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Broad spectrum proteomics analysis of the inferior colliculus following acute hydrogen sulfide exposure.
Acute exposure to high concentrations of H2S causes severe brain injury and long-term neurological disorders, but the mechanisms involved are not known. To better understand the cellular and molecular mechanisms involved in acute H2S-induced neurodegeneration we used a broad-spectrum proteomic analysis approach to identify key molecules and molecular pathways involved in the pathogenesis of acute H2S-induced neurotoxicity and neurodegeneration. Mice were subjected to acute inhalation exposure of up to750 ppm of H2S. H2S induced behavioral deficits and severe lesions including hemorrhage in the inferior colliculus (IC). The IC was microdissected for proteomic analysis. Tandem mass tags (TMT) liquid chromatography mass spectrometry (LC-MS/MS)-based quantitative proteomics was applied for protein identification and quantitation. LC-MS/MS identified 598, 562, and 546 altered proteomic changes at 2 h, and on days 2 and 4 post-H2S exposure, respectively. Of these, 77 proteomic changes were statistically significant at any of the 3 time points. Mass spectrometry data were subjected to Perseus 1.5.5.3 statistical analysis, and gene ontology heat map clustering. Expressions of several key molecules were verified to confirm H2S-dependent proteomics changes. Webgestalt pathway overrepresentation enrichment analysis with Panther engine revealed H2S exposure disrupted several biological processes including metabotropic glutamate receptor group 1 and inflammation mediated by chemokine and cytokine signaling pathways among others. Further analysis showed that energy metabolism, integrity of blood-brain barrier, hypoxic, and oxidative stress signaling pathways were also implicated. Collectively, this broad-spectrum proteomics data has provided important clues to follow up in future studies to further elucidate mechanisms of H2S-induced neurotoxicity
Nutrient Digestibility of Condensed Algal Residue Solubles in Beef Cattle Fishing Diets
Condensed algal residue solubles (CARS) were evaluated in finishing cattle diets. Six treatments were evaluated (2 × 3 factorial arrangement), CARS inclusion in the diet at 0, 5, or 10% of diet dry matter with 0 or 20% wet distillers grains. Th e remainder of the diets consisted of 57.5– 87.5% dry rolled corn, 7.5% sorghum silage and 5% supplement. Increasing wet distillers grains in the diet had no effect on dry matter and organic matter intake but decreased dry matter and organic matter digestibility. Increasing CARS inclusion in the diet resulted in lower dry matter and organic matter intake with no effect on dry matter and organic matter digestibility. Replacing up to 10% dry rolled corn with CARS in diets with or without wet distillers grains had little effect on digestibility of finishing beef cattle diets
Agri-Environmental Policy at the Crossroads: Guideposts on a Changing Landscape
Agri-environmental policy is at a crossroads. Over the past 20 years, a wide range of policies addressing the environmental implications of agricultural production have been implemented at the Federal level. Those policies have played an important role in reducing soil erosion, protecting and restoring wetlands, and creating wildlife habitat. However, emerging agri-environmental issues, evolution of farm income support policies, and limits imposed by trade agreements may point toward a rethinking of agri-environmental policy. This report identifies the types of policy tools available and the design features that have improved the effectiveness of current programs. It provides an indepth analysis of one policy tool that may be an important component of a future policy package-agri-environmental payments. The analysis focuses on issues and tradeoffs that policymakers would face in designing a program of agri-environmental payments.conservation programs, environmental policy, agricultural policy, policy instruments, agricultural program design, soil erosion, nitrogen runoff, Environmental Economics and Policy,
Targeting the Complement Serine Protease MASP-2 as a Therapeutic Strategy for Coronavirus Infections
MASP-2, mannose-binding protein-associated serine protease 2, is a key enzyme in the lectin pathway of complement activation. Hyperactivation of this protein by human coronaviruses SARS-CoV, MERS-CoV and SARS-CoV-2 has been found to contribute to aberrant complement activation in patients, leading to aggravated lung injury with potentially fatal consequences. This hyperactivation is triggered in the lungs through a conserved, direct interaction between MASP-2 and coronavirus nucleocapsid (N) proteins. Blocking this interaction with monoclonal antibodies and interfering directly with the catalytic activity of MASP-2, have been found to alleviate coronavirus-induced lung injury both in vitro and in vivo. In this study, a virtual library of 8736 licensed drugs and clinical agents has been screened in silico according to two parallel strategies. The first strategy aims at identifying direct inhibitors of MASP-2 catalytic activity, while the second strategy focusses on finding protein-protein interaction inhibitors (PPIs) of MASP-2 and coronaviral N proteins. Such agents could represent promising support treatment options to prevent lung injury and reduce mortality rates of infections caused by both present and future-emerging coronaviruses. Forty-six drug repurposing candidates were purchased and, for the ones selected as potential direct inhibitors of MASP-2, a preliminary in vitro assay was conducted to assess their interference with the lectin pathway of complement activation. Some of the tested agents displayed a dose-response inhibitory activity of the lectin pathway, potentially providing the basis for a viable support strategy to prevent the severe complications of coronavirus infections
Documentation of Atlantic Tarpon (Megalops atlanticus) Space Use and Move Persistence in the Northern Gulf of Mexico Facilitated by Angler Advocates
