucleic acids researchNucleic acids research ER - TY - Generic T1 - Diarrhea in young children from low-income countries leads to large-scale alterations in intestinal microbiota composition. Y1 - 2014 A1 - Pop, Mihai A1 - Walker, Alan W A1 - Paulson, Joseph A1 - Lindsay, Brianna A1 - Antonio, Martin A1 - Hossain, M Anowar A1 - Oundo, Joseph A1 - Tamboura, Boubou A1 - Mai, Volker A1 - Astrovskaya, Irina A1 - Corrada Bravo, Hector A1 - Rance, Richard A1 - Stares, Mark A1 - Levine, Myron M A1 - Panchalingam, Sandra A1 - Kotloff, Karen A1 - Ikumapayi, Usman N A1 - Ebruke, Chinelo A1 - Adeyemi, Mitchell A1 - Ahmed, Dilruba A1 - Ahmed, Firoz A1 - Alam, Meer Taifur A1 - Amin, Ruhul A1 - Siddiqui, Sabbir A1 - Ochieng, John B A1 - Ouma, Emmanuel A1 - Juma, Jane A1 - Mailu, Euince A1 - Omore, Richard A1 - Morris, J Glenn A1 - Breiman, Robert F A1 - Saha, Debasish A1 - Parkhill, Julian A1 - Nataro, James P A1 - Stine, O Colin KW - Bangladesh KW - Base Sequence KW - Case-Control Studies KW - Child, Preschool KW - Diarrhea, Infantile KW - Dysentery KW - Feces KW - Female KW - Gambia KW - HUMANS KW - Infant KW - Infant, Newborn KW - Intestines KW - Kenya KW - Male KW - Mali KW - Microbiota KW - Molecular Typing KW - Poverty KW - RNA, Bacterial KW - RNA, Ribosomal, 16S AB -

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.

JA - Genome Biol VL - 15 CP - 6 M3 - 10.1186/gb-2014-15-6-r76 ER - TY - Generic T1 - Glycan Degradation (GlyDeR) Analysis Predicts Mammalian Gut Microbiota Abundance and Host Diet-Specific Adaptations Y1 - 2014 A1 - Eilam, O. A1 - Zarecki, R. A1 - Oberhardt, M. A1 - Ursell, L. K. A1 - Kupiec, M. A1 - Knight, R. A1 - Gophna, U. A1 - Ruppin, E. JA - mBio VL - 5 UR - http://mbio.asm.org/cgi/doi/10.1128/mBio.01526-14 CP - 4 J1 - mBio M3 - 10.1128/mBio.01526-14 ER - TY - Generic T1 - Correlated evolution of positions within mammalian cis elements Y1 - 2013 A1 - R. Mukherjee A1 - L. N. S. Singh A1 - Evans, P. A1 - Sridhar Hannenhalli JA - Plos One VL - 8 ER - TY - Generic T1 - Genomic analysis of sequence-dependent DNA curvature in Leishmania. Y1 - 2013 A1 - Smircich, Pablo A1 - Forteza, Diego A1 - El-Sayed, Najib M A1 - Garat, Beatriz KW - Chromosome mapping KW - Comparative Genomic Hybridization KW - Computational Biology KW - DNA, Protozoan KW - Genome, Protozoan KW - Genomics KW - HUMANS KW - Leishmania KW - Nucleic Acid Conformation AB -

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.

JA - PLoS One VL - 8 CP - 4 M3 - 10.1371/journal.pone.0063068 ER - TY - JOUR T1 - Functional genomics of trypanosomatids. JF - Parasite Immunol Y1 - 2012 A1 - Choi, J A1 - El-Sayed, N M KW - Animals KW - Genome, Protozoan KW - Genomics KW - HUMANS KW - Proteome KW - Protozoan Proteins KW - Transcriptome KW - Trypanosomatina AB -

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.

VL - 34 CP - 2-3 M3 - 10.1111/j.1365-3024.2011.01347.x ER - TY - Generic T1 - Plasmodium falciparum merozoite surface protein 1 blocks the proinflammatory protein S100P. Y1 - 2012 A1 - Waisberg, Michael A1 - Cerqueira, Gustavo C A1 - Yager, Stephanie B A1 - Francischetti, Ivo M B A1 - Lu, Jinghua A1 - Gera, Nidhi A1 - Srinivasan, Prakash A1 - Miura, Kazutoyo A1 - Rada, Balazs A1 - Lukszo, Jan A1 - Barbian, Kent D A1 - Leto, Thomas L A1 - Porcella, Stephen F A1 - Narum, David L A1 - El-Sayed, Najib A1 - Miller, Louis H A1 - Pierce, Susan K KW - Amino Acid Sequence KW - Animals KW - Calcium-Binding Proteins KW - Chromatography, Gel KW - Electrophoresis, Polyacrylamide Gel KW - Enzyme-Linked Immunosorbent Assay KW - HUMANS KW - Merozoite Surface Protein 1 KW - Microscopy, Confocal KW - Molecular Sequence Data KW - Neoplasm Proteins KW - Plasmodium falciparum KW - Sequence Homology, Amino Acid KW - Surface Plasmon Resonance AB -

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.

JA - Proc Natl Acad Sci U S A VL - 109 CP - 14 M3 - 10.1073/pnas.1202689109 ER - TY - JOUR T1 - Role of Shrimp Chitin in the Ecology of Toxigenic Vibrio cholerae and Cholera Transmission JF - Frontiers in MicrobiologyFront MicrobiolFrontiers in MicrobiologyFront Microbiol Y1 - 2012 A1 - Nahar, Shamsun A1 - Sultana, Marzia A1 - Naser, M. Niamul A1 - Nair, Gopinath B. A1 - Watanabe, Haruo A1 - Ohnishi, Makoto A1 - Yamamoto, Shouji A1 - Endtz, Hubert A1 - Cravioto, Alejandro A1 - Sack, R. Bradley A1 - Hasan, Nur A. A1 - Sadique, Abdus A1 - Huq, Anwar A1 - Rita R. Colwell A1 - Alam, Munirul AB - 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–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. VL - 2 SN - 1664-302X ER - TY - JOUR T1 - Structure, function and diversity of the healthy human microbiome JF - NatureNature Y1 - 2012 A1 - Huttenhower, C. A1 - Gevers, D. A1 - Knight, R. A1 - Abubucker, S. A1 - Badger, J. H. A1 - Chinwalla, A. T. A1 - Creasy, H. H. A1 - Earl, A. M. A1 - Fitzgerald, M. G. A1 - Fulton, R. S. A1 - others, VL - 486 ER - TY - JOUR T1 - Complete Columbian mammoth mitogenome suggests interbreeding with woolly mammoths JF - Genome biology Y1 - 2011 A1 - Enk, Jacob A1 - Devault, Alison A1 - Debruyne, Regis A1 - King, Christine E A1 - Todd Treangen A1 - O'Rourke, Dennis A1 - Salzberg, Steven L A1 - Fisher, Daniel A1 - MacPhee, Ross A1 - Poinar, Hendrik VL - 12 ER - TY - Generic T1 - Direct targeting of Sec23a by miR-200s influences cancer cell secretome and promotes metastatic colonization Y1 - 2011 A1 - Korpal, Manav A1 - Ell, Brian J A1 - Buffa, Francesca M A1 - Ibrahim, Toni A1 - Blanco, Mario A A1 - à-Terrassa, Toni A1 - Mercatali, Laura A1 - Khan, Zia A1 - Goodarzi, Hani A1 - Hua, Yuling A1 - Wei, Yong A1 - Hu, Guohong A1 - Garcia, Benjamin A A1 - Ragoussis, Jiannis A1 - Amadori, Dino A1 - Harris, Adrian L A1 - Kang, Yibin JA - Nature Medicine VL - 17 UR - http://www.nature.com/doifinder/10.1038/nm.2401 CP - 9 J1 - Nat Med M3 - 10.1038/nm.2401 ER - TY - JOUR T1 - Direct targeting of Sec23a by miR-200s influences cancer cell secretome and promotes metastatic colonization. JF - Nat Med Y1 - 2011 A1 - Korpal, Manav A1 - Ell, Brian J A1 - Buffa, Francesca M A1 - Ibrahim, Toni A1 - Blanco, Mario A A1 - Celià-Terrassa, Toni A1 - Mercatali, Laura A1 - Khan, Zia A1 - Goodarzi, Hani A1 - Hua, Yuling A1 - Wei, Yong A1 - Hu, Guohong A1 - Garcia, Benjamin A A1 - Ragoussis, Jiannis A1 - Amadori, Dino A1 - Harris, Adrian L A1 - Kang, Yibin KW - Animals KW - Cadherins KW - Cell Line, Tumor KW - Female KW - Gene Expression Profiling KW - Gene Expression Regulation, Neoplastic KW - HUMANS KW - Mass Spectrometry KW - Mice KW - Mice, Inbred BALB C KW - Microarray Analysis KW - MicroRNAs KW - Neoplasm Metastasis KW - Statistics, Nonparametric KW - Vesicular Transport Proteins AB -

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.

VL - 17 CP - 9 M3 - 10.1038/nm.2401 ER - TY - JOUR T1 - The genome and its implications. JF - Adv Parasitol Y1 - 2011 A1 - Teixeira, Santuza M A1 - El-Sayed, Najib M A1 - Araújo, Patrícia R KW - Animals KW - Antigens, Protozoan KW - Chagas Disease KW - Chromosomes KW - Comparative Genomic Hybridization KW - DNA, Protozoan KW - Gene Expression Regulation KW - Genetic Variation KW - Genome, Protozoan KW - Host-Parasite Interactions KW - HUMANS KW - Species Specificity KW - Synteny KW - Transcription, Genetic KW - Transfection KW - Trypanosoma cruzi AB -

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.

VL - 75 M3 - 10.1016/B978-0-12-385863-4.00010-1 ER - TY - JOUR T1 - Identification of Schistosoma mansoni microRNAs. JF - BMC Genomics Y1 - 2011 A1 - Simões, Mariana C A1 - Lee, Jonathan A1 - Djikeng, Appolinaire A1 - Cerqueira, Gustavo C A1 - Zerlotini, Adhemar A1 - da Silva-Pereira, Rosiane A A1 - Dalby, Andrew R A1 - LoVerde, Philip A1 - El-Sayed, Najib M A1 - Oliveira, Guilherme KW - Animals KW - Computational Biology KW - Genome, Helminth KW - MicroRNAs KW - Schistosoma mansoni AB -

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.

VL - 12 M3 - 10.1186/1471-2164-12-47 ER - TY - JOUR T1 - Metagenomic 16S rDNA Targeted PCR-DGGE in Determining Bacterial Diversity in Aquatic Ecosystem JF - Bangladesh Journal of MicrobiologyBangladesh Journal of Microbiology Y1 - 2011 A1 - Hasan, Nur A. A1 - Chowdhury, W. Bari A1 - Rahim, Niaz A1 - Sultana, Marzia A1 - Shabnam, S. Antara A1 - Mai, Volker A1 - Ali, Afsar A1 - Morris, Glen J. A1 - Sack, R. Bradley A1 - Huq, Anwar A1 - Rita R. Colwell A1 - Endtz, Hubert Ph A1 - Cravioto, Alejandro A1 - Alam, Munirul AB - 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 – 106 CFU/ mL for HPC and 104 – 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. VL - 27 SN - 1011-9981 ER - TY - JOUR T1 - Transcriptional Regulation Via TF-Modifying Enzymes: An Integrative Model-Based Analysis JF - Nucleic Acids ResearchNucl. Acids Res.Nucleic Acids ResearchNucl. Acids Res. Y1 - 2011 A1 - Everett, Logan J. A1 - Jensen, Shane T. A1 - Sridhar Hannenhalli AB - 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. VL - 39 SN - 0305-1048, 1362-4962 ER - TY - JOUR T1 - The Alveolate Perkinsus marinus: biological insights from EST gene discovery. JF - BMC Genomics Y1 - 2010 A1 - Joseph, Sandeep J A1 - Fernández-Robledo, José A A1 - Gardner, Malcolm J A1 - El-Sayed, Najib M A1 - Kuo, Chih-Horng A1 - Schott, Eric J A1 - Wang, Haiming A1 - Kissinger, Jessica C A1 - Vasta, Gerardo R KW - Alveolata KW - Animals KW - Expressed Sequence Tags KW - Ostreidae KW - Phylogeny AB -

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's virulence and pathogenesis mechanisms, and to identify genes encoding potential targets for intervention, we generated>31,000 5' 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.

VL - 11 M3 - 10.1186/1471-2164-11-228 ER - TY - CHAP T1 - Genetics of Trypanosoma cruzi in American Trypanosomiasis: Chagas Disease One hundred Years of Research Y1 - 2010 A1 - Bartholomeu, D. A1 - Buck, G. A1 - Teixeira, S. A1 - El-Sayed, N.M. PB - Elsevier Press CY - Burlington ER - TY - JOUR T1 - Genome-wide analysis reveals novel genes essential for heme homeostasis in Caenorhabditis elegans. JF - PLoS Genet Y1 - 2010 A1 - Severance, Scott A1 - Rajagopal, Abbhirami A1 - Rao, Anita U A1 - Cerqueira, Gustavo C A1 - Mitreva, Makedonka A1 - El-Sayed, Najib M A1 - Krause, Michael A1 - Hamza, Iqbal KW - Animals KW - Caenorhabditis elegans KW - Dose-Response Relationship, Drug KW - Gene Expression Profiling KW - Gene Expression Regulation KW - genes KW - Genome-Wide Association Study KW - Heme KW - Homeostasis KW - HUMANS KW - Leishmania KW - Nematoda KW - Trypanosoma AB -

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.

VL - 6 CP - 7 M3 - 10.1371/journal.pgen.1001044 ER - TY - JOUR T1 - Hopx and Hdac2 Interact to Modulate Gata4 Acetylation and Embryonic Cardiac Myocyte Proliferation JF - Developmental CellDevelopmental Cell Y1 - 2010 A1 - Trivedi, Chinmay M. A1 - Zhu, Wenting A1 - Wang, Qiaohong A1 - Jia, Cheng A1 - Kee, Hae Jin A1 - Li, Li A1 - Sridhar Hannenhalli A1 - Epstein, Jonathan A. AB - 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. VL - 19 SN - 1534-5807 ER - TY - JOUR T1 - Mimosa: Mixture model of co-expression to detect modulators of regulatory interaction JF - Algorithms for Molecular BiologyAlgorithms for Molecular Biology Y1 - 2010 A1 - Hansen, Matthew A1 - Everett, Logan A1 - Singh, Larry A1 - Sridhar Hannenhalli AB - 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. VL - 5 SN - 1748-7188 ER - TY - JOUR T1 - A model for using a concept inventory as a tool for students' assessment and faculty professional development. JF - CBE Life Sci Educ Y1 - 2010 A1 - Marbach-Ad, Gili A1 - McAdams, Katherine C A1 - Benson, Spencer A1 - Briken, Volker A1 - Cathcart, Laura A1 - Chase, Michael A1 - El-Sayed, Najib M A1 - Frauwirth, Kenneth A1 - Fredericksen, Brenda A1 - Joseph, Sam W A1 - Lee, Vincent A1 - McIver, Kevin S A1 - Mosser, David A1 - Quimby, B Booth A1 - Shields, Patricia A1 - Song, Wenxia A1 - Stein, Daniel C A1 - Stewart, Richard A1 - Thompson, Katerina V A1 - Smith, Ann C KW - Curriculum KW - Faculty KW - Models, Theoretical KW - Research KW - Students KW - Teaching AB -

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's discussions of student learning. Reading and discussing students' responses revealed the gap between our understanding and the students' understanding. We provide evidence to support the concept inventory as a tool for assessing student understanding of HPI concepts and faculty development.

