Genetic diversity and population structure of the Eurosian otte (Lutra lutra) in France

During the last century, the Eurasian otter (Lutra lutra) suffered a dramatic decline in Europe. In France, the same pattern of sharp decline was observed with local extinctions in many regions. Before the recolonisation process, two main populations still remained along the Atlantic coast and in the Massif Central. To investigate the impact of this decline on the genetic diversity and structure of the French otter population, tissue samples of 144 otter carcasses from road kills that were found during 1992–2011 along the Atlantic coast and in the Massif Central were used. They were analysed using 10 microsatellites loci. Observed (Ho = 0.64) and expected heterozygosity (He = 0.62) were moderate, but consistent with results found in other European populations. The bottleneck test showed an excess of heterozygotes, providing evidence of a recent decline. There was evidence for weak but significant allelic frequencies divergence between otters from the Atlantic coast and those from the Massif Central (Fst=0.040, p<0.05), probably resulting from their isolation prior to the recolonisation process. As the French otter population has been expanding for several years, genetic intermixing is now occurring. Although this expansion has not yet genetically homogenised all populations, this is may be a matter a time

Oxidative stress precedes skeletal muscle mitochondrial dysfunction during experimental aortic cross-clamping but is not associated with early lung, heart, brain, liver, or kidney mitochondrial impairment

ObjectiveLower limb ischemia-reperfusion results in skeletal muscle mitochondrial alterations, production of reactive oxygen species (ROS), and remote organ impairments that are largely involved in patient prognosis. However, whether ischemia without reperfusion increases ROS production and precedes mitochondrial alteration and whether mitochondrial dysfunction occurs early in remote organs is unknown. This study determined muscle mitochondrial function and ROS production after ischemia alone, or followed by two periods of reperfusion, and investigated heart, lung, liver, kidney, and brain mitochondrial functions after lower limb ischemia-reperfusion.MethodsWistar rats were randomized into four groups: sham (aortic exposure but no ischemia, n = 9), I3 (ischemia alone induced by aortic cross-clamping for 3 hours, n = 9), I3R10′ and I3R2 (aortic cross-clamping, followed by reperfusion for 10 minutes [n = 8] or 2 hours [n = 9]). Blood lactate, alanine aminotransferase, aspartate aminotransferase, and creatinine were measured. Mitochondrial respiratory chain complexes I, II, III, and IV activities and mitochondrial coupling (acceptor control ratio) were analyzed using a Clark oxygen electrode in skeletal muscle, lung, heart, brain, liver, and kidney. ROS production was determined using dihydroethidium staining in muscle, heart, liver, and kidney. Inflammation was also investigated in remote organs (heart, liver, and kidney) using monocyte-macrophage-2 antibody staining.ResultsLactate level increased after ischemia in all groups. In muscle, ROS increased significantly after ischemia alone (+324% ± 66%; P = .038), normalized after 10 minutes of reperfusion, and increased again at 2 hours of reperfusion (+349.2 ± 67%; P = .024). Interestingly, mitochondrial function was unaffected by ischemia alone or followed by 10 minutes of reperfusion, but maximal mitochondrial oxidative capacity (6.10 ± 0.51 vs 4.24 ± 0.36 μmol/min/g, −30%; P < .05) and mitochondrial coupling decreased after 2 hours of reperfusion (1.93 ± 0.17 vs 1.33 ± 0.07, −45%; P < .01), in sham and I3R2 rats, respectively. Despite increased serum aspartate aminotransferase (×13; P < .0001), alanine aminotransferase (×6; P = .0019), and creatinine (×3; P = .0004), remote organs did not show mitochondrial alteration, inflammation, or ROS production enhancement after 2 hours of reperfusion.ConclusionsOxidative stress precedes skeletal muscle mitochondrial dysfunction during lower limb ischemia. Such a kinetic explains the efficacy of ischemic preconditioning and supports that therapy should be conducted even during ongoing ischemia, suggesting that ischemic preconditioning might be a successful approach.Clinical RelevanceAortic cross-clamping increases reactive oxygen species (ROS) and impairs skeletal muscle and remote organs, which is involved in patient prognosis. However, the temporal relationship between ROS production and mitochondrial dysfunction during lower limb ischemia reperfusion is unknown. This study demonstrates for the first time that ROS production occurs during ischemia alone, without reperfusion, and precedes skeletal muscle mitochondrial impairments. Although involved in multiorgan failure, lung, heart, brain, liver, and kidney mitochondria are not affected early. These results support a need for muscle protection even during lower limb ischemia and that ischemic preconditioning (conditioning performed during ongoing ischemia) might be a successful approach

