Obesity-induced insulin resistance in human skeletal muscle is characterised by defective activation of p42/p44 MAP kinase

Insulin resistance (IR), an impaired cellular, tissue and whole body response to insulin, is a major pathophysiological defect of type 2 diabetes mellitus. Although IR is closely associated with obesity, the identity of the molecular defect(s) underlying obesity-induced IR in skeletal muscle remains controversial; reduced post-receptor signalling of the insulin receptor substrate 1 (IRS1) adaptor protein and downstream effectors such as protein kinase B (PKB) have previously been implicated. We examined expression and/or activation of a number of components of the insulin-signalling cascade in skeletal muscle of 22 healthy young men (with body mass index (BMI) range, 20–37 kg/m2). Whole body insulin sensitivity (M value) and body composition was determined by the hyperinsulinaemic (40 mU. min−1.m−2.), euglycaemic clamp and by dual energy X-ray absorptiometry (DEXA) respectively. Skeletal muscle (vastus lateralis) biopsies were taken before and after one hour of hyperinsulinaemia and the muscle insulin signalling proteins examined by western blot and immunoprecipitation assay. There was a strong inverse relationship between M-value and BMI. The most striking abnormality was significantly reduced insulin-induced activation of p42/44 MAP kinase, measured by specific assay, in the volunteers with poor insulin sensitivity. However, there was no relationship between individuals' BMI or M-value and protein expression/phosphorylation of IRS1, PKB, or p42/44 MAP kinase protein, under basal or hyperinsulinaemic conditions. In the few individuals with poor insulin sensitivity but preserved p42/44 MAP kinase activation, other signalling defects were evident. These findings implicate defective p42/44 MAP kinase signalling as a potential contributor to obesity-related IR in a non-diabetic population, although clearly multiple signalling defects underlie obesity associated IR

Predicting consumer biomass, size-structure, production, catch potential, responses to fishing and associated uncertainties in the world's marine ecosystems

Existing estimates of fish and consumer biomass in the world’s oceans are disparate. This creates uncertainty about the roles of fish and other consumers in biogeochemical cycles and ecosystem processes, the extent of human and environmental impacts and fishery potential. We develop and use a size-based macroecological model to assess the effects of parameter uncertainty on predicted consumer biomass, production and distribution. Resulting uncertainty is large (e.g. median global biomass 4.9 billion tonnes for consumers weighing 1 g to 1000 kg; 50% uncertainty intervals of 2 to 10.4 billion tonnes; 90% uncertainty intervals of 0.3 to 26.1 billion tonnes) and driven primarily by uncertainty in trophic transfer efficiency and its relationship with predator-prey body mass ratios. Even the upper uncertainty intervals for global predictions of consumer biomass demonstrate the remarkable scarcity of marine consumers, with less than one part in 30 million by volume of the global oceans comprising tissue of macroscopic animals. Thus the apparently high densities of marine life seen in surface and coastal waters and frequently visited abundance hotspots will likely give many in society a false impression of the abundance of marine animals. Unexploited baseline biomass predictions from the simple macroecological model were used to calibrate a more complex size- and trait-based model to estimate fisheries yield and impacts. Yields are highly dependent on baseline biomass and fisheries selectivity. Predicted global sustainable fisheries yield increases ≈4 fold when smaller individuals (< 20 cm from species of maximum mass < 1kg) are targeted in all oceans, but the predicted yields would rarely be accessible in practice and this fishing strategy leads to the collapse of larger species if fishing mortality rates on different size classes cannot be decoupled. Our analyses show that models with minimal parameter demands that are based on a few established ecological principles can support equitable analysis and comparison of diverse ecosystems. The analyses provide insights into the effects of parameter uncertainty on global biomass and production estimates, which have yet to be achieved with complex models, and will therefore help to highlight priorities for future research and data collection. However, the focus on simple model structures and global processes means that non-phytoplankton primary production and several groups, structures and processes of ecological and conservation interest are not represented. Consequently, our simple models become increasingly less useful than more complex alternatives when addressing questions about food web structure and function, biodiversity, resilience and human impacts at smaller scales and for areas closer to coasts

Evidence for a common progenitor of epithelial and mesenchymal components of the liver

