Can Blood Flow Restriction En hance the Effectiveness of Electrical Stimulations for Treating Muscle Damage?

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MRI adipose tissue segmentation and quantification in R (RAdipoSeg)

Background: Excess adipose tissue is associated with increased cardiovascular and metabolic risk, but the volume of visceral and subcutaneous adipose tissue poses different metabolic risks. MRI with fat suppression can be used to accurately quantify adipose depots. We have developed a new semi-automatic method, RAdipoSeg, for MRI adipose tissue segmentation and quantification in the free and open source statistical software R. Methods: MRI images were obtained from wild-type mice on high- or low-fat diet, and from 20 human subjects without clinical signs of metabolic dysfunction. For each mouse and human subject, respectively, 10 images were segmented with RAdipoSeg and with the commercially available software SliceOmatic. Jaccard difference, relative volume difference and Spearman’s rank correlation coefficients were calculated for each group. Agreement between the two methods were analysed with Bland–Altman plots. Results: RAdipoSeg performed similarly to the commercial software. The mean Jaccard differences were 10–29% and the relative volume differences were below ( ±) 20%. Spearman’s rank correlation coefficient gave p-values below 0.05 for both mouse and human images. The Bland–Altman plots indicated some systematic and proporitional bias, which can be countered by the flexible nature of the method. Conclusion: RAdipoSeg is a reliable and low cost method for fat segmentation in studies of mice and humans.publishedVersio

Evolutionary impact assessment: accounting for evolutionary consequences of fishing in an ecosystem approach to fisheries management

Managing fisheries resources to maintain healthy ecosystems is one of the main goals of the ecosystem approach to fisheries (EAF). while the number of international treaties call for the implementation of EAF, there are still gaps in the underlying methodology. One aspect that has received substantial scientific attention recently in fisheries-induced evolution (FIE). Increasing evidence indicates that intensive fishing has the potential to exert strong directional selection on life-history traits, behavior, physiology, and morphology of exploited fish. Of particular concern is that reversing evolutionary responses to fishing can be much more difficult than reversing demographic or phenotypically plastic responses. Furthermore, like climate change, multiple agents cause fisheries-induced evolution with effects accumulating over time. Consequently, FIE may alter then utility derived from fish stocks, which in turn can modify the monetary value living aquatic resources provide to society. Quantifying and predicting the evolutionary effects of fishing is therefore important for both ecological and economic reasons, An important reason this is not happening is the lack of an appropriate assessment framework. We therefor describe the evolutionary impact assessment (EvoIA) as a structured approach for assessing the evolutionary outcomes of alternative management options. EvoIA can contribute to the ecosystem approach to fisheries management by clarifying how evolution may alter stock properties and ecological relations, support the precautionary approach to fisheries management by addressing a previously overlooked source of uncertainty and risk, and thus contribute to sustainable fisheries

FTO Obesity Variant Circuitry and Adipocyte Browning in Humans

Background Genomewide association studies can be used to identify disease-relevant genomic regions, but interpretation of the data is challenging. The FTO region harbors the strongest genetic association with obesity, yet the mechanistic basis of this association remains elusive. Methods We examined epigenomic data, allelic activity, motif conservation, regulator expression, and gene coexpression patterns, with the aim of dissecting the regulatory circuitry and mechanistic basis of the association between the FTO region and obesity. We validated our predictions with the use of directed perturbations in samples from patients and from mice and with endogenous CRISPR–Cas9 genome editing in samples from patients. Results Our data indicate that the FTO allele associated with obesity represses mitochondrial thermogenesis in adipocyte precursor cells in a tissue-autonomous manner. The rs1421085 T-to-C single-nucleotide variant disrupts a conserved motif for the ARID5B repressor, which leads to derepression of a potent preadipocyte enhancer and a doubling of IRX3 and IRX5 expression during early adipocyte differentiation. This results in a cell-autonomous developmental shift from energy-dissipating beige (brite) adipocytes to energy-storing white adipocytes, with a reduction in mitochondrial thermogenesis by a factor of 5, as well as an increase in lipid storage. Inhibition of Irx3 in adipose tissue in mice reduced body weight and increased energy dissipation without a change in physical activity or appetite. Knockdown of IRX3 or IRX5 in primary adipocytes from participants with the risk allele restored thermogenesis, increasing it by a factor of 7, and overexpression of these genes had the opposite effect in adipocytes from nonrisk-allele carriers. Repair of the ARID5B motif by CRISPR–Cas9 editing of rs1421085 in primary adipocytes from a patient with the risk allele restored IRX3 and IRX5 repression, activated browning expression programs, and restored thermogenesis, increasing it by a factor of 7. Conclusions Our results point to a pathway for adipocyte thermogenesis regulation involving ARID5B, rs1421085, IRX3, and IRX5, which, when manipulated, had pronounced pro-obesity and anti-obesity effects. (Funded by the German Research Center for Environmental Health and others.)National Institutes of Health (U.S.) (R01HG004037)National Institutes of Health (U.S.) (R01GM113708)National Institutes of Health (U.S.) (R01HG008155)National Institutes of Health (U.S.) (RC1HG005334

