The current standard to assess pentavalent antimonial (SSG) susceptibility of Leishmania is a laborious in vitro assay of which the result has little clinical value because SSG-resistant parasites are also found in SSG-cured patients.... more
The current standard to assess pentavalent antimonial (SSG) susceptibility of Leishmania is a laborious in vitro assay of which the result has little clinical value because SSG-resistant parasites are also found in SSG-cured patients. Candidate genetic markers for clinically relevant SSG-resistant parasites identified by full genome sequencing were here validated on a larger set of clinical strains. We show that 3 genomic locations suffice to specifically detect the SSG-resistant parasites found only in patients experiencing SSG treatment failure. This finding allows the development of rapid assays to monitor the emergence and spread of clinically relevant SSG-resistant Leishmania parasites.
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Leishmaniasis is a disease complex caused by protozoan parasites of the genus Leishmania, which are transmitted by sandflies. It affects 350 million people worldwide, but the most severe form, visceral leishmaniasis (VL), is most... more
Leishmaniasis is a disease complex caused by protozoan parasites of the genus Leishmania, which are transmitted by sandflies. It affects 350 million people worldwide, but the most severe form, visceral leishmaniasis (VL), is most prevalent in India, Nepal, Bangladesh, Sudan and Brazil. In the Indian subcontinent, VL is caused by Leishmania donovani, and efficient treatment is highly challenged by the emergence of drug resistance. We are running two projects–Kaladrug (2) and GeMInI (3)–to characterize the genetic and ...
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We present a minimal model for proteins, which is able to capture the structural conversion between the alpha-helix and beta-hairpin. In most regimes of the parameter space, the model produces a stable structure at a low temperature; in a... more
We present a minimal model for proteins, which is able to capture the structural conversion between the alpha-helix and beta-hairpin. In most regimes of the parameter space, the model produces a stable structure at a low temperature; in a few limited regimes of the parameter space, the model displays an beta-hairpin transition as the physical conditions vary. These variations include a perturbation on hydrogen bonding propensity at the middle of the modeled chain, or the change of the hydrophobicity of a designated pair along the chain. Using Monte Carlo simulations, we demonstrate the structural conversion by means of state diagrams, heat capacity maps, and free energy maps.
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Two key biological features distinguish Trypanosoma evansi from the T. brucei group: independence from the tsetse fly as obligatory vector, and independence from the need for functional mitochondrial DNA (kinetoplast or kDNA). In an... more
Two key biological features distinguish Trypanosoma evansi from the T. brucei group: independence from the tsetse fly as obligatory vector, and independence from the need for functional mitochondrial DNA (kinetoplast or kDNA). In an effort to better understand the molecular causes and consequences of these differences, we sequenced the genome of an akinetoplastic T. evansi strain from China and compared it to the T. b. brucei reference strain. The annotated T. evansi genome shows extensive similarity to the reference, with 94.9% of the predicted T. b. brucei coding sequences (CDS) having an ortholog in T. evansi, and 94.6% of the non-repetitive orthologs having a nucleotide identity of 95% or greater. Interestingly, several procyclin-associated genes (PAGs) were disrupted or not found in this T. evansi strain, suggesting a selective loss of function in the absence of the insect life-cycle stage. Surprisingly, orthologous sequences were found in T. evansi for all 978 nuclear CDS pred...
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Genomic stability and maintenance of the correct chromosome number are assumed to be essential for normal development in eukaryotes. Aneuploidy is usually associated with severe abnormalities and decrease of cell fitness, but some... more
Genomic stability and maintenance of the correct chromosome number are assumed to be essential for normal development in eukaryotes. Aneuploidy is usually associated with severe abnormalities and decrease of cell fitness, but some organisms appear to rely on aneuploidy for rapid adaptation to changing environments. This phenomenon is mostly described in pathogenic fungi and cancer cells. However, recent genome studies highlight the importance of Leishmania as a new model for studies on aneuploidy. Several reports revealed extensive variation in chromosome copy number, indicating that aneuploidy is a constitutive feature of this protozoan parasite genus. Aneuploidy appears to be beneficial in organisms that are primarily asexual, unicellular, and that undergo sporadic epidemic expansions, including common pathogens as well as cancer.
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We present a unified potential-energy model that successfully reproduces the hydrogen bonding effect in proteins and can be used to represent well-defined secondary structures, both α-helices and β-sheets. The native structures of the... more
We present a unified potential-energy model that successfully reproduces the hydrogen bonding effect in proteins and can be used to represent well-defined secondary structures, both α-helices and β-sheets. The native structures of the model contain both α-helices and β-sheets and are entirely dependent on the sequence of the modelled protein. The model provides structural insight into the physical mechanism of such problems as structural conversion due to mutation and double native conformations with different α-helix and β-sheet contents.