VL - 9 CP - 4 M3 - 10.1187/cbe.10-05-0069 ER - TY - JOUR T1 - Regulating the regulators: modulators of transcription factor activity JF - Methods Mol. BiolMethods Mol. Biol Y1 - 2010 A1 - Everett, L. A1 - Hansen, M. A1 - Sridhar Hannenhalli PB - Springer VL - 674 ER - TY - JOUR T1 - Assessing Student Understanding of Host Pathogen Interactions Using a Concept Inventory JF - J. Microbiol. Biol. Ed. Y1 - 2009 A1 - Marbach-Ad, G. A1 - Briken, V. A1 - El-Sayed, N.M. A1 - Frauwirth, K. A1 - Fredericksen, B. A1 - Hutcheson, S. A1 - Gao, L.-Y. A1 - Joseph, S. A1 - Lee, V. A1 - McIver, K.S. A1 - Mosser, D. A1 - Quimby, B.B. A1 - Shields, P. A1 - Song, W. A1 - Stein, D.C. A1 - Yuan, R.T. A1 - Smith, A.C. VL - 10 ER - TY - JOUR T1 - CTCF binding site classes exhibit distinct evolutionary, genomic, epigenomic and transcriptomic features JF - Genome BiologyGenome Biology Y1 - 2009 A1 - Essien, Kobby A1 - Vigneau, Sebastien A1 - Apreleva, Sofia A1 - Singh, Larry N. A1 - Bartolomei, Marisa S. A1 - Sridhar Hannenhalli AB - 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's functional diversity. If so, the CTCF binding sites may belong to distinct classes, each compatible with a specific functional role. VL - 10 SN - 1465-6906 ER - TY - JOUR T1 - Estimating Tree-Structured Covariance Matrices via Mixed-Integer Programming JF - J Mach Learn Res Y1 - 2009 A1 - Corrada Bravo, Hector A1 - Wright, Stephen A1 - Eng, Kevin H. A1 - Keles, Sündüz A1 - Wahba, Grace VL - 5 ER - TY - JOUR T1 - Extreme polymorphism in a vaccine antigen and risk of clinical malaria: implications for vaccine development JF - Sci Transl MedSci Transl Med Y1 - 2009 A1 - Takala, S. L. A1 - Coulibaly, D. A1 - Thera, M. A. A1 - Batchelor, A. H. A1 - Michael P. Cummings A1 - Escalante, A. A. A1 - Ouattara, A. A1 - Traoré, K. A1 - Niangaly, A. A1 - Djimdé, A. A. A1 - Doumbo, O. K. A1 - Plowe, C. V. AB - 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. VL - 1 ER - TY - JOUR T1 - The genome of the blood fluke Schistosoma mansoni. JF - Nature Y1 - 2009 A1 - Berriman, Matthew A1 - Haas, Brian J A1 - LoVerde, Philip T A1 - Wilson, R Alan A1 - Dillon, Gary P A1 - Cerqueira, Gustavo C A1 - Mashiyama, Susan T A1 - Al-Lazikani, Bissan A1 - Andrade, Luiza F A1 - Ashton, Peter D A1 - Aslett, Martin A A1 - Bartholomeu, Daniella C A1 - Blandin, Gaëlle A1 - Caffrey, Conor R A1 - Coghlan, Avril A1 - Coulson, Richard A1 - Day, Tim A A1 - Delcher, Art A1 - DeMarco, Ricardo A1 - Djikeng, Appolinaire A1 - Eyre, Tina A1 - Gamble, John A A1 - Ghedin, Elodie A1 - Gu, Yong A1 - Hertz-Fowler, Christiane A1 - Hirai, Hirohisha A1 - Hirai, Yuriko A1 - Houston, Robin A1 - Ivens, Alasdair A1 - Johnston, David A A1 - Lacerda, Daniela A1 - Macedo, Camila D A1 - McVeigh, Paul A1 - Ning, Zemin A1 - Oliveira, Guilherme A1 - Overington, John P A1 - Parkhill, Julian A1 - Pertea, Mihaela A1 - Pierce, Raymond J A1 - Protasio, Anna V A1 - Quail, Michael A A1 - Rajandream, Marie-Adèle A1 - Rogers, Jane A1 - Sajid, Mohammed A1 - Salzberg, Steven L A1 - Stanke, Mario A1 - Tivey, Adrian R A1 - White, Owen A1 - Williams, David L A1 - Wortman, Jennifer A1 - Wu, Wenjie A1 - Zamanian, Mostafa A1 - Zerlotini, Adhemar A1 - Fraser-Liggett, Claire M A1 - Barrell, Barclay G A1 - El-Sayed, Najib M KW - Animals KW - Biological Evolution KW - Exons KW - Genes, Helminth KW - Genome, Helminth KW - Host-Parasite Interactions KW - Introns KW - Molecular Sequence Data KW - Physical Chromosome Mapping KW - Schistosoma mansoni KW - Schistosomiasis mansoni AB -

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.

VL - 460 CP - 7253 M3 - 10.1038/nature08160 ER - TY - JOUR T1 - Genomic organization and expression profile of the mucin-associated surface protein (masp) family of the human pathogen Trypanosoma cruzi. JF - Nucleic Acids Res Y1 - 2009 A1 - Bartholomeu, Daniella C A1 - Cerqueira, Gustavo C A1 - Leão, Ana Carolina A A1 - daRocha, Wanderson D A1 - Pais, Fabiano S A1 - Macedo, Camila A1 - Djikeng, Appolinaire A1 - Teixeira, Santuza M R A1 - El-Sayed, Najib M KW - 3' Flanking Region KW - 5' Flanking Region KW - Amino Acid Sequence KW - Animals KW - Base Sequence KW - Conserved Sequence KW - Gene Expression Profiling KW - Genes, Protozoan KW - Genome, Protozoan KW - Membrane Proteins KW - Molecular Sequence Data KW - Mucins KW - Multigene Family KW - Protozoan Proteins KW - RNA, Messenger KW - Trypanosoma cruzi AB -

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' and 3' 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.

VL - 37 CP - 10 M3 - 10.1093/nar/gkp172 ER - TY - JOUR T1 - Mimosa: mixture model of co-expression to detect modulators of regulatory interaction JF - Algorithms in BioinformaticsAlgorithms in Bioinformatics Y1 - 2009 A1 - Hansen, M. A1 - Everett, L. A1 - Singh, L. A1 - Sridhar Hannenhalli PB - Springer Berlin/Heidelberg ER - TY - JOUR T1 - A phylogenetic mixture model for the evolution of gene expression JF - Molecular biology and evolutionMolecular biology and evolution Y1 - 2009 A1 - Eng, K. H. A1 - Héctor Corrada Bravo A1 - Keles, S. VL - 26 ER - TY - JOUR T1 - PTM-Switchboard—a database of posttranslational modifications of transcription factors, the mediating enzymes and target genes JF - Nucleic acids researchNucleic Acids Research Y1 - 2009 A1 - Everett, L. A1 - Vo, A. A1 - Sridhar Hannenhalli PB - Oxford Univ Press VL - 37 ER - TY - CHAP T1 - Salient Frame Detection for Molecular Dynamics Simulations T2 - Scientific VisualizationScientific Visualization Y1 - 2009 A1 - Kim, Youngmin A1 - Patro, Robert A1 - Ip, Cheuk Yiu A1 - O'Leary, Dianne P. A1 - Anishkin, Andriy A1 - Sukharev, Sergei A1 - Varshney, Amitabh ED - Ebert, D. S. ED - Gr, ED - x6f, ED - x, ED - ller, E. ED - Hagen, H. ED - Kaufman, A. JA - Scientific VisualizationScientific Visualization PB - Dagstuhl Seminar Proceedings 09251 ER - TY - JOUR T1 - Serogroup, Virulence, and Genetic Traits of Vibrio Parahaemolyticus in the Estuarine Ecosystem of Bangladesh JF - Applied and Environmental MicrobiologyAppl. Environ. Microbiol.Applied and Environmental MicrobiologyAppl. Environ. Microbiol. Y1 - 2009 A1 - Alam, Munirul A1 - Chowdhury, Wasimul B. A1 - Bhuiyan, N. A. A1 - Islam, Atiqul A1 - Hasan, Nur A. A1 - Nair, G. Balakrish A1 - Watanabe, H. A1 - Siddique, A. K. A1 - Huq, Anwar A1 - Sack, R. Bradley A1 - Akhter, M. Z. A1 - Grim, Christopher J. A1 - Kam, K. M. A1 - Luey, C. K. Y. A1 - Endtz, Hubert P. A1 - Cravioto, Alejandro A1 - Rita R. Colwell AB - 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., “clonal cluster,” 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. VL - 75 SN - 0099-2240, 1098-5336 ER - TY - JOUR T1 - Toward reconstructing the evolution of advanced moths and butterflies (Lepidoptera: Ditrysia): an initial molecular study JF - BMC Evol BiolBMC Evol Biol Y1 - 2009 A1 - Regier, J. C. A1 - Zwick, A. A1 - Michael P. Cummings A1 - Kawahara, A. Y. A1 - Cho, S. A1 - Weller, S. A1 - Roe, A. A1 - Baixeras, J. A1 - Brown, J. W. A1 - Parr, C. A1 - Davis, D. R. A1 - Epstein, M. A1 - Hallwachs, W. A1 - Hausmann, A. A1 - Janzen, D. H. A1 - Kitching, I. J. A1 - Solis, M. A. A1 - Yen, S. H. A1 - Adam L. Bazinet A1 - Mitter, C. AB - 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. VL - 9 ER - TY - JOUR T1 - Computational Analysis of Constraints on Noncoding Regions, Coding Regions and Gene Expression in Relation to Plasmodium Phenotypic Diversity JF - PLoS ONEPLoS ONEPLoS ONEPLoS ONE Y1 - 2008 A1 - Essien, Kobby A1 - Sridhar Hannenhalli A1 - Stoeckert, Christian J. AB - 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'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's protein coding regions confirm observations from other eukaryotes in that transcription factors are under relatively lower constraint. Proteins relevant to the parasite'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. VL - 3 ER - TY - JOUR T1 - The draft genome of the transgenic tropical fruit tree papaya (Carica papaya Linnaeus). JF - Nature Y1 - 2008 A1 - Ming, Ray A1 - Hou, Shaobin A1 - Feng, Yun A1 - Yu, Qingyi A1 - Dionne-Laporte, Alexandre A1 - Saw, Jimmy H A1 - Senin, Pavel A1 - Wang, Wei A1 - Ly, Benjamin V A1 - Lewis, Kanako L T A1 - Salzberg, Steven L A1 - Feng, Lu A1 - Jones, Meghan R A1 - Skelton, Rachel L A1 - Murray, Jan E A1 - Chen, Cuixia A1 - Qian, Wubin A1 - Shen, Junguo A1 - Du, Peng A1 - Eustice, Moriah A1 - Tong, Eric A1 - Tang, Haibao A1 - Lyons, Eric A1 - Paull, Robert E A1 - Michael, Todd P A1 - Wall, Kerr A1 - Rice, Danny W A1 - Albert, Henrik A1 - Wang, Ming-Li A1 - Zhu, Yun J A1 - Schatz, Michael A1 - Nagarajan, Niranjan A1 - Acob, Ricelle A A1 - Guan, Peizhu A1 - Blas, Andrea A1 - Wai, Ching Man A1 - Ackerman, Christine M A1 - Ren, Yan A1 - Liu, Chao A1 - Wang, Jianmei A1 - Wang, Jianping A1 - Na, Jong-Kuk A1 - Shakirov, Eugene V A1 - Haas, Brian A1 - Thimmapuram, Jyothi A1 - Nelson, David A1 - Wang, Xiyin A1 - Bowers, John E A1 - Gschwend, Andrea R A1 - Delcher, Arthur L A1 - Singh, Ratnesh A1 - Suzuki, Jon Y A1 - Tripathi, Savarni A1 - Neupane, Kabi A1 - Wei, Hairong A1 - Irikura, Beth A1 - Paidi, Maya A1 - Jiang, Ning A1 - Zhang, Wenli A1 - Presting, Gernot A1 - Windsor, Aaron A1 - Navajas-Pérez, Rafael A1 - Torres, Manuel J A1 - Feltus, F Alex A1 - Porter, Brad A1 - Li, Yingjun A1 - Burroughs, A Max A1 - Luo, Ming-Cheng A1 - Liu, Lei A1 - Christopher, David A A1 - Mount, Stephen M A1 - Moore, Paul H A1 - Sugimura, Tak A1 - Jiang, Jiming A1 - Schuler, Mary A A1 - Friedman, Vikki A1 - Mitchell-Olds, Thomas A1 - Shippen, Dorothy E A1 - dePamphilis, Claude W A1 - Palmer, Jeffrey D A1 - Freeling, Michael A1 - Paterson, Andrew H A1 - Gonsalves, Dennis A1 - Wang, Lei A1 - Alam, Maqsudul KW - Arabidopsis KW - Carica KW - Contig Mapping KW - Databases, Genetic KW - Genes, Plant KW - Genome, Plant KW - Molecular Sequence Data KW - Plants, Genetically Modified KW - sequence alignment KW - Sequence Analysis, DNA KW - Transcription Factors KW - Tropical Climate AB -

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 'SunUp' 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's distinguishing morpho-physiological, medicinal and nutritional properties.

