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51.
Larson Boundenga Boris Makanga Benjamin Ollomo Aude Gilabert Virginie Rougeron Bertrand Mve-Ondo Céline Arnathau Patrick Durand Nancy Diamella Moukodoum Alain-Prince Okouga Lucresse Delicat-Loembet Lauriane Yacka-Mouele Nil Rahola Eric Leroy Cheikh Tidiane BA Francois Renaud Franck Prugnolle Christophe Paupy 《PloS one》2016,11(2)
Re-examination, using molecular tools, of the diversity of haemosporidian parasites (among which the agents of human malaria are the best known) has generally led to rearrangements of traditional classifications. In this study, we explored the diversity of haemosporidian parasites infecting vertebrate species (particularly mammals, birds and reptiles) living in the forests of Gabon (Central Africa), by analyzing a collection of 492 bushmeat samples. We found that samples from five mammalian species (four duiker and one pangolin species), one bird and one turtle species were infected by haemosporidian parasites. In duikers (from which most of the infected specimens were obtained), we demonstrated the existence of at least two distinct parasite lineages related to Polychromophilus species (i.e., bat haemosporidian parasites) and to sauropsid Plasmodium (from birds and lizards). Molecular screening of sylvatic mosquitoes captured during a longitudinal survey revealed the presence of these haemosporidian parasite lineages also in several Anopheles species, suggesting a potential role in their transmission. Our results show that, differently from what was previously thought, several independent clades of haemosporidian parasites (family Plasmodiidae) infect mammals and are transmitted by anopheline mosquitoes. 相似文献
52.
Collins C. Iwuji Joanna Orne-Gliemann Joseph Larmarange Nonhlanhla Okesola Frank Tanser Rodolphe Thiebaut Claire Rekacewicz Marie-Louise Newell Francois Dabis ANRS TasP trial group 《PLoS medicine》2016,13(8)
BackgroundThe 2015 WHO recommendation of antiretroviral therapy (ART) for all immediately following HIV diagnosis is partially based on the anticipated impact on HIV incidence in the surrounding population. We investigated this approach in a cluster-randomised trial in a high HIV prevalence setting in rural KwaZulu-Natal. We present findings from the first phase of the trial and report on uptake of home-based HIV testing, linkage to care, uptake of ART, and community attitudes about ART.ConclusionsHome-based HIV testing was well received in this rural population, although men were less easily contactable at home; immediate ART was acceptable, with good viral suppression and retention. However, only about half of HIV-positive people accessed care within 6 mo of being identified, with nearly two-thirds accessing care by 12 mo. The observed delay in linkage to care would limit the individual and public health ART benefits of universal testing and treatment in this population.
Trial registration
ClinicalTrials.gov NCT01509508相似文献53.
Germana Bancone Nongnud Chowwiwat Raweewan Somsakchaicharoen Lalita Poodpanya Paw Khu Moo Gornpan Gornsawun Ladda Kajeechiwa May Myo Thwin Santisuk Rakthinthong Suphak Nosten Suradet Thinraow Slight Naw Nyo Clare L. Ling Jacher Wiladphaingern Naw Lily Kiricharoen Kerryn A. Moore Nicholas J. White Francois Nosten 《PloS one》2016,11(3)
Background
Primaquine is the only drug consistently effective against mature gametocytes of Plasmodium falciparum. The transmission blocking dose of primaquine previously recommended was 0.75mg/kg (adult dose 45mg) but its deployment was limited because of concerns over haemolytic effects in patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency. G6PD deficiency is an inherited X-linked enzymatic defect that affects an estimated 400 million people around the world with high frequencies (15–20%) in populations living in malarious areas. To reduce transmission in low transmission settings and facilitate elimination of P. falciparum, the World Health Organization now recommends adding a single dose of 0.25mg/kg (adult dose 15mg) to Artemisinin-based Combination Therapies (ACTs) without G6PD testing. Direct evidence of the safety of this low dose is lacking. Adverse events and haemoglobin variations after this treatment were assessed in both G6PD normal and deficient subjects in the context of targeted malaria elimination in a malaria endemic area on the North-Western Myanmar-Thailand border where prevalence of G6PD deficiency (Mahidol variant) approximates 15%.Methods and Findings
