The action of obestatin in skeletal muscle repair: stem cell expansion, muscle growth, and microenvironment remodeling

The development of therapeutic strategies for skeletal muscle diseases, such as physical injuries and myopathies, depends on the knowledge of regulatory signals that control the myogenic process. The obestatin/GPR39 system operates as an autocrine signal in the regulation of skeletal myogenesis. Using a mouse model of skeletal muscle regeneration after injury and several cellular strategies, we explored the potential use of obestatin as a therapeutic agent for the treatment of trauma-induced muscle injuries. Our results evidenced that the overexpression of the preproghrelin, and thus obestatin, and GPR39 in skeletal muscle increased regeneration after muscle injury. More importantly, the intramuscular injection of obestatin significantly enhanced muscle regeneration by simulating satellite stem cell expansion as well as myofiber hypertrophy through a kinase hierarchy. Added to the myogenic action, the obestatin administration resulted in an increased expression of VEGF/VEGFR2 and the consequent microvascularization, with no effect on collagen deposition in skeletal muscle. Furthermore, the potential inhibition of myostatin during obestatin treatment might contribute to its myogenic action improving muscle growth and regeneration. Taken together, our data demonstrate successful improvement of muscle regeneration, indicating obestatin is a potential therapeutic agent for skeletal muscle injury and would benefit other myopathies related to muscle regeneration

EJVES vol 34, issue 2 (August 2007) - Spanish Translated Abstracts

Chronic exposure to arsenic (As) through the consumption of contaminated groundwaters is a major threat to public health in South and Southeast Asia. The source of As-affected groundwaters is important to the fundamental understanding of the controls on As mobilization and subsequent transport throughout shallow aquifers. Using the stable isotopes of hydrogen and oxygen, the source of groundwater and the interactions between various water bodies were investigated in Cambodia’s Kandal Province, an area which is heavily affected by As and typical of many circum-Himalayan shallow aquifers. Two-point mixing models based on δD and δ18O allowed the relative extent of evaporation of groundwater sources to be estimated and allowed various water bodies to be broadly distinguished within the aquifer system. Model limitations are discussed, including the spatial and temporal variation in end member compositions. The conservative tracer Cl/Br is used to further discriminate between groundwater bodies. The stable isotopic signatures of groundwaters containing high As and/or high dissolved organic carbon plot both near the local meteoric water line and near more evaporative lines. The varying degrees of evaporation of high As groundwater sources are indicative of differing recharge contributions (and thus indirectly inferred associated organic matter contributions). The presence of high As groundwaters with recharge derived from both local precipitation and relatively evaporated surface water sources, such as ponds or flooded wetlands, are consistent with (but do not provide direct evidence for) models of a potential dual role of surface-derived and sedimentary organic matter in As mobilization

Weight regain after a diet-induced loss is predicted by higher baseline leptin and lower ghrelin plasma levels

CONTEXT: Appetite-related hormones may play an important role in weight regain after obesity therapy. OBJECTIVE: Our objective was to investigate the potential involvement of ghrelin, leptin, and insulin plasma levels in weight regain after a therapeutic hypocaloric diet. DESIGN: A group of obese/overweight volunteers (49 women and 55 men; 35 ± 7 yr; 30.7 ± 2.4 kg/m(2)) followed an 8-wk hypocaloric diet (-30% energy expenditure) and were evaluated again 32 wk after treatment. Body weight as well as plasma fasting ghrelin, leptin, and insulin concentrations were measured at three points (wk 0, 8, and 32). RESULTS: After the 8-wk hypocaloric diet, the average weight loss was -5.0 ± 2.2% (P < 0.001). Plasma leptin and insulin concentrations decreased significantly, whereas ghrelin levels did not markedly change. In the group regaining more than 10% of the weight loss, leptin levels were higher (P < 0.01), whereas ghrelin levels were lower (P < 0.05). No differences were observed in insulin levels. Weight regain at wk 32 was negatively correlated with ghrelin and positively associated with leptin levels at baseline (wk 0) and endpoint (wk 8). These outcomes showed a gender-specific influence, being statistically significant among men for ghrelin and between women for leptin. Moreover, a decrease in ghrelin after an 8-wk hypocaloric diet was related to an increased risk for weight regain (odds ratio = 3.109; P = 0.008) whereas a greater reduction in leptin (odds ratio = 0.141; P = 0.001) was related to weight-loss maintenance. CONCLUSIONS: Subjects with higher plasma leptin and lower ghrelin levels at baseline could be more prone to regain lost weight, and hormones levels could be proposed as biomarkers for predicting obesity-treatment outcomes

