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Michel, P.

Publications and source records attributed to Michel, P..

3 recordsLinked to original sources

Stepwise recombination suppression around the mating-type locus associated with a diploid-like life cycle in Schizothecium fungi

Recombination suppression often evolves around sex-determining loci and extends stepwise, resulting in adjacent regions with different levels of divergence between sex chromosomes, called evolutionary strata. In Ascomycota fungi, evolutionary strata have been found around the mating-type (MAT) locus only in pseudo-homothallic species, i.e., with a diploid-like lifecycle and mycelia carrying nuclei of both mating types. In contrast, no recombination suppression has been observed in fungi with a haploid-like lifecycle, such as heterothallic fungi (with mycelial colonies of a single mating type each). Here, we investigated the evolution of recombination suppression in a clade of dung fungi encompassing 16 pseudo-homothallic and three heterothallic sibling species from the Schizothecium genus (Ascomycota, Sordariales). The analysis of genetic divergence based on genome sequencing indicated recombination suppression around the MAT locus in all investigated 13 pseudo-homothallic species. The non-recombining region ranged from 600 kb to 1.6 Mb and harbored multiple evolutionary strata, varying in size and number among species. The separation of alleles associated with alternative mating types in gene genealogies across strains within species, the high linkage disequilibrium and an inversion in one species supported the lack of recombination in the MAT-proximal region in pseudo-homothallic species. The overall lack of trans-specific polymorphism suggested multiple independent events of recombination suppression or the occurrence of rare events of recombination or genic conversion. Progeny analyses showed the occurrence of recombination close to the MAT locus in heterothallic strains. We thus revealed here multiple and likely independent evolutionary strata, associated with an extended diploid-like stage in Schizothecium fungi, which provides a good model for research on sex-related chromosome evolution.

evolutionary biology↗

Do you see what I see? Diffusion imaging protocol heterogeneity biases ischemic core volume, location, and clinical associations in acute stroke

PurposeDiffusion-weighted magnetic resonance imaging (DWI) is essential for diagnosing ischemic stroke and identifying targets for emergency revascularization. Apparent diffusion coefficient (ADC) maps derived from DWI are commonly used to locate the infarct core, but they are not strictly quantitative and can vary across platforms and sites due to technical factors. This retrospective study was conducted to examine how differences in ADC map generation, resulting from varied protocols across platforms and sites, affect the determination of infarct core size, location, and related clinical outcomes in acute stroke. MethodsIn this retrospective study, 726 acute anterior circulation stroke patients admitted to the Lausanne University Hospital between May 2018 and January 2021 were selected. DWI data were used to generate ADC maps as they would appear from different protocols: two simulated with low and medium angular resolution (4 and 12 diffusion gradient directions) and one with high angular resolution (20 directions). Using a DEFUSE like criteria and image post-processing, ischemic cores were localized; core volume, location, and associations to National Institutes of Health Stroke Scale (NIHSS) and modified Rankin Scale (mRS) scores were compared between the two imaging sequences. ResultsSignificant differences were observed in the ADC distribution within white matter, particularly in the kurtosis and skewness, with the segmented infarct core volume being higher in protocols with reduced angular resolution compared to the 20-directions data (7.63 ml vs. 3.78 ml). The volumetric differences persisted after correcting for age, sex, and type of intervention. Infarcted voxels locations varied significantly between the two protocols. This variability affected associations between infarct core volume and clinical scores, with lower associations observed for 4-directions data compared to 20-directions data for NIHSS at admission and after 24 hours, and mRS after 3 months, further confirmed by multivariate regression. ConclusionsImaging protocol heterogeneity leads to significant changes in the ADC distribution, ischemic core location, size, and association with clinical scores. Work is needed in standardizing imaging protocols to improve the reliability of ADC as an imaging biomarker in stroke management.protocols to improve the reliability of ADC as an imaging biomarker in stroke management. Key ResultsO_LIOrientation changes in diffusion imaging significantly impact ADC distribution and threshold-based infarct core volume determination, affecting multi-centric studies. C_LIO_LILower number of directions in DWI acquisitions weakens associations between infarct volume measurements and clinical scores. C_LIO_LIFindings emphasize the impact of DWI acquisition protocol heterogeneity and image processing on acute stroke workups. C_LI

neuroscience↗

A matter of food and substrain: obesogenic diets induce differential severity of cardiac remodeling and diastolic dysfunction in C57Bl/6J and C57Bl/6N substrains

The prevalence of metabolic syndrome in cardiac diseases such as heart failure with preserved ejection fraction (HFpEF) prompts the scientific community to investigate its adverse effects on cardiac function and remodeling and its associated mechanisms. However, the choice of a preclinical model of obesity-induced cardiac remodeling has proven more challenging with inconsistencies often found in very similar mouse models. Here, we invesgated the implication of both genetic background of mouse substrains as well as diet composition to identify a suitable model of diet-induced cardiac alterations. C57Bl/6J and C57Bl/6N male mice were subjected to distinct obesogenic diets consisting of high-fat and moderate-sucrose content (HF-S) or High-Sucrose and moderate lipid content (F-HS) versus matching control diets. 5-month dietary intervention with obesogenic diets induced weight gain, adipocyte hypertrophy and increased visceral and subcutaneous fat mass in both substrains. Obese mice showed similar impairment of glucose disposition and insulin tolerance among genotypes, both strains developing insulin resistance within two months. However, echocardiographic follow-up and histological analysis confirmed that HF-S diet increases cardiac hypertrophy, interstitial fibrosis as well as le atrial area in the C57Bl/6J strain only. On the contrary C57Bl/6N exhibit cardiac eccentric remodeling under control diets, possibly owing to a genetic mutation in the myosin light chain kinase 3 (Mylk3) gene, specific to this substrain, which was not further enhanced under obesogenic diets. Altogether, the present results highlight the importance of carefully selecting the suitable mouse strain and diets to model diet-induced cardiac remodeling. In this regard, C57Bl/6J mice develop significant cardiac remodeling in response to HF-S, and seem a suitable model for cardiometabolic disease.

physiology↗