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In the mammalian host, African trypanosomes generate consecutive waves of parasitaemia by changing their antigenic coat. Because this coat consists of a single type of variant surface glycoprotein (VSG), the question arises of how a trypanosome accomplishes the transcription of only one of a multi-allelic family of VSG expression site loci to display a(More)
More than 20 years ago, biochemical analysis of the eukaryotic cell cytoskeleton revealed the major component proteins. The heterodimeric (α/β) protein tubulin was defined as the building block of microtubules, assembled in a polar manner into specifically arranged protofilaments in the microtubule wall [1]. The next two members of the tubulin protein(More)
Antigenic variation allows Trypanosoma brucei to evade the host immune response by switching the expression of 1 out of approximately 15 telomeric variant surface glycoprotein (VSG) expression sites (ESs). VSG ES transcription is mediated by RNA polymerase I in a discrete nuclear site named the ES body (ESB). However, nothing is known about how the(More)
We study finite-dimensional extra symmetries of generic 2D dilaton gravity models. Using a non-linear sigma model formulation we show that the unique theories admitting an extra (conformal) symmetry are the models with an exponential potential V ∝ e βφ (S = 1 2π d 2 x √ −g[Rφ + 4λ 2 e βφ ]), which include the model of Callan, Giddings, Harvey and Strominger(More)
A unifying feature of eukaryotic nuclear organization is genome segregation into transcriptionally active euchromatin and transcriptionally repressed heterochromatin. In metazoa, lamin proteins preserve nuclear integrity and higher order heterochromatin organization at the nuclear periphery, but no non-metazoan lamin orthologues have been identified,(More)
Interphase nuclear repositioning of chromosomes has been implicated in the epigenetic regulation of RNA polymerase (pol) II transcription. However, little is known about the nuclear position-dependent regulation of RNA pol I-transcribed loci. Trypanosoma brucei is an excellent model system to address this question because its two main surface protein genes,(More)
Target of rapamycin (TOR) kinases control cell growth through two functionally distinct multiprotein complexes. TOR complex 1 (TORC1) controls temporal cell growth and is sensitive to rapamycin, whereas TOR complex 2 (TORC2) is rapamycin resistant and regulates spatial cell growth. Here, we identified two TOR orthologues, TbTOR1 and TbTOR2, in the protozoan(More)
We study global symmetries of generic 2D dilaton gravity models. Using a non-linear sigma model formulation we show that the unique theories admitting special conformal symmetries are the models with an exponential potential V ∝ e βφ (S = 1 2π d 2 x √ −g[Rφ + 4λ 2 e βφ ]), which include the model of Callan, Giddings, Harvey and Strominger (CGHS) as a(More)
BACKGROUND Target repurposing utilizes knowledge of "druggable" targets obtained in one organism and exploits this information to pursue new potential drug targets in other organisms. Here we describe such studies to evaluate whether inhibitors targeting the kinase domain of the mammalian Target of Rapamycin (mTOR) and human phosphoinositide-3-kinases(More)
Using whole-cell phenotypic assays, the GlaxoSmithKline high-throughput screening (HTS) diversity set of 1.8 million compounds was screened against the three kinetoplastids most relevant to human disease, i.e. Leishmania donovani, Trypanosoma cruzi and Trypanosoma brucei. Secondary confirmatory and orthogonal intracellular anti-parasiticidal assays were(More)