Localization of protein aggregation in Escherichia coli is governed by diffusion and nucleoid macromolecular crowding effect

Aggregates of misfolded proteins are a hallmark of many age-related diseases. Recently, they have been linked to aging of Escherichia coli (E. coli) where protein aggregates accumulate at the old pole region of the aging bacterium. Because of the potential of E. coli as a model organism, elucidating aging and protein aggregation in this bacterium may pave the way to significant advances in our global understanding of aging. A first obstacle along this path is to decipher the mechanisms by which protein aggregates are targeted to specific intercellular locations. Here, using an integrated approach based on individual-based modeling, time-lapse fluorescence microscopy and automated image analysis, we show that the movement of aging-related protein aggregates in E. coli is purely diffusive (Brownian). Using single-particle tracking of protein aggregates in live E. coli cells, we estimated the average size and diffusion constant of the aggregates. Our results evidence that the aggregates passively diffuse within the cell, with diffusion constants that depend on their size in agreement with the Stokes-Einstein law. However, the aggregate displacements along the cell long axis are confined to a region that roughly corresponds to the nucleoid-free space in the cell pole, thus confirming the importance of increased macromolecular crowding in the nucleoids. We thus used 3d individual-based modeling to show that these three ingredients (diffusion, aggregation and diffusion hindrance in the nucleoids) are sufficient and necessary to reproduce the available experimental data on aggregate localization in the cells. Taken together, our results strongly support the hypothesis that the localization of aging-related protein aggregates in the poles of E. coli results from the coupling of passive diffusion- aggregation with spatially non-homogeneous macromolecular crowding. They further support the importance of "soft" intracellular structuring (based on macromolecular crowding) in diffusion-based protein localization in E. coli.Comment: PLoS Computational Biology (2013

Patient perspectives on the role of community pharmacists for antidepressant treatment : a qualitative study

Objectives : Patients prescribed antidepressant drug treatment (ADT) for major depression report several needs in relation to their treatment, and a large proportion of these patients will end ADT prematurely. Community pharmacists may play an important role in monitoring ADT and supporting these patients. However, little is known about patient experiences of the services provided in community pharmacies. The objectives of this study were to 1) explore patients’ experiences with the services community pharmacists provide for ADT and 2) identify potential avenues for improvement of pharmacists’ services within the context of ADT. Methods : A qualitative descriptive exploratory study was conducted among individuals diagnosed with major depression who had initiated ADT at some point in the 12 months prior to their participation in the study. A total of 14 persons recruited in a local health centre and a community-based organization participated in individual interviews. A thematic analysis of the interview transcripts was conducted. Results : Pharmacists tend to concentrate their involvement in treatment at initiation and at the first refill when questions, uncertainties and side effects are major issues. Patients felt that the pharmacists’ contributions consisted of providing information and reassurance; in these respects, their needs were met. Participants had few ideas as to what additional services pharmacists could implement to improve patients’ experience with ADT. Patients’ sole expectations were that pharmacists extend this information role to the whole length of the treatment and enhance the confidentiality of discussions in pharmacy. Conclusion : Pharmacists should provide counselling throughout the entire treatment rather than passively waiting for patients to ask their questions. However, facilitation of open discussions may not be achieved unless confidentiality at pharmacies is secured

Evolution of HIV-1 groups M and O: genetic comparative analysis of 23 HIV-1/MO inter-group recombinant forms

International audienc

Le mal-être active les gènes codant pour l'inflammation

Les chevaux agressifs ne sont pas simplement des chevaux mal éduqués ou caractériels. Cette agressivité peut révéler des souffrances physiques et un état de mal-être qui peuvent être profonds. Cet état de mal-être va jusqu’à modifier l’expression de certains de leurs gènes : ceux impliqués dans la réponse immunitaire et au stress, et la mort cellulaire programmée. Cela montre à quel point ce trouble ne doit pas être pris à la légère. Les chevaux qui présentent un trouble agressif doivent être pris en charge afin de faire évoluer leurs conditions de vie et de travail vers une meilleure prise en compte de leur bien-être

Analyse des régions LTR du génome d'un VIH-1 recombinant inter-groupes M et O : étude de l'émergence des points de cassure et caractérisation des différentes populations

International audienc

The impact of lake shape and size on lake breezes and air-lake exchanges on Titan

Titan, the largest moon of Saturn, has many lakes on its surface, formed mainly of liquid methane. Like water lakes on Earth, these methane lakes on Titan likely profoundly affect the local climate. Previous studies (Rafkin and Soto 2020, Chatain et al 2022) showed that Titan's lakes create lake breeze circulations with characteristic dimensions similar to the ones observed on Earth. However, such studies used a model in two dimensions; this work investigates the consequences of the addition of a third dimension to the model. Our results show that 2D simulations tend to overestimate the extension of the lake breeze over the land, and underestimate the strength of the subsidence over the lake, due to divergence/convergence geometrical effects in the mass conservation equations. In addition, 3D simulations including a large scale background wind show the formation of a pocket of accelerated wind behind the lake, which did not form in 2D simulations. An investigation of the effect of shoreline concavity on the resulting air circulation shows the formation of wind currents over peninsulas. Simulations with several lakes can either result in the formation of several individual lake breeze cells (during the day), or the emergence of a large merged cell with internal wind currents between lakes (during the night). Simulations of several real-shaped lakes located at a latitude of 74{\deg}N on Titan at the spring equinox show that larger lakes trigger stronger winds, and that some sections of lakes might accumulate enough methane vapor to form a thin fog. The addition of a third dimension, along with adjustments in the parametrizations of turbulence and subsurface land temperature, results in a reduction in the magnitude of the average lake evaporate rate, namely to ~6 cm/Earth year.Comment: Submitted to Icarus on 2023-07-21. Dataset available at the DOI: 10.5281/zenodo.817227

