Project description:Human African trypanosomiasis (HAT) is a protozoal disease transmitted by bites of tsetse flies. Infection with trypanosomes can lead directly to active HAT or latent infection with no detectable parasites, which may progress to active HAT or to spontaneous self-cure. Genetic variation could explain these differences in the outcome of infection. To test this hypothesis, 96 polymorphisms in 17 candidate genes were tested for association with phenotype in a case control design. The genes tested were: APOL1, CFH, HLA-A, HPR, HP, IL1B, IL12B, IL12RB1, IL10, IL4R, MIF ,TNFA, IL6, IL4, IL8, IFNG, and HLA-G.
Project description:Wild type T. brucei bloodstream form were incubated with increasing concentrations of AN7973, a benzoxaborole compound developed by Anacor Pharmaceuticals Inc. against Animal African Trypanosomiasis. Cells had a tendency to lose resistance, only roughly 2x EC50 resistance was obtained. This experiment include the sequencing of wild type cells, intermediate stages (80C and 80D) and final resistant cell lines (80C3005 and 80D2004)
Project description:The host central nervous system (CNS) response to infection with Trypanosoma brucei (T. b.) gambiense or T. b. rhodesiense parasites, the causing agent of human African trypanosomiasis (HAT), is a poorly explored area. The two parasites are responsible for respectively a chronic and an acute form of HAT. In both cases, however, the disease progresses from a haemolymphatic first stage (S1) to a meningo-encephalitic second stage (S2) due to the penetration of parasites into the CNS. In the present study, we investigated and compared the cerebrospinal fluid (CSF) from S2 patients affected by either T. b. gambiense or T. b. rhodesiense HAT, using a mass spectrometry quantitative proteomics approach. Gene ontology and pathway analyses on the 222 quantified proteins, revealed a predominant activation of the innate immune and the acute phase responses in rhodesiense HAT. These results were further confirmed through the verification of the over-expression of two proteins involved in these mechanisms, C-reactive protein (CRP) and orosomucoid 1 (ORM1), in 126 S2 HAT patients suffering from either the chronic or the acute form of HAT. Both proteins were significantly increased (p<0.0001) in the CSF of rhodesiense HAT patients. These findings contribute in better understanding the pathophysiological mechanisms of late stage HAT caused by T. b. gambiense or T. b. rhodesiense and pave the way for further investigations on the clinical significance of CRP and ORM1. See article: <a href="http://www.sciencedirect.com/science/article/pii/S2212963414000126">Increased acute immune response during the meningo-encephalitic stage of Trypanosoma brucei rhodesiense sleeping sickness compared to Trypanosoma brucei gambiense</a>
Project description:We examine the function of the TbRAP1 Myb domain in gene expression regulation in Trypanosoma brucei that causes human African trypanosomiasis. TbRAP1 is required for normal VSG monoallelic expression, a key aspect of antigenic variation that is used by T. brucei to evade the host immune response.
Project description:We examine the function of the TbRAP1 DB domain in gene expression regulation in Trypanosoma brucei that causes human African trypanosomiasis. TbRAP1 is required for normal VSG monoallelic expression, a key aspect of antigenic variation that is used by T. brucei to evade the host immune response.
Project description:The study aimed to define transcriptional signatures for detection of active TB (TB) compared to latent TB infection (LTBI) as well as to other diseases (OD) with similar clinical phenotypes in patients with and without HIV in two African paediatric populations. Transcriptional signatures were identified that distinguished active TB from LTBI, and active TB from other diseases.
Project description:Previous study showed that there are more cell cycle active cardiomyocytes (CMs) in 3-month-old (3M) than1-year-old (1Y) human atria, and extracellular matrix (ECM) from mouse atria benefits neonatal CMs proliferation. We investigate the global changes of transcriptomes between 3M and 1Y human atria and whether ECM from 3M human atria improves myocardium infarct recovery. RNAseq results showed that the major changes between 3M and 1Y human atria were ECM. 3M –ECM increased CM cell cycle activities and rescue mouse heart from injury. We conclude that 3M-ECM hold a therapeutic effect on myocardium infarction.
Project description:The study aimed to define transcriptional signatures for detection of active TB (TB) compared to latent TB infection (LTBI) as well as to other diseases (OD) with similar clinical phenotypes in patients with and without HIV in two African adult populations. Transcriptional signatures were identified that distinguished active TB from LTBI, active TB from other diseases, and active TB from both LTBI and other diseases in HIV+/- patients.
