Myoglobin Overexpression Inhibits Reperfusion in the Ischemic Mouse Hindlimb through Impaired Angiogenesis but Not Arteriogenesis

Adaptive vascular remodeling in response to arterial occlusion takes the form of capillary growth (angiogenesis) and outward remodeling of pre-existing collateral arteries (arteriogenesis). However, the relative contributions of angiogenesis and arteriogenesis toward the overall reperfusion response are both highly debated and poorly understood. Here, we tested the hypothesis that myoglobin overexpressing transgenic mice (MbTg+) exhibit impaired angiogenesis in the setting of normal arteriogenesis in response to femoral artery ligation, and thereby serve as a model for disconnecting these two vascular growth processes. After femoral artery ligation, MbTg+ mice were characterized by delayed distal limb reperfusion (by laser Doppler perfusion imaging), decreased foot use, and impaired distal limb muscle angiogenesis in both glycolytic and oxidative muscle fiber regions at day 7. Substantial arteriogenesis occurred in the primary collaterals supplying the ischemic limb in both wild-type and MbTg+ mice; however, there were no significant differences between groups, indicating that myoglobin overexpression does not affect arteriogenesis. Together, these results uniquely demonstrate that functional collateral arteriogenesis alone is not necessarily sufficient for adequate reperfusion after arterial occlusion. Angiogenesis is a key component of an effective reperfusion response, and clinical strategies that target both angiogenesis and arteriogenesis could yield the most efficacious treatments for peripheral arterial disease

Capillary Density of Skeletal Muscle: A Contributing Mechanism for Exercise Intolerance in Class II–III Chronic Heart Failure Independent of Other Peripheral Alterations

AbstractOBJECTIVESThe study was conducted to determine if the capillary density of skeletal muscle is a potential contributor to exercise intolerance in class II–III chronic heart failure (CHF).BACKGROUNDPrevious studies suggest that abnormalities in skeletal muscle histology, contractile protein content and enzymology contribute to exercise intolerance in CHF.METHODSThe present study examined skeletal muscle biopsies from 22 male patients with CHF compared with 10 age-matched normal male control patients. Aerobic capacities, myosin heavy chain (MHC) isoforms, enzymes, and capillary density were measured.RESULTSThe patients with CHF demonstrated a reduced peak oxygen consumption when compared to controls (15.0 ± 2.5 vs. 19.8 ± 5.0 ml·kg−1·min−1, p <0.05). Using cell-specific antibodies to directly assess vascular density, there was a reduction in capillary density in CHF measured as the number of endothelial cells/fiber (1.42 ± 0.28 vs. 1.74 ± 0.35, p = 0.02). In CHF, capillary density was inversely related to maximal oxygen consumption (r = 0.479, p = 0.02). The MHC IIx isoform was found to be higher in patients with CHF versus normal subjects (28.5 ± 13.6 vs. 19.5 ± 9.4, p <0.05).CONCLUSIONSThere was a significant reduction in microvascular density in patients with CHF compared with the control group, without major differences in other usual histologic and biochemical aerobic markers. The inverse relationship with peak oxygen consumption seen in the CHF group suggests that a reduction in microvascular density of skeletal muscle may precede other skeletal muscle alterations and play a critical role in the exercise intolerance characteristic of patients with CHF

Snakes on a Spaceship - An Overview of Python in Heliophysics

Computational analysis has become ubiquitous within the heliophysics community. However, community standards for peer review of codes and analysis have lagged behind these developments. This absence has contributed to the reproducibility crisis, where inadequate analysis descriptions and loss of scientific data have made scientific studies difficult or impossible to replicate. The heliophysics community has responded to this challenge by expressing a desire for a more open, collaborative set of analysis tools. This article summarizes the current state of these efforts and presents an overview of many of the existing Python heliophysics tools. It also outlines the challenges facing community members who are working toward the goal of an open, collaborative, Python heliophysics toolkit and presents guidelines that can ease the transition from individualistic data analysis practices to an accountable, communalistic environment

Impact of Hormone Replacement Therapy on Exercise Training-Induced Improvements in Insulin Action in Sedentary Overweight Adults