VL - 452 CP - 7190 M3 - 10.1038/nature06856 ER - TY - RPRT T1 - Estimating Tree-Structured Covariance Matrices via Mixed-Integer Programming with an Application to Phylogenetic Analysis of Gene Expression Y1 - 2008 A1 - Héctor Corrada Bravo A1 - Eng, K. H. A1 - Keles, S. A1 - Wahba, G. A1 - Wright, S. AB - 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. PB - Department of Statistics, University of Wisconsin VL - 1142 ER - TY - JOUR T1 - The minimum information about a genome sequence (MIGS) specification JF - Nature biotechnologyNature biotechnology Y1 - 2008 A1 - Field, Dawn A1 - Garrity, George A1 - Gray, Tanya A1 - Morrison, Norman A1 - J. Selengut A1 - Sterk, Peter A1 - Tatusova, Tatiana A1 - Thomson, Nicholas A1 - Allen, Michael J. A1 - Angiuoli, Samuel V. A1 - Ashburner, Michael A1 - Axelrod, Nelson A1 - Baldauf, Sandra A1 - Ballard, Stuart A1 - Boore, Jeffrey A1 - Cochrane, Guy A1 - Cole, James A1 - Dawyndt, Peter A1 - De Vos, Paul A1 - DePamphilis, Claude A1 - Edwards, Robert A1 - Faruque, Nadeem A1 - Feldman, Robert A1 - Gilbert, Jack A1 - Gilna, Paul A1 - Glöckner, Frank Oliver A1 - Goldstein, Philip A1 - Guralnick, Robert A1 - Haft, Dan A1 - Hancock, David A1 - Hermjakob, Henning A1 - Hertz-Fowler, Christiane A1 - Hugenholtz, Phil A1 - Joint, Ian A1 - Kagan, Leonid A1 - Kane, Matthew A1 - Kennedy, Jessie A1 - Kowalchuk, George A1 - Kottmann, Renzo A1 - Kolker, Eugene A1 - Kravitz, Saul A1 - Kyrpides, Nikos A1 - Leebens-Mack, Jim A1 - Lewis, Suzanna E. A1 - Li, Kelvin A1 - Lister, Allyson L. A1 - Lord, Phillip A1 - Maltsev, Natalia A1 - Markowitz, Victor A1 - Martiny, Jennifer A1 - Methe, Barbara A1 - Mizrachi, Ilene A1 - Moxon, Richard A1 - Nelson, Karen A1 - Parkhill, Julian A1 - Proctor, Lita A1 - White, Owen A1 - Sansone, Susanna-Assunta A1 - Spiers, Andrew A1 - Stevens, Robert A1 - Swift, Paul A1 - Taylor, Chris A1 - Tateno, Yoshio A1 - Tett, Adrian A1 - Turner, Sarah A1 - Ussery, David A1 - Vaughan, Bob A1 - Ward, Naomi A1 - Whetzel, Trish A1 - San Gil, Ingio A1 - Wilson, Gareth A1 - Wipat, Anil KW - Chromosome mapping KW - Databases, Factual KW - information dissemination KW - Information Storage and Retrieval KW - Information Theory KW - Internationality AB - 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 'transparency' of the information contained in existing genomic databases. VL - 26 N1 - http://www.ncbi.nlm.nih.gov/pubmed/18464787?dopt=Abstract ER - TY - JOUR T1 - Role of transposable elements in trypanosomatids JF - Microbes and InfectionMicrobes and Infection Y1 - 2008 A1 - Bringaud, Frederic A1 - Ghedin, Elodie A1 - Najib M. El‐Sayed A1 - Papadopoulou, Barbara KW - Cellular function KW - Domestication KW - Evolution KW - Gene expression KW - Leishmania KW - Regulation of mRNA stability KW - Retroposon KW - Transposable element KW - Trypanosoma AB - 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. VL - 10 SN - 1286-4579 ER - TY - JOUR T1 - Schistosoma mansoni: Microarray analysis of gene expression induced by host sex. JF - Exp Parasitol Y1 - 2008 A1 - Waisberg, M A1 - Lobo, F P A1 - Cerqueira, G C A1 - Passos, L K J A1 - Carvalho, O S A1 - El-Sayed, N M A1 - Franco, G R KW - Animals KW - Biomphalaria KW - Female KW - Gene expression KW - Host-Parasite Interactions KW - Male KW - Mice KW - Oligonucleotide Array Sequence Analysis KW - Reverse Transcriptase Polymerase Chain Reaction KW - RNA, Helminth KW - Schistosoma mansoni KW - Schistosomiasis mansoni KW - Sex Factors AB -

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.

VL - 120 CP - 4 M3 - 10.1016/j.exppara.2008.09.005 ER - TY - JOUR T1 - Sequence diversity and evolution of multigene families in Trypanosoma cruzi JF - Molecular and Biochemical ParasitologyMolecular and Biochemical Parasitology Y1 - 2008 A1 - Cerqueira, Gustavo C. A1 - Bartholomeu, Daniella C. A1 - DaRocha, Wanderson D. A1 - Hou, Lihua A1 - Freitas-Silva, Danielle M. A1 - Machado, Carlos Renato A1 - Najib M. El‐Sayed A1 - Teixeira, Santuza M. R. KW - Amastin KW - Gene conversion KW - Genetic diversity KW - Multigene families KW - Trypanosoma cruzi AB - 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. VL - 157 SN - 0166-6851 ER - TY - JOUR T1 - Cofactor-independent phosphoglycerate mutase is an essential gene in procyclic form Trypanosoma brucei JF - Parasitology researchParasitology research Y1 - 2007 A1 - Djikeng, A. A1 - Raverdy, S. A1 - Foster, Jeffrey S. A1 - Bartholomeu, D. A1 - Zhang, Y. A1 - Najib M. El‐Sayed A1 - Carlow, C. VL - 100 ER - TY - JOUR T1 - Evolution of genes and genomes on the Drosophila phylogeny JF - NatureNature Y1 - 2007 A1 - Clark, Andrew G. A1 - Eisen, Michael B. A1 - Smith, Douglas R. A1 - Bergman, Casey M. A1 - Oliver, Brian A1 - Markow, Therese A. A1 - Kaufman, Thomas C. A1 - Kellis, Manolis A1 - Gelbart, William A1 - Iyer, Venky N. A1 - Pollard, Daniel A. A1 - Sackton, Timothy B. A1 - Larracuente, Amanda M. A1 - Singh, Nadia D. A1 - Abad, Jose P. A1 - Abt, Dawn N. A1 - Adryan, Boris A1 - Aguade, Montserrat A1 - Akashi, Hiroshi A1 - Anderson, Wyatt W. A1 - Aquadro, Charles F. A1 - Ardell, David H. A1 - Arguello, Roman A1 - Artieri, Carlo G. A1 - Barbash, Daniel A. A1 - Barker, Daniel A1 - Barsanti, Paolo A1 - Batterham, Phil A1 - Batzoglou, Serafim A1 - Begun, Dave A1 - Bhutkar, Arjun A1 - Blanco, Enrico A1 - Bosak, Stephanie A. A1 - Bradley, Robert K. A1 - Brand, Adrianne D. A1 - Brent, Michael R. A1 - Brooks, Angela N. A1 - Brown, Randall H. A1 - Butlin, Roger K. A1 - Caggese, Corrado A1 - Calvi, Brian R. A1 - Carvalho, A. Bernardo de A1 - Caspi, Anat A1 - Castrezana, Sergio A1 - Celniker, Susan E. A1 - Chang, Jean L. A1 - Chapple, Charles A1 - Chatterji, Sourav A1 - Chinwalla, Asif A1 - Civetta, Alberto A1 - Clifton, Sandra W. A1 - Comeron, Josep M. A1 - Costello, James C. A1 - Coyne, Jerry A. A1 - Daub, Jennifer A1 - David, Robert G. A1 - Delcher, Arthur L. 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A1 - Jordan, William C. A1 - Karpen, Gary H. A1 - Kataoka, Eiko A1 - Keightley, Peter D. A1 - Kheradpour, Pouya A1 - Kirkness, Ewen F. A1 - Koerich, Leonardo B. A1 - Kristiansen, Karsten A1 - Kudrna, Dave A1 - Kulathinal, Rob J. A1 - Kumar, Sudhir A1 - Kwok, Roberta A1 - Lander, Eric A1 - Langley, Charles H. A1 - Lapoint, Richard A1 - Lazzaro, Brian P. A1 - Lee, So-Jeong A1 - Levesque, Lisa A1 - Li, Ruiqiang A1 - Lin, Chiao-Feng A1 - Lin, Michael F. A1 - Lindblad-Toh, Kerstin A1 - Llopart, Ana A1 - Long, Manyuan A1 - Low, Lloyd A1 - Lozovsky, Elena A1 - Lu, Jian A1 - Luo, Meizhong A1 - Machado, Carlos A. A1 - Makalowski, Wojciech A1 - Marzo, Mar A1 - Matsuda, Muneo A1 - Matzkin, Luciano A1 - McAllister, Bryant A1 - McBride, Carolyn S. A1 - McKernan, Brendan A1 - McKernan, Kevin A1 - Mendez-Lago, Maria A1 - Minx, Patrick A1 - Mollenhauer, Michael U. A1 - Montooth, Kristi A1 - Stephen M. 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A1 - Franke, Alicia A1 - Friedrich, Dennis A1 - Gadbois, Loryn A1 - Gearin, Gary A1 - Gearin, Christina R. A1 - Giannoukos, Georgia A1 - Goode, Tina A1 - Graham, Joseph A1 - Grandbois, Edward A1 - Grewal, Sharleen A1 - Gyaltsen, Kunsang A1 - Hafez, Nabil A1 - Hagos, Birhane A1 - Hall, Jennifer A1 - Henson, Charlotte A1 - Hollinger, Andrew A1 - Honan, Tracey A1 - Huard, Monika D. A1 - Hughes, Leanne A1 - Hurhula, Brian A1 - Husby, M. Erii A1 - Kamat, Asha A1 - Kanga, Ben A1 - Kashin, Seva A1 - Khazanovich, Dmitry A1 - Kisner, Peter A1 - Lance, Krista A1 - Lara, Marcia A1 - Lee, William A1 - Lennon, Niall A1 - Letendre, Frances A1 - LeVine, Rosie A1 - Lipovsky, Alex A1 - Liu, Xiaohong A1 - Liu, Jinlei A1 - Liu, Shangtao A1 - Lokyitsang, Tashi A1 - Lokyitsang, Yeshi A1 - Lubonja, Rakela A1 - Lui, Annie A1 - MacDonald, Pen A1 - Magnisalis, Vasilia A1 - Maru, Kebede A1 - Matthews, Charles A1 - McCusker, William A1 - McDonough, Susan A1 - Mehta, Teena A1 - Meldrim, James A1 - Meneus, Louis A1 - Mihai, Oana A1 - Mihalev, Atanas A1 - Mihova, Tanya A1 - Mittelman, Rachel A1 - Mlenga, Valentine A1 - Montmayeur, Anna A1 - Mulrain, Leonidas A1 - Navidi, Adam A1 - Naylor, Jerome A1 - Negash, Tamrat A1 - Nguyen, Thu A1 - Nguyen, Nga A1 - Nicol, Robert A1 - Norbu, Choe A1 - Norbu, Nyima A1 - Novod, Nathaniel A1 - O'Neill, Barry A1 - Osman, Sahal A1 - Markiewicz, Eva A1 - Oyono, Otero L. A1 - Patti, Christopher A1 - Phunkhang, Pema A1 - Pierre, Fritz A1 - Priest, Margaret A1 - Raghuraman, Sujaa A1 - Rege, Filip A1 - Reyes, Rebecca A1 - Rise, Cecil A1 - Rogov, Peter A1 - Ross, Keenan A1 - Ryan, Elizabeth A1 - Settipalli, Sampath A1 - Shea, Terry A1 - Sherpa, Ngawang A1 - Shi, Lu A1 - Shih, Diana A1 - Sparrow, Todd A1 - Spaulding, Jessica A1 - Stalker, John A1 - Stange-Thomann, Nicole A1 - Stavropoulos, Sharon A1 - Stone, Catherine A1 - Strader, Christopher A1 - Tesfaye, Senait A1 - Thomson, Talene A1 - Thoulutsang, Yama A1 - Thoulutsang, Dawa A1 - Topham, Kerri A1 - Topping, Ira A1 - Tsamla, Tsamla A1 - Vassiliev, Helen A1 - Vo, Andy A1 - Wangchuk, Tsering A1 - Wangdi, Tsering A1 - Weiand, Michael A1 - Wilkinson, Jane A1 - Wilson, Adam A1 - Yadav, Shailendra A1 - Young, Geneva A1 - Yu, Qing A1 - Zembek, Lisa A1 - Zhong, Danni A1 - Zimmer, Andrew A1 - Zwirko, Zac A1 - Jaffe, David B. A1 - Alvarez, Pablo A1 - Brockman, Will A1 - Butler, Jonathan A1 - Chin, CheeWhye A1 - Gnerre, Sante A1 - Grabherr, Manfred A1 - Kleber, Michael A1 - Mauceli, Evan A1 - MacCallum, Iain AB - 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. VL - 450 SN - 0028-0836 N1 - [szlig] ER - TY - JOUR T1 - Evolution of genes and genomes on the Drosophila phylogeny. JF - Nature Y1 - 2007 A1 - Clark, Andrew G A1 - Eisen, Michael B A1 - Smith, Douglas R A1 - Bergman, Casey M A1 - Oliver, Brian A1 - Markow, Therese A A1 - Kaufman, Thomas C A1 - Kellis, Manolis A1 - Gelbart, William A1 - Iyer, Venky N A1 - Pollard, Daniel A A1 - Sackton, Timothy B A1 - Larracuente, Amanda M A1 - Singh, Nadia D A1 - Abad, Jose P A1 - Abt, Dawn N A1 - Adryan, Boris A1 - Aguade, Montserrat A1 - Akashi, Hiroshi A1 - Anderson, Wyatt W A1 - Aquadro, Charles F A1 - Ardell, David H A1 - Arguello, Roman A1 - Artieri, Carlo G A1 - Barbash, Daniel A A1 - Barker, Daniel A1 - Barsanti, Paolo A1 - Batterham, Phil A1 - Batzoglou, Serafim A1 - Begun, Dave A1 - Bhutkar, Arjun A1 - Blanco, Enrico A1 - Bosak, Stephanie A A1 - Bradley, Robert K A1 - Brand, Adrianne D A1 - Brent, Michael R A1 - Brooks, Angela N A1 - Brown, Randall H A1 - Butlin, Roger K A1 - Caggese, Corrado A1 - Calvi, Brian R A1 - Bernardo de Carvalho, A A1 - Caspi, Anat A1 - Castrezana, Sergio A1 - Celniker, Susan E A1 - Chang, Jean L A1 - Chapple, Charles A1 - Chatterji, Sourav A1 - Chinwalla, Asif A1 - Civetta, Alberto A1 - Clifton, Sandra W A1 - Comeron, Josep M A1 - Costello, James C A1 - Coyne, Jerry A A1 - Daub, Jennifer A1 - David, Robert G A1 - Delcher, Arthur L A1 - Delehaunty, Kim A1 - Do, Chuong B A1 - Ebling, Heather A1 - Edwards, Kevin A1 - Eickbush, Thomas A1 - Evans, Jay D A1 - Filipski, Alan A1 - Findeiss, Sven A1 - Freyhult, Eva A1 - Fulton, Lucinda A1 - Fulton, Robert A1 - Garcia, Ana C L A1 - Gardiner, Anastasia A1 - Garfield, David A A1 - Garvin, Barry E A1 - Gibson, Greg A1 - Gilbert, Don A1 - Gnerre, Sante A1 - Godfrey, Jennifer A1 - Good, Robert A1 - Gotea, Valer A1 - Gravely, Brenton A1 - Greenberg, Anthony J A1 - Griffiths-Jones, Sam A1 - Gross, Samuel A1 - Guigo, Roderic A1 - Gustafson, Erik A A1 - Haerty, Wilfried A1 - Hahn, Matthew W A1 - Halligan, Daniel L A1 - Halpern, Aaron L A1 - Halter, Gillian M A1 - Han, Mira V A1 - Heger, Andreas A1 - Hillier, LaDeana A1 - Hinrichs, Angie S A1 - Holmes, Ian A1 - Hoskins, Roger A A1 - Hubisz, Melissa J A1 - Hultmark, Dan A1 - Huntley, Melanie A A1 - Jaffe, David B A1 - Jagadeeshan, Santosh A1 - Jeck, William R A1 - Johnson, Justin A1 - Jones, Corbin D A1 - Jordan, William C A1 - Karpen, Gary H A1 - Kataoka, Eiko A1 - Keightley, Peter D A1 - Kheradpour, Pouya A1 - Kirkness, Ewen F A1 - Koerich, Leonardo B A1 - Kristiansen, Karsten A1 - Kudrna, Dave A1 - Kulathinal, Rob J A1 - Kumar, Sudhir A1 - Kwok, Roberta A1 - Lander, Eric A1 - Langley, Charles H A1 - Lapoint, Richard A1 - Lazzaro, Brian P A1 - Lee, So-Jeong A1 - Levesque, Lisa A1 - Li, Ruiqiang A1 - Lin, Chiao-Feng A1 - Lin, Michael F A1 - Lindblad-Toh, Kerstin A1 - Llopart, Ana A1 - Long, Manyuan A1 - Low, Lloyd A1 - Lozovsky, Elena A1 - Lu, Jian A1 - Luo, Meizhong A1 - Machado, Carlos A A1 - Makalowski, Wojciech A1 - Marzo, Mar A1 - Matsuda, Muneo A1 - Matzkin, Luciano A1 - McAllister, Bryant A1 - McBride, Carolyn S A1 - McKernan, Brendan A1 - McKernan, Kevin A1 - Mendez-Lago, Maria A1 - Minx, Patrick A1 - Mollenhauer, Michael U A1 - Montooth, Kristi A1 - Mount, Stephen M A1 - Mu, Xu A1 - Myers, Eugene A1 - Negre, Barbara A1 - Newfeld, Stuart A1 - Nielsen, Rasmus A1 - Noor, Mohamed A F A1 - O'Grady, Patrick A1 - Pachter, Lior A1 - Papaceit, Montserrat A1 - Parisi, Matthew J A1 - Parisi, Michael A1 - Parts, Leopold A1 - Pedersen, Jakob S A1 - Pesole, Graziano A1 - Phillippy, Adam M A1 - Ponting, Chris P A1 - Pop, Mihai A1 - Porcelli, Damiano A1 - Powell, Jeffrey R A1 - Prohaska, Sonja A1 - Pruitt, Kim A1 - Puig, Marta A1 - Quesneville, Hadi A1 - Ram, Kristipati Ravi A1 - Rand, David A1 - Rasmussen, Matthew D A1 - Reed, Laura K A1 - Reenan, Robert A1 - Reily, Amy A1 - Remington, Karin A A1 - Rieger, Tania T A1 - Ritchie, Michael G A1 - Robin, Charles A1 - Rogers, Yu-Hui A1 - Rohde, Claudia A1 - Rozas, Julio A1 - Rubenfield, Marc J A1 - Ruiz, Alfredo A1 - Russo, Susan A1 - Salzberg, Steven L A1 - Sanchez-Gracia, Alejandro A1 - Saranga, David J A1 - Sato, Hajime A1 - Schaeffer, Stephen W A1 - Schatz, Michael C A1 - Schlenke, Todd A1 - Schwartz, Russell A1 - Segarra, Carmen A1 - Singh, Rama S A1 - Sirot, Laura A1 - Sirota, Marina A1 - Sisneros, Nicholas B A1 - Smith, Chris D A1 - Smith, Temple F A1 - Spieth, John A1 - Stage, Deborah E A1 - Stark, Alexander A1 - Stephan, Wolfgang A1 - Strausberg, Robert L A1 - Strempel, Sebastian A1 - Sturgill, David A1 - Sutton, Granger A1 - Sutton, Granger G A1 - Tao, Wei A1 - Teichmann, Sarah A1 - Tobari, Yoshiko N A1 - Tomimura, Yoshihiko A1 - Tsolas, Jason M A1 - Valente, Vera L S A1 - Venter, Eli A1 - Venter, J Craig A1 - Vicario, Saverio A1 - Vieira, Filipe G A1 - Vilella, Albert J A1 - Villasante, Alfredo A1 - Walenz, Brian A1 - Wang, Jun A1 - Wasserman, Marvin A1 - Watts, Thomas A1 - Wilson, Derek A1 - Wilson, Richard K A1 - Wing, Rod A A1 - Wolfner, Mariana F A1 - Wong, Alex A1 - Wong, Gane Ka-Shu A1 - Wu, Chung-I A1 - Wu, Gabriel A1 - Yamamoto, Daisuke A1 - Yang, Hsiao-Pei A1 - Yang, Shiaw-Pyng A1 - Yorke, James A A1 - Yoshida, Kiyohito A1 - Zdobnov, Evgeny A1 - Zhang, Peili A1 - Zhang, Yu A1 - Zimin, Aleksey V A1 - Baldwin, Jennifer A1 - Abdouelleil, Amr A1 - Abdulkadir, Jamal A1 - Abebe, Adal A1 - Abera, Brikti A1 - Abreu, Justin A1 - Acer, St Christophe A1 - Aftuck, Lynne A1 - Alexander, Allen A1 - An, Peter A1 - Anderson, Erica A1 - Anderson, Scott A1 - Arachi, Harindra A1 - Azer, Marc A1 - Bachantsang, Pasang A1 - Barry, Andrew A1 - Bayul, Tashi A1 - Berlin, Aaron A1 - Bessette, Daniel A1 - Bloom, Toby A1 - Blye, Jason A1 - Boguslavskiy, Leonid A1 - Bonnet, Claude A1 - Boukhgalter, Boris A1 - Bourzgui, Imane A1 - Brown, Adam A1 - Cahill, Patrick A1 - Channer, Sheridon A1 - Cheshatsang, Yama A1 - Chuda, Lisa A1 - Citroen, Mieke A1 - Collymore, Alville A1 - Cooke, Patrick A1 - Costello, Maura A1 - D'Aco, Katie A1 - Daza, Riza A1 - De Haan, Georgius A1 - DeGray, Stuart A1 - DeMaso, Christina A1 - Dhargay, Norbu A1 - Dooley, Kimberly A1 - Dooley, Erin A1 - Doricent, Missole A1 - Dorje, Passang A1 - Dorjee, Kunsang A1 - Dupes, Alan A1 - Elong, Richard A1 - Falk, Jill A1 - Farina, Abderrahim A1 - Faro, Susan A1 - Ferguson, Diallo A1 - Fisher, Sheila A1 - Foley, Chelsea D A1 - Franke, Alicia A1 - Friedrich, Dennis A1 - Gadbois, Loryn A1 - Gearin, Gary A1 - Gearin, Christina R A1 - Giannoukos, Georgia A1 - Goode, Tina A1 - Graham, Joseph A1 - Grandbois, Edward A1 - Grewal, Sharleen A1 - Gyaltsen, Kunsang A1 - Hafez, Nabil A1 - Hagos, Birhane A1 - Hall, Jennifer A1 - Henson, Charlotte A1 - Hollinger, Andrew A1 - Honan, Tracey A1 - Huard, Monika D A1 - Hughes, Leanne A1 - Hurhula, Brian A1 - Husby, M Erii A1 - Kamat, Asha A1 - Kanga, Ben A1 - Kashin, Seva A1 - Khazanovich, Dmitry A1 - Kisner, Peter A1 - Lance, Krista A1 - Lara, Marcia A1 - Lee, William A1 - Lennon, Niall A1 - Letendre, Frances A1 - LeVine, Rosie A1 - Lipovsky, Alex A1 - Liu, Xiaohong A1 - Liu, Jinlei A1 - Liu, Shangtao A1 - Lokyitsang, Tashi A1 - Lokyitsang, Yeshi A1 - Lubonja, Rakela A1 - Lui, Annie A1 - MacDonald, Pen A1 - Magnisalis, Vasilia A1 - Maru, Kebede A1 - Matthews, Charles A1 - McCusker, William A1 - McDonough, Susan A1 - Mehta, Teena A1 - Meldrim, James A1 - Meneus, Louis A1 - Mihai, Oana A1 - Mihalev, Atanas A1 - Mihova, Tanya A1 - Mittelman, Rachel A1 - Mlenga, Valentine A1 - Montmayeur, Anna A1 - Mulrain, Leonidas A1 - Navidi, Adam A1 - Naylor, Jerome A1 - Negash, Tamrat A1 - Nguyen, Thu A1 - Nguyen, Nga A1 - Nicol, Robert A1 - Norbu, Choe A1 - Norbu, Nyima A1 - Novod, Nathaniel A1 - O'Neill, Barry A1 - Osman, Sahal A1 - Markiewicz, Eva A1 - Oyono, Otero L A1 - Patti, Christopher A1 - Phunkhang, Pema A1 - Pierre, Fritz A1 - Priest, Margaret A1 - Raghuraman, Sujaa A1 - Rege, Filip A1 - Reyes, Rebecca A1 - Rise, Cecil A1 - Rogov, Peter A1 - Ross, Keenan A1 - Ryan, Elizabeth A1 - Settipalli, Sampath A1 - Shea, Terry A1 - Sherpa, Ngawang A1 - Shi, Lu A1 - Shih, Diana A1 - Sparrow, Todd A1 - Spaulding, Jessica A1 - Stalker, John A1 - Stange-Thomann, Nicole A1 - Stavropoulos, Sharon A1 - Stone, Catherine A1 - Strader, Christopher A1 - Tesfaye, Senait A1 - Thomson, Talene A1 - Thoulutsang, Yama A1 - Thoulutsang, Dawa A1 - Topham, Kerri A1 - Topping, Ira A1 - Tsamla, Tsamla A1 - Vassiliev, Helen A1 - Vo, Andy A1 - Wangchuk, Tsering A1 - Wangdi, Tsering A1 - Weiand, Michael A1 - Wilkinson, Jane A1 - Wilson, Adam A1 - Yadav, Shailendra A1 - Young, Geneva A1 - Yu, Qing A1 - Zembek, Lisa A1 - Zhong, Danni A1 - Zimmer, Andrew A1 - Zwirko, Zac A1 - Jaffe, David B A1 - Alvarez, Pablo A1 - Brockman, Will A1 - Butler, Jonathan A1 - Chin, CheeWhye A1 - Gnerre, Sante A1 - Grabherr, Manfred A1 - Kleber, Michael A1 - Mauceli, Evan A1 - MacCallum, Iain KW - Animals KW - Codon KW - DNA Transposable Elements KW - Drosophila KW - Drosophila Proteins KW - Evolution, Molecular KW - Gene Order KW - Genes, Insect KW - Genome, Insect KW - Genome, Mitochondrial KW - Genomics KW - Immunity KW - Multigene Family KW - Phylogeny KW - Reproduction KW - RNA, Untranslated KW - sequence alignment KW - Sequence Analysis, DNA KW - Synteny AB -

