2,788 research outputs found

    The combined effects of acidification and acute warming on the embryos of Pacific herring (Clupea pallasii)

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    Anthropogenic climate change is projected to affect marine ecosystems by challenging the environmental tolerance of individuals. Marine fishes may be particularly vulnerable to emergent climate stressors during early life stages. Here we focus on embryos of Pacific herring (Clupea pallasii), an important forage fish species widely distributed across the North Pacific. Embryos were reared under a range of temperatures (10-16°C) crossed with two pCO2 levels (600 and 2000 μatm) to investigate effects on metabolism and survival. We further tested how elevated pCO2 affects critical thermal tolerance (CTmax) by challenging embryos to short-term temperature fluctuations. Experiments were repeated on embryos collected from winter and spring spawning populations to determine if spawning phenology corresponds with different limits of environmental tolerance in offspring. We found that embryos could withstand acute exposure to 20°C regardless of spawning population or incubation treatment, but that survival was greatly reduced after 2-3 hours at 25°C. We found that pCO2 had limited effects on CTmax. The survival of embryos reared under chronically warm conditions (12°, 14°, or 16°C) was significantly lower relative to 10°C treatments in both populations. Oxygen consumption rates (MO2) were also higher at elevated temperatures and pCO2 levels. However, heart contraction measurements made 48 hours after CTmax exposure revealed a greater increase in heart rate in embryos reared at 10°C compared to 16°C, suggesting acclimation at higher incubation temperatures. Our results indicate that Pacific herring are generally tolerant of pCO2 but are vulnerable to acute temperature stress. Importantly, spring-spawning embryos did not clearly exhibit a higher tolerance to heat stress compared to winter offspring

    Differences in gene expression and cytokine production by crystalline vs. amorphous silica in human lung epithelial cells

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    <p>Abstract</p> <p>Background</p> <p>Exposure to respirable crystalline silica particles, as opposed to amorphous silica, is associated with lung inflammation, pulmonary fibrosis (silicosis), and potentially with lung cancer. We used Affymetrix/GeneSifter microarray analysis to determine whether gene expression profiles differed in a human bronchial epithelial cell line (BEAS 2B) exposed to cristobalite vs. amorphous silica particles at non-toxic and equal surface areas (75 and 150 × 10<sup>6</sup>μm<sup>2</sup>/cm<sup>2</sup>). Bio-Plex analysis was also used to determine profiles of secreted cytokines and chemokines in response to both particles. Finally, primary human bronchial epithelial cells (NHBE) were used to comparatively assess silica particle-induced alterations in gene expression.</p> <p>Results</p> <p>Microarray analysis at 24 hours in BEAS 2B revealed 333 and 631 significant alterations in gene expression induced by cristobalite at low (75) and high (150 × 10<sup>6</sup>μm<sup>2</sup>/cm<sup>2</sup>) amounts, respectively (p < 0.05/cut off ≥ 2.0-fold change). Exposure to amorphous silica micro-particles at high amounts (150 × 10<sup>6</sup>μm<sup>2</sup>/cm<sup>2</sup>) induced 108 significant gene changes. Bio-Plex analysis of 27 human cytokines and chemokines revealed 9 secreted mediators (p < 0.05) induced by crystalline silica, but none were induced by amorphous silica. QRT-PCR revealed that cristobalite selectively up-regulated stress-related genes and cytokines (<it>FOS, ATF3, IL6 </it>and <it>IL8</it>) early and over time (2, 4, 8, and 24 h). Patterns of gene expression in NHBE cells were similar overall to BEAS 2B cells. At 75 × 10<sup>6</sup>μm<sup>2</sup>/cm<sup>2</sup>, there were 339 significant alterations in gene expression induced by cristobalite and 42 by amorphous silica. Comparison of genes in response to cristobalite (75 × 10<sup>6</sup>μm<sup>2</sup>/cm<sup>2</sup>) revealed 60 common, significant gene alterations in NHBE and BEAS 2B cells.</p> <p>Conclusions</p> <p>Cristobalite silica, as compared to synthetic amorphous silica particles at equal surface area concentrations, had comparable effects on the viability of human bronchial epithelial cells. However, effects on gene expression, as well as secretion of cytokines and chemokines, drastically differed, as the crystalline silica induced more intense responses. Our studies indicate that toxicological testing of particulates by surveying viability and/or metabolic activity is insufficient to predict their pathogenicity. Moreover, they show that acute responses of the lung epithelium, including up-regulation of genes linked to inflammation, oxidative stress, and proliferation, as well as secretion of inflammatory and proliferative mediators, can be indicative of pathologic potential using either immortalized lines (BEAS 2B) or primary cells (NHBE). Assessment of the degree and magnitude of these responses <it>in vitro </it>are suggested as predictive in determining the pathogenicity of potentially harmful particulates.</p