Atlantic tarpon (Megalops atlanticus, hereafter tarpon) are facing a multitude of stressors and are considered Vulnerable by the IUCN; however, significant gaps remain in our understanding of tarpon space use and movement. From 2018 to 2019, citizen scientists facilitated tagging of 23 tarpon with SPOT tags to examine space use and movement across the northern Gulf of Mexico. Movement-based kernel densities were used to estimate simplified biased random bridge-based utilization distributions and a joint move persistence model was used to estimate a behavioral index for each fish. Tarpon showed consistent east–west movement from the Alabama/Florida border to Louisiana, and utilization distributions were highest in the Mississippi River Delta. Move persistence was highest in Alabama and Mississippi and lowest in Louisiana. Our examination of tarpon space use and movement indicates that Louisiana is a critical, yet understudied, part of their range
Evaluation of an Algal Biomass as an Ingredient in Cattle Feed
A study was conducted evaluating the effects of feeding condensed algal residue solubles (CARS; available in 2019 in Blair, NE area) to finishing cattle for 100 days. Four levels of CARS were evaluated with 5 steers and 5 heifers individually fed per level of inclusion. The diets consisted of 70% dry rolled corn with CARS displacing corn at 0, 2.5, 5, and 7.5% of dry matter. Increasing CARS inclusion resulted in a linear decrease in intake, a quadratic increase in daily gain, and a linear decrease in feed:gain. Calculations showed a linear increase in dietary net energy as CARS increased in the diet. Minimal differences in organ weights, blood chemistry, hematology, and urine were observed. Daily observations and histology results suggest no differences in cattle health due to dietary treatment. Including CARS at 5% of diet dry matter increased gain 4.2% and feed:gain 10.1% relative to a corn based finishing diet
Infant BMI or Weight-for-Length and Obesity Risk in Early Childhood
Weight-for-length (WFL) is currently used to assess adiposity under 2 years. We assessed WFL- versus BMI-based estimates of adiposity in healthy infants in determining risk for early obesity
Deep-coverage whole genome sequences and blood lipids among 16,324 individuals.
Large-scale deep-coverage whole-genome sequencing (WGS) is now feasible and offers potential advantages for locus discovery. We perform WGS in 16,324 participants from four ancestries at mean depth >29X and analyze genotypes with four quantitative traits-plasma total cholesterol, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol, and triglycerides. Common variant association yields known loci except for few variants previously poorly imputed. Rare coding variant association yields known Mendelian dyslipidemia genes but rare non-coding variant association detects no signals. A high 2M-SNP LDL-C polygenic score (top 5th percentile) confers similar effect size to a monogenic mutation (~30 mg/dl higher for each); however, among those with severe hypercholesterolemia, 23% have a high polygenic score and only 2% carry a monogenic mutation. At these sample sizes and for these phenotypes, the incremental value of WGS for discovery is limited but WGS permits simultaneous assessment of monogenic and polygenic models to severe hypercholesterolemia
Environmental fate and exposure; neonicotinoids and fipronil
Systemic insecticides are applied to plants using a wide variety of methods, ranging from foliar sprays to seed treatments and soil drenches. Neonicotinoids and fipronil are among the most widely used pesticides in the world. Their popularity is largely due to their high toxicity to invertebrates, the ease and flexibility with which they can be applied, their long persistence, and their systemic nature, which ensures that they spread to all parts of the target crop. However, these properties also increase the probability of environmental contamination and exposure of nontarget organisms. Environmental contamination occurs via a number of routes including dust generated during drilling of dressed seeds, contamination and accumulation in arable soils and soil water, runoff into waterways, and uptake of pesticides by nontarget plants via their roots or dust deposition on leaves. Persistence in soils, waterways, and nontarget plants is variable but can be prolonged; for example, the half-lives of neonicotinoids in soils can exceed 1,000 days, so they can accumulate when used repeatedly. Similarly, they can persist inwoody plants for periods exceeding 1 year. Breakdown results in toxic metabolites, though concentrations of these in the environment are rarely measured. Overall, there is strong evidence that soils, waterways, and plants in agricultural environments and neighboring areas are contaminated with variable levels of neonicotinoids or fipronil mixtures and their metabolites (soil, parts per billion (ppb)-parts per million (ppm) range; water, parts per trillion (ppt)-ppb range; and plants, ppb-ppm range). This provides multiple routes for chronic (and acute in some cases) exposure of nontarget animals. For example, pollinators are exposed through direct contact with dust during drilling; consumption of pollen, nectar, or guttation drops from seed-treated crops, water, and consumption of contaminated pollen and nectar from wild flowers and trees growing near-treated crops. Studies of food stores in honeybee colonies from across the globe demonstrate that colonies are routinely and chronically exposed to neonicotinoids, fipronil, and their metabolites (generally in the 1-100 ppb range), mixed with other pesticides some of which are known to act synergistically with neonicotinoids. Other nontarget organisms, particularly those inhabiting soils, aquatic habitats, or herbivorous insects feeding on noncrop plants in farmland, will also inevitably receive exposure, although data are generally lacking for these groups. We summarize the current state of knowledge regarding the environmental fate of these compounds by outlining what is known about the chemical properties of these compounds, and placing these properties in the context of modern agricultural practices
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