KCNK3 mutation causes altered immune function in pulmonary arterial hypertension patients and mouse models

Loss of function KCNK3 mutation is one of the gene variants driving hereditary pulmonary arterial hypertension (PAH). KCNK3 is expressed in several cell and tissue types on both membrane and endoplasmic reticulum and potentially plays a role in multiple pathological process associated with PAH. However, the role of various stressors driving the susceptibility of KCNK3 mutation to PAH is unknown. Hence, we expose

Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy

KCNK3 Mutation Causes Altered Immune Function in Pulmonary Arterial Hypertension Patients and Mouse Models

Loss of function KCNK3 mutation is one of the gene variants driving hereditary pulmonary arterial hypertension (PAH). KCNK3 is expressed in several cell and tissue types on both membrane and endoplasmic reticulum and potentially plays a role in multiple pathological process associated with PAH. However, the role of various stressors driving the susceptibility of KCNK3 mutation to PAH is unknown. Hence, we exposed kcnk3fl/fl animals to hypoxia, metabolic diet and low dose lipopolysaccharide (LPS) and performed molecular characterization of their tissue. We also used tissue samples from KCNK3 patients (skin fibroblast derived inducible pluripotent stem cells, blood, lungs, peripheral blood mononuclear cells) and performed microarray, immunohistochemistry (IHC) and mass cytometry time of flight (CyTOF) experiments. Although a hypoxic insult did not alter vascular tone in kcnk3fl/fl mice, RNASeq study of these lungs implied that inflammatory and metabolic factors were altered, and the follow-up diet study demonstrated a dysregulation of bone marrow cells in kcnk3fl/fl mice. Finally, a low dose LPS study clearly showed that inflammation could be a possible second hit driving PAH in kcnk3fl/fl mice. Multiplex, IHC and CyTOF immunophenotyping studies on human samples confirmed the mouse data and strongly indicated that cell mediated, and innate immune responses may drive PAH susceptibility in these patients. In conclusion, loss of function KCNK3 mutation alters various physiological processes from vascular tone to metabolic diet through inflammation. Our data suggests that altered circulating immune cells may drive PAH susceptibility in patients with KCNK3 mutation

Cardiovascular hemodynamics in mice with tumor necrosis factor receptor—associated factor 2 mediated cytoprotection in the heart

IntroductionMany studies in mice have demonstrated that cardiac-specific innate immune signaling pathways can be reprogrammed to modulate inflammation in response to myocardial injury and improve outcomes. While the echocardiography standard parameters of left ventricular (LV) ejection fraction, fractional shortening, end-diastolic diameter, and others are used to assess cardiac function, their dependency on loading conditions somewhat limits their utility in completely reflecting the contractile function and global cardiovascular efficiency of the heart. A true measure of global cardiovascular efficiency should include the interaction between the ventricle and the aorta (ventricular-vascular coupling, VVC) as well as measures of aortic impedance and pulse wave velocity.MethodsWe measured cardiac Doppler velocities, blood pressures, along with VVC, aortic impedance, and pulse wave velocity to evaluate global cardiac function in a mouse model of cardiac-restricted low levels of TRAF2 overexpression that conferred cytoprotection in the heart.ResultsWhile previous studies reported that response to myocardial infarction and reperfusion was improved in the TRAF2 overexpressed mice, we found that TRAF2 mice had significantly lower cardiac systolic velocities and accelerations, diastolic atrial velocity, aortic pressures, rate-pressure product, LV contractility and relaxation, and stroke work when compared to littermate control mice. Also, we found significantly longer aortic ejection time, isovolumic contraction and relaxation times, and significantly higher mitral early/atrial ratio, myocardial performance index, and ventricular vascular coupling in the TRAF2 overexpression mice compared to their littermate controls. We found no significant differences in the aortic impedance and pulse wave velocity.DiscussionWhile the reported tolerance to ischemic insults in TRAF2 overexpression mice may suggest enhanced cardiac reserve, our results indicate diminished cardiac function in these mice

Global, regional, and national burden of traumatic brain injury and spinal cord injury, 1990-2016 : a systematic analysis for the Global Burden of Disease Study 2016

