Effect of prolonged, heavy exercise on pulmonary gas exchange in athletes

During maximalexercise, ventilation-perfusion inequality increases, especially inathletes. The mechanism remains speculative. Wehypothesized that, if interstitial pulmonary edema is involved, prolonged exercise would result in increasing ventilation-perfusion inequality over time by exposing the pulmonary vascular bed to highpressures for a long duration. The response to short-term exercise wasfirst characterized in six male athletes [maximal O₂ uptake(O_{2 max}) = 63 ml · kg¹ · min¹] by using 5 minof cycling exercise at 30, 65, and 90%O_{2 max}. Multiple inert-gas, blood-gas, hemodynamic, metabolic rate, and ventilatory data were obtained. Resting log SD of the perfusion distribution (logSD) was normal [0.50 ± 0.03 (SE)] and increased with exercise (logSD = 0.65 ± 0.04, P < 0.005), alveolar-arterialO₂ difference increased (to 24 ± 3 Torr), and end-capillary pulmonary diffusion limitation occurred at 90%O_{2 max}. The subjectsrecovered for 30 min, then, after resting measurements were taken,exercised for 60 min at ~65%O_{2 max}.O₂ uptake, ventilation, cardiacoutput, and alveolar-arterial O₂difference were unchanged after the first 5 min of this test, but logSD increased from0.59 ± 0.03 at 5 min to 0.66 ± 0.05 at 60 min(P < 0.05), without pulmonary diffusion limitation. LogSD was negativelyrelated to total lung capacity normalized for body surface area(r = 0.97,P < 0.005 at 60 min). These data are compatible with interstitial edema as a mechanism and suggest that lungsize is an important determinant of the efficiency of gas exchangeduring exercise.

     

Meta-analysis in applied ecology

This overview examines research synthesis in applied ecology and conservation. Vote counting and pooling unweighted averages are widespread despite the superiority of syntheses based on weighted combination of effects. Such analyses allow exploration of methodological uncertainty in addition to consistency of effects across species, space and time, but exploring heterogeneity remains controversial. Meta-analyses are required to generalize in ecology, and to inform evidence-based decision-making, but the more sophisticated statistical techniques and registers of research used in other disciplines must be employed in ecology to fully realize their benefits.     

Metabolomic Fingerprint of Heart Failure with Preserved Ejection Fraction

BackgroundHeart failure (HF) with preserved ejection fraction (HFpEF) is increasingly recognized as an important clinical entity. Preclinical studies have shown differences in the pathophysiology between HFpEF and HF with reduced ejection fraction (HFrEF). Therefore, we hypothesized that a systematic metabolomic analysis would reveal a novel metabolomic fingerprint of HFpEF that will help understand its pathophysiology and assist in establishing new biomarkers for its diagnosis.ConclusionsThe metabolomics approach employed in this study identified a unique metabolomic fingerprint of HFpEF that is distinct from that of HFrEF. This metabolomic fingerprint has been utilized to identify two novel panels of metabolites that can separate HFpEF patients from both non-HF controls and HFrEF patients.

Clinical Trial Registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT02052804","term_id":"NCT02052804"}}NCT02052804     

Sustained Action of Developmental Ethanol Exposure on the Cortisol Response to Stress in Zebrafish Larvae and Adults

Background

Ethanol exposure during pregnancy is one of the leading causes of preventable birth defects, leading to a range of symptoms collectively known as fetal alcohol spectrum disorder. More moderate levels of prenatal ethanol exposure lead to a range of behavioural deficits including aggression, poor social interaction, poor cognitive performance and increased likelihood of addiction in later life. Current theories suggest that adaptation in the hypothalamo-pituitary-adrenal (HPA) axis and neuroendocrine systems contributes to mood alterations underlying behavioural deficits and vulnerability to addiction. In using zebrafish (Danio rerio), the aim is to determine whether developmental ethanol exposure provokes changes in the hypothalamo-pituitary-interrenal (HPI) axis (the teleost equivalent of the HPA), as it does in mammalian models, therefore opening the possibilities of using zebrafish to elucidate the mechanisms involved, and to test novel therapeutics to alleviate deleterious symptoms.

Results and Conclusions

The results showed that developmental exposure to ambient ethanol, 20mM-50mM 1-9 days post fertilisation, had immediate effects on the HPI, markedly reducing the cortisol response to air exposure stress, as measured by whole body cortisol content. This effect was sustained in adults 6 months later. Morphology, growth and locomotor activity of the animals were unaffected, suggesting a specific action of ethanol on the HPI. In this respect the data are consistent with mammalian results, although they contrast with the higher corticosteroid stress response reported in rats after developmental ethanol exposure. The mechanisms that underlie the specific sensitivity of the HPI to ethanol require elucidation.     