    Vitamin D Promotes Skeletal Muscle Regeneration and Mitochondrial Health

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    Vitamin D is an essential nutrient for the maintenance of skeletal muscle and bone health. The vitamin D receptor (VDR) is present in muscle, as is CYP27B1, the enzyme that hydroxylates 25(OH)D to its active form, 1,25(OH)D. Furthermore, mounting evidence suggests that vitamin D may play an important role during muscle damage and regeneration. Muscle damage is characterized by compromised muscle fiber architecture, disruption of contractile protein integrity, and mitochondrial dysfunction. Muscle regeneration is a complex process that involves restoration of mitochondrial function and activation of satellite cells (SC), the resident skeletal muscle stem cells. VDR expression is strongly upregulated following injury, particularly in central nuclei and SCs in animal models of muscle injury. Mechanistic studies provide some insight into the possible role of vitamin D activity in injured muscle. In vitro and in vivo rodent studies show that vitamin D mitigates reactive oxygen species (ROS) production, augments antioxidant capacity, and prevents oxidative stress, a common antagonist in muscle damage. Additionally, VDR knockdown results in decreased mitochondrial oxidative capacity and ATP production, suggesting that vitamin D is crucial for mitochondrial oxidative phosphorylation capacity; an important driver of muscle regeneration. Vitamin D regulation of mitochondrial health may also have implications for SC activity and self-renewal capacity, which could further affect muscle regeneration. However, the optimal timing, form and dose of vitamin D, as well as the mechanism by which vitamin D contributes to maintenance and restoration of muscle strength following injury, have not been determined. More research is needed to determine mechanistic action of 1,25(OH)D on mitochondria and SCs, as well as how this action manifests following muscle injury in vivo. Moreover, standardization in vitamin D sufficiency cut-points, time-course study of the efficacy of vitamin D administration, and comparison of multiple analogs of vitamin D are necessary to elucidate the potential of vitamin D as a significant contributor to muscle regeneration following injury. Here we will review the contribution of vitamin D to skeletal muscle regeneration following injury

    Galaxy Zoo: comparing the demographics of spiral arm number and a new method for correcting redshift bias

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    The majority of galaxies in the local Universe exhibit spiral structure with a variety of forms. Many galaxies possess two prominent spiral arms, some have more, while others display a many-armed flocculent appearance. Spiral arms are associated with enhanced gas content and star formation in the discs of low-redshift galaxies, so are important in the understanding of star formation in the local universe. As both the visual appearance of spiral structure, and the mechanisms responsible for it vary from galaxy to galaxy, a reliable method for defining spiral samples with different visual morphologies is required. In this paper, we develop a new debiasing method to reliably correct for redshift-dependent bias in Galaxy Zoo 2, and release the new set of debiased classifications. Using these, a luminosity-limited sample of ∼18 000 Sloan Digital Sky Survey spiral galaxies is defined, which are then further sub-categorized by spiral arm number. In order to explore how different spiral galaxies form, the demographics of spiral galaxies with different spiral arm numbers are compared. It is found that whilst all spiral galaxies occupy similar ranges of stellar mass and environment, many-armed galaxies display much bluer colours than their two-armed counterparts. We conclude that two-armed structure is ubiquitous in star-forming discs, whereas many-armed spiral structure appears to be a short-lived phase, associated with more recent, stochastic star-formation activity

    SER-109: An Oral Investigational Microbiome Therapeutic for Patients with Recurrent Clostridioides difficile Infection (rCDI)

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    Clostridioides difficile infection (CDI) is classified as an urgent health threat by the Centers for Disease Control and Prevention (CDC), and affects nearly 500,000 Americans annually. Approximately 20–25% of patients with a primary infection experience a recurrence, and the risk of recurrence increases with subsequent episodes to greater than 40%. The leading risk factor for CDI is broad-spectrum antibiotics, which leads to a loss of microbial diversity and impaired colonization resistance. Current FDA-approved CDI treatment strategies target toxin or toxin-producing bacteria, but do not address microbiome disruption, which is key to the pathogenesis of recurrent CDI. Fecal microbiota transplantation (FMT) reduces the risk of recurrent CDI through the restoration of microbial diversity. However, FDA safety alerts describing hospitalizations and deaths related to pathogen transmission have raised safety concerns with the use of unregulated and unstandardized donor-derived products. SER-109 is an investigational oral microbiome therapeutic composed of purified spore-forming Firmicutes. SER-109 was superior to a placebo in reducing CDI recurrence at Week 8 (12% vs. 40%, respectively; p \u3c 0.001) in adults with a history of recurrent CDI with a favorable observed safety profile. Here, we discuss the role of the microbiome in CDI pathogenesis and the clinical development of SER-109, including its rigorous manufacturing process, which mitigates the risk of pathogen transmission. Additionally, we discuss compositional and functional changes in the gastrointestinal microbiome in patients with recurrent CDI following treatment with SER-109 that are critical to a sustained clinical response

    Relationship Difficulties Among U.K. Military Personnel: Impact of Sociodemographic, Military, and Deployment-Related Factors

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    © 2015, Taylor & Francis Group, LLC. Military work, especially operational deployments, may impact the romantic relationships of military personnel. Using a subsample of 7,581 participants from a cohort study of U.K. military personnel (data collected between 2007 and 2009), the prevalence of relationship difficulties and associations with sociodemographic, military-, and deployment-related characteristics was examined. Most participants did not report experiencing relationship difficulties. Adjusted regression analyses indicate that childhood adversity, limited support for and from partners, being in unmarried relationships, financial problems, deploying for more than 13 months in 3 years, and work being above trade, ability, and experience were key factors associated with relationship difficulties. The likelihood of U.K. military personnel experiencing relationship difficulties is increased because of personal vulnerabilities that may be exacerbated in the military context
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