Genetic Variants in the Bone Morphogenic Protein Gene Family Modify the Association between Residential Exposure to Traffic and Peripheral Arterial Disease

There is a growing literature indicating that genetic variants modify many of the associations between environmental exposures and clinical outcomes, potentially by increasing susceptibility to these exposures. However, genome-scale investigations of these interactions have been rarely performed particularly in the case of air pollution exposures. We performed race-stratified genome-wide gene-environment interaction association studies on European-American (EA, N = 1623) and African-American (AA, N = 554) cohorts to investigate the joint influence of common single nucleotide polymorphisms (SNPs) and residential exposure to traffic (“traffic exposure”)—a recognized vascular disease risk factor—on peripheral arterial disease (PAD). Traffic exposure was estimated via the distance from the primary residence to the nearest major roadway, defined as the nearest limited access highways or major arterial. The rs755249-traffic exposure interaction was associated with PAD at a genome-wide significant level (P = 2.29x10^-8) in European-Americans. Rs755249 is located in the 3’ untranslated region of BMP8A, a member of the bone morphogenic protein (BMP) gene family. Further investigation revealed several variants in BMP genes associated with PAD via an interaction with traffic exposure in both the EA and AA cohorts; this included interactions with non-synonymous variants in BMP2, which is regulated by air pollution exposure. The BMP family of genes is linked to vascular growth and calcification and is a novel gene family for the study of PAD pathophysiology. Further investigation of BMP8A using the Genotype Tissue Expression Database revealed multiple variants with nominally significant (P < 0.05) interaction P-values in our EA cohort were significant BMP8A eQTLs in tissue types highlight relevant for PAD such as rs755249 (tibial nerve, eQTL P = 3.6x10^-6) and rs1180341 (tibial artery, eQTL P = 5.3x10^-6). Together these results reveal a novel gene, and possibly gene family, associated with PAD via an interaction with traffic air pollution exposure. These results also highlight the potential for interactions studies, particularly at the genome scale, to reveal novel biology linking environmental exposures to clinical outcomes.     

Applying population and community ecology theory to advance understanding of belowground biogeochemistry

Approaches to quantifying and predicting soil biogeochemical cycles mostly consider microbial biomass and community composition as products of the abiotic environment. Current numerical approaches then primarily emphasise the importance of microbe–environment interactions and physiology as controls on biogeochemical cycles. Decidedly less attention has been paid to understanding control exerted by community dynamics and biotic interactions. Yet a rich literature of theoretical and empirical contributions highlights the importance of considering how variation in microbial population ecology, especially biotic interactions, is related to variation in key biogeochemical processes like soil carbon formation. We demonstrate how a population and community ecology perspective can be used to (1) understand the impact of microbial communities on biogeochemical cycles and (2) reframe current theory and models to include more detailed microbial ecology. Through a series of simulations we illustrate how density dependence and key biotic interactions, such as competition and predation, can determine the degree to which microbes regulate soil biogeochemical cycles. The ecological perspective and model simulations we present lay the foundation for developing empirical research and complementary models that explore the diversity of ecological mechanisms that operate in microbial communities to regulate biogeochemical processes.     

Hydration, thermoregulation, and performance effects of two sport drinks during soccer training sessions

In the present study, we aimed to compare the thermoregulatory response and soccer-specific training performance aspects of two commercially available sport drinks, both of similar carbohydrate concentration, but one containing 5.2% glycerol. Ten players participated in two similar outdoor training sessions and were randomly assigned to each of two drinks: a carbohydrate (C) beverage or a carbohydrate-glycerol (CG) beverage. Players consumed 500 mL of C or CG 30 minutes pre-exercise and at half-time. Pre- and postexercise body mass, core temperature (CT), and heart rate (HR) were recorded, and urine and blood samples were taken. No difference was observed between days for wet bulb globe temperature (session 1: 17.0 +/- 1.1 degrees C, session 2: 16.9 +/- 1.1 degrees C; P = 0.944). The degree of dehydration (% Delta BM) was greater after the C trial (P = 0.041). Similarly, percent change in plasma volume was greater in the C trial (P = 0.049). No overall main affect was observed between CT and mean exercise HRs during either training session (CT: P = 0.350; mean HR: P = 0.256), and there was no difference observed between groups in time to failure during the session-ending fatigue test (P = 0.547). Ingestion of a CG beverage provided players with better hydration than C alone. However, if training sessions are short (<75 minute), with adequate time for recovery, both drinks are sufficient for maintaining performance intensities during soccer-specific training.     

