Embouche intensive des zébus de l'Adamaoua. II. Influence de la durée de la période d'embouche (1971)

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RNA Biol

The HIV-1 Vif protein plays an essential role in the regulation of the infectivity of HIV-1 virion and in vivo pathogenesis. Vif neutralizes the human DNA-editing enzyme APOBEC3 protein, an antiretroviral cellular factor from the innate immune system, allowing the virus to escape the host defence system. It was shown that Vif is packaged into viral particles through specific interactions with the viral genomic RNA. Conserved and structured sequences from the 5'-noncoding region, such as the Tat-responsive element (TAR) or the genomic RNA dimerization initiation site (DIS), are primary binding sites for Vif. In the present study we used isothermal titration calorimetry to investigate sequence and structure determinants important for Vif binding to short viral RNA corresponding to TAR and DIS stem-loops. We showed that Vif specifically binds TAR and DIS in the low nanomolar range. In addition, Vif primarily binds the TAR UCU bulge, but not the apical loop. Determinants for Vif binding to the DIS loop-loop complex are likely more complex and involve the self-complementary loop together with the upper part of the stem. These results suggest that Tat-TAR inhibitors or DIS small molecule binders might be also effective to disturb Vif-TAR and Vif-DIS binding in order to reduce Vif packaging into virions

Quantitative and predictive model of kinetic regulation by E. coli TPP riboswitches.

Riboswitches are non-coding elements upstream or downstream of mRNAs that, upon binding of a specific ligand, regulate transcription and/or translation initiation in bacteria, or alternative splicing in plants and fungi. We have studied thiamine pyrophosphate (TPP) riboswitches regulating translation of thiM operon and transcription and translation of thiC operon in E. coli, and that of THIC in the plant A. thaliana. For all, we ascertained an induced-fit mechanism involving initial binding of the TPP followed by a conformational change leading to a higher-affinity complex. The experimental values obtained for all kinetic and thermodynamic parameters of TPP binding imply that the regulation by A. thaliana riboswitch is governed by mass-action law, whereas it is of kinetic nature for the two bacterial riboswitches. Kinetic regulation requires that the RNA polymerase pauses after synthesis of each riboswitch aptamer to leave time for TPP binding, but only when its concentration is sufficient. A quantitative model of regulation highlighted how the pausing time has to be linked to the kinetic rates of initial TPP binding to obtain an ON/OFF switch in the correct concentration range of TPP. We verified the existence of these pauses and the model prediction on their duration. Our analysis also led to quantitative estimates of the respective efficiency of kinetic and thermodynamic regulations, which shows that kinetically regulated riboswitches react more sharply to concentration variation of their ligand than thermodynamically regulated riboswitches. This rationalizes the interest of kinetic regulation and confirms empirical observations that were obtained by numerical simulations

Insight into the prebiotic concept: lessons from an exploratory, double blind intervention study with inulin-type fructans in obese women

Objective To highlight the contribution of the gut microbiota to the modulation of host metabolism by dietary inulin-type fructans (ITF prebiotics) in obese women. Methods A double blind, placebo controlled, intervention study was performed with 30 obese women treated with ITF prebiotics (inulin/oligofructose 50/50 mix; n=15) or placebo (maltodextrin; n=15) for 3 months (16 g/day). Blood, faeces and urine sampling, oral glucose tolerance test, homeostasis model assessment and impedancemetry were performed before and after treatment. The gut microbial composition in faeces was analysed by phylogenetic microarray and qPCR analysis of 16S rDNA. Plasma and urine metabolic profiles were analysed by 1H-NMR spectroscopy. Results Treatment with ITF prebiotics, but not the placebo, led to an increase in Bifidobacterium and Faecalibacterium prausnitzii; both bacteria negatively correlated with serum lipopolysaccharide levels. ITF prebiotics also decreased Bacteroides intestinalis, Bacteroides vulgatus and Propionibacterium, an effect associated with a slight decrease in fat mass and with plasma lactate and phosphatidylcholine levels. No clear treatment clustering could be detected for gut microbial analysis or plasma and urine metabolomic profile analyses. However, ITF prebiotics led to subtle changes in the gut microbiota that may importantly impact on several key metabolites implicated in obesity and/or diabetes. Conclusions ITF prebiotics selectively changed the gut microbiota composition in obese women, leading to modest changes in host metabolism, as suggested by the correlation between some bacterial species and metabolic endotoxaemia or metabolomic signatures

The future sea-level contribution of the Greenland ice sheet: A multi-model ensemble study of ISMIP6

The Greenland ice sheet is one of the largest contributors to global mean sea-level rise today and is expected to continue to lose mass as the Arctic continues to warm. The two predominant mass loss mechanisms are increased surface meltwater run-off and mass loss associated with the retreat of marine-terminating outlet glaciers. In this paper we use a large ensemble of Greenland ice sheet models forced by output from a representative subset of the Coupled Model Intercomparison Project (CMIP5) global climate models to project ice sheet changes and sea-level rise contributions over the 21st century. The simulations are part of the Ice Sheet Model Intercomparison Project for CMIP6 (ISMIP6).We estimate the sea-level contribution together with uncertainties due to future climate forcing, ice sheet model formulations and ocean forcing for the two greenhouse gas concentration scenarios RCP8.5 and RCP2.6. The results indicate that the Greenland ice sheet will continue to lose mass in both scenarios until 2100, with contributions of 90-50 and 32-17mm to sea-level rise for RCP8.5 and RCP2.6, respectively. The largest mass loss is expected from the south-west of Greenland, which is governed by surface mass balance changes, continuing what is already observed today. Because the contributions are calculated against an unforced control experiment, these numbers do not include any committed mass loss, i.e. mass loss that would occur over the coming century if the climate forcing remained constant. Under RCP8.5 forcing, ice sheet model uncertainty explains an ensemble spread of 40 mm, while climate model uncertainty and ocean forcing uncertainty account for a spread of 36 and 19 mm, respectively. Apart from those formally derived uncertainty ranges, the largest gap in our knowledge is about the physical understanding and implementation of the calving process, i.e. the interaction of the ice sheet with the ocean. © Author(s) 2020