Tissues of the adult organism maintain the homeostasis and respond to injury by means of progenitor/stem cell compartments capable to give rise to appropriate progeny. In organs composed by histotypes of different embryological origins (e.g. The liver), the tissue turnover may in theory involve different stem/precursor cells able to respond coordinately to physiological or pathological stimuli. In the liver, a progenitor cell compartment, giving rise to hepatocytes and cholangiocytes, can be activated by chronic injury inhibiting hepatocyte proliferation. The precursor compartment guaranteeing turnover of hepatic stellate cells (HSCs) (perisinusoidal cells implicated with the origin of the liver fibrosis) in adult organ is yet unveiled. We show here that epithelial and mesenchymal liver cells (hepatocytes and HSCs) may arise from a common progenitor. Sca+ murine progenitor cells were found to coexpress markers of epithelial and mesenchymal lineages and to give rise, within few generations, to cells that segregate the lineage-specific markers into two distinct subpopulations. Notably, these progenitor cells, clonally derived, when transplanted in healthy livers, were found to generate epithelial and mesenchymal liver-specific derivatives (i.e. hepatocytes and HSCs) properly integrated in the liver architecture. These evidences suggest the existence of a 'bona fide' organ-specific meso-endodermal precursor cell, thus profoundly modifying current models of adult progenitor commitment believed, so far, to be lineage-restricted. Heterotopic transplantations, which confirm the dual differentiation potentiality of those cells, indicates as tissue local cues are necessary to drive a full hepatic differentiation. These data provide first evidences for an adult stem/precursor cell capable to differentiate in both parenchymal and non-parenchymal organ-specific components and candidate the liver as the instructive site for the reservoir compartment of HSC precursors as yet non-localized in the adult. © 2013 Macmillan Publishers Limited All rights reserved

Sources of variability in childhood obesity indicators and related behaviors

The purpose of this study was to describe sources of variability in obesity-related variables in 6022 children aged 9-11 years from 12 countries. The study design involved recruitment of students, nested within schools, which were nested within study sites. Height, weight and waist circumference (WC) were measured and body mass index (BMI) was calculated; sleep duration and total and in-school moderate-to-vigorous physical activity (MVPA) and sedentary time were measured by accelerometry; and diet scores were obtained by questionnaire. Variance in most variables was largely explained at the student level: BMI (91.9%), WC (93.5%), sleep (75.3%), MVPA (72.5%), sedentary time (76.9%), healthy diet score (88.3%), unhealthy diet score (66.2%), with the exception of in-school MVPA (53.8%) and in-school sedentary time (25.1%). Variance explained at the school level ranged from 3.3% for BMI to 29.8% for in-school MVPA, and variance explained at the site level ranged from 3.2% for WC to 54.2% for in-school sedentary time. In general, more variance was explained at the school and site levels for behaviors than for anthropometric traits. Given the variance in obesity-related behaviors in primary school children explained at school and site levels, interventions that target policy and environmental changes may enhance obesity intervention efforts.Peer reviewe

Staphylococcus aureus forms spreading dendrites that have characteristics of active motility

Staphylococcus aureus is historically regarded as a non-motile organism. More recently it has been shown that S. aureus can passively move across agar surfaces in a process called spreading. We re-analysed spreading motility using a modified assay and fo- cused on observing the formation of dendrites: branching structures that emerge from the central colony. We discovered that S. aureus can spread across the surface of media in struc- tures that we term ‘comets’, which advance outwards and precede the formation of dendrites. We observed comets in a diverse selection of S. aureus isolates and they exhibit the following behaviours: (1) They consist of phenotypically distinct cores of cells that move forward and seed other S. aureus cells behind them forming a comet ‘tail’; (2) they move when other cells in the comet tail have stopped moving; (3) the comet core is held together by a matrix of slime; and (4) the comets etch trails in the agar as they move forwards. Comets are not con- sistent with spreading motility or other forms of passive motility. Comet behaviour does share many similarities with a form of active motility known as gliding. Our observations therefore suggest that S. aureus is actively motile under certain conditions

Should public health interventions aimed at reducing childhood overweight and obesity be gender-focused?