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.

VL - 450 CP - 7167 M3 - 10.1038/nature06341 ER - TY - JOUR T1 - The Expression of a Plant-type Ferredoxin Redox System provides Molecular Evidence for a Plastid in the Early Dinoflagellate Perkinsus marinus JF - ProtistProtist Y1 - 2007 A1 - Stelter, Kathrin A1 - Najib M. El‐Sayed A1 - Seeber, Frank KW - Apicomplexa KW - ferredoxin KW - Perkinsozoa KW - plastid KW - transit peptide AB - 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). VL - 158 SN - 1434-4610 ER - TY - JOUR T1 - Members of a large retroposon family are determinants of post-transcriptional gene expression in Leishmania. JF - PLoS Pathog Y1 - 2007 A1 - Bringaud, Frederic A1 - Müller, Michaela A1 - Cerqueira, Gustavo Coutinho A1 - Smith, Martin A1 - Rochette, Annie A1 - el-Sayed, Najib M A A1 - Papadopoulou, Barbara A1 - Ghedin, Elodie KW - 3' Untranslated Regions KW - Animals KW - Base Sequence KW - Biological Evolution KW - Down-Regulation KW - Gene Expression Regulation KW - Genome, Protozoan KW - Leishmania KW - Leishmania major KW - Molecular Sequence Data KW - Retroelements KW - RNA, Messenger KW - sequence alignment KW - Trypanosoma brucei brucei KW - Trypanosoma cruzi AB -

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'-untranslated regions (3'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'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.

VL - 3 CP - 9 M3 - 10.1371/journal.ppat.0030136 ER - TY - JOUR T1 - Microarray analysis of gene expression induced by sexual contact in Schistosoma mansoni JF - BMC GenomicsBMC Genomics Y1 - 2007 A1 - Waisberg, Michael A1 - Lobo, Francisco A1 - Cerqueira, Gustavo A1 - Passos, Liana A1 - Carvalho, Omar A1 - Franco, Gloria A1 - Najib M. El‐Sayed AB - 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. VL - 8 SN - 1471-2164 ER - TY - JOUR T1 - New Trypanosoma cruzi Repeated Element That Shows Site Specificity for Insertion JF - Eukaryotic CellEukaryotic Cell Y1 - 2007 A1 - Souza, Renata T. A1 - Santos, Marcia R. M. A1 - Lima, Fabio M. A1 - Najib M. El‐Sayed A1 - Myler, Peter J. A1 - Ruiz, Jeronimo C. A1 - da Silveira, Jose Franco AB - 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' end of the element and a sequence domain of [~]500 bp without a well-defined borderline at the 3' 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. VL - 6 ER - TY - JOUR T1 - Schistosoma mansoni genome: Closing in on a final gene set JF - Experimental ParasitologyExperimental Parasitology Y1 - 2007 A1 - Haas, Brian J. A1 - Berriman, Matthew A1 - Hirai, Hirohisa A1 - Cerqueira, Gustavo G. A1 - LoVerde, Philip T. A1 - Najib M. El‐Sayed KW - Annotation KW - Gene finding KW - Genome KW - Schistosoma mansoni AB - 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. VL - 117 SN - 0014-4894 ER - TY - JOUR T1 - Analysis of fat body transcriptome from the adult tsetse fly, Glossina morsitans morsitans. JF - Insect Mol Biol Y1 - 2006 A1 - Attardo, G M A1 - Strickler-Dinglasan, P A1 - Perkin, S A H A1 - Caler, E A1 - Bonaldo, M F A1 - Soares, M B A1 - El-Sayeed, N A1 - Aksoy, S KW - Adipose Tissue KW - Animals KW - Base Sequence KW - Computational Biology KW - DNA Primers KW - Egg Proteins KW - Expressed Sequence Tags KW - Female KW - Gene Expression Profiling KW - Insect Vectors KW - Male KW - Molecular Sequence Data KW - Reverse Transcriptase Polymerase Chain Reaction KW - Sequence Analysis, DNA KW - Sex Factors KW - Tsetse Flies AB -

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'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.

