Modulation of extracellular matrix genes reflects the magnitude of physiological adaptation to aerobic exercise training in humans

BACKGROUND: Regular exercise reduces cardiovascular and metabolic disease partly through improved aerobic fitness. The determinants of exercise-induced gains in aerobic fitness in humans are not known. We have demonstrated that over 500 genes are activated in response to endurance-exercise training, including modulation of muscle extracellular matrix (ECM) genes. Real-time quantitative PCR, which is essential for the characterization of lower abundance genes, was used to examine 15 ECM genes potentially relevant for endurance-exercise adaptation. Twenty-four sedentary male subjects undertook six weeks of high-intensity aerobic cycle training with muscle biopsies being obtained both before and 24 h after training. Subjects were ranked based on improvement in aerobic fitness, and two cohorts were formed (n = 8 per group): the high-responder group (HRG; peak rate of oxygen consumption increased by +0.71 ± 0.1 L min(-1); p < 0.0001) while the low-responder group (LRG; peak rate of oxygen consumption did not change, +0.17 ± 0.1 L min(-1), ns). ECM genes profiled included the angiopoietin 1 and related genes (angiopoietin 2, tyrosine kinase with immunoglobulin-like and EGF-like domains 1 (TIE1) and 2 (TIE2), vascular endothelial growth factor (VEGF) and related receptors (VEGF receptor 1, VEGF receptor 2 and neuropilin-1), thrombospondin-4, α2-macroglobulin and transforming growth factor β2. RESULTS: neuropilin-1 (800%; p < 0.001) and VEGF receptor 2 (300%; p < 0.01) transcript abundance increased only in the HRG, whereas levels of VEGF receptor 1 mRNA actually declined in the LRG (p < 0.05). TIE1 and TIE2 mRNA levels were unaltered in the LRG, whereas transcription levels of both genes were increased by 2.5-fold in the HRG (p < 0.01). Levels of thrombospondin-4 (900%; p < 0.001) and α2-macroglobulin (300%, p < 0.05) mRNA increased substantially in the HRG. In contrast, the amount of transforming growth factor β2 transcript increased only in the HRG (330%; p < 0.01), whereas it remained unchanged in the LRG (-80%). CONCLUSION: We demonstrate for the first time that aerobic training activates angiopoietin 1 and TIE2 genes in human muscle, but only when aerobic capacity adapts to exercise-training. The fourfold-greater increase in aerobic fitness and markedly differing gene expression profile in the HRG indicates that these ECM genes may be critical for physiological adaptation to exercise in humans. In addition, we show that, without careful demonstration of physiological adaptation, conclusions derived from gene expression profiling of human skeletal muscle following exercise may be of limited value. We propose that future studies should (a) investigate the mechanisms that underlie the apparent link between physiological adaptation and gene expression and (b) use the genes profiled in this paper as candidates for population genetic studies

Lipogenesis by Isolated Human Apocrine Sweat Glands: Testosterone Has no Effect During Long-Term Organ Maintenance

Lipid synthesis by freshly isolated human apocrine glands has been measured by the incorporation of [U-14C] acetate. Incorporation is linear over 6h at 1010 ± 282 pmol/mg wet weight/h (n = 11; mean ± sem). The lipid classes, as percentages of the total lipid synthesized, were found by TLC to be cholesterol 12.3 ± 2.0, mono-glycerides 7.5 ± 1.5, 1,2 di-glycerides 3.0 ± 0.9, 1,3 di-glycerides 3.5 ± 0.5, tri-glycerides 28.4 ± 1.8, free fatty acids 2.0 ± 0.4, lysolecithin 15.4 ± 3.9, sphingomyelin 9.9 ± 4.3, phosphatidyl-choline 8.4 ± 0.4, phosphatidyl-ethanolamine -inositol and -serine 1.8 ± 0.1, phosphatidic acid and cardiolipin 3.3 ± 0.5, and unidentified 3.3 ± 0.5 (mean ± sem, n = 5); Glands were maintained on permeable supports. After 10 d maintenance, electron microscopy showed that the cellular architecture had been preserved, that the ATP contents were the same as in freshly isolated glands, and that [U-14]C] acetate incorporation was not significantly altered at 851 ± 237 pmol/mg/h (n = 18). The addition of 3μM testosterone had no effect on acetate incorporation at 844 ± 231 pmol/mg/h (n = 18). The lipid classes and their proportions were similar to the values for fresh glands after 10 d maintenance both with and without testosterone

A large ground-based observing campaign of the disintegrating planet K2-22b

We present 45 ground-based photometric observations of the K2-22 system collected between 2016 December and 2017 May, which we use to investigate the evolution of the transit of the disintegrating planet K2-22b. Last observed in early 2015, in these new observations we recover the transit at multiple epochs and measure a typical depth of <1.5%. We find that the distribution of our measured transit depths is comparable to the range of depths measured in observations from 2014 and 2015. These new observations also support ongoing variability in the K2-22b transit shape and time, although the overall shallowness of the transit makes a detailed analysis of these transit parameters difficult. We find no strong evidence of wavelength-dependent transit depths for epochs where we have simultaneous coverage at multiple wavelengths, although our stacked Las Cumbres Observatory data collected over days-to-months timescales are suggestive of a deeper transit at blue wavelengths. We encourage continued high-precision photometric and spectroscopic monitoring of this system in order to further constrain the evolution timescale and to aid comparative studies with the other few known disintegrating planets

Keys to school leadership

Keys to School Leadership reviews the core concepts that are fundamental to leadership success today. The book works because it comes from a principal and an academic whose dual perspectives inform and underpin this practical, highly accessible guide. Each chapter contains sections that scaffold the developing themes. Moving from leadership to influence, from individual to team, from classroom to school, and beyond, Keys to School Leadership embeds a critically reflective mindset not just for principals, but for all school-based people who lead or who aspire to lead.1.Administration, leadership and influence -- From administration to leadership -- Beyond leadership to influence -- 2.Tasks, goals and achievement -- From tasks to goals -- Beyond goals to achievement -- 3.Maintenance, improvement and alignment -- From maintenance to improvement -- Beyond improvement to alignment -- 4.Individuals, teams and partnerships -- From individual to team -- Beyond team to partnership -- 5.Delegation, negotiation and collaboration -- From delegation to negotiation -- Beyond negotiation to collaboration -- 6.The classroom, the school and the world -- From the classroom to the school -- Beyond the school to the world -- 7.Dependency, empowerment and succession -- From dependency to empowerment -- Beyond empowerment to succession -- 8.Roles, relationships and community -- From role to relationship -- Beyond relationship to community -- 9.Certainty, uncertainty and coherence -- From certainty to uncertainty -- Beyond uncertainty to coherence -- 10.The top, the centre and the heart and soul -- From the top to the centre -- Beyond the centre to the heart and soul -- 11.The critically reflective leader.182 page(s

Middle leaders in schools : who are they and what do they do?

This article explores the role of middle leaders in schools. Using the extant literature from schools and other contexts it attempts to define middle leadership and describe what middle leaders do in schools, presenting a conceptual framework for consideration. Using data from the authors own recent experiences in research and working with school leaders it then compares theory with practice in order to try to answer the question, or at least begin to answer the question : who are the middle leaders in schools and what do they do?4 page(s