<p>Abstract</p> <p>Background</p> <p>Overweight in childhood is a major public health concern that calls for immediate preventative action. An increasing number of reports suggest that gender specific approaches to prevention may be more effective. However, there is a paucity of information to guide gender-sensitive health promotion and population health interventions for the prevention of overweight in childhood. In the present study, we sought to determine gender-differentials in overweight and underlying behaviors, nutrition and physical activity, among pre-adolescents in Alberta, Canada, to inform the discussion on gender-focused interventions for chronic disease prevention.</p> <p>Methods</p> <p>In 2008, we surveyed 3421 grade five students and their parents of 148 randomly selected schools. Students completed the Harvard food frequency questionnaire, questions on physical activities, and had their height and weight measured. Parents completed questions on socio-economic background and child's lifestyle. We applied multilevel regression methods to assess gender differentials in overweight, nutrition and physical activity.</p> <p>Results</p> <p>Overall, the prevalence of overweight was slightly higher among boys (29.1%) than girls (27.9%) with more pronounced differences in towns and urban geographies. Boys reported to be much more physically active relative to girls (OR = 2.12, 95% CI: 1.73-2.60). Diets of boys, relative to those of girls, reportedly constituted more fat and were less likely to meet the recommendation of 6 daily servings of vegetables and fruits (OR = 0.81, 95% CI: 0.71-0.93).</p> <p>Conclusion</p> <p>Our findings confirm the existence of gender differences in physical activity and nutrition, and support gender-focused health promotion whereby priority is given to physical activity among girls and to healthy eating among boys.</p

Wind, Waves, and Wing Loading: Morphological Specialization May Limit Range Expansion of Endangered Albatrosses

Among the varied adaptations for avian flight, the morphological traits allowing large-bodied albatrosses to capitalize on wind and wave energy for efficient long-distance flight are unparalleled. Consequently, the biogeographic distribution of most albatrosses is limited to the windiest oceanic regions on earth; however, exceptions exist. Species breeding in the North and Central Pacific Ocean (Phoebastria spp.) inhabit regions of lower wind speed and wave height than southern hemisphere genera, and have large intrageneric variation in body size and aerodynamic performance. Here, we test the hypothesis that regional wind and wave regimes explain observed differences in Phoebastria albatross morphology and we compare their aerodynamic performance to representatives from the other three genera of this globally distributed avian family. In the North and Central Pacific, two species (short-tailed P. albatrus and waved P. irrorata) are markedly larger, yet have the smallest breeding ranges near highly productive coastal upwelling systems. Short-tailed albatrosses, however, have 60% higher wing loading (weight per area of lift) compared to waved albatrosses. Indeed, calculated aerodynamic performance of waved albatrosses, the only tropical albatross species, is more similar to those of their smaller congeners (black-footed P. nigripes and Laysan P. immutabilis), which have relatively low wing loading and much larger foraging ranges that include central oceanic gyres of relatively low productivity. Globally, the aerodynamic performance of short-tailed and waved albatrosses are most anomalous for their body sizes, yet consistent with wind regimes within their breeding season foraging ranges. Our results are the first to integrate global wind and wave patterns with albatross aerodynamics, thereby identifying morphological specialization that may explain limited breeding ranges of two endangered albatross species. These results are further relevant to understanding past and potentially predicting future distributional limits of albatrosses globally, particularly with respect to climate change effects on basin-scale and regional wind fields

Visualization of Spatiotemporal Energy Dynamics of Hippocampal Neurons by Mass Spectrometry during a Kainate-Induced Seizure

We report the use of matrix-assisted laser desorption/ionization (MALDI) imaging mass spectrometry combined with capillary electrophoresis (CE) mass spectrometry to visualize energy metabolism in the mouse hippocampus by imaging energy-related metabolites. We show the distribution patterns of ATP, ADP, and AMP in the hippocampus as well as changes in their amounts and distribution patterns in a murine model of limbic, kainate-induced seizure. As an acute response to kainate administration, we found massive and moderate reductions in ATP and ADP levels, respectively, but no significant changes in AMP levels—especially in cells of the CA3 layer. The results suggest the existence of CA3 neuron-selective energy metabolism at the anhydride bonds of ATP and ADP in the hippocampal neurons during seizure. In addition, metabolome analysis of energy synthesis pathways indicates accelerated glycolysis and possibly TCA cycle activity during seizure, presumably due to the depletion of ATP. Consistent with this result, the observed energy depletion significantly recovered up to 180 min after kainate administration. However, the recovery rate was remarkably low in part of the data-pixel population in the CA3 cell layer region, which likely reflects acute and CA3-selective neural death. Taken together, the present approach successfully revealed the spatiotemporal energy metabolism of the mouse hippocampus at a cellular resolution—both quantitatively and qualitatively. We aim to further elucidate various metabolic processes in the neural system