VL - 15 CP - 4 M3 - 10.1111/j.1365-2583.2006.00649.x ER - TY - JOUR T1 - Comparative genomics of emerging human ehrlichiosis agents JF - PLoS geneticsPLoS genetics Y1 - 2006 A1 - Dunning Hotopp, Julie C. A1 - Lin, Mingqun A1 - Madupu, Ramana A1 - Crabtree, Jonathan A1 - Angiuoli, Samuel V. A1 - Eisen, Jonathan A. A1 - Eisen, Jonathan A1 - Seshadri, Rekha A1 - Ren, Qinghu A1 - Wu, Martin A1 - Utterback, Teresa R. A1 - Smith, Shannon A1 - Lewis, Matthew A1 - Khouri, Hoda A1 - Zhang, Chunbin A1 - Niu, Hua A1 - Lin, Quan A1 - Ohashi, Norio A1 - Zhi, Ning A1 - Nelson, William A1 - Brinkac, Lauren M. A1 - Dodson, Robert J. A1 - Rosovitz, M. J. A1 - Sundaram, Jaideep A1 - Daugherty, Sean C. A1 - Davidsen, Tanja A1 - Durkin, Anthony S. A1 - Gwinn, Michelle A1 - Haft, Daniel H. A1 - J. Selengut A1 - Sullivan, Steven A. A1 - Zafar, Nikhat A1 - Zhou, Liwei A1 - Benahmed, Faiza A1 - Forberger, Heather A1 - Halpin, Rebecca A1 - Mulligan, Stephanie A1 - Robinson, Jeffrey A1 - White, Owen A1 - Rikihisa, Yasuko A1 - Tettelin, Hervé KW - Animals KW - Biotin KW - DNA Repair KW - Ehrlichia KW - Ehrlichiosis KW - Genome KW - Genomics KW - HUMANS KW - Models, Biological KW - Phylogeny KW - Rickettsia KW - Ticks AB - 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. VL - 2 N1 - http://www.ncbi.nlm.nih.gov/pubmed/16482227?dopt=Abstract ER - TY - CHAP T1 - Conservation Patterns in cis-Elements Reveal Compensatory Mutations T2 - Comparative GenomicsComparative Genomics Y1 - 2006 A1 - Evans, Perry A1 - Donahue, Greg A1 - Sridhar Hannenhalli ED - Bourque, Guillaume ED - El-Mabrouk, Nadia AB - 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—Elk-1 and SAP-1 where the inferred compensatory mutation is consistent with known TF-DNA crystal structure. JA - Comparative GenomicsComparative Genomics T3 - Lecture Notes in Computer Science PB - Springer Berlin / Heidelberg VL - 4205 SN - 978-3-540-44529-6 ER - TY - JOUR T1 - Dense Subgraph Computation Via Stochastic Search: Application to Detect Transcriptional Modules JF - BioinformaticsBioinformaticsBioinformaticsBioinformatics Y1 - 2006 A1 - Everett, Logan A1 - Wang, Li-San A1 - Sridhar Hannenhalli AB - 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—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 VL - 22 SN - 1367-4803, 1460-2059 ER - TY - JOUR T1 - Evolution of non-LTR retrotransposons in the trypanosomatid genomes: Leishmania major has lost the active elements JF - Molecular and Biochemical ParasitologyMolecular and Biochemical Parasitology Y1 - 2006 A1 - Bringaud, Frederic A1 - Ghedin, Elodie A1 - Blandin, Gaëlle A1 - Bartholomeu, Daniella C. A1 - Caler, Elisabet A1 - Levin, Mariano J. A1 - Baltz, Théo A1 - Najib M. El‐Sayed KW - Degenerate retroelement KW - Evolution KW - Ingi KW - L1Tc KW - Leishmania major KW - Non-LTR retrotransposon KW - Retroposon KW - Trypanosoma brucei KW - Trypanosoma cruzi AB - 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'-extremity of all the full length DIREs and suggests a possible role for this conserved motif, as well as for DIREs. VL - 145 SN - 0166-6851 ER - TY - JOUR T1 - Metagenomic Analysis of the Human Distal Gut Microbiome JF - ScienceScienceScienceScience Y1 - 2006 A1 - Gill, Steven R. A1 - M. Pop A1 - DeBoy, Robert T. A1 - Eckburg, Paul B. A1 - Turnbaugh, Peter J. A1 - Samuel, Buck S. A1 - Gordon, Jeffrey I. A1 - Relman, David A. A1 - Fraser-Liggett, Claire M. A1 - Nelson, Karen E. AB - The human intestinal microbiota is composed of 1013 to 1014 microorganisms whose collective genome (“microbiome”) 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–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–mediated biosynthesis of vitamins and isoprenoids. Thus, humans are superorganisms whose metabolism represents an amalgamation of microbial and human attributes. VL - 312 SN - 0036-8075, 1095-9203 ER - TY - JOUR T1 - Retroviral DNA integration: viral and cellular determinants of target-site selection JF - PLoS pathogensPLoS pathogens Y1 - 2006 A1 - Lewinski, M. K. A1 - Yamashita, M. A1 - Emerman, M. A1 - Ciuffi, A. A1 - Marshall, H. A1 - Crawford, G. A1 - Collins, F. A1 - Shinn, P. A1 - Leipzig, J. A1 - Sridhar Hannenhalli A1 - others, PB - Public Library of Science VL - 2 ER - TY - JOUR T1 - Schistosoma mansoni (Platyhelminthes, Trematoda) nuclear receptors: Sixteen new members and a novel subfamily JF - GeneGene Y1 - 2006 A1 - Wu, Wenjie A1 - Niles, Edward G. A1 - Najib M. El‐Sayed A1 - Berriman, Matthew A1 - LoVerde, Philip T. KW - Nuclear receptors KW - Schistosoma mansoni AB - 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. VL - 366 SN - 0378-1119 ER - TY - JOUR T1 - Transcriptional Genomics Associates FOX Transcription Factors With Human Heart Failure JF - CirculationCirculation Y1 - 2006 A1 - Sridhar Hannenhalli A1 - Putt, Mary E. A1 - Gilmore, Joan M. A1 - Wang, Junwen A1 - Parmacek, Michael S. A1 - Epstein, Jonathan A. A1 - Morrisey, Edward E. A1 - Margulies, Kenneth B. A1 - Cappola, Thomas P. AB - Background— 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— 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— 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. VL - 114 ER - TY - JOUR T1 - The Trypanosoma cruzi L1Tc and NARTc non-LTR retrotransposons show relative site specificity for insertion JF - Molecular biology and evolutionMolecular biology and evolution Y1 - 2006 A1 - Bringaud, F. A1 - Bartholomeu, D. C. A1 - Blandin, G. A1 - Delcher, A. A1 - Baltz, T. A1 - Najib M. El‐Sayed A1 - Ghedin, E. VL - 23 ER - TY - JOUR T1 - The Trypanosoma cruzi L1Tc and NARTc non-LTR retrotransposons show relative site specificity for insertion. JF - Mol Biol Evol Y1 - 2006 A1 - Bringaud, Frederic A1 - Bartholomeu, Daniella C A1 - Blandin, Gaëlle A1 - Delcher, Arthur A1 - Baltz, Théo A1 - el-Sayed, Najib M A A1 - Ghedin, Elodie KW - Animals KW - DNA, Protozoan KW - DNA-(Apurinic or Apyrimidinic Site) Lyase KW - Mutagenesis, Insertional KW - Retroelements KW - Sequence Deletion KW - Trypanosoma cruzi AB -

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'-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.

VL - 23 CP - 2 M3 - 10.1093/molbev/msj046 ER - TY - JOUR T1 - Trypanosoma cruzi mitochondrial maxicircles display species- and strain-specific variation and a conserved element in the non-coding region. JF - BMC Genomics Y1 - 2006 A1 - Westenberger, Scott J A1 - Cerqueira, Gustavo C A1 - El-Sayed, Najib M A1 - Zingales, Bianca A1 - Campbell, David A A1 - Sturm, Nancy R KW - Amino Acid Sequence KW - Animals KW - Animals, Inbred Strains KW - Base Composition KW - Conserved Sequence KW - DNA, Kinetoplast KW - Frameshifting, Ribosomal KW - Gene Deletion KW - Gene Order KW - Genetic Variation KW - Leishmania KW - Models, Biological KW - Molecular Sequence Data KW - Muscle Proteins KW - NADH Dehydrogenase KW - Open Reading Frames KW - Regulatory Elements, Transcriptional KW - RNA Editing KW - Sequence Homology, Amino Acid KW - Species Specificity KW - Trypanosoma brucei brucei KW - Trypanosoma cruzi KW - Ubiquitin-Protein Ligases KW - Untranslated Regions AB -

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'-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.

VL - 7 M3 - 10.1186/1471-2164-7-60 ER - TY - JOUR T1 - Trypanosoma cruzi mitochondrial maxicircles display species- and strain-specific variation and a conserved element in the non-coding region JF - BMC GenomicsBMC Genomics Y1 - 2006 A1 - Westenberger, Scott A1 - Cerqueira, Gustavo A1 - Najib M. El‐Sayed A1 - Zingales, Bianca A1 - Campbell, David A1 - Sturm, Nancy AB - 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'-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. VL - 7 SN - 1471-2164 ER - TY - JOUR T1 - Comparative Genomics of Trypanosomatid Parasitic Protozoa JF - ScienceScience Y1 - 2005 A1 - Najib M. El‐Sayed A1 - Myler, Peter J. A1 - Blandin, Gaëlle A1 - Berriman, Matthew A1 - Crabtree, Jonathan A1 - Aggarwal, Gautam A1 - Caler, Elisabet A1 - Renauld, Hubert A1 - Worthey, Elizabeth A. A1 - Hertz-Fowler, Christiane A1 - Ghedin, Elodie A1 - Peacock, Christopher A1 - Bartholomeu, Daniella C. A1 - Haas, Brian J. A1 - Tran, Anh-Nhi A1 - Wortman, Jennifer R. A1 - Alsmark, U. Cecilia M. A1 - Angiuoli, Samuel A1 - Anupama, Atashi A1 - Badger, Jonathan A1 - Bringaud, Frederic A1 - Cadag, Eithon A1 - Carlton, Jane M. A1 - Cerqueira, Gustavo C. A1 - Creasy, Todd A1 - Delcher, Arthur L. A1 - Djikeng, Appolinaire A1 - Embley, T. Martin A1 - Hauser, Christopher A1 - Ivens, Alasdair C. A1 - Kummerfeld, Sarah K. A1 - Pereira-Leal, Jose B. A1 - Nilsson, Daniel A1 - Peterson, Jeremy A1 - Salzberg, Steven L. A1 - Shallom, Joshua A1 - Silva, Joana C. A1 - Sundaram, Jaideep A1 - Westenberger, Scott A1 - White, Owen A1 - Melville, Sara E. A1 - Donelson, John E. A1 - Andersson, Björn A1 - Stuart, Kenneth D. A1 - Hall, Neil AB - 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—along with gene divergence, acquisition and loss, and rearrangement within the syntenic regions—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. VL - 309 ER - TY - JOUR T1 - The genetic map and comparative analysis with the physical map of Trypanosoma brucei JF - Nucleic acids researchNucleic Acids Research Y1 - 2005 A1 - MacLeod, A. A1 - Tweedie, A. A1 - McLellan, S. A1 - Taylor, S. A1 - Hall, N. A1 - Berriman, M. A1 - Najib M. El‐Sayed A1 - Hope, M. A1 - Turner, C. M. R. A1 - Tait, A. VL - 33 ER - TY - JOUR T1 - The genome sequence of Trypanosoma cruzi, etiologic agent of Chagas disease JF - ScienceScience Y1 - 2005 A1 - Najib M. El‐Sayed A1 - Myler, P. J. A1 - Bartholomeu, D. C. A1 - Nilsson, D. A1 - Aggarwal, G. A1 - Tran, A. N. A1 - Ghedin, E. A1 - Worthey, E. A. A1 - Delcher, A. L. A1 - Blandin, G. A1 - others, PB - American Association for the Advancement of Science VL - 309 ER - TY - JOUR T1 - Genome-Wide Analysis of Chromosomal Features Repressing Human Immunodeficiency Virus Transcription JF - Journal of VirologyJ. Virol.Journal of VirologyJ. Virol. Y1 - 2005 A1 - Lewinski, M. K. A1 - Bisgrove, D. A1 - Shinn, P. A1 - Chen, H. A1 - Hoffmann, C. A1 - Sridhar Hannenhalli A1 - Verdin, E. A1 - Berry, C. C. A1 - Ecker, J. R. A1 - Bushman, F. D. AB - 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. VL - 79 SN - 0022-538X, 1098-5514 ER - TY - JOUR T1 - Promoter architecture and response to a positive regulator of archaeal transcription JF - Molecular MicrobiologyMolecular Microbiology Y1 - 2005 A1 - Ouhammouch, Mohamed A1 - Langham, Geoffrey E. A1 - Hausner, Winfried A1 - Simpson, Anjana J. A1 - Najib M. El‐Sayed A1 - Geiduschek, E. Peter AB - 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 ‘one-site’ 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. VL - 56 SN - 1365-2958 ER - TY - JOUR T1 - Serendipitous discovery of Wolbachia genomes in multiple Drosophila species JF - Genome BiologyGenome Biology Y1 - 2005 A1 - Salzberg, Steven L. A1 - Hotopp, Julie C. D. A1 - Delcher, Arthur L. A1 - M. Pop A1 - Smith, Douglas R. A1 - Eisen, Michael B. A1 - Nelson, William C. AB - 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. VL - 6 SN - 1465-6906 ER - TY - JOUR T1 - 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. JF - Gene Y1 - 2005 A1 - Kim, Dong A1 - Chiurillo, Miguel Angel A1 - El-Sayed, Najib A1 - Jones, Kristin A1 - Santos, Márcia R M A1 - Porcile, Patricio E A1 - Andersson, Björn A1 - Myler, Peter A1 - da Silveira, Jose Franco A1 - Ramírez, José Luis KW - Amino Acid Sequence KW - Animals KW - Base Sequence KW - Chromosomes KW - Chromosomes, Artificial, Bacterial KW - DNA, Protozoan KW - Genes, Protozoan KW - Glycoproteins KW - Molecular Sequence Data KW - Multigene Family KW - Neuraminidase KW - Pseudogenes KW - Retroelements KW - Sequence Homology, Amino Acid KW - Sequence Homology, Nucleic Acid KW - Telomere KW - Trypanosoma cruzi AB -

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.

