Alpha adrenergic receptor blockade increases capillarisation and O2 extraction and lowers blood flow in contracting human skeletal muscle

Aim: To investigate the effect of increased basal shear stress on angiogenesis, and the role of enhanced skeletal muscle capillarisation on blood flow and oxygen extraction. Methods: Limb haemodynamics and oxygen extraction were measured at rest and during one-leg knee-extensor exercise (12 and 24W) in 10 healthy untrained young men before and after 4 weeks treatment with an α1 receptor-antagonist (Terazosin, 1-2 mg day-1). Biopsies were taken from the m. vastus lateralis. Results: Resting leg blood flow was > 6 hours following Terazosin treatment (P<0.05). Basal capillary-to-fibre ratio was 1.68±0.07 and increased to 1.89±0.08 after treatment (P<0.05). Leg oxygen extraction during knee-extensor exercise was higher (4-5% ; P<0.05), leg blood flow and venous lactate levels lower (6-7%; P<0.05) and leg VO2 similar after Terazosin treatment. Conclusion: These results demonstrate that daily treatment with an α-adrenergic receptor blocker and a consequent increase in resting blood flow induces capillary growth in human skeletal muscle, likely due to increased shear stress. The increase in capillarisation led to enhanced O2 extraction in the exercising leg, concomitant with a lower blood flow and venous lactate levels

Large-scale benchmarking reveals false discoveries and count transformation sensitivity in 16S rRNA gene amplicon data analysis methods used in microbiome studies

BACKGROUND: There is an immense scientific interest in the human microbiome and its effects on human physiology, health, and disease. A common approach for examining bacterial communities is high-throughput sequencing of 16S rRNA gene hypervariable regions, aggregating sequence-similar amplicons into operational taxonomic units (OTUs). Strategies for detecting differential relative abundance of OTUs between sample conditions include classical statistical approaches as well as a plethora of newer methods, many borrowing from the related field of RNA-seq analysis. This effort is complicated by unique data characteristics, including sparsity, sequencing depth variation, and nonconformity of read counts to theoretical distributions, which is often exacerbated by exploratory and/or unbalanced study designs. Here, we assess the robustness of available methods for (1) inference in differential relative abundance analysis and (2) beta-diversity-based sample separation, using a rigorous benchmarking framework based on large clinical 16S microbiome datasets from different sources. RESULTS: Running more than 380,000 full differential relative abundance tests on real datasets with permuted case/control assignments and in silico-spiked OTUs, we identify large differences in method performance on a range of parameters, including false positive rates, sensitivity to sparsity and case/control balances, and spike-in retrieval rate. In large datasets, methods with the highest false positive rates also tend to have the best detection power. For beta-diversity-based sample separation, we show that library size normalization has very little effect and that the distance metric is the most important factor in terms of separation power. CONCLUSIONS: Our results, generalizable to datasets from different sequencing platforms, demonstrate how the choice of method considerably affects analysis outcome. Here, we give recommendations for tools that exhibit low false positive rates, have good retrieval power across effect sizes and case/control proportions, and have low sparsity bias. Result output from some commonly used methods should be interpreted with caution. We provide an easily extensible framework for benchmarking of new methods and future microbiome datasets. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s40168-016-0208-8) contains supplementary material, which is available to authorized users

Photonic-plasmonic hybrid single-molecule nanosensor measures the effect of fluorescent labels on DNA-protein dynamics

Current methods to study molecular interactions require labeling the subject molecules with fluorescent reporters. However, the effect of the fluorescent reporters on molecular dynamics has not been quantified because of a lack of alternative methods. We develop a hybrid photonic-plasmonic antenna-in-a-nanocavity single-molecule biosensor to study DNA-protein dynamics without using fluorescent labels. Our results indicate that the fluorescein and fluorescent protein labels decrease the interaction between a single DNA and a protein due to weakened electrostatic interaction. Although the study is performed on the DNA-XPA system, the conclusion has a general implication that the traditional fluorescent labeling methods might be misestimating the molecular interactions

Improving asthma during pregnancy with dietary antioxidants: the current evidence

The complication of asthma during pregnancy is associated with a number of poor outcomes for the mother and fetus. This may be partially driven by increased oxidative stress induced by the combination of asthma and pregnancy. Asthma is a chronic inflammatory disease of the airways associated with systemic inflammation and oxidative stress, which contributes to worsening asthma symptoms. Pregnancy alone also intensifies oxidative stress through the systemic generation of excess reactive oxidative species (ROS). Antioxidants combat the damaging effects of ROS; yet antioxidant defenses are reduced in asthma. Diet and nutrition have been postulated as potential factors to combat the damaging effects of asthma. In particular, dietary antioxidants may play a role in alleviating the heightened oxidative stress in asthma. Although there are some observational and interventional studies that have shown protective effects of antioxidants in asthma, assessment of antioxidants in pregnancy are limited and there are no antioxidant intervention studies in asthmatic pregnancies on asthma outcomes. The aims of this paper are to (i) review the relationships between oxidative stress and dietary antioxidants in adults with asthma and asthma during pregnancy, and (ii) provide the rationale for which dietary management strategies, specifically increased dietary antioxidants, might positively impact maternal asthma outcomes. Improving asthma control through a holistic antioxidant dietary approach might be valuable in reducing asthma exacerbations and improving asthma management during pregnancy, subsequently impacting perinatal health.Jessica A. Grieger, Lisa G. Wood and Vicki L. Clifto