Escalating environmental summer heat exposure - a future threat for the European workforce

Heat exposure constitutes a major threat for European workers, with significant impacts on the workers' health and productivity. Climate projections over the next decades show a continuous and accelerated warming over Europe together with longer, more intense and more frequent heatwaves on regional and local scales. In this work, we assess the increased risk in future occupational heat stress levels using the wet bulb globe temperature (WBGT), an index adopted by the International Standards Organization as regulatory index to measure the heat exposure of working people. Our results show that, in large parts of Europe, future heat exposure will indeed exceed critical levels for physically active humans far more often than in today?s climate, and labour productivity might be largely reduced in southern Europe. European industries should adapt to the projected changes to prevent major consequences for the workers? health and to preserve economic productivity.Financial support for this work is provided by the HEAT-SHIELD Project (European Commission HORIZON 2020, research and innovation programme under the grant agreement 668786). The authors wish to thank the Swiss National Supercomputing Centre (CSCS) for providing the technical infrastructure

Anarquismo epistemológico y la individualidad en la apropiación del conocimiento

En el presente artículo abordamos la problemática del uso de materiales alternativos como apoyo en el proceso de la enseñanza/aprendizaje, en función de la visión feyerabendiana. El propio profesor actúa aparentemente en forma individualista cuando opta por un determinado libro didáctico, en desmedro de material producido a partir de su vivencia y experiencia en el aula, por lo cual estará atendiendo a dos situaciones implícitas en su acto. Primero, a un currículo oculto que lo obliga a mantener un proceso hegemónico según las normas en la escuela y, segundo, la presión directa o indirecta de las escuelas, editoriales y de la familia del alumno para el uso del libro texto como único recurso didáctico. Nuestro objetivo es fundamentar el necesario apoyo al profesor en la producción de su propio material didáctico, manifestándose libre e individualmente en la producción del conocimiento generado en su clase

Active vitamin D (1,25-dihydroxyvitamin D) and bone health in middle-aged and elderly men: the European male aging study (EMAS)

&lt;p&gt;Context: There is little information on the potential impact of serum 1,25-dihydroxyvitamin D [1,25(OH)2D] on bone health including turnover.&lt;/p&gt; &lt;p&gt;Objective: The objective of the study was to determine the influence of 1,25(OH)2D and 25-hydroxyvitamin D [25(OH)D] on bone health in middle-aged and older European men.&lt;/p&gt; &lt;p&gt;Design, Setting, and Participants: Men aged 40–79 years were recruited from population registers in 8 European centers. Subjects completed questionnaires that included questions concerning lifestyle and were invited to attend for quantitative ultrasound (QUS) of the heel, assessment of height and weight, and a fasting blood sample from which 1,25(OH)2D, 25(OH)D, and PTH were measured. 1,25(OH)2D was measured using liquid chromatography tandem mass spectrometry. Bone markers serum N-terminal propeptide of type 1 procollagen (P1NP) and crosslinks (β-cTX) were also measured. Dual-energy x-ray absorptiometry (DXA) of the hip and lumbar spine was performed in 2 centers.&lt;/p&gt; &lt;p&gt;Main Outcome Measure(s): QUS of the heel, bone markers P1NP and β-cTX, and DXA of the hip and lumbar spine were measured.&lt;/p&gt; &lt;p&gt;Results: A total of 2783 men, mean age 60.0 years (SD 11.0) were included in the analysis. After adjustment for age and center, 1,25(OH)2D was positively associated with 25(OH)D but not with PTH. 25(OH)D was negatively associated with PTH. After adjustment for age, center, height, weight, lifestyle factors, and season, 1,25(OH)2D was associated negatively with QUS and DXA parameters and associated positively with β-cTX. 1,25(OH)2D was not correlated with P1NP. 25(OH)D was positively associated with the QUS and DXA parameters but not related to either bone turnover marker. Subjects with both high 1,25(OH)2D (upper tertile) and low 25(OH)D (lower tertile) had the lowest QUS and DXA parameters and the highest β-cTX levels.&lt;/p&gt; &lt;p&gt;Conclusions: Serum 1,25(OH)2D is associated with higher bone turnover and poorer bone health despite being positively related to 25(OH)D. A combination of high 1,25(OH)2D and low 25(OH)D is associated with the poorest bone health.&lt;/p&gt

The emerging structure of the Extended Evolutionary Synthesis: where does Evo-Devo fit in?