Can fisheries-induced evolution shift reference points for fisheries management?

Heino, M., Baulier, L., Boukal, D. S., Ernande, B., Johnston, F. D., Mollet, F. M., Pardoe, H., Therkildsen, N. O., Uusi-Heikkilä, S., Vainikka, A., Arlinghaus, R., Dankel, D. J., Dunlop, E. S., Eikeset, A. M., Enberg, K., Engelhard G. H., Jørgensen, C., Laugen, A. T., Matsumura, S., Nusslé, S., Urbach, D., Whitlock, R., Rijnsdorp, A. D., and Dieckmann, U. 2013. Can fisheries-induced evolution shift reference points for fisheries management? - ICES Journal of Marine Science, 70: 707-721. Biological reference points are important tools for fisheries management. Reference points are not static, but may change when a population's environment or the population itself changes. Fisheries-induced evolution is one mechanism that can alter population characteristics, leading to "shifting” reference points by modifying the underlying biological processes or by changing the perception of a fishery system. The former causes changes in "true” reference points, whereas the latter is caused by changes in the yardsticks used to quantify a system's status. Unaccounted shifts of either kind imply that reference points gradually lose their intended meaning. This can lead to increased precaution, which is safe, but potentially costly. Shifts can also occur in more perilous directions, such that actual risks are greater than anticipated. Our qualitative analysis suggests that all commonly used reference points are susceptible to shifting through fisheries-induced evolution, including the limit and "precautionary” reference points for spawning-stock biomass, Blim and Bpa, and the target reference point for fishing mortality, F0.1. Our findings call for increased awareness of fisheries-induced changes and highlight the value of always basing reference points on adequately updated information, to capture all changes in the biological processes that drive fish population dynamic

Diets differing in carbohydrate cellularity and amount similarly reduced visceral fat in people with obesity - a randomized controlled trial (CARBFUNC)

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High-fat diet impact on intestinal cholesterol conversion by the microbiota and serum cholesterol levels

Cholesterol-to-coprostanol conversion by the intestinal microbiota has been suggested to reduce intestinal and serum cholesterol availability, but the relationship between intestinal cholesterol conversion and the gut microbiota, dietary habits, and serum lipids has not been characterized in detail. We measured conserved proportions of cholesterol high and low-converter types in individuals with and without obesity from two distinct, independent low-carbohydrate high-fat (LCHF) dietary intervention studies. Across both cohorts, cholesterol conversion increased in previous low-converters after LCHF diet and was positively correlated with the fecal relative abundance of Eubacterium coprostanoligenes. Lean cholesterol high-converters had increased serum triacylglycerides and decreased HDL-C levels before LCHF diet and responded to the intervention with increased LDL-C, independently of fat, cholesterol, and saturated fatty acid intake. Our findings identify the cholesterol high-converter type as a microbiome marker, which in metabolically healthy lean individuals is associated with increased LDL-C in response to LCHF.publishedVersio