VL - 346 M3 - 10.1016/j.gene.2004.10.014 ER - TY - JOUR T1 - Transcriptional profiling of the hyperthermophilic methanarchaeon Methanococcus jannaschii in response to lethal heat and non-lethal cold shock. JF - Environ Microbiol Y1 - 2005 A1 - Boonyaratanakornkit, Boonchai B A1 - Simpson, Anjana J A1 - Whitehead, Timothy A A1 - Fraser, Claire M A1 - el-Sayed, Najib M A A1 - Clark, Douglas S KW - Adaptation, Physiological KW - Archaeal Proteins KW - Cold Temperature KW - Gene Expression Profiling KW - Gene Expression Regulation, Archaeal KW - Heat-Shock Proteins KW - Hot Temperature KW - Methanococcus KW - Temperature KW - Transcription, Genetic AB -

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.

VL - 7 CP - 6 M3 - 10.1111/j.1462-2920.2005.00751.x ER - TY - JOUR T1 - Transcriptional profiling of the hyperthermophilic methanarchaeon Methanococcus jannaschii in response to lethal heat and non‐lethal cold shock JF - Environmental MicrobiologyEnvironmental Microbiology Y1 - 2005 A1 - Boonyaratanakornkit, Boonchai B. A1 - Simpson, Anjana J. A1 - Whitehead, Timothy A. A1 - Fraser, Claire M. A1 - Najib M. El‐Sayed A1 - Clark, Douglas S. AB - Temperature shock of the hyperthermophilic methanarchaeon Methanococcus jannaschii from its optimal growth temperature of 85°C to 65°C and 95°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°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°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. VL - 7 SN - 1462-2920 ER - TY - CONF T1 - What Are the Ants Doing? Vision-Based Tracking and Reconstruction of Control Programs T2 - 2005 IEEE International Conference on Robotics and AutomationProceedings of the 2005 IEEE International Conference on Robotics and Automation Y1 - 2005 A1 - Egerstedt, M. A1 - Balch, T. A1 - Dellaert, F. A1 - Delmotte, F. A1 - Khan, Z. JA - 2005 IEEE International Conference on Robotics and AutomationProceedings of the 2005 IEEE International Conference on Robotics and Automation PB - IEEE CY - Barcelona, Spain UR - http://ieeexplore.ieee.org/lpdocs/epic03/wrapper.htm?arnumber=1570762 M3 - 10.1109/ROBOT.2005.1570762 ER - TY - JOUR T1 - What the genome sequence is revealing about trypanosome antigenic variation. JF - Biochem Soc Trans Y1 - 2005 A1 - Barry, J D A1 - Marcello, L A1 - Morrison, L J A1 - Read, A F A1 - Lythgoe, K A1 - Jones, N A1 - Carrington, M A1 - Blandin, G A1 - Böhme, U A1 - Caler, E A1 - Hertz-Fowler, C A1 - Renauld, H A1 - El-Sayed, N A1 - Berriman, M KW - Animals KW - Antigens, Protozoan KW - Evolution, Molecular KW - Genetic Variation KW - Genome KW - Trypanosomatina KW - Variant Surface Glycoproteins, Trypanosoma AB -

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.

VL - 33 CP - Pt 5 M3 - 10.1042/BST20050986 ER - TY - JOUR T1 - Advances in schistosome genomics JF - Trends in ParasitologyTrends in Parasitology Y1 - 2004 A1 - Najib M. El‐Sayed A1 - Bartholomeu, Daniella A1 - Ivens, Alasdair A1 - Johnston, David A. A1 - LoVerde, Philip T. AB - 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. VL - 20 SN - 1471-4922 ER - TY - JOUR T1 - Comparison of the genome of the oral pathogen Treponema denticola with other spirochete genomes JF - 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 Y1 - 2004 A1 - Seshadri, Rekha A1 - Myers, Garry S. A. A1 - Tettelin, Hervé A1 - Eisen, Jonathan A. A1 - Heidelberg, John F. A1 - Dodson, Robert J. A1 - Davidsen, Tanja M. A1 - DeBoy, Robert T. A1 - Fouts, Derrick E. A1 - Haft, Dan H. A1 - J. Selengut A1 - Ren, Qinghu A1 - Brinkac, Lauren M. A1 - Madupu, Ramana A1 - Kolonay, Jamie A1 - Durkin, A. Scott A1 - Daugherty, Sean C. A1 - Shetty, Jyoti A1 - Shvartsbeyn, Alla A1 - Gebregeorgis, Elizabeth A1 - Geer, Keita A1 - Tsegaye, Getahun A1 - Malek, Joel A1 - Ayodeji, Bola A1 - Shatsman, Sofiya A1 - McLeod, Michael P. A1 - Smajs, David A1 - Howell, Jerrilyn K. A1 - Pal, Sangita A1 - Amin, Anita A1 - Vashisth, Pankaj A1 - McNeill, Thomas Z. A1 - Xiang, Qin A1 - Sodergren, Erica A1 - Baca, Ernesto A1 - Weinstock, George M. A1 - Norris, Steven J. A1 - Fraser, Claire M. A1 - Paulsen, Ian T. KW - ATP-Binding Cassette Transporters KW - Bacterial Proteins KW - Base Sequence KW - Borrelia burgdorferi KW - Genes, Bacterial KW - Genome, Bacterial KW - Leptospira interrogans KW - Models, Genetic KW - Molecular Sequence Data KW - Mouth KW - Sequence Homology, Amino Acid KW - Treponema KW - Treponema pallidum AB - 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. VL - 101 N1 - http://www.ncbi.nlm.nih.gov/pubmed/15064399?dopt=Abstract ER - TY - JOUR T1 - Gene synteny and evolution of genome architecture in trypanosomatids. JF - Mol Biochem Parasitol Y1 - 2004 A1 - Ghedin, Elodie A1 - Bringaud, Frederic A1 - Peterson, Jeremy A1 - Myler, Peter A1 - Berriman, Matthew A1 - Ivens, Alasdair A1 - Andersson, Björn A1 - Bontempi, Esteban A1 - Eisen, Jonathan A1 - Angiuoli, Sam A1 - Wanless, David A1 - Von Arx, Anna A1 - Murphy, Lee A1 - Lennard, Nicola A1 - Salzberg, Steven A1 - Adams, Mark D A1 - White, Owen A1 - Hall, Neil A1 - Stuart, Kenneth A1 - Fraser, Claire M A1 - el-Sayed, Najib M A KW - Animals KW - Computational Biology KW - Evolution, Molecular KW - Gene Order KW - Genome, Protozoan KW - Genomics KW - Leishmania major KW - Multigene Family KW - Recombination, Genetic KW - Retroelements KW - Selection, Genetic KW - Synteny KW - Trypanosoma brucei brucei KW - Trypanosoma cruzi KW - Trypanosomatina AB -

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.

VL - 134 CP - 2 M3 - 10.1016/j.molbiopara.2003.11.012 ER - TY - JOUR T1 - Genome sequence of Silicibacter pomeroyi reveals adaptations to the marine environment JF - NatureNature Y1 - 2004 A1 - Moran, Mary Ann A1 - Buchan, Alison A1 - González, José M. A1 - Heidelberg, John F. A1 - Whitman, William B. A1 - Kiene, Ronald P. A1 - Henriksen, James R. A1 - King, Gary M. A1 - Belas, Robert A1 - Fuqua, Clay A1 - Brinkac, Lauren A1 - Lewis, Matt A1 - Johri, Shivani A1 - Weaver, Bruce A1 - Pai, Grace A1 - Eisen, Jonathan A. A1 - Rahe, Elisha A1 - Sheldon, Wade M. A1 - Ye, Wenying A1 - Miller, Todd R. A1 - Carlton, Jane A1 - Rasko, David A. A1 - Paulsen, Ian T. A1 - Ren, Qinghu A1 - Daugherty, Sean C. A1 - DeBoy, Robert T. A1 - Dodson, Robert J. A1 - Durkin, A. Scott A1 - Madupu, Ramana A1 - Nelson, William C. A1 - Sullivan, Steven A. A1 - Rosovitz, M. J. A1 - Haft, Daniel H. A1 - J. Selengut A1 - Ward, Naomi KW - Adaptation, Physiological KW - Carrier Proteins KW - Genes, Bacterial KW - Genome, Bacterial KW - marine biology KW - Molecular Sequence Data KW - Oceans and Seas KW - Phylogeny KW - plankton KW - RNA, Ribosomal, 16S KW - Roseobacter KW - Seawater AB - 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. VL - 432 N1 - http://www.ncbi.nlm.nih.gov/pubmed/15602564?dopt=Abstract ER - TY - JOUR T1 - The genome sequence of the anaerobic, sulfate-reducing bacterium Desulfovibrio vulgaris Hildenborough JF - Nature biotechnologyNature biotechnology Y1 - 2004 A1 - Heidelberg, John F. A1 - Seshadri, Rekha A1 - Haveman, Shelley A. A1 - Hemme, Christopher L. A1 - Paulsen, Ian T. A1 - Kolonay, James F. A1 - Eisen, Jonathan A. A1 - Ward, Naomi A1 - Methe, Barbara A1 - Brinkac, Lauren M. A1 - Daugherty, Sean C. A1 - DeBoy, Robert T. A1 - Dodson, Robert J. A1 - Durkin, A. Scott A1 - Madupu, Ramana A1 - Nelson, William C. A1 - Sullivan, Steven A. A1 - Fouts, Derrick A1 - Haft, Daniel H. A1 - J. Selengut A1 - Peterson, Jeremy D. A1 - Davidsen, Tanja M. A1 - Zafar, Nikhat A1 - Zhou, Liwei A1 - Radune, Diana A1 - Dimitrov, George A1 - Hance, Mark A1 - Tran, Kevin A1 - Khouri, Hoda A1 - Gill, John A1 - Utterback, Terry R. A1 - Feldblyum, Tamara V. A1 - Wall, Judy D. A1 - Voordouw, Gerrit A1 - Fraser, Claire M. KW - Desulfovibrio vulgaris KW - Energy Metabolism KW - Genome, Bacterial KW - Molecular Sequence Data AB - 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 'hydrogen-cycling' 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's complex anaerobic respiration. VL - 22 N1 - http://www.ncbi.nlm.nih.gov/pubmed/15077118?dopt=Abstract ER - TY - JOUR T1 - The ingi and RIME non-LTR retrotransposons are not randomly distributed in the genome of Trypanosoma brucei JF - Molecular biology and evolutionMolecular biology and evolution Y1 - 2004 A1 - Bringaud, F. A1 - Biteau, N. A1 - Zuiderwijk, E. A1 - Berriman, M. A1 - Najib M. El‐Sayed A1 - Ghedin, E. A1 - Melville, S. E. A1 - Hall, N. A1 - Baltz, T. VL - 21 ER - TY - JOUR T1 - The ingi and RIME non-LTR retrotransposons are not randomly distributed in the genome of Trypanosoma brucei. JF - Mol Biol Evol Y1 - 2004 A1 - Bringaud, Frederic A1 - Biteau, Nicolas A1 - Zuiderwijk, Eduard A1 - Berriman, Matthew A1 - El-Sayed, Najib M A1 - Ghedin, Elodie A1 - Melville, Sara E A1 - Hall, Neil A1 - Baltz, Théo KW - Amino Acid Sequence KW - Animals KW - Base Sequence KW - Consensus Sequence KW - Genome, Protozoan KW - Molecular Sequence Data KW - Retroelements KW - Sequence Analysis KW - Trypanosoma brucei brucei AB -

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'-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'-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.

VL - 21 CP - 3 M3 - 10.1093/molbev/msh045 ER - TY - JOUR T1 - Pandemic strains of O3:K6 Vibrio parahaemolyticus in the aquatic environment of Bangladesh JF - Canadian Journal of MicrobiologyCanadian Journal of Microbiology Y1 - 2004 A1 - Islam, M. S. A1 - Tasmin, Rizwana A1 - Khan, Sirajul I. s l a m A1 - Bakht, Habibul B. M. A1 - Mahmood, Zahid H. a y a t A1 - Rahman, M. Z. i a u r A1 - Bhuiyan, Nurul A. m i n A1 - Nishibuchi, Mitsuaki A1 - Nair, G. B. a l a k r i s h A1 - Sack, R. B. r a d l e y A1 - Huq, Anwar A1 - Rita R. Colwell A1 - Sack, David A. AB - 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. VL - 50 ER - TY - JOUR T1 - Polylysogeny and prophage induction by secondary infection in Vibrio cholerae JF - Environmental MicrobiologyEnvironmental Microbiology Y1 - 2004 A1 - Espeland, Eric M. A1 - Lipp, Erin K. A1 - Huq, Anwar A1 - Rita R. Colwell AB - 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. VL - 6 SN - 1462-2920 ER - TY - JOUR T1 - Schistosoma mansoni genome project: an update JF - Parasitology InternationalParasitology International Y1 - 2004 A1 - LoVerde, Philip T. A1 - Hirai, Hirohisa A1 - Merrick, Joseph M. A1 - Lee, Norman H. A1 - Najib M. El‐Sayed KW - Chromosome mapping KW - Gene discovery KW - Genomics KW - Schistosoma mansoni AB - 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. VL - 53 SN - 1383-5769 ER - TY - JOUR T1 - Sequencing strategies for parasite genomes. JF - Methods Mol Biol Y1 - 2004 A1 - Bartholomeu, Daniella A1 - El-Sayed, Najib M KW - Animals KW - Chromosome Walking KW - Chromosomes, Artificial, Bacterial KW - Genetic Markers KW - Genome, Protozoan KW - Plasmodium falciparum AB -

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.