Opposite effects of statins on mitochondria of cardiac and skeletal muscles: a ‘mitohormesis' mechanism involving reactive oxygen species and PGC-1

Aims Statins protect against cardiovascular-related mortality but induce skeletal muscle toxicity. To investigate mechanisms of statins, we tested the hypothesis that statins optimized cardiac mitochondrial function but impaired vulnerable skeletal muscle by inducing different level of reactive oxygen species (ROS). Methods and results In atrium of patients treated with statins, ROS production was decreased and oxidative capacities were enhanced together with an extensive augmentation of mRNAs expression of peroxisome proliferator-activated receptor gamma co-activator (PGC-1) family. However, in deltoid biopsies from patients with statin-induced muscular myopathy, oxidative capacities were decreased together with ROS increase and a collapse of PGC-1 mRNA expression. Several animal and cell culture experiments were conducted and showed by using ROS scavengers that ROS production was the triggering factor responsible of atorvastatin-induced activation of mitochondrial biogenesis pathway and improvement of antioxidant capacities in heart. Conversely, in skeletal muscle, the large augmentation of ROS production following treatment induced mitochondrial impairments, and reduced mitochondrial biogenesis mechanisms. Quercetin, an antioxidant molecule, was able to counteract skeletal muscle deleterious effects of atorvastatin in rat. Conclusion Our findings identify statins as a new activating factor of cardiac mitochondrial biogenesis and antioxidant capacities, and suggest the importance of ROS/PGC-1 signalling pathway as a key element in regulation of mitochondrial function in cardiac as well as skeletal muscle

A cold-water fish striving in a warming ocean: Insights from whole-genome sequencing of the Greenland halibut in the Northwest Atlantic

Characterizing the extent of genetic differentiation among individuals and its distribution across the genome is increasingly important to inform both conservation and management of exploited species. The Greenland Halibut is one of the main demersal fish species to be commercially exploited in Eastern Canada, and accurate information on geographic population structure and local adaptation is required to ensure the long-term presence of this species. We generated high-quality whole-genome sequencing data for 1,297 Greenland Halibut sampled across 32 locations throughout the Northwest Atlantic (from Arctic Canadian and Greenlandic coasts to the Gulf of St Lawrence). Population genetic structure was analyzed, revealing an absence of population differentiation between Canada and west Greenland but significant genetic differentiation between the Gulf of Saint Lawrence and the remainder of the Northwest Atlantic. Except for Gulf of Saint Lawrence, Greenland Halibut thus appear to be panmictic throughout the Northwest Atlantic. Environmental Association Analyses revealed that the environment explained up to 51 % might be replaced by 51% of the differentiation observed between the two stocks, with both ocean-bottom and surface variables (e.g., temperature and oxygen) involved in the observed genomic differentiation. Altogether, these results indicate that phenotypic differences previously observed between the Gulf of Saint Lawrence and the Northwest Atlantic likely resulted from functional adaptive divergence to their respective environmental conditions. Using coalescent simulations, we also assessed how high levels of migration between the two stocks would allow Greenland Halibut to potentially escape unfavorable environmental conditions in the Gulf of Saint Lawrence. In addition to supporting the management of this important exploited species, this work highlights the utility of using comprehensive genomic datasets to characterize the effects of climate change across a wider range of species