Exercise training (ET) and hormone replacement therapy (HRT) are both recognized influences on insulin action, but the influence of HRT on responses to ET has not been examined. In order to determine if HRT use provided additive benefits for the response of insulin action to ET, we evaluated the impact of HRT use on changes in insulin during the course of a randomized, controlled, aerobic ET intervention. Subjects at baseline were sedentary, dyslipidemic, and overweight. These individuals were randomized to six months of one of three aerobic ET interventions or continued physical inactivity. In 206 subjects, an insulin sensitivity index (SI) was obtained with a frequently sampled intravenous glucose tolerance test pre- and post-ET. Baseline and post-intervention fitness, regional adiposity, general adiposity, skeletal muscle biochemistry and histology, and serum lipoproteins were measured as other putative mediators influencing insulin action. Two-way analyses of variance were used to determine if gender or HRT use influenced responses to exercise training. Linear modeling was used to determine if predictors for response in SI differed by gender or HRT use. Women who used HRT (HRT+) demonstrated significantly greater improvements in SI with ET than women not using HRT (HRT-). In those HRT+ women, plasma triglyceride change best correlated with change in SI. For HRT- women, capillary density change, and for men, subcutaneous adiposity change, best correlated with change in SI. In summary, in an ET intervention, HRT use appears associated with more robust responses in insulin action. Also, relationships between ET induced changes in insulin action and potential mediators of change in insulin action are different for men, and for women on or off HRT. These findings have implications for the relative utility of ET for improving insulin action in middle-aged men and women, particularly in the setting of differences in HRT use. Address Originally published Metabolism, Vol. 57, No. 7, July 200

Influence of environmental parameters on movements and habitat utilization of humpback whales (Megaptera novaeangliae) in the Madagascar breeding ground

© The Author(s), 2016. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Royal Society Open Science 3 (2016): 160616, doi:10.1098/rsos.160616.Assessing the movement patterns and key habitat features of breeding humpback whales is a prerequisite for the conservation management of this philopatric species. To investigate the interactions between humpback whale movements and environmental conditions off Madagascar, we deployed 25 satellite tags in the northeast and southwest coast of Madagascar. For each recorded position, we collated estimates of environmental variables and computed two behavioural metrics: behavioural state of ‘transiting’ (consistent/directional) versus ‘localized’ (variable/non-directional), and active swimming speed (i.e. speed relative to the current). On coastal habitats (i.e. bathymetry < 200 m and in adjacent areas), females showed localized behaviour in deep waters (191 ± 20 m) and at large distances (14 ± 0.6 km) from shore, suggesting that their breeding habitat extends beyond the shallowest waters available close to the coastline. Males' active swimming speed decreased in shallow waters, but environmental parameters did not influence their likelihood to exhibit localized movements, which was probably dominated by social factors instead. In oceanic habitats, both males and females showed localized behaviours in shallow waters and favoured high chlorophyll-a concentrations. Active swimming speed accounts for a large proportion of observed movement speed; however, breeding humpback whales probably exploit prevailing ocean currents to maximize displacement. This study provides evidence that coastal areas, generally subject to strong human pressure, remain the core habitat of humpback whales off Madagascar. Our results expand the knowledge of humpback whale habitat use in oceanic habitat and response to variability of environmental factors such as oceanic current and chlorophyll level.Funding was provided by Total Foundation to NeuroPSI, and by individuals and foundations to the WCS Ocean Giants Program

Neuromuscular Electrical Stimulation as a Method to Maximize the Beneficial Effects of Muscle Stem Cells Transplanted into Dystrophic Skeletal Muscle

Cellular therapy is a potential approach to improve the regenerative capacity of damaged or diseased skeletal muscle. However, its clinical use has often been limited by impaired donor cell survival, proliferation and differentiation following transplantation. Additionally, functional improvements after transplantation are all-too-often negligible. Because the host microenvironment plays an important role in the fate of transplanted cells, methods to modulate the microenvironment and guide donor cell behavior are warranted. The purpose of this study was to investigate whether the use of neuromuscular electrical stimulation (NMES) for 1 or 4 weeks following muscle-derived stem cell (MDSC) transplantation into dystrophic skeletal muscle can modulate the fate of donor cells and enhance their contribution to muscle regeneration and functional improvements. Animals submitted to 4 weeks of NMES after transplantation demonstrated a 2-fold increase in the number of dystrophin+ myofibers as compared to control transplanted muscles. These findings were concomitant with an increased vascularity in the MDSC+NMES group when compared to non-stimulated counterparts. Additionally, animals subjected to NMES (with or without MDSC transplantation) presented an increased maximal specific tetanic force when compared to controls. Although cell transplantation and/or the use of NMES resulted in no changes in fatigue resistance, the combination of both MDSC transplantation and NMES resulted in a faster recovery from fatigue, when compared to non-injected and non-stimulated counterparts. We conclude that NMES is a viable method to improve MDSC engraftment, enhance dystrophic muscle strength, and, in combination with MDSC transplantation, improve recovery from fatigue. These findings suggest that NMES may be a clinically-relevant adjunct approach for cell transplantation into skeletal muscle. © 2013 Distefano et al