The tolerability and safety of primaquine (single dose 0.25 mg base/kg) combined with dihydroartemisinin-piperaquine (DHA-PPQ) given three times at monthly intervals was assessed in 819 subjects. Haemoglobin concentrations were estimated over the six months preceding the ACT + primaquine rounds of mass drug administration. G6PD deficiency was assessed with a phenotypic test and genotyping was performed in male subjects with deficient phenotypes and in all females. Fractional haemoglobin changes in relation to G6PD phenotype and genotype and primaquine round were assessed using linear mixed-effects models. No adverse events related to primaquine were reported during the trial. Mean fractional haemoglobin changes after each primaquine treatment in G6PD deficient subjects (-5.0%, -4.2% and -4.7%) were greater than in G6PD normal subjects (0.3%, -0.8 and -1.7%) but were clinically insignificant. Fractional drops in haemoglobin concentration larger than 25% following single dose primaquine were observed in 1.8% of the population but were asymptomatic.Conclusions
The single low dose (0.25mg/kg) of primaquine is clinically well tolerated and can be used safely without prior G6PD testing in populations with high prevalence of G6PD deficiency. The present evidence supports a broader use of low dose primaquine without G6PD testing for the treatment and elimination of falciparum malaria.Trial Registration
ClinicalTrials.gov NCT01872702相似文献54.
Surface polysaccharides and quorum sensing are involved in the attachment and survival of Xanthomonas albilineans on sugarcane leaves
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Imene Mensi Jean‐Heinrich Daugrois Isabelle Pieretti Daniel Gargani Laura A. Fleites Julie Noell Francois Bonnot Dean W. Gabriel Philippe Rott 《Molecular Plant Pathology》2016,17(2):236-246
Xanthomonas albilineans, the causal agent of sugarcane leaf scald, is a bacterial plant pathogen that is mainly spread by infected cuttings and contaminated harvesting tools. However, some strains of this pathogen are known to be spread by aerial means and are able to colonize the phyllosphere of sugarcane before entering the host plant and causing disease. The objective of this study was to identify the molecular factors involved in the survival or growth of X. albilineans on sugarcane leaves. We developed a bioassay to test for the attachment of X. albilineans on sugarcane leaves using tissue‐cultured plantlets grown in vitro. Six mutants of strain XaFL07‐1 affected in surface polysaccharide production completely lost their capacity to survive on the sugarcane leaf surface. These mutants produced more biofilm in vitro and accumulated more cellular poly‐β‐hydroxybutyrate than the wild‐type strain. A mutant affected in the production of small molecules (including potential biosurfactants) synthesized by non‐ribosomal peptide synthetases (NRPSs) attached to the sugarcane leaves as well as the wild‐type strain. Surprisingly, the attachment of bacteria on sugarcane leaves varied among mutants of the rpf gene cluster involved in bacterial quorum sensing. Therefore, quorum sensing may affect polysaccharide production, or both polysaccharides and quorum sensing may be involved in the survival or growth of X. albilineans on sugarcane leaves. 相似文献
55.
Ga?lle Letort Francois Nedelec Laurent Blanchoin Manuel Théry 《Molecular biology of the cell》2016,27(18):2833-2843
The centrosome is positioned at the cell center by pushing and pulling forces transmitted by microtubules (MTs). Centrosome decentering is often considered to result from asymmetric, cortical pulling forces exerted in particular by molecular motors on MTs and controlled by external cues affecting the cell cortex locally. Here we used numerical simulations to investigate the possibility that it could equally result from the redistribution of pushing forces due to a reorientation of MTs. We first showed that MT gliding along cell edges and pivoting around the centrosome regulate MT rearrangement and thereby direct the spatial distribution of pushing forces, whereas the number, dynamics, and stiffness of MTs determine the magnitude of these forces. By modulating these parameters, we identified different regimes, involving both pushing and pulling forces, characterized by robust centrosome centering, robust off-centering, or “reactive” positioning. In the last-named conditions, weak asymmetric cues can induce a misbalance of pushing and pulling forces, resulting in an abrupt transition from a centered to an off-centered position. Taken together, these results point to the central role played by the configuration of the MTs on the distribution of pushing forces that position the centrosome. We suggest that asymmetric external cues should not be seen as direct driver of centrosome decentering and cell polarization but instead as inducers of an effective reorganization of the MT network, fostering centrosome motion to the cell periphery. 相似文献
56.
