Staphylococcus aureus infective endocarditis versus bacteremia strains: Subtle genetic differences at stake

AbstractInfective endocarditis (IE)(1) is a severe condition complicating 10–25% of Staphylococcus aureus bacteremia. Although host-related IE risk factors have been identified, the involvement of bacterial features in IE complication is still unclear. We characterized strictly defined IE and bacteremia isolates and searched for discriminant features. S. aureus isolates causing community-acquired, definite native-valve IE (n=72) and bacteremia (n=54) were collected prospectively as part of a French multicenter cohort. Phenotypic traits previously reported or hypothesized to be involved in staphylococcal IE pathogenesis were tested. In parallel, the genotypic profiles of all isolates, obtained by microarray, were analyzed by discriminant analysis of principal components (DAPC)(2). No significant difference was observed between IE and bacteremia strains, regarding either phenotypic or genotypic univariate analyses. However, the multivariate statistical tool DAPC, applied on microarray data, segregated IE and bacteremia isolates: IE isolates were correctly reassigned as such in 80.6% of the cases (C-statistic 0.83, P<0.001). The performance of this model was confirmed with an independent French collection IE and bacteremia isolates (78.8% reassignment, C-statistic 0.65, P<0.01). Finally, a simple linear discriminant function based on a subset of 8 genetic markers retained valuable performance both in study collection (86.1%, P<0.001) and in the independent validation collection (81.8%, P<0.01). We here show that community-acquired IE and bacteremia S. aureus isolates are genetically distinct based on subtle combinations of genetic markers. This finding provides the proof of concept that bacterial characteristics may contribute to the occurrence of IE in patients with S. aureus bacteremia

Genetic integrity of European wildcats: Variation across biomes mandates geographically tailored conservation strategies

Hybridisation between domestic and wild taxa can pose severe threats to wildlife conservation, and human-induced hybridisation, often linked to species' introductions and habitat degradation, may promote reproductive opportunities between species for which natural interbreeding would be highly unlikely. Using a biome-specific approach, we examine the effects of a suite of ecological drivers on the European wildcat's genetic integrity, while assessing the role played by protected areas in this process. We used genotype data from 1217 putative European wildcat samples from 13 European countries to assess the effects of landcover, disturbance and legal landscape protection on the European wildcat's genetic integrity across European biomes, through generalised linear models within a Bayesian framework. Overall, we found European wildcats to have genetic integrity levels above the wildcat-hybrid threshold (ca. 83%; threshold = 80%). However, Mediterranean and Temperate Insular biomes (i.e., Scotland) revealed lower levels, with 74% and 46% expected genetic integrity, respectively. We found that different drivers shape the level of genetic introgression across biomes, although forest integrity seems to be a common factor promoting European wildcat genetic integrity. Wildcat genetic integrity remains high, regardless of landscape legal protection, in biomes where populations appear to be healthy and show recent local range expansions. However, in biomes more susceptible to hybridisation, even protected areas show limited effectiveness in mitigating this threat. In the face of the detected patterns, we recommend that species conservation and management plans should be biome- and landscape-context-specific to ensure effective wildcat conservation, especially in the Mediterranean and Temperate Insular biomes.Thanks are due to FCT/MCTES for the financial support to cE3c (UIDB/00329/2020), through national funds, and the co-funding by the FEDER, within the PT2020 Partnership Agreement and Compete 2020. PM was supported by UID/BIA/50027/2021 with funding from FCT/MCTES through national funds. FDR was supported by a postdoctoral contract from the University of Málaga (I Plan Propio de Investigación y Transferencia, call 2020). This study was partly funded by research projects CGL2009-10741, funded by the Spanish Ministry of Science and Innovation and EU-FEDER, and OAPN 352/2011, funded by the Organismo Autónomo Parques Nacionales (Spain). Luxembourg sample collection has been co-funded by the Ministry of Environment, Climate and Sustainable Development of Luxembourg. We would like to thank the Bavarian Forest National Park Administration for the approval and support in collecting samples.Peer reviewe

Autophagy-lysosomal pathway in response to fasting/refeeding in C2C12 myotubes

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Validity and reliability of the Huet questionnaire to assess maximal oxygen uptake

Research substantiates children of parents with mental disorders including substance abuse face increased risk for emotional and behavioral problems. Although evidence suggests that support programs for children enhance resiliency, recruiting children to these groups remains problematic. This study identifies successful recruitment strategies for prevention programs for children of parental mental illness. The participants were recruited from an international network of researchers. E-mail invitations requested that researchers forward a web-based questionnaire to five colleagues with recruitment experience. Forty-five individuals from nine countries practicing in mental health responded. Descriptive statistics and qualitative content analysis techniques were used. Results: Schools, adult, and youth mental health services were recruitment sources. Nine themes were identified: Relationships, diversified information output, logistics, program consistency, family involvement, recruitment through adults, stigma, recruiting locations, social media. Recruitment barriers were: stigma, inadequate knowledge about parental mental illness and limited time. Transportation to programming was an essential component of successful recruitment