赣南地区森林地表死可燃物载量与环境因子的关系

森林可燃物载量分布格局是植被与地形等环境因子之间相互作用的结果。本研究通过野外实测赣南地区主要7种森林类型地表死可燃物载量数据,依据时滞可燃物分类标准,构建了地表可燃物载量与地形、植被等环境因子间的结构方程模型,并分析了各因子的影响路径及其直接、间接和总效应。结果表明: 7种不同森林类型中,1、10和100 h时滞可燃物载量均是针阔混交林内最高,毛竹林内最低。对1 h时滞载量影响最大的变量依次为:坡度(影响系数为0.40)＞树冠高度(0.07)＞树种(-0.03)＞郁闭度(0.01);对10 h时滞载量影响最大的变量依次为:胸径(0.15)＞树种(-0.09)＞坡向(-0.08)＞郁闭度(-0.06);对100 h时滞载量影响最大的变量依次为:坡向(0.25)＞胸径(0.19)＞郁闭度(-0.08)＞树种(0.02);对可燃物总载量影响最大的变量依次为:坡度(0.22)＞树种(-0.04)、郁闭度(-0.04)＞树冠高度(-0.01)。     

Estimating fish swimming metrics and metabolic rates with accelerometers: the influence of sampling frequency

Accelerometry is growing in popularity for remotely measuring fish swimming metrics, but appropriate sampling frequencies for accurately measuring these metrics are not well studied. This research examined the influence of sampling frequency (1–25 Hz) with tri‐axial accelerometer biologgers on estimates of overall dynamic body acceleration (ODBA), tail‐beat frequency, swimming speed and metabolic rate of bonefish Albula vulpes in a swim‐tunnel respirometer and free‐swimming in a wetland mesocosm. In the swim tunnel, sampling frequencies of ≥ 5 Hz were sufficient to establish strong relationships between ODBA, swimming speed and metabolic rate. However, in free‐swimming bonefish, estimates of metabolic rate were more variable below 10 Hz. Sampling frequencies should be at least twice the maximum tail‐beat frequency to estimate this metric effectively, which is generally higher than those required to estimate ODBA, swimming speed and metabolic rate. While optimal sampling frequency probably varies among species due to tail‐beat frequency and swimming style, this study provides a reference point with a medium body‐sized sub‐carangiform teleost fish, enabling researchers to measure these metrics effectively and maximize study duration.     

Gene flow and rapid differentiation characterize a rapid insular radiation in the southwest Pacific (Aves: Zosterops)

As a dispersive lineage expands its distribution across a heterogeneous landscape, it leaves behind allopatric populations with varying degrees of geographic isolation that often differentiate rapidly. In the case of oceanic islands, even narrowly separated populations often differentiate, which seems contrary to the highly dispersive nature of the founding lineage. This pattern of highly dispersive lineages differentiating across narrow sea barriers has perplexed biologists for more than a century. We used two reduced-representation genomic datasets to examine the diversification of a recent, rapid geographic radiation, the white-eyes (Aves: Zosterops) of the Solomon Islands. We incorporated methods that targeted phylogenetic structure, population structure, and explicit tests for gene flow. Both datasets showed evidence of gene flow among species, but not involving the closely spaced islands in the New Georgia Group. Instead, gene flow has occurred among the larger islands in the archipelago, including those recently connected by land bridges as well as those isolated by large expanses of deep ocean. Populations separated by shallow seas, and connected by land bridges during glacial cycles, ranged from no differentiation to both phenotypic and genomic differentiation. These complex patterns of gene flow and divergence support a model of rapid geographic radiation in which lineages differentially evolve dispersal disparity and phenotypic differences.     