VL - 270 M3 - 10.1385/1-59259-793-9:001 ER - TY - JOUR T1 - Sequencing Strategies for Parasite Genomes JF - METHODS IN MOLECULAR BIOLOGY-CLIFTON THEN TOTOWA-METHODS IN MOLECULAR BIOLOGY-CLIFTON THEN TOTOWA- Y1 - 2004 A1 - Bartholomeu, D. A1 - Najib M. El‐Sayed A1 - Melville, S. E. VL - 270 ER - TY - JOUR T1 - Direct Detection of Vibrio Cholerae and ctxA in Peruvian Coastal Water and Plankton by PCR JF - Applied and Environmental MicrobiologyAppl. Environ. Microbiol.Applied and Environmental MicrobiologyAppl. Environ. Microbiol. Y1 - 2003 A1 - Lipp, Erin K. A1 - Rivera, Irma N. G. A1 - Gil, Ana I. A1 - Espeland, Eric M. A1 - Choopun, Nipa A1 - Louis, Valérie R. A1 - Russek-Cohen, Estelle A1 - Huq, Anwar A1 - Rita R. Colwell AB - 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. VL - 69 SN - 0099-2240, 1098-5336 ER - TY - JOUR T1 - Genome of Geobacter sulfurreducens: metal reduction in subsurface environments JF - Science (New York, N.Y.)Science (New York, N.Y.) Y1 - 2003 A1 - Methé, B. A. A1 - Nelson, K. E. A1 - Eisen, J. A. A1 - Paulsen, I. T. A1 - Nelson, W. A1 - Heidelberg, J. F. A1 - Wu, D. A1 - Wu, M. A1 - Ward, N. A1 - Beanan, M. J. A1 - Dodson, R. J. A1 - Madupu, R. A1 - Brinkac, L. M. A1 - Daugherty, S. C. A1 - DeBoy, R. T. A1 - Durkin, A. S. A1 - Gwinn, M. A1 - Kolonay, J. F. A1 - Sullivan, S. A. A1 - Haft, D. H. A1 - J. Selengut A1 - Davidsen, T. M. A1 - Zafar, N. A1 - White, O. A1 - Tran, B. A1 - Romero, C. A1 - Forberger, H. A. A1 - Weidman, J. A1 - Khouri, H. A1 - Feldblyum, T. V. A1 - Utterback, T. R. A1 - Van Aken, S. E. A1 - Lovley, D. R. A1 - Fraser, C. M. KW - Acetates KW - Acetyl Coenzyme A KW - Aerobiosis KW - Anaerobiosis KW - Bacterial Proteins KW - Carbon KW - Chemotaxis KW - Chromosomes, Bacterial KW - Cytochromes c KW - Electron Transport KW - Energy Metabolism KW - Genes, Bacterial KW - Genes, Regulator KW - Genome, Bacterial KW - Geobacter KW - Hydrogen KW - Metals KW - Movement KW - Open Reading Frames KW - Oxidation-Reduction KW - Phylogeny AB - 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. VL - 302 N1 - http://www.ncbi.nlm.nih.gov/pubmed/14671304?dopt=Abstract ER - TY - JOUR T1 - The genome sequence of Bacillus anthracis Ames and comparison to closely related bacteria JF - NatureNature Y1 - 2003 A1 - Read, Timothy D. A1 - Peterson, Scott N. A1 - Tourasse, Nicolas A1 - Baillie, Les W. A1 - Paulsen, Ian T. A1 - Nelson, Karen E. A1 - Tettelin, Herv A1 - Fouts, Derrick E. A1 - Eisen, Jonathan A. A1 - Gill, Steven R. A1 - Holtzapple, Erik K. A1 - kstad, Ole Andreas A1 - Helgason, Erlendur A1 - Rilstone, Jennifer A1 - Wu, Martin A1 - Kolonay, James F. A1 - Beanan, Maureen J. A1 - Dodson, Robert J. A1 - Brinkac, Lauren M. A1 - Gwinn, Michelle A1 - DeBoy, Robert T. A1 - Madpu, Ramana A1 - Daugherty, Sean C. A1 - Durkin, A. Scott A1 - Haft, Daniel H. A1 - Nelson, William C. A1 - Peterson, Jeremy D. A1 - M. Pop A1 - Khouri, Hoda M. A1 - Radune, Diana A1 - Benton, Jonathan L. A1 - Mahamoud, Yasmin A1 - Jiang, Lingxia A1 - Hance, Ioana R. A1 - Weidman, Janice F. A1 - Berry, Kristi J. A1 - Plaut, Roger D. A1 - Wolf, Alex M. A1 - Watkins, Kisha L. A1 - Nierman, William C. A1 - Hazen, Alyson A1 - Cline, Robin A1 - Redmond, Caroline A1 - Thwaite, Joanne E. A1 - White, Owen A1 - Salzberg, Steven L. A1 - Thomason, Brendan A1 - Friedlander, Arthur M. A1 - Koehler, Theresa M. A1 - Hanna, Philip C. A1 - Kolst, A1 - Anne-Brit A1 - Fraser, Claire M. AB - 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—including haemolysins, phospholipases and iron acquisition functions—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. VL - 423 SN - 0028-0836 N1 - [eacute]
[Oslash] ER - TY - JOUR T1 - The sequence and analysis of Trypanosoma brucei chromosome II JF - Nucleic acids researchNucleic Acids Research Y1 - 2003 A1 - Najib M. El‐Sayed A1 - Ghedin, E. A1 - Song, J. A1 - MacLeod, A. A1 - Bringaud, F. A1 - Larkin, C. A1 - Wanless, D. A1 - Peterson, J. A1 - Hou, L. A1 - Taylor, S. A1 - others, VL - 31 ER - TY - JOUR T1 - The sequence and analysis of Trypanosoma brucei chromosome II. JF - Nucleic Acids Res Y1 - 2003 A1 - el-Sayed, Najib M A A1 - Ghedin, Elodie A1 - Song, Jinming A1 - MacLeod, Annette A1 - Bringaud, Frederic A1 - Larkin, Christopher A1 - Wanless, David A1 - Peterson, Jeremy A1 - Hou, Lihua A1 - Taylor, Sonya A1 - Tweedie, Alison A1 - Biteau, Nicolas A1 - Khalak, Hanif G A1 - Lin, Xiaoying A1 - Mason, Tanya A1 - Hannick, Linda A1 - Caler, Elisabet A1 - Blandin, Gaëlle A1 - Bartholomeu, Daniella A1 - Simpson, Anjana J A1 - Kaul, Samir A1 - Zhao, Hong A1 - Pai, Grace A1 - Van Aken, Susan A1 - Utterback, Teresa A1 - Haas, Brian A1 - Koo, Hean L A1 - Umayam, Lowell A1 - Suh, Bernard A1 - Gerrard, Caroline A1 - Leech, Vanessa A1 - Qi, Rong A1 - Zhou, Shiguo A1 - Schwartz, David A1 - Feldblyum, Tamara A1 - Salzberg, Steven A1 - Tait, Andrew A1 - Turner, C Michael R A1 - Ullu, Elisabetta A1 - White, Owen A1 - Melville, Sara A1 - Adams, Mark D A1 - Fraser, Claire M A1 - Donelson, John E KW - Animals KW - Antigens, Protozoan KW - Chromosome mapping KW - Chromosomes KW - DNA, Protozoan KW - Gene Duplication KW - Genes, Protozoan KW - Molecular Sequence Data KW - Pseudogenes KW - Recombination, Genetic KW - Sequence Analysis, DNA KW - Trypanosoma brucei brucei AB -

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 'hot' and 'cold' 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.

VL - 31 CP - 16 ER - TY - JOUR T1 - Analysis of stage-specific gene expression in the bloodstream and the procyclic form of Trypanosoma brucei using a genomic DNA-microarray. JF - Mol Biochem Parasitol Y1 - 2002 A1 - Diehl, Susanne A1 - Diehl, Frank A1 - El-Sayed, Najib M A1 - Clayton, Christine A1 - Hoheisel, Jörg D KW - Animals KW - Blotting, Northern KW - Escherichia coli KW - Gene expression KW - Gene Expression Profiling KW - Genes, Protozoan KW - HUMANS KW - Life Cycle Stages KW - Molecular Sequence Data KW - Oligonucleotide Array Sequence Analysis KW - Polymerase Chain Reaction KW - Transcription, Genetic KW - Trypanosoma brucei brucei AB -

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.

VL - 123 CP - 2 ER - TY - JOUR T1 - Analysis of stage-specific gene expression in the bloodstream and the procyclic form of Trypanosoma brucei using a genomic DNA-microarray JF - Molecular and Biochemical ParasitologyMolecular and Biochemical Parasitology Y1 - 2002 A1 - Diehl, Susanne A1 - Diehl, Frank A1 - Najib M. El‐Sayed A1 - Clayton, Christine A1 - Hoheisel, Jörg D. KW - Expression KW - Gene KW - Microarray KW - Regulation KW - Trypanosoma brucei AB - 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. VL - 123 SN - 0166-6851 ER - TY - CHAP T1 - Combinatorial Algorithms for Design of DNA Arrays T2 - Chip TechnologyChip Technology Y1 - 2002 A1 - Sridhar Hannenhalli A1 - Hubbell, Earl A1 - Lipshutz, Robert A1 - Pevzner, Pavel ED - Hoheisel, Jörg ED - Brazma, A. ED - Büssow, K. ED - Cantor, C. ED - Christians, F. ED - Chui, G. ED - Diaz, R. ED - Drmanac, R. ED - Drmanac, S. ED - Eickhoff, H. ED - Fellenberg, K. ED - Sridhar Hannenhalli ED - Hoheisel, J. ED - Hou, A. ED - Hubbell, E. ED - Jin, H. ED - Jin, P. ED - Jurinke, C. ED - Konthur, Z. ED - Köster, H. ED - Kwon, S. ED - Lacy, S. ED - Lehrach, H. ED - Lipshutz, R. ED - Little, D. ED - Lueking, A. ED - McGall, G. ED - Moeur, B. ED - Nordhoff, E. ED - Nyarsik, L. ED - Pevzner, P. ED - Robinson, A. ED - Sarkans, U. ED - Shafto, J. ED - Sohail, M. ED - Southern, E. ED - Swanson, D. ED - Ukrainczyk, T. ED - van den Boom, D. ED - Vilo, J. ED - Vingron, M. ED - Walter, G. ED - Xu, C. AB - 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 20–30% 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. JA - Chip TechnologyChip Technology T3 - Advances in Biochemical Engineering/Biotechnology PB - Springer Berlin / Heidelberg VL - 77 SN - 978-3-540-43215-9 ER - TY - JOUR T1 - Genome sequence and comparative analysis of the model rodent malaria parasite Plasmodium yoelii yoelii JF - NatureNature Y1 - 2002 A1 - Carlton, Jane M. A1 - Angiuoli, Samuel V. A1 - Suh, Bernard B. A1 - Kooij, Taco W. A1 - Pertea, Mihaela A1 - Silva, Joana C. A1 - Ermolaeva, Maria D. A1 - Allen, Jonathan E. A1 - J. Selengut A1 - Koo, Hean L. A1 - Peterson, Jeremy D. A1 - M. Pop A1 - Kosack, Daniel S. A1 - Shumway, Martin F. A1 - Bidwell, Shelby L. A1 - Shallom, Shamira J. A1 - Aken, Susan E. van A1 - Riedmuller, Steven B. A1 - Feldblyum, Tamara V. A1 - Cho, Jennifer K. A1 - Quackenbush, John A1 - Sedegah, Martha A1 - Shoaibi, Azadeh A1 - Cummings, Leda M. A1 - Florens, Laurence A1 - Yates, John R. A1 - Raine, J. Dale A1 - Sinden, Robert E. A1 - Harris, Michael A. A1 - Cunningham, Deirdre A. A1 - Preiser, Peter R. A1 - Bergman, Lawrence W. A1 - Vaidya, Akhil B. A1 - Lin, Leo H. van A1 - Janse, Chris J. A1 - Waters, Andrew P. A1 - Smith, Hamilton O. A1 - White, Owen R. A1 - Salzberg, Steven L. A1 - Venter, J. Craig A1 - Fraser, Claire M. A1 - Hoffman, Stephen L. A1 - Gardner, Malcolm J. A1 - Carucci, Daniel J. AB - 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. VL - 419 SN - 0028-0836 ER - TY - JOUR T1 - Genome sequence of the human malaria parasite Plasmodium falciparum JF - NatureNature Y1 - 2002 A1 - Gardner, Malcolm J. A1 - Hall, Neil A1 - Fung, Eula A1 - White, Owen A1 - Berriman, Matthew A1 - Hyman, Richard W. A1 - Carlton, Jane M. A1 - Pain, Arnab A1 - Nelson, Karen E. A1 - Bowman, Sharen A1 - Paulsen, Ian T. A1 - James, Keith A1 - Eisen, Jonathan A. A1 - Rutherford, Kim A1 - Salzberg, Steven L. A1 - Craig, Alister A1 - Kyes, Sue A1 - Chan, Man-Suen A1 - Nene, Vishvanath A1 - Shallom, Shamira J. A1 - Suh, Bernard A1 - Peterson, Jeremy A1 - Angiuoli, Sam A1 - Pertea, Mihaela A1 - Allen, Jonathan A1 - J. Selengut A1 - Haft, Daniel A1 - Mather, Michael W. A1 - Vaidya, Akhil B. A1 - Martin, David M. A. A1 - Fairlamb, Alan H. A1 - Fraunholz, Martin J. A1 - Roos, David S. A1 - Ralph, Stuart A. A1 - McFadden, Geoffrey I. A1 - Cummings, Leda M. A1 - Subramanian, G. Mani A1 - Mungall, Chris A1 - Venter, J. Craig A1 - Carucci, Daniel J. A1 - Hoffman, Stephen L. A1 - Newbold, Chris A1 - Davis, Ronald W. A1 - Fraser, Claire M. A1 - Barrell, Bart KW - Animals KW - Chromosome Structures KW - DNA Repair KW - DNA Replication KW - DNA, Protozoan KW - Evolution, Molecular KW - Genome, Protozoan KW - HUMANS KW - Malaria Vaccines KW - Malaria, Falciparum KW - Membrane Transport Proteins KW - Molecular Sequence Data KW - Plasmodium falciparum KW - Plastids KW - Proteome KW - Protozoan Proteins KW - Recombination, Genetic KW - Sequence Analysis, DNA AB - 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. VL - 419 N1 - http://www.ncbi.nlm.nih.gov/pubmed/12368864?dopt=Abstract ER - TY - JOUR T1 - Identification of non-autonomous non-LTR retrotransposons in the genome of Trypanosoma cruzi JF - Molecular and Biochemical ParasitologyMolecular and Biochemical Parasitology Y1 - 2002 A1 - Bringaud, Frederic A1 - García-Pérez, José Luis A1 - Heras, Sara R. A1 - Ghedin, Elodie A1 - Najib M. El‐Sayed A1 - Andersson, Björn A1 - Baltz, Théo A1 - Lopez, Manuel C. KW - Ingi KW - L1Tc KW - Non-LTR retrotransposon KW - RIME KW - Trypanosoma brucei KW - Trypanosoma cruzi AB - 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'-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. VL - 124 SN - 0166-6851 ER - TY - JOUR T1 - Identification of non-autonomous non-LTR retrotransposons in the genome of Trypanosoma cruzi. JF - Mol Biochem Parasitol Y1 - 2002 A1 - Bringaud, Frederic A1 - García-Pérez, José Luis A1 - Heras, Sara R A1 - Ghedin, Elodie A1 - El-Sayed, Najib M A1 - Andersson, Björn A1 - Baltz, Théo A1 - Lopez, Manuel C KW - Animals KW - Base Sequence KW - Computational Biology KW - Genome, Protozoan KW - Long Interspersed Nucleotide Elements KW - Molecular Sequence Data KW - Retroelements KW - Short Interspersed Nucleotide Elements KW - Trypanosoma cruzi AB -

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'-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.

VL - 124 CP - 1-2 ER - TY - JOUR T1 - A new, expressed multigene family containing a hot spot for insertion of retroelements is associated with polymorphic subtelomeric regions of Trypanosoma brucei JF - Eukaryotic cellEukaryotic Cell Y1 - 2002 A1 - Bringaud, F. A1 - Biteau, N. A1 - Melville, S. E. A1 - Hez, S. A1 - Najib M. El‐Sayed A1 - Leech, V. A1 - Berriman, M. A1 - Hall, N. A1 - Donelson, J. E. A1 - Baltz, T. VL - 1 ER - TY - JOUR T1 - A new, expressed multigene family containing a hot spot for insertion of retroelements is associated with polymorphic subtelomeric regions of Trypanosoma brucei. JF - Eukaryot Cell Y1 - 2002 A1 - Bringaud, Frederic A1 - Biteau, Nicolas A1 - Melville, Sara E A1 - Hez, Stéphanie A1 - El-Sayed, Najib M A1 - Leech, Vanessa A1 - Berriman, Matthew A1 - Hall, Neil A1 - Donelson, John E A1 - Baltz, Théo KW - Amino Acid Sequence KW - Animals KW - Base Sequence KW - Cloning, Molecular KW - DNA Primers KW - DNA, Protozoan KW - Escherichia coli KW - Genes, Protozoan KW - Molecular Sequence Data KW - Multigene Family KW - Mutagenesis, Insertional KW - Phylogeny KW - Polymorphism, Genetic KW - Protozoan Proteins KW - Pseudogenes KW - Retroelements KW - sequence alignment KW - Sequence Homology, Amino Acid KW - Telomere KW - Trypanosoma brucei brucei KW - Trypanosoma cruzi AB -

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.