Post-transcriptional regulation of autophagy in C2C12 myotubes following starvation and nutrient restoration

Times Cited: 0International audienceIn skeletal muscle, autophagy is activated in multiple physiological and pathological conditions, notably through the transcriptional regulation of autophagy-related genes by FoxO3. However, recent evidence suggests that autophagy could also be regulated by post-transcriptional mechanisms. The purpose of the study was therefore to determine the temporal regulation of transcriptional and post-transcriptional events involved in the control of autophagy during starvation (4 h) and nutrient restoration (4 h) in C2C12 myotubes. Starvation was associated with an activation of autophagy (decrease in mTOR activity, increase in AMPK activity and Ulk1 phosphorylation on Ser467), an increase in autophagy flux (increased LC3B-II/LC3B-I ratio, LC3B-II level and LC3B-positive punctate), and an increase in the content of autophagy-related proteins (Ulk1, Atg13, Vps34, and Atg5-Atg12 conjugate). Our data also indicated that the content of autophagy-related proteins was essentially maintained when nutrient sufficiency was restored. By contrast, mRNA level of Ulk1, Atg5, Bnip3, LC3B and Gabarapl1 did not increase in response to starvation. Accordingly, binding of FoxO3 transcription factor on LC3B promoter was only increased at the end of the starvation period, whereas mRNA levels of Atrogin1/MAFbx and MuRF1, two transcriptional targets of FoxO involved in ubiquitin-proteasome pathway, were markedly increased at this time. Together, these data provide evidence that target genes of FoxO3 are differentially regulated during starvation and that starvation of C2C12 myotubes is associated with a post-transcriptional regulation of autophagy

Molecular mechanisms of skeletal muscle atrophy in a mouse model of cerebral ischemia

CERVOXY COLLInternational audienc

Pharmacological inhibition of myostatin improves skeletal muscle mass and function in a mouse model of stroke

Abstract In stroke patients, loss of skeletal muscle mass leads to prolonged weakness and less efficient rehabilitation. We previously showed that expression of myostatin, a master negative regulator of skeletal muscle mass, was strongly increased in skeletal muscle in a mouse model of stroke. We therefore tested the hypothesis that myostatin inhibition would improve recovery of skeletal muscle mass and function after cerebral ischemia. Cerebral ischemia (45 minutes) was induced by intraluminal right middle cerebral artery occlusion (MCAO). Swiss male mice were randomly assigned to Sham-operated mice (n = 10), MCAO mice receiving the vehicle (n = 15) and MCAO mice receiving an anti-myostatin PINTA745 (n = 12; subcutaneous injection of 7.5 mg.kg−1 PINTA745 immediately after surgery, 3, 7 and 10 days after MCAO). PINTA745 reduced body weight loss and improved body weight recovery after cerebral ischemia, as well as muscle strength and motor function. PINTA745 also increased muscle weight recovery 15 days after cerebral ischemia. Mechanistically, the better recovery of skeletal muscle mass in PINTA745-MCAO mice involved an increased expression of genes encoding myofibrillar proteins. Therefore, an anti-myostatin strategy can improve skeletal muscle recovery after cerebral ischemia and may thus represent an interesting strategy to combat skeletal muscle loss and weakness in stroke patients

Staphylococcus aureus infective endocarditis versus bacteremia strains: Subtle genetic differences at stake

International audienceInfective endocarditis (IE)((1)) is a severe condition complicating 10-25% of Staphylococcus aureus bacteremia. Although host-related IE risk factors have been identified, the involvement of bacterial features in IE complication is still unclear. We characterized strictly defined IE and bacteremia isolates and searched for discriminant features. S. aureus isolates causing community-acquired, definite native-valve IE (n=72) and bacteremia (n=54) were collected prospectively as part of a French multicenter cohort. Phenotypic traits previously reported or hypothesized to be involved in staphylococcal IE pathogenesis were tested. In parallel, the genotypic profiles of all isolates, obtained by microarray, were analyzed by discriminant analysis of principal components (DAPC)((2)). No significant difference was observed between IE and bacteremia strains, regarding either phenotypic or genotypic univariate analyses. However, the multivariate statistical tool DAPC, applied on microarray data, segregated IE and bacteremia isolates: IE isolates were correctly reassigned as such in 80.6% of the cases (C-statistic 0.83, P<0.001). The performance of this model was confirmed with an independent French collection IE and bacteremia isolates (78.8% reassignment, C-statistic 0.65, P<0.01). Finally, a simple linear discriminant function based on a subset of 8 genetic markers retained valuable performance both in study collection (86.1%, P<0.001) and in the independent validation collection (81.8%, P<0.01). We here show that community-acquired IE and bacteremia S. aureus isolates are genetically distinct based on subtle combinations of genetic markers. This finding provides the proof of concept that bacterial characteristics may contribute to the occurrence of IE in patients with S. aureus bacteremia