Photoacoustically‐guided photothermal killing of mosquitoes targeted by nanoparticles

In biomedical applications, nanoparticles have demonstrated the potential to eradicate abnormal cells in small localized pathological zones associated with cancer or infections. Here, we introduce a method for nanotechnology‐based photothermal (PT) killing of whole organisms considered harmful to humans or the environment. We demonstrate that laser‐induced thermal, and accompanying nano‐ and microbubble phenomena, can injure or kill C. elegans and mosquitoes fed carbon nanotubes, gold nanospheres, gold nanoshells, or magnetic nanoparticles at laser energies that are safe for humans. In addition, a photoacoustic (PA) effect was used to control nanoparticle delivery. Through the integration of this technique with molecular targeting, nanoparticle clustering, magnetic capturing and spectral sharpening of PA and PT plasmonic resonances, our laser‐based PA‐PT nano‐theranostic platform can be applied to detection and the physical destruction of small organisms and carriers of pathogens, such as malaria vectors, spiders, bed bugs, fleas, ants, locusts, grasshoppers, phytophagous mites, or other arthropod pests, irrespective of their resistance to conventional treatments. (© 2014 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)     

Skeletal muscle Nur77 expression enhances oxidative metabolism and substrate utilization

Mitochondrial dysfunction has been implicated in the pathogenesis of type 2 diabetes. Identifying novel regulators of mitochondrial bioenergetics will broaden our understanding of regulatory checkpoints that coordinate complex metabolic pathways. We previously showed that Nur77, an orphan nuclear receptor of the NR4A family, regulates the expression of genes linked to glucose utilization. Here we demonstrate that expression of Nur77 in skeletal muscle also enhances mitochondrial function. We generated MCK-Nur77 transgenic mice that express wild-type Nur77 specifically in skeletal muscle. Nur77-overexpressing muscle had increased abundance of oxidative muscle fibers and mitochondrial DNA content. Transgenic muscle also exhibited enhanced oxidative metabolism, suggestive of increased mitochondrial activity. Metabolomic analysis confirmed that Nur77 transgenic muscle favored fatty acid oxidation over glucose oxidation, mimicking the metabolic profile of fasting. Nur77 expression also improved the intrinsic respiratory capacity of isolated mitochondria, likely due to the increased abundance of complex I of the electron transport chain. These changes in mitochondrial metabolism translated to improved muscle contractile function ex vivo and improved cold tolerance in vivo. Our studies outline a novel role for Nur77 in the regulation of oxidative metabolism and mitochondrial activity in skeletal muscle.     

Probing the effect of glycosaminoglycan depletion on integrin interactions with collagen I fibrils in the native extracellular matrix environment

Fibrillar collagen–integrin interactions in the extracellular matrix (ECM) regulate a multitude of cellular processes and cell signalling. Collagen I fibrils serve as the molecular scaffolding for connective tissues throughout the human body and are the most abundant protein building blocks in the ECM. The ECM environment is diverse, made up of several ECM proteins, enzymes, and proteoglycans. In particular, glycosaminoglycans (GAGs), anionic polysaccharides that decorate proteoglycans, become depleted in the ECM with natural aging and their mis-regulation has been linked to cancers and other diseases. The impact of GAG depletion in the ECM environment on collagen I protein interactions and on mechanical properties is not well understood. Here, we integrate ELISA protein binding assays with liquid high-resolution atomic force microscopy (AFM) to assess the effects of GAG depletion on the interaction of collagen I fibrils with the integrin α2I domain using separate rat tails. ELISA binding assays demonstrate that α2I preferentially binds to GAG-depleted collagen I fibrils in comparison to native fibrils. By amplitude modulated AFM in air and in solution, we find that GAG-depleted collagen I fibrils retain structural features of the native fibrils, including their characteristic D-banding pattern, a key structural motif. AFM fast force mapping in solution shows that GAG depletion reduces the stiffness of individual fibrils, lowering the indentation modulus by half compared to native fibrils. Together these results shed new light on how GAGs influence collagen I fibril–integrin interactions and may aid in strategies to treat diseases that result from GAG mis-regulation.