Mise au point d'une méthode de quantification de l'ARN plasmatique spécifique des VIH-1 de groupe M

International audienc

Priming for welfare: gut microbiota is associated with equitation conditions and behavior in horse athletes

We simultaneously measured the fecal microbiota and multiple environmental and host-related variables in a cohort of 185 healthy horses reared in similar conditions during a period of eight months. The pattern of rare bacteria varied from host to host and was largely different between two time points. Among a suite of variables examined, equitation factors were highly associated with the gut microbiota variability, evoking a relationship between gut microbiota and high levels of physical and mental stressors. Behavioral indicators that pointed toward a compromised welfare state (e.g. stereotypies, hypervigilance and aggressiveness) were also associated with the gut microbiota, reinforcing the notion for the existence of the microbiota-gut-brain axis. These observations were consistent with the microbiability of behaviour traits (> 15%), illustrating the importance of gut microbial composition to animal behaviour. As more elite athletes suffer from stress, targeting the microbiota offers a new opportunity to investigate the bidirectional interactions within the brain gut microbiota axis.info:eu-repo/semantics/publishedVersio

Gut microbiota resilience in horse athletes following holidays out to pasture

Elite horse athletes that live in individual boxes and train and compete for hours experience longterm physical and mental stress that compromises animal welfare and alters the gut microbiota. We therefore assessed if a temporary period out to pasture with conspecifics could improve animal welfare and in turn, favorably affect intestinal microbiota composition. A total of 27 athletes were monitored before and after a period of 1.5 months out to pasture, and their fecal microbiota and behavior profiles were compared to those of 18 horses kept in individual boxes. The overall diversity and microbiota composition of pasture and control individuals were temporally similar, suggesting resilience to environmental challenges. However, pasture exposure induced an increase in Ruminococcus and Coprococcus that lasted 1-month after the return to individual boxes, which may have promoted beneficial effects on health and welfare. Associations between the gut microbiota composition and behavior indicating poor welfare were established. Furthermore, withdrawn behavior was associated with the relative abundances of Lachnospiraceae AC2044 group and Clostridiales family XIII. Both accommodate a large part of butyrate-producing bacterial genera. While we cannot infer causality within this study, arguably, these findings suggest that management practices maintained over a longer period of time may moderate the behavior link to the gut ecosystem beyond its resilience potential

Yeast Screens Identify the RNA Polymerase II CTD and SPT5 as Relevant Targets of BRCA1 Interaction

BRCA1 has been implicated in numerous DNA repair pathways that maintain genome integrity, however the function responsible for its tumor suppressor activity in breast cancer remains obscure. To identify the most highly conserved of the many BRCA1 functions, we screened the evolutionarily distant eukaryote Saccharomyces cerevisiae for mutants that suppressed the G1 checkpoint arrest and lethality induced following heterologous BRCA1 expression. A genome-wide screen in the diploid deletion collection combined with a screen of ionizing radiation sensitive gene deletions identified mutants that permit growth in the presence of BRCA1. These genes delineate a metabolic mRNA pathway that temporally links transcription elongation (SPT4, SPT5, CTK1, DEF1) to nucleopore-mediated mRNA export (ASM4, MLP1, MLP2, NUP2, NUP53, NUP120, NUP133, NUP170, NUP188, POM34) and cytoplasmic mRNA decay at P-bodies (CCR4, DHH1). Strikingly, BRCA1 interacted with the phosphorylated RNA polymerase II (RNAPII) carboxy terminal domain (P-CTD), phosphorylated in the pattern specified by the CTDK-I kinase, to induce DEF1-dependent cleavage and accumulation of a RNAPII fragment containing the P-CTD. Significantly, breast cancer associated BRCT domain defects in BRCA1 that suppressed P-CTD cleavage and lethality in yeast also suppressed the physical interaction of BRCA1 with human SPT5 in breast epithelial cells, thus confirming SPT5 as a relevant target of BRCA1 interaction. Furthermore, enhanced P-CTD cleavage was observed in both yeast and human breast cells following UV-irradiation indicating a conserved eukaryotic damage response. Moreover, P-CTD cleavage in breast epithelial cells was BRCA1-dependent since damage-induced P-CTD cleavage was only observed in the mutant BRCA1 cell line HCC1937 following ectopic expression of wild type BRCA1. Finally, BRCA1, SPT5 and hyperphosphorylated RPB1 form a complex that was rapidly degraded following MMS treatment in wild type but not BRCA1 mutant breast cells. These results extend the mechanistic links between BRCA1 and transcriptional consequences in response to DNA damage and suggest an important role for RNAPII P-CTD cleavage in BRCA1-mediated cancer suppression