The developing hypopharyngeal microbiota in early life

BACKGROUND: The airways of healthy humans harbor a distinct microbial community. Perturbations in the microbial community have been associated with disease, yet little is known about the formation and development of a healthy airway microbiota in early life. Our goal was to understand the establishment of the airway microbiota within the first 3 months of life. We investigated the hypopharyngeal microbiota in the unselected COPSAC(2010) cohort of 700 infants, using 16S rRNA gene sequencing of hypopharyngeal aspirates from 1 week, 1 month, and 3 months of age. RESULTS: Our analysis shows that majority of the hypopharyngeal microbiota of healthy infants belong to each individual’s core microbiota and we demonstrate five distinct community pneumotypes. Four of these pneumotypes are dominated by the genera Staphylococcus, Streptococcus, Moraxella, and Corynebacterium, respectively. Furthermore, we show temporal pneumotype changes suggesting a rapid development towards maturation of the hypopharyngeal microbiota and a significant effect from older siblings. Despite an overall common trajectory towards maturation, individual infants’ microbiota are more similar to their own, than to others, over time. CONCLUSIONS: Our findings demonstrate a consolidation of the population of indigenous bacteria in healthy airways and indicate distinct trajectories in the early development of the hypopharyngeal microbiota. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s40168-016-0215-9) contains supplementary material, which is available to authorized users

Exercise-mediated angiogenesis

Skeletal muscle is among the most plastic of tissues, remodelling to accommodate altered demands. Exercise induces a range of adaptations, notably a growth of capillaries (angiogenesis), while inactivity results in a loss of capillaries (rarefaction). As endurance activity relies on an adequate O2 supply to support oxidative phosphorylation, hypoxia within working muscle may act as an angiogenic stimulus, but additional candidates include chemical factors such as metabolic by-products (e.g. acidosis) or release of signalling molecules (e.g. VEGF, NO), and mechanical factors including response to muscle contractions (strain) or increased blood flow (hyperaemia). Optimising training interventions, for performance or rehabilitation, will benefit from better understanding of the local environment controlling the pattern of capillary distribution and its consequences for tissue oxygenation

Predicting global habitat suitability for stony corals on seamounts

Aim Globally, species distribution patterns in the deep sea are poorly resolved, with spatial coverage being sparse for most taxa and true absence data missing. Increasing human impacts on deep-sea ecosystems mean that reaching a better understanding of such patterns is becoming more urgent. Cold-water stony corals (Order Scleractinia) form structurally complex habitats (dense thickets or reefs) that can support a diversity of other associated fauna. Despite their widely accepted ecological importance, records of scleractinian corals on seamounts are patchy and simply not available for most of the global ocean. The objective of this paper is to model the global distribution of suitable habitat for stony corals on seamounts. Location Seamounts worldwide. Methods We compiled a database containing all accessible records of scleractinian corals on seamounts. Two modelling approaches developed for presence-only data were used to predict global habitat suitability for seamount scleractinians: maximum entropy modelling (Maxent) and environmental niche factor analysis (ENFA). We generated habitat-suitability maps and used a cross-validation process with a threshold-independent metric to evaluate the performance of the models. Results Both models performed well in cross-validation, although the Maxent method consistently outperformed ENFA. Highly suitable habitat for seamount stony corals was predicted to occur at most modelled depths in the North Atlantic, and in a circumglobal strip in the Southern Hemisphere between 20° and 50° S and shallower than around 1500 m. Seamount summits in most other regions appeared much less likely to provide suitable habitat, except for small near-surface patches. The patterns of habitat suitability largely reflect current biogeographical knowledge. Environmental variables positively associated with high predicted habitat suitability included the aragonite saturation state, and oxygen saturation and concentration. By contrast, low levels of dissolved inorganic carbon, nitrate, phosphate and silicate were associated with high predicted suitability. High correlation among variables made assessing individual drivers difficult. Main conclusions Our models predict environmental conditions likely to play a role in determining large-scale scleractinian coral distributions on seamounts, and provide a baseline scenario on a global scale. These results present a first-order hypothesis that can be tested by further sampling. Given the high vulnerability of cold-water corals to human impacts, such predictions are crucial tools in developing worldwide conservation and management strategies for seamount ecosystems. © 2009 Blackwell Publishing Ltd

Light enhanced calcification in Stylophora pistillata: effects of glucose, glycerol and oxygen

Zooxanthellate corals have long been known to calcify faster in the light than in the dark, however the mechanism underlying this process has been uncertain. Here we tested the effects of oxygen under controlled pCO2 conditions and fixed carbon sources on calcification in zooxanthellate and bleached microcolonies of the branching coral Stylophora pistillata. In zooxanthellate microcolonies, oxygen increased dark calcification rates to levels comparable to those measured in the light. However in bleached microcolonies oxygen alone did not enhance calcification, but when combined with a fixed carbon source (glucose or glycerol), calcification increased. Respiration rates increased in response to oxygen with greater increases when oxygen is combined with fixed carbon. ATP content was largely unaffected by treatments, with the exception of glycerol which decreased ATP levels