PGC-1β modulates statin-associated myotoxicity in mice

Statins inhibit cholesterol biosynthesis and lower serum LDL-cholesterol levels. Statins are generally well tolerated, but can be associated with potentially life-threatening myopathy of unknown mechanism. We have shown previously that statins impair PGC-1β expression in human and rat skeletal muscle, suggesting that PGC-1β may play a role in statininduced myopathy. PGC-1β is a transcriptional co-regulator controlling the expression of important genes in mitochondrial biogenesis, antioxidative capacity and energy metabolism. The principle aim of the current study was to investigate the interaction between atorvastatin and PGC-1β in more detail. We therefore treated wild-type mice and mice with selective skeletal muscle knockout of PGC-1β (PGC-1β(i)skm−/− mice) with oral atorvastatin (5 mg/kg/day) for 2 weeks. At the end of treatment, we determined body parameters, muscle function, structure, and composition as well as the function of muscle mitochondria, mitochondrial biogenesis and activation of apoptotic pathways. In wild-type mice, atorvastatin selectively impaired mitochondrial function in glycolytic muscle and caused a conversion of oxidative type IIA to glycolytic type IIB myofibers. Conversely, in oxidative muscle of wild-type mice, atorvastatin enhanced mitochondrial function via activation of mitochondrial biogenesis pathways and decreased apoptosis. In PGC-1β(i)skm−/− mice, atorvastatin induced a switch towards glycolytic fibers, caused mitochondrial dysfunction, increased mitochondrial ROS production, impaired mitochondrial proliferation and induced apoptosis in both glycolytic and oxidative skeletal muscle. Our work reveals that atorvastatin mainly affects glycolytic muscle in wild-type mice and demonstrates the importance of PGC-1β for oxidative muscle integrity during long-term exposure to a myotoxic agent.Peer reviewe

Activity Coefficients at Infinite Dilution for Organic Compounds Dissolved in 1-Alkyl-1-methylpyrrolidinium Bis(trifluoromethylsulfonyl)imide Ionic Liquids Having Six-, Eight-, and Ten-Carbon Alkyl Chains

Article on activity coefficients at infinite dilution for organic compounds dissolved in 1-alkyl-1-methylpyrrolidinium bis(trifluoromethylsulfonyl)imide ionic liquids having six-, eight-, and ten-carbon alkyl chains

Hypercaloric low-carbohydrate high-fat diet protects against the development of nonalcoholic fatty liver disease in obese mice in contrast to isocaloric Western diet

ObjectiveObesity and metabolic complications, such as type 2 diabetes and nonalcoholic fatty liver disease (NAFLD), are one of the greatest public health challenges of the 21st century. The major role of high sugar and carbohydrate consumption rather than caloric intake in obesity and NAFLD pathophysiology remains a subject of debate. A low-carbohydrate but high-fat diet (LCHFD) has shown promising results in obesity management, but its effects in preventing NAFLD need to be detailed. This study aims to compare the effects of a LCHFD with a high-fat high-sugar obesogenic Western diet (WD) on the progression of obesity, type 2 diabetes, and nonalcoholic fatty liver disease.MethodsMale C57BL/6J mice were initially fed a WD for 10 weeks. Subsequently, they were either switched to a LCHFD or maintained on the WD for an additional 6 weeks. Hepatic effects of the diet were explored by histological staining and RT-qPCR.ResultsAfter the initial 10 weeks WD feeding, LCHF diet demonstrated effectiveness in halting weight gain, maintaining a normal glucose tolerance and insulin levels, in comparison to the WD-fed mice, which developed obesity, glucose intolerance, increased insulin levels and induced NAFLD. In the liver, LCHFD mitigated the accumulation of hepatic triglycerides and the increase in Fasn relative gene expression compared to the WD mice. Beneficial effects of the LCHFD occurred despite a similar calorie intake compared to the WD mice.ConclusionOur results emphasize the negative impact of a high sugar/carbohydrate and lipid association for obesity progression and NAFLD development. LCHFD has shown beneficial effects for NAFLD management, notably improving weight management, and maintaining a normal glucose tolerance and liver health