Background Traumatic brain injury (TBI) and spinal cord injury (SCI) are increasingly recognised as global health priorities in view of the preventability of most injuries and the complex and expensive medical care they necessitate. We aimed to measure the incidence, prevalence, and years of life lived with disability (YLDs) for TBI and SCI from all causes of injury in every country, to describe how these measures have changed between 1990 and 2016, and to estimate the proportion of TBI and SCI cases caused by different types of injury. Methods We used results from the Global Burden of Diseases, Injuries, and Risk Factors (GBD) Study 2016 to measure the global, regional, and national burden of TBI and SCI by age and sex. We measured the incidence and prevalence of all causes of injury requiring medical care in inpatient and outpatient records, literature studies, and survey data. By use of clinical record data, we estimated the proportion of each cause of injury that required medical care that would result in TBI or SCI being considered as the nature of injury. We used literature studies to establish standardised mortality ratios and applied differential equations to convert incidence to prevalence of long-term disability. Finally, we applied GBD disability weights to calculate YLDs. We used a Bayesian meta-regression tool for epidemiological modelling, used cause-specific mortality rates for non-fatal estimation, and adjusted our results for disability experienced with comorbid conditions. We also analysed results on the basis of the Socio-demographic Index, a compound measure of income per capita, education, and fertility. Findings In 2016, there were 27.08 million (95% uncertainty interval [UI] 24.30-30.30 million) new cases of TBI and 0.93 million (0.78-1.16 million) new cases of SCI, with age-standardised incidence rates of 369 (331-412) per 100 000 population for TBI and 13 (11-16) per 100 000 for SCI. In 2016, the number of prevalent cases of TBI was 55.50 million (53.40-57.62 million) and of SCI was 27.04 million (24 .98-30 .15 million). From 1990 to 2016, the age-standardised prevalence of TBI increased by 8.4% (95% UI 7.7 to 9.2), whereas that of SCI did not change significantly (-0.2% [-2.1 to 2.7]). Age-standardised incidence rates increased by 3.6% (1.8 to 5.5) for TBI, but did not change significantly for SCI (-3.6% [-7.4 to 4.0]). TBI caused 8.1 million (95% UI 6. 0-10. 4 million) YLDs and SCI caused 9.5 million (6.7-12.4 million) YLDs in 2016, corresponding to age-standardised rates of 111 (82-141) per 100 000 for TBI and 130 (90-170) per 100 000 for SCI. Falls and road injuries were the leading causes of new cases of TBI and SCI in most regions. Interpretation TBI and SCI constitute a considerable portion of the global injury burden and are caused primarily by falls and road injuries. The increase in incidence of TBI over time might continue in view of increases in population density, population ageing, and increasing use of motor vehicles, motorcycles, and bicycles. The number of individuals living with SCI is expected to increase in view of population growth, which is concerning because of the specialised care that people with SCI can require. Our study was limited by data sparsity in some regions, and it will be important to invest greater resources in collection of data for TBI and SCI to improve the accuracy of future assessments. Copyright (C) 2018 The Author(s). Published by Elsevier Ltd.Peer reviewe