Stable-isotope probing and metagenomics reveal predation by protozoa drives E. coli removal in slow sand filters

Stable-isotope probing and metagenomics were applied to study samples taken from laboratory-scale slow sand filters 0.5, 1, 2, 3 and 4 h after challenging with ¹³C-labelled Escherichia coli to determine the mechanisms and organisms responsible for coliform removal. Before spiking, the filters had been continuously operated for 7 weeks using water from the River Kelvin, Glasgow as their influent source. Direct counts and quantitative PCR assays revealed a clear predator–prey response between protozoa and E. coli. The importance of top-down trophic-interactions was confirmed by metagenomic analysis, identifying several protozoan and viral species connected to E. coli attrition, with protozoan grazing responsible for the majority of the removal. In addition to top-down mechanisms, indirect mechanisms, such as algal reactive oxygen species-induced lysis, and mutualistic interactions between algae and fungi, were also associated with coliform removal. The findings significantly further our understanding of the processes and trophic interactions underpinning E. coli removal. This study provides an example for similar studies, and the opportunity to better understand, manage and enhance E. coli removal by allowing the creation of more complex trophic interaction models.     

Novel Mechanism of Arenavirus-Induced Liver Pathology

Viral hemorrhagic fevers (VHFs) encompass a group of diseases with cardinal symptoms of fever, hemorrhage, and shock. The liver is a critical mediator of VHF disease pathogenesis and high levels of ALT/AST transaminases in plasma correlate with poor prognosis. In fact, Lassa Fever (LF), the most prevalent VHF in Africa, was initially clinically described as hepatitis. Previous studies in non-human primate (NHP) models also correlated LF pathogenesis with a robust proliferative response in the liver. The purpose of the current study was to gain insight into the mechanism of liver injury and to determine the potential role of proliferation in LF pathogenesis. C57Bl/6J mice were infected with either the pathogenic (for NHPs) strain of lymphocytic choriomeningitis virus (LCMV, the prototypic arenavirus), LCMV-WE, or with the non-pathogenic strain, LCMV-ARM. As expected, LCMV-WE, but not ARM, caused a hepatitis-like infection. LCMV-WE also induced a robust increase in the number of actively cycling hepatocytes. Despite this increase in proliferation, there was no significant difference in liver size between LCMV-WE and LCMV-ARM, suggesting that cell cycle was incomplete. Indeed, cells appeared arrested in the G₁ phase and LCMV-WE infection increased the number of hepatocytes that were simultaneously stained for proliferation and apoptosis. LCMV-WE infection also induced expression of a non-conventional virus receptor, AXL-1, from the TAM (TYRO3/AXL/MERTK) family of receptor tyrosine kinases and this expression correlated with proliferation. Taken together, these results shed new light on the mechanism of liver involvement in VHF pathogenesis. Specifically, it is hypothesized that the induction of hepatocyte proliferation contributes to expansion of the infection to parenchymal cells. Elevated levels of plasma transaminases are likely explained, at least in part, by abortive cell cycle arrest induced by the infection. These results may lead to the development of new therapies to prevent VHF progression.     

Weathering a Dynamic Seascape: Influences of Wind and Rain on a Seabird’s Year-Round Activity Budgets

How animals respond to varying environmental conditions is fundamental to ecology and is a question that has gained impetus due to mounting evidence indicating negative effects of global change on biodiversity. Behavioural plasticity is one mechanism that enables individuals and species to deal with environmental changes, yet for many taxa information on behavioural parameters and their capacity to change are lacking or restricted to certain periods within the annual cycle. This is particularly true for seabirds where year-round behavioural information is intrinsically challenging to acquire due to their reliance on the marine environment where they are difficult to study. Using data from over 13,000 foraging trips throughout the annual cycle, acquired using new-generation automated VHF technology, we described sex-specific, year-round activity budgets in Cape gannets. Using these data we investigated the role of weather (wind and rain) on foraging activity and time allocated to nest attendance. Foraging activity was clearly influenced by wind speed, wind direction and rainfall during and outside the breeding season. Generally, strong wind conditions throughout the year resulted in relatively short foraging trips. Birds spent longer periods foraging when rainfall was moderate. Nest attendance, which was sex-specific outside of the breeding season, was also influenced by meteorological conditions. Large amounts of rainfall (> 2.5 mm per hour) and strong winds (> 13 m s^-1) resulted in gannets spending shorter amounts of time at their nests. We discuss these findings in terms of life history strategies and implications for the use of seabirds as bio-indicators.