The future sea-level contribution of the Greenland ice sheet: a multi-model ensemble study of ISMIP6

The Greenland ice sheet is one of the largest contributors to global mean sea-level rise today and is expected to continue to lose mass as the Arctic continues to warm. The two predominant mass loss mechanisms are increased surface meltwater run-off and mass loss associated with the retreat of marine-terminating outlet glaciers. In this paper we use a large ensemble of Greenland ice sheet models forced by output from a representative subset of the Coupled Model Intercomparison Project (CMIP5) global climate models to project ice sheet changes and sea-level rise contributions over the 21st century. The simulations are part of the Ice Sheet Model Intercomparison Project for CMIP6 (ISMIP6). We estimate the sea-level contribution together with uncertainties due to future climate forcing, ice sheet model formulations and ocean forcing for the two greenhouse gas concentration scenarios RCP8.5 and RCP2.6. The results indicate that the Greenland ice sheet will continue to lose mass in both scenarios until 2100, with contributions of 90±50 and 32±17 mm to sea-level rise for RCP8.5 and RCP2.6, respectively. The largest mass loss is expected from the south-west of Greenland, which is governed by surface mass balance changes, continuing what is already observed today. Because the contributions are calculated against an unforced control experiment, these numbers do not include any committed mass loss, i.e. mass loss that would occur over the coming century if the climate forcing remained constant. Under RCP8.5 forcing, ice sheet model uncertainty explains an ensemble spread of 40 mm, while climate model uncertainty and ocean forcing uncertainty account for a spread of 36 and 19 mm, respectively. Apart from those formally derived uncertainty ranges, the largest gap in our knowledge is about the physical understanding and implementation of the calving process, i.e. the interaction of the ice sheet with the ocean

Multiple Mutations in Heterogeneous Miltefosine-Resistant Leishmania major Population as Determined by Whole Genome Sequencing

Leishmania spp. are parasitic protozoa responsible for a spectrum of diseases known as leishmaniasis. There are few drugs available for the treatment of these diseases, and miltefosine is the first oral drug used in treatment of visceral leishmaniasis, a form of the disease that can be lethal if not treated. In this study, we seek to understand the mechanism of action and identify targets of the drug by generating promastigote mutants highly resistant to miltefosine. Two independent mutants were submitted to short read whole genome sequencing. Genome analysis of these mutants has permitted us to identify point mutations in three genes (P-type ATPase, pyridoxal kinase and α-adaptin like protein) that were also present in other independent miltefosine resistant mutants. Some of the new genes identified here could be useful as potential markers for miltefosine resistance in Leishmania. Moreover, our approach has permitted us to highlight that resistance can be highly heterogeneous at the population level with individual clones derived from this population differing both in terms of genotypes but also susceptibility phenotypes. This may have practical applications while studying resistance

Polyandry Is a Common Event in Wild Populations of the Tsetse Fly Glossina fuscipes fuscipes and May Impact Population Reduction Measures

Glossina fuscipes fuscipes is the most common tsetse species in Uganda where it is responsible for transmitting Trypanosoma brucei rhodensiense and Trypanosoma brucei gambiense parasites causing sleeping sickness in humans in addition to related trypanosomes that cause Nagana in cattle. An understanding of the reproductive biology of this vector is essential for the application of sustainable control/eradication methods such as Sterile Insect Technique (SIT). We have analysed the number of times a female mates in the wild as this aspect of the reproductive behaviour may affect the stability and size of populations. We provide evidence that remating is a common event in the wild and females store sperm from multiple males, which may potentially be used for insemination. In vector eradication programmes, re-infestation of cleared areas and/or in cases of residual populations, the occurrence of remating may unfortunately enhance the reproductive potential of the re-invading propagules. We suggest that population age structure may influence remating frequency. Considering the seasonal demographic changes that this fly undergoes during the dry and wet seasons, control programmes based on SIT should release large numbers of sterile males, even in residual surviving target populations, in the dry season

Future Sea Level Change Under Coupled Model Intercomparison Project Phase 5 and Phase 6 Scenarios From the Greenland and Antarctic Ice Sheets

Projections of the sea level contribution from the Greenland and Antarctic ice sheets (GrIS and AIS) rely on atmospheric and oceanic drivers obtained from climate models. The Earth System Models participating in the Coupled Model Intercomparison Project phase 6 (CMIP6) generally project greater future warming compared with the previous Coupled Model Intercomparison Project phase 5 (CMIP5) effort. Here we use four CMIP6 models and a selection of CMIP5 models to force multiple ice sheet models as part of the Ice Sheet Model Intercomparison Project for CMIP6 (ISMIP6). We find that the projected sea level contribution at 2100 from the ice sheet model ensemble under the CMIP6 scenarios falls within the CMIP5 range for the Antarctic ice sheet but is significantly increased for Greenland. Warmer atmosphere in CMIP6 models results in higher Greenland mass loss due to surface melt. For Antarctica, CMIP6 forcing is similar to CMIP5 and mass gain from increased snowfall counteracts increased loss due to ocean warming