The genome sequence of Trypanosoma cruzi, etiologic agent of Chagas disease

Fil: El-Sayed, Najib M. The Institute for Genomic Research. Department of Parasite Genomics; Estados Unidos.Fil: Myler, Peter J. Seattle Biomedical Research Institute; Estados Unidos.Fil: Bartholomeu, Daniella C. The Institute for Genomic Research. Department of Parasite Genomics; Estados Unidos.Fil: Nilsson, Daniel. Karolinska Institutet. Center for Genomics and Bioinformatics; Suecia.Fil: Aggarwal, Gautam. Seattle Biomedical Research Institute; Estados Unidos.Fil: Tran, Anh-Nhi. Karolinska Institutet. Center for Genomics and Bioinformatics; Suecia.Fil: Ghedin, Elodie. The Institute for Genomic Research. Department of Parasite Genomics; Estados Unidos.Fil: Worthey, Elizabeth A. Seattle Biomedical Research Institute; Estados Unidos.Fil: Delcher, Arthur L. The Institute for Genomic Research. Department of Parasite Genomics; Estados Unidos.Fil: Blandin, Gaëlle. The Institute for Genomic Research. Department of Parasite Genomics; Estados Unidos.Fil: Westenberger, Scott J. The Institute for Genomic Research. Department of Parasite Genomics; Estados Unidos.Fil: Caler, Elisabet. The Institute for Genomic Research. Department of Parasite Genomics; Estados Unidos.Fil: Cerqueira, Gustavo C. The Institute for Genomic Research. Department of Parasite Genomics; Estados Unidos.Fil: Haas, Carole Branched Brian. Karolinska Institutet. Center for Genomics and Bioinformatics; Suecia.Fil: Anupama, Atashi. Seattle Biomedical Research Institute; Estados Unidos.Fil: Arner, Erik. Karolinska Institutet. Center for Genomics and Bioinformatics; Suecia.Fil: Åslund, Lena. Uppsala University. Department of Genetics and Pathology; Suecia.Fil: Attipoe, Philip. Seattle Biomedical Research Institute; Estados Unidos.Fil: Bontempi, Esteban. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Parasitología; Argentina.Fil: Bringaud, Frédéric. Université Victor Segalen Bordeaux II. Laboratoire de Génomique Fonctionnelle des Trypanosomatides; Francia.Fil: Burton, Peter. University of Glasgow. Wellcome Centre for Molecular Parasitology; Reino Unido.Fil: Cadag, Eithon. Seattle Biomedical Research Institute; Estados Unidos.Fil: Campbell, David A. University of California. Department of Microbiology; Estados Unidos.Fil: Carrington, Mark. University of Cambridge. Department of Biochemistry; Reino Unido.Fil: Crabtree, Jonathan. The Institute for Genomic Research. Department of Parasite Genomics; Estados Unidos.Fil: Darban, Hamid. Karolinska Institutet. Center for Genomics and Bioinformatics; Suecia.Fil: Silveira, Jose Franco da. Universidade Federal de Sao Paulo. Departamento de Microbiologia; Brasil.Fil: Jong, Pieter de. Children’s Hospital Oakland Research Institute. BACPAC Resources; Estados Unidos.Fil: Edwards, Kimberly. Karolinska Institutet. Center for Genomics and Bioinformatics; Suecia.Fil: Englund, Paul T. Johns Hopkins University School of Medicine. Department of Biological Chemistry; Estados Unidos.Fil: Fazelina, Gholam. Seattle Biomedical Research Institute; Estados Unidos.Fil: Feldblyum, Tamara. The Institute for Genomic Research. Department of Parasite Genomics; Estados Unidos.Fil: Ferella, Marcela. Karolinska Institutet. Center for Genomics and Bioinformatics; Suecia.Fil: Frasch, Alberto Carlos. Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas; Argentina.Fil: Gull, Keith. University of Oxford. Sir William Dunn School of Pathology; Reino Unido.Fil: Horn, David. London School of Hygiene and Tropical Medicine; Reino Unido.Fil: Hou, Lihua. The Institute for Genomic Research. Department of Parasite Genomics; Estados Unidos.Fil: Huang, Yiting. Seattle Biomedical Research Institute; Estados Unidos.Fil: Kindlund, Ellen. Karolinska Institutet. Center for Genomics and Bioinformatics; Suecia.Fil: Klingbeil, Michele. University of Massachusetts. Department of Microbiology; Estados Unidos.Fil: Kluge, Sindy. Karolinska Institutet. Center for Genomics and Bioinformatics; Suecia.Fil: Koo, Hean. The Institute for Genomic Research. Department of Parasite Genomics; Estados Unidos.Fil: Lacerda, Daniela. The Institute for Genomic Research. Department of Parasite Genomics; Estados Unidos.Fil: Levin, Mariano J. Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET-CYTED project). Laboratorio de Biología Molecular de la Enfermedad de Chagas; Argentina.Fil: Lorenzi, Hernan. Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET-CYTED project). Laboratorio de Biología Molecular de la Enfermedad de Chagas; Argentina.Fil: Louie, Tin. Seattle Biomedical Research Institute; Estados Unidos.Fil: Machado, Carlos Renato. Universidade Federal de Minas Gerais. Departamento de Bioquímica e Imunologia; Brasil.Fil: McCulloch, Richard. University of Glasgow. Wellcome Centre for Molecular Parasitology; Reino Unido.Fil: McKenna, Alan. Karolinska Institutet. Center for Genomics and Bioinformatics; Suecia.Fil: Mizuno, Yumi. Karolinska Institutet. Center for Genomics and Bioinformatics; Suecia.Fil: Mottram, Jeremy C. University of Glasgow. Wellcome Centre for Molecular Parasitology; Reino Unido.Fil: Nelson, Siri. Seattle Biomedical Research Institute; Estados Unidos.Fil: Ochaya, Stephen. Karolinska Institutet. Center for Genomics and Bioinformatics; Suecia.Fil: Osoegawa, Kazutoyo. Children’s Hospital Oakland Research Institute. BACPAC Resources; Estados Unidos.Fil: Pai, Grace. The Institute for Genomic Research. Department of Parasite Genomics; Estados Unidos.Fil: Parsons, Marilyn. Seattle Biomedical Research Institute; Estados Unidos.Fil: Pentony, Martin. Seattle Biomedical Research Institute; Estados Unidos.Fil: Pettersson, Ulf. Uppsala University. Department of Genetics and Pathology; Suecia.Fil: Pop, Mihai. The Institute for Genomic Research. Department of Parasite Genomics; Estados Unidos.Fil: Ramirez, Jose Luis. Universidad Central de Venezuela. Instituto de Biología Experimental; Venezuela.Fil: Rinta, Joel. Seattle Biomedical Research Institute; Estados Unidos.Fil: Robertson, Laura. Seattle Biomedical Research Institute; Estados Unidos.Fil: Salzberg, Steven L. The Institute for Genomic Research. Department of Parasite Genomics; Estados Unidos.Fil: Sanchez, Daniel O. Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas; Argentina.Fil: Seyler, Amber. Seattle Biomedical Research Institute; Estados Unidos.Fil: Sharma, Reuben. University of Cambridge. Department of Biochemistry; Reino Unido.Fil: Shetty, Jyoti. The Institute for Genomic Research. Department of Parasite Genomics; Estados Unidos.Fil: Simpson, Anjana J. The Institute for Genomic Research. Department of Parasite Genomics; Estados Unidos.Fil: Sisk, Ellen. Seattle Biomedical Research Institute; Estados Unidos.Fil: Tammi, Martti T. Karolinska Institutet. Center for Genomics and Bioinformatics; Suecia.Fil: Tarleton, Rick. University of Georgia. Center for Tropical and Emerging Global Diseases; Estados Unidos.Fil: Teixeira, Santuza. Universidade Federal de Minas Gerais. Departamento de Bioquímica e Imunologia; Brasil.Fil: Aken, Susan Van. The Institute for Genomic Research. Department of Parasite Genomics; Estados Unidos.Fil: Vogt, Christy. Seattle Biomedical Research Institute; Estados Unidos.Fil: Ward, Pauline N. University of Glasgow. Wellcome Centre for Molecular Parasitology; Reino Unido.Fil: Wickstead, Bill. University of Oxford. Sir William Dunn School of Pathology; Reino Unido.Fil: Wortman, Jennifer. The Institute for Genomic Research. Department of Parasite Genomics; Estados Unidos.Fil: White, Owen. The Institute for Genomic Research. Department of Parasite Genomics; Estados Unidos.Fil: Fraser, Claire M. The Institute for Genomic Research. Department of Parasite Genomics; Estados Unidos.Fil: Stuart, Kenneth D. Seattle Biomedical Research Institute; Estados Unidos.Fil: Andersson, Björn. Karolinska Institutet. Center for Genomics and Bioinformatics; Suecia.Whole-genome sequencing of the protozoan pathogen Trypanosoma cruzi revealed that the diploid genome contains a predicted 22,570 proteins encoded by genes, of which 12,570 represent allelic pairs. Over 50% of the genome consists of repeated sequences, such as retrotransposons and genes for large families of surface molecules, which include trans-sialidases, mucins, gp63s, and a large novel family (>1300 copies) of mucin-associated surface protein (MASP) genes. Analyses of the T. cruzi, T. brucei, and Leishmania major (Tritryp) genomes imply differences from other eukaryotes in DNA repair and initiation of replication and reflect their unusual mitochondrial DNA. Although the Tritryp lack several classes of signaling molecules, their kinomes contain a large and diverse set of protein kinases and phosphatases; their size and diversity imply previously unknown interactions and regulatory processes, which may be targets for intervention