The Extended Evolutionary Synthesis (EES) debate is gaining ground in contemporary evolutionary biology. In parallel, a number of philosophical standpoints have emerged in an attempt to clarify what exactly is represented by the EES. For Massimo Pigliucci, we are in the wake of the newest instantiation of a persisting Kuhnian paradigm; in contrast, Telmo Pievani has contended that the transition to an EES could be best represented as a progressive reformation of a prior Lakatosian scientific research program, with the extension of its Neo-Darwinian core and the addition of a brand-new protective belt of assumptions and auxiliary hypotheses. Here, we argue that those philosophical vantage points are not the only ways to interpret what current proposals to ‘extend’ the Modern Synthesis-derived ‘standard evolutionary theory’ (SET) entail in terms of theoretical change in evolutionary biology. We specifically propose the image of the emergent EES as a vast network of models and interweaved representations that, instantiated in diverse practices, are connected and related in multiple ways. Under that assumption, the EES could be articulated around a paraconsistent network of evolutionary theories (including some elements of the SET), as well as models, practices and representation systems of contemporary evolutionary biology, with edges and nodes that change their position and centrality as a consequence of the co-construction and stabilization of facts and historical discussions revolving around the epistemic goals of this area of the life sciences. We then critically examine the purported structure of the EES—published by Laland and collaborators in 2015—in light of our own network-based proposal. Finally, we consider which epistemic units of Evo-Devo are present or still missing from the EES, in preparation for further analyses of the topic of explanatory integration in this conceptual framework

The ESR1 (6q25) locus is associated with calcaneal ultrasound parameters and radial volumetric bone mineral density in European men

&lt;p&gt;&lt;b&gt;Purpose:&lt;/b&gt; Genome-wide association studies (GWAS) have identified 6q25, which incorporates the oestrogen receptor alpha gene (ESR1), as a quantitative trait locus for areal bone mineral density (BMD(a)) of the hip and lumbar spine. The aim of this study was to determine the influence of this locus on other bone health outcomes; calcaneal ultrasound (QUS) parameters, radial peripheral quantitative computed tomography (pQCT) parameters and markers of bone turnover in a population sample of European men.&lt;/p&gt; &lt;p&gt;&lt;b&gt;Methods:&lt;/b&gt; Eight single nucleotide polymorphisms (SNP) in the 6q25 locus were genotyped in men aged 40-79 years from 7 European countries, participating in the European Male Ageing Study (EMAS). The associations between SNPs and measured bone parameters were tested under an additive genetic model adjusting for centre using linear regression.&lt;/p&gt; &lt;p&gt;&lt;b&gt;Results:&lt;/b&gt; 2468 men, mean (SD) aged 59.9 (11.1) years had QUS measurements performed and bone turnover marker levels measured. A subset of 628 men had DXA and pQCT measurements. Multiple independent SNPs showed significant associations with BMD using all three measurement techniques. Most notably, rs1999805 was associated with a 0.10 SD (95%CI 0.05, 0.16; p = 0.0001) lower estimated BMD at the calcaneus, a 0.14 SD (95%CI 0.05, 0.24; p = 0.004) lower total hip BMD(a), a 0.12 SD (95%CI 0.02, 0.23; p = 0.026) lower lumbar spine BMD(a) and a 0.18 SD (95%CI 0.06, 0.29; p = 0.003) lower trabecular BMD at the distal radius for each copy of the minor allele. There was no association with serum levels of bone turnover markers and a single SNP which was associated with cortical density was also associated with cortical BMC and thickness.&lt;/p&gt; &lt;p&gt;&lt;b&gt;Conclusions:&lt;/b&gt; Our data replicate previous associations found between SNPs in the 6q25 locus and BMD(a) at the hip and extend these data to include associations with calcaneal ultrasound parameters and radial volumetric BMD.&lt;/p&gt