VL - 1 CP - 1 ER - TY - JOUR T1 - Trypanosoma cruzi: RNA structure and post-transcriptional control of tubulin gene expression JF - Experimental ParasitologyExperimental Parasitology Y1 - 2002 A1 - Bartholomeu, Daniella C. A1 - Silva, Rosiane A. A1 - Galvão, Lucia M. C. A1 - Najib M. El‐Sayed A1 - Donelson, John E. A1 - Teixeira, Santuza M. R. AB - 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' 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' 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. VL - 102 SN - 0014-4894 ER - TY - JOUR T1 - Trypanosoma cruzi: RNA structure and post-transcriptional control of tubulin gene expression. JF - Exp Parasitol Y1 - 2002 A1 - Bartholomeu, Daniella C A1 - Silva, Rosiane A A1 - Galvão, Lucia M C A1 - el-Sayed, Najib M A A1 - Donelson, John E A1 - Teixeira, Santuza M R KW - Animals KW - Base Sequence KW - Blotting, Northern KW - DNA, Complementary KW - DNA, Protozoan KW - Gene Expression Regulation KW - Half-Life KW - Life Cycle Stages KW - Molecular Sequence Data KW - RNA Processing, Post-Transcriptional KW - RNA, Messenger KW - RNA, Protozoan KW - Transcription, Genetic KW - Transfection KW - Trypanosoma cruzi KW - Tubulin AB -

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' 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' 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.

VL - 102 CP - 3-4 ER - TY - JOUR T1 - Analysis of a donor gene region for a variant surface glycoprotein and its expression site in African trypanosomes JF - Nucleic acids researchNucleic Acids Research Y1 - 2001 A1 - LaCount, D. J. A1 - Najib M. El‐Sayed A1 - Kaul, S. A1 - Wanless, D. A1 - Turner, C. M. R. A1 - Donelson, J. E. VL - 29 ER - TY - JOUR T1 - The African trypanosome genome JF - International Journal for ParasitologyInternational Journal for Parasitology Y1 - 2000 A1 - Najib M. El‐Sayed A1 - Hegde, Priti A1 - Quackenbush, John A1 - Melville, Sara E. A1 - Donelson, John E. AB - 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. VL - 30 SN - 0020-7519 ER - TY - JOUR T1 - A Case for Evolutionary Genomics and the Comprehensive Examination of Sequence Biodiversity JF - Molecular Biology and EvolutionMol Biol EvolMolecular Biology and EvolutionMol Biol Evol Y1 - 2000 A1 - Pollock, David D. A1 - Eisen, Jonathan A. A1 - Doggett, Norman A. A1 - Michael P. Cummings AB - 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. VL - 17 SN - 0737-4038, 1537-1719 ER - TY - JOUR T1 - The genome sequence of Drosophila melanogaster. JF - Science Y1 - 2000 A1 - Adams, M D A1 - Celniker, S E A1 - Holt, R A A1 - Evans, C A A1 - Gocayne, J D A1 - Amanatides, P G A1 - Scherer, S E A1 - Li, P W A1 - Hoskins, R A A1 - Galle, R F A1 - George, R A A1 - Lewis, S E A1 - Richards, S A1 - Ashburner, M A1 - Henderson, S N A1 - Sutton, G G A1 - Wortman, J R A1 - Yandell, M D A1 - Zhang, Q A1 - Chen, L X A1 - Brandon, R C A1 - Rogers, Y H A1 - Blazej, R G A1 - Champe, M A1 - Pfeiffer, B D A1 - Wan, K H A1 - Doyle, C A1 - Baxter, E G A1 - Helt, G A1 - Nelson, C R A1 - Gabor, G L A1 - Abril, J F A1 - Agbayani, A A1 - An, H J A1 - Andrews-Pfannkoch, C A1 - Baldwin, D A1 - Ballew, R M A1 - Basu, A A1 - Baxendale, J A1 - Bayraktaroglu, L A1 - Beasley, E M A1 - Beeson, K Y A1 - Benos, P V A1 - Berman, B P A1 - Bhandari, D A1 - Bolshakov, S A1 - Borkova, D A1 - Botchan, M R A1 - Bouck, J A1 - Brokstein, P A1 - Brottier, P A1 - Burtis, K C A1 - Busam, D A A1 - Butler, H A1 - Cadieu, E A1 - Center, A A1 - Chandra, I A1 - Cherry, J M A1 - Cawley, S A1 - Dahlke, C A1 - Davenport, L B A1 - Davies, P A1 - de Pablos, B A1 - Delcher, A A1 - Deng, Z A1 - Mays, A D A1 - Dew, I A1 - Dietz, S M A1 - Dodson, K A1 - Doup, L E A1 - Downes, M A1 - Dugan-Rocha, S A1 - Dunkov, B C A1 - Dunn, P A1 - Durbin, K J A1 - Evangelista, C C A1 - Ferraz, C A1 - Ferriera, S A1 - Fleischmann, W A1 - Fosler, C A1 - Gabrielian, A E A1 - Garg, N S A1 - Gelbart, W M A1 - Glasser, K A1 - Glodek, A A1 - Gong, F A1 - Gorrell, J H A1 - Gu, Z A1 - Guan, P A1 - Harris, M A1 - Harris, N L A1 - Harvey, D A1 - Heiman, T J A1 - Hernandez, J R A1 - Houck, J A1 - Hostin, D A1 - Houston, K A A1 - Howland, T J A1 - Wei, M H A1 - Ibegwam, C A1 - Jalali, M A1 - Kalush, F A1 - Karpen, G H A1 - Ke, Z A1 - Kennison, J A A1 - Ketchum, K A A1 - Kimmel, B E A1 - Kodira, C D A1 - Kraft, C A1 - Kravitz, S A1 - Kulp, D A1 - Lai, Z A1 - Lasko, P A1 - Lei, Y A1 - Levitsky, A A A1 - Li, J A1 - Li, Z A1 - Liang, Y A1 - Lin, X A1 - Liu, X A1 - Mattei, B A1 - McIntosh, T C A1 - McLeod, M P A1 - McPherson, D A1 - Merkulov, G A1 - Milshina, N V A1 - Mobarry, C A1 - Morris, J A1 - Moshrefi, A A1 - Mount, S M A1 - Moy, M A1 - Murphy, B A1 - Murphy, L A1 - Muzny, D M A1 - Nelson, D L A1 - Nelson, D R A1 - Nelson, K A A1 - Nixon, K A1 - Nusskern, D R A1 - Pacleb, J M A1 - Palazzolo, M A1 - Pittman, G S A1 - Pan, S A1 - Pollard, J A1 - Puri, V A1 - Reese, M G A1 - Reinert, K A1 - Remington, K A1 - Saunders, R D A1 - Scheeler, F A1 - Shen, H A1 - Shue, B C A1 - Sidén-Kiamos, I A1 - Simpson, M A1 - Skupski, M P A1 - Smith, T A1 - Spier, E A1 - Spradling, A C A1 - Stapleton, M A1 - Strong, R A1 - Sun, E A1 - Svirskas, R A1 - Tector, C A1 - Turner, R A1 - Venter, E A1 - Wang, A H A1 - Wang, X A1 - Wang, Z Y A1 - Wassarman, D A A1 - Weinstock, G M A1 - Weissenbach, J A1 - Williams, S M A1 - Worley, K C A1 - Wu, D A1 - Yang, S A1 - Yao, Q A A1 - Ye, J A1 - Yeh, R F A1 - Zaveri, J S A1 - Zhan, M A1 - Zhang, G A1 - Zhao, Q A1 - Zheng, L A1 - Zheng, X H A1 - Zhong, F N A1 - Zhong, W A1 - Zhou, X A1 - Zhu, S A1 - Zhu, X A1 - Smith, H O A1 - Gibbs, R A A1 - Myers, E W A1 - Rubin, G M A1 - Venter, J C KW - Animals KW - Biological Transport KW - Chromatin KW - Cloning, Molecular KW - Computational Biology KW - Contig Mapping KW - Cytochrome P-450 Enzyme System KW - DNA Repair KW - DNA Replication KW - Drosophila melanogaster KW - Euchromatin KW - Gene Library KW - Genes, Insect KW - Genome KW - Heterochromatin KW - Insect Proteins KW - Nuclear Proteins KW - Protein Biosynthesis KW - Sequence Analysis, DNA KW - Transcription, Genetic AB -

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.

VL - 287 CP - 5461 ER - TY - JOUR T1 - More surprises from Kinetoplastida JF - 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 Y1 - 1999 A1 - Donelson, J. E. A1 - Gardner, M. J. A1 - Najib M. El‐Sayed VL - 96 ER - TY - CHAP T1 - Multiple mechanisms of immune evasion by African trypanosomes T2 - The Trypanosome Surface Y1 - 1999 A1 - Donelson, J.E. A1 - Hill, K.L. A1 - El-Sayed, N.M.A. JA - The Trypanosome Surface PB - De Boeck & Larcier s.a. CY - Brussels ER - TY - JOUR T1 - Genetic nomenclature for Trypanosoma and Leishmania. JF - Mol Biochem Parasitol Y1 - 1998 A1 - Clayton, C A1 - Adams, M A1 - Almeida, R A1 - Baltz, T A1 - Barrett, M A1 - Bastien, P A1 - Belli, S A1 - Beverley, S A1 - Biteau, N A1 - Blackwell, J A1 - Blaineau, C A1 - Boshart, M A1 - Bringaud, F A1 - Cross, G A1 - Cruz, A A1 - Degrave, W A1 - Donelson, J A1 - El-Sayed, N A1 - Fu, G A1 - Ersfeld, K A1 - Gibson, W A1 - Gull, K A1 - Ivens, A A1 - Kelly, J A1 - Vanhamme, L KW - Animals KW - Leishmania KW - Terminology as Topic KW - Trypanosoma VL - 97 CP - 1-2 ER - TY - JOUR T1 - Multiple mechanisms of immune evasion by African trypanosomes JF - Molecular and Biochemical ParasitologyMolecular and Biochemical Parasitology Y1 - 1998 A1 - Donelson, John E. A1 - Hill, Kent L. A1 - Najib M. El‐Sayed KW - Leishmania KW - Recombinant cloning KW - T cell KW - Trypanosomes KW - VSG genes AB - During infection of a mammalian host, African trypanosomes are in constant contact with the host'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'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. VL - 91 SN - 0166-6851 ER - TY - JOUR T1 - Trends in the early careers of life scientists - Preface and executive summary JF - Mol Biol CellMol Biol Cell Y1 - 1998 A1 - Tilghman, S. A1 - Astin, H. S. A1 - Brinkley, W. A1 - Chilton, M. D. A1 - Michael P. Cummings A1 - Ehrenberg, R. G. A1 - Fox, M. F. A1 - Glenn, K. A1 - Green, P. J. A1 - Hans, S. A1 - Kelman, A. A1 - LaPidus, J. A1 - Levin, B. A1 - McIntosh, J. R. A1 - Riecken, H. A1 - Stephen, P. E. VL - 9 ER - TY - JOUR T1 - African trypanosomes have differentially expressed genes encoding homologues of the Leishmania GP63 surface protease JF - Journal of Biological ChemistryJournal of Biological Chemistry Y1 - 1997 A1 - Najib M. El‐Sayed A1 - Donelson, J. E. VL - 272 ER - TY - CHAP T1 - Sequencing and mapping the African trypanosome genome T2 - Trypanosomiasis and Leishmaniasis: Biology and Control Y1 - 1997 A1 - El-Sayed, N.M.A A1 - Donelson, J.E. JA - Trypanosomiasis and Leishmaniasis: Biology and Control PB - CAB International and the British Society for Parasitology pubs ER - TY - JOUR T1 - A survey of the Trypanosoma brucei rhodesiense genome using shotgun sequencing JF - Molecular and Biochemical ParasitologyMolecular and Biochemical Parasitology Y1 - 1997 A1 - Najib M. El‐Sayed A1 - Donelson, John E. KW - Expressed sequence tag KW - Genome survey sequence KW - Trypanosoma brucei rhodesiense AB - 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. VL - 84 SN - 0166-6851 ER - TY - JOUR T1 - Differential expression of the expression site-associated gene I family in African trypanosomes JF - Journal of Biological ChemistryJournal of Biological Chemistry Y1 - 1996 A1 - Morgan, R. W. A1 - Najib M. El‐Sayed A1 - Kepa, J. K. A1 - Pedram, M. A1 - Donelson, J. E. VL - 271 ER - TY - JOUR T1 - cDNA expressed sequence tags of Trypanosoma brucei rhodesiense provide new insights into the biology of the parasite JF - Molecular and Biochemical ParasitologyMolecular and Biochemical Parasitology Y1 - 1995 A1 - Najib M. El‐Sayed A1 - Alarcon, Clara M. A1 - Beck, John C. A1 - Sheffield, Val C. A1 - Donelson, John E. KW - cDNA KW - Expressed sequence tag KW - Trypanosoma brucei rhodesiense AB - 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. VL - 73 SN - 0166-6851 ER - TY - JOUR T1 - Crystallization and preliminary X-ray investigation of the recombinant Trypanosoma brucei rhodesiense calmodulin JF - Proteins: Structure, Function, and BioinformaticsProteins: Structure, Function, and Bioinformatics Y1 - 1995 A1 - Najib M. El‐Sayed A1 - Patton, C. L. A1 - Harkins, P. C. A1 - Fox, R. O. A1 - Anderson, K. VL - 21 ER - TY - JOUR T1 - Detection of alloantigens during preimplantation development and early trophoblast differentiation in the mouse by immunoperoxidase labeling. JF - J Exp Med Y1 - 1976 A1 - Searle, R F A1 - Sellens, M H A1 - Elson, J A1 - Jenkinson, E J A1 - Billington, W D KW - Animals KW - Binding Sites, Antibody KW - Blastocyst KW - Cell Differentiation KW - Cell Membrane KW - Embryo Implantation KW - Embryonic Development KW - Epitopes KW - Female KW - Histocompatibility Antigens KW - HLA Antigens KW - Horseradish Peroxidase KW - Mice KW - Mice, Inbred Strains KW - Pregnancy KW - Pregnancy, Animal KW - Trophoblasts AB -

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.

VL - 143 CP - 2 ER -