The genome sequence of Trypanosoma cruzi, etiologic agent of Chagas disease

Fil: El-Sayed, Najib M. The Institute for Genomic Research. Department of Parasite Genomics; Estados Unidos.Fil: Myler, Peter J. Seattle Biomedical Research Institute; Estados Unidos.Fil: Bartholomeu, Daniella C. The Institute for Genomic Research. Department of Parasite Genomics; Estados Unidos.Fil: Nilsson, Daniel. Karolinska Institutet. Center for Genomics and Bioinformatics; Suecia.Fil: Aggarwal, Gautam. Seattle Biomedical Research Institute; Estados Unidos.Fil: Tran, Anh-Nhi. Karolinska Institutet. Center for Genomics and Bioinformatics; Suecia.Fil: Ghedin, Elodie. The Institute for Genomic Research. Department of Parasite Genomics; Estados Unidos.Fil: Worthey, Elizabeth A. Seattle Biomedical Research Institute; Estados Unidos.Fil: Delcher, Arthur L. The Institute for Genomic Research. Department of Parasite Genomics; Estados Unidos.Fil: Blandin, Gaëlle. The Institute for Genomic Research. Department of Parasite Genomics; Estados Unidos.Fil: Westenberger, Scott J. The Institute for Genomic Research. Department of Parasite Genomics; Estados Unidos.Fil: Caler, Elisabet. The Institute for Genomic Research. Department of Parasite Genomics; Estados Unidos.Fil: Cerqueira, Gustavo C. The Institute for Genomic Research. Department of Parasite Genomics; Estados Unidos.Fil: Haas, Carole Branched Brian. Karolinska Institutet. Center for Genomics and Bioinformatics; Suecia.Fil: Anupama, Atashi. Seattle Biomedical Research Institute; Estados Unidos.Fil: Arner, Erik. Karolinska Institutet. Center for Genomics and Bioinformatics; Suecia.Fil: Åslund, Lena. Uppsala University. Department of Genetics and Pathology; Suecia.Fil: Attipoe, Philip. Seattle Biomedical Research Institute; Estados Unidos.Fil: Bontempi, Esteban. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Parasitología; Argentina.Fil: Bringaud, Frédéric. Université Victor Segalen Bordeaux II. Laboratoire de Génomique Fonctionnelle des Trypanosomatides; Francia.Fil: Burton, Peter. University of Glasgow. Wellcome Centre for Molecular Parasitology; Reino Unido.Fil: Cadag, Eithon. Seattle Biomedical Research Institute; Estados Unidos.Fil: Campbell, David A. University of California. Department of Microbiology; Estados Unidos.Fil: Carrington, Mark. University of Cambridge. Department of Biochemistry; Reino Unido.Fil: Crabtree, Jonathan. The Institute for Genomic Research. Department of Parasite Genomics; Estados Unidos.Fil: Darban, Hamid. Karolinska Institutet. Center for Genomics and Bioinformatics; Suecia.Fil: Silveira, Jose Franco da. Universidade Federal de Sao Paulo. Departamento de Microbiologia; Brasil.Fil: Jong, Pieter de. Children’s Hospital Oakland Research Institute. BACPAC Resources; Estados Unidos.Fil: Edwards, Kimberly. Karolinska Institutet. Center for Genomics and Bioinformatics; Suecia.Fil: Englund, Paul T. Johns Hopkins University School of Medicine. Department of Biological Chemistry; Estados Unidos.Fil: Fazelina, Gholam. Seattle Biomedical Research Institute; Estados Unidos.Fil: Feldblyum, Tamara. The Institute for Genomic Research. Department of Parasite Genomics; Estados Unidos.Fil: Ferella, Marcela. Karolinska Institutet. Center for Genomics and Bioinformatics; Suecia.Fil: Frasch, Alberto Carlos. Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas; Argentina.Fil: Gull, Keith. University of Oxford. Sir William Dunn School of Pathology; Reino Unido.Fil: Horn, David. London School of Hygiene and Tropical Medicine; Reino Unido.Fil: Hou, Lihua. The Institute for Genomic Research. Department of Parasite Genomics; Estados Unidos.Fil: Huang, Yiting. Seattle Biomedical Research Institute; Estados Unidos.Fil: Kindlund, Ellen. Karolinska Institutet. Center for Genomics and Bioinformatics; Suecia.Fil: Klingbeil, Michele. University of Massachusetts. Department of Microbiology; Estados Unidos.Fil: Kluge, Sindy. Karolinska Institutet. Center for Genomics and Bioinformatics; Suecia.Fil: Koo, Hean. The Institute for Genomic Research. Department of Parasite Genomics; Estados Unidos.Fil: Lacerda, Daniela. The Institute for Genomic Research. Department of Parasite Genomics; Estados Unidos.Fil: Levin, Mariano J. Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET-CYTED project). Laboratorio de Biología Molecular de la Enfermedad de Chagas; Argentina.Fil: Lorenzi, Hernan. Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET-CYTED project). Laboratorio de Biología Molecular de la Enfermedad de Chagas; Argentina.Fil: Louie, Tin. Seattle Biomedical Research Institute; Estados Unidos.Fil: Machado, Carlos Renato. Universidade Federal de Minas Gerais. Departamento de Bioquímica e Imunologia; Brasil.Fil: McCulloch, Richard. University of Glasgow. Wellcome Centre for Molecular Parasitology; Reino Unido.Fil: McKenna, Alan. Karolinska Institutet. Center for Genomics and Bioinformatics; Suecia.Fil: Mizuno, Yumi. Karolinska Institutet. Center for Genomics and Bioinformatics; Suecia.Fil: Mottram, Jeremy C. University of Glasgow. Wellcome Centre for Molecular Parasitology; Reino Unido.Fil: Nelson, Siri. Seattle Biomedical Research Institute; Estados Unidos.Fil: Ochaya, Stephen. Karolinska Institutet. Center for Genomics and Bioinformatics; Suecia.Fil: Osoegawa, Kazutoyo. Children’s Hospital Oakland Research Institute. BACPAC Resources; Estados Unidos.Fil: Pai, Grace. The Institute for Genomic Research. Department of Parasite Genomics; Estados Unidos.Fil: Parsons, Marilyn. Seattle Biomedical Research Institute; Estados Unidos.Fil: Pentony, Martin. Seattle Biomedical Research Institute; Estados Unidos.Fil: Pettersson, Ulf. Uppsala University. Department of Genetics and Pathology; Suecia.Fil: Pop, Mihai. The Institute for Genomic Research. Department of Parasite Genomics; Estados Unidos.Fil: Ramirez, Jose Luis. Universidad Central de Venezuela. Instituto de Biología Experimental; Venezuela.Fil: Rinta, Joel. Seattle Biomedical Research Institute; Estados Unidos.Fil: Robertson, Laura. Seattle Biomedical Research Institute; Estados Unidos.Fil: Salzberg, Steven L. The Institute for Genomic Research. Department of Parasite Genomics; Estados Unidos.Fil: Sanchez, Daniel O. Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas; Argentina.Fil: Seyler, Amber. Seattle Biomedical Research Institute; Estados Unidos.Fil: Sharma, Reuben. University of Cambridge. Department of Biochemistry; Reino Unido.Fil: Shetty, Jyoti. The Institute for Genomic Research. Department of Parasite Genomics; Estados Unidos.Fil: Simpson, Anjana J. The Institute for Genomic Research. Department of Parasite Genomics; Estados Unidos.Fil: Sisk, Ellen. Seattle Biomedical Research Institute; Estados Unidos.Fil: Tammi, Martti T. Karolinska Institutet. Center for Genomics and Bioinformatics; Suecia.Fil: Tarleton, Rick. University of Georgia. Center for Tropical and Emerging Global Diseases; Estados Unidos.Fil: Teixeira, Santuza. Universidade Federal de Minas Gerais. Departamento de Bioquímica e Imunologia; Brasil.Fil: Aken, Susan Van. The Institute for Genomic Research. Department of Parasite Genomics; Estados Unidos.Fil: Vogt, Christy. Seattle Biomedical Research Institute; Estados Unidos.Fil: Ward, Pauline N. University of Glasgow. Wellcome Centre for Molecular Parasitology; Reino Unido.Fil: Wickstead, Bill. University of Oxford. Sir William Dunn School of Pathology; Reino Unido.Fil: Wortman, Jennifer. The Institute for Genomic Research. Department of Parasite Genomics; Estados Unidos.Fil: White, Owen. The Institute for Genomic Research. Department of Parasite Genomics; Estados Unidos.Fil: Fraser, Claire M. The Institute for Genomic Research. Department of Parasite Genomics; Estados Unidos.Fil: Stuart, Kenneth D. Seattle Biomedical Research Institute; Estados Unidos.Fil: Andersson, Björn. Karolinska Institutet. Center for Genomics and Bioinformatics; Suecia.Whole-genome sequencing of the protozoan pathogen Trypanosoma cruzi revealed that the diploid genome contains a predicted 22,570 proteins encoded by genes, of which 12,570 represent allelic pairs. Over 50% of the genome consists of repeated sequences, such as retrotransposons and genes for large families of surface molecules, which include trans-sialidases, mucins, gp63s, and a large novel family (>1300 copies) of mucin-associated surface protein (MASP) genes. Analyses of the T. cruzi, T. brucei, and Leishmania major (Tritryp) genomes imply differences from other eukaryotes in DNA repair and initiation of replication and reflect their unusual mitochondrial DNA. Although the Tritryp lack several classes of signaling molecules, their kinomes contain a large and diverse set of protein kinases and phosphatases; their size and diversity imply previously unknown interactions and regulatory processes, which may be targets for intervention