Erasmus Elardus Mason Shayne van Reenen Mari Steffens Francois E. Vorster B. Chris Reinecke Carolus J. 《Metabolomics : Official journal of the Metabolomic Society》2019,15(12):1-10
Metabolomics - Pre-eclampsia is a hypertensive gestational disorder that affects approximately 5% of all pregnancies. As the pathophysiological processes of pre-eclampsia are still uncertain, the... 相似文献
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59.
Communities are mostly composed of rare species; yet, the factors that determine their patterns of occurrence remain obscure. Theory predicts that, in contrast with common species, the occurrence of rare species will be poorly correlated with environmental variables (niches) and more affected by stochasticity (ecological drift), but how this pattern varies across different trophic groups is still poorly understood. Here, we compared the ability of environmental variables (bottom–up biotic niches) to predict the occurrence of plant‐dwelling arthropods across different abundance classes in the Cape Floristic Region of South Africa. We compared three trophic groups, including 104 herbivorous hemipteran, 171 parasitoid wasp and 84 spider species, totalling 4511 individuals in 48 quadrats. To quantify bottom–up biotic niches, we studied the influences of species composition of plants on hemipterans, and of plants and hemipterans on spiders and wasps. We compared the observed strength of the correlation between rare species and their niches with expectations that were generated by repeatedly rarefying abundant species. A large proportion of arthropod species were very rare, i.e. with only one or two individuals (49–55%). Although rarefying abundant species greatly decreased the correlation with bottom–up biotic niches, bottom–up biotic niches generally better predicted the occurrence of rarefied abundant species than very rare ones, suggesting a greater influence of drift on very rare arthropods. That is, (very) rare arthropods are distributed more randomly than rarefied abundant species. Nevertheless, trophic groups differed in the details of their response to bottom–up biotic niches. Plant species composition was a better predictor of rarefied abundant than truly rare hemipterans. In contrast, the importance of bottom–up biotic niches among abundance classes varied less visibly in spiders and wasps. Our study thus suggests that the importance of niches in structuring arthropod communities depends on species rarity and trophic group. 相似文献
60.
Violette Azzoni Julien Wicinski Manon Macario Martin Castagn Pascal Finetti Katerina Ambrosova Clia D. Rouault Arnaud Serg Anne Farina Emilie Agavnian Sergiu Coslet Emmanuelle Josselin Arnaud Guille Jos Adelaide Emmanouil Zacharioudakis Rmy Castellano Francois Bertucci Daniel Birnbaum Raphael Rodriguez Emmanuelle Charafe-Jauffret Christophe Ginestier 《Cell death & disease》2022,13(2)
Replication stress (RS) has a pivotal role in tumor initiation, progression, or therapeutic resistance. In this study, we depicted the mechanism of breast cancer stem cells’ (bCSCs) response to RS and its clinical implication. We demonstrated that bCSCs present a limited level of RS compared with non-bCSCs in patient samples. We described for the first time that the spatial nuclear location of BMI1 protein triggers RS response in breast cancers. Hence, in bCSCs, BMI1 is rapidly located to stalled replication forks to recruit RAD51 and activate homologous-recombination machinery, whereas in non-bCSCs BMI1 is trapped on demethylated 1q12 megasatellites precluding effective RS response. We further demonstrated that BMI1/RAD51 axis activation is necessary to prevent cisplatin-induced DNA damage and that treatment of patient-derived xenografts with a RAD51 inhibitor sensitizes tumor-initiating cells to cisplatin. The comprehensive view of replicative-stress response in bCSC has profound implications for understanding and improving therapeutic resistance.Subject terms: Breast cancer, Cancer stem cells 相似文献