The Role of Genetics with Alcoholism and its Effects on Genes ALDH2, ADH1B by Causing Mutations in the Genome

Alcohol use disorder, an illness described by harmful drinking patterns leading to negative ramifications both emotional and physical, has become more predominantly associated with genetics rather than behavioral. There are many factors that play into alcoholism, some being environmental, heritability, and now genetics related. There are two genes believed to be related to alcoholism, ADH1B and ALDH2. Alcoholism can lead to cirrhosis of the liver, cancer and necrosis. In efforts to understanding the role of genetics and alcoholism, a genome mapping evaluation would allow for researchers to understand the effect of alcoholism and the role of genes ALDH2 and ADH1B, and what mutations may occur to cause such results

Assessing physical vulnerability of the coast in light of a changing climate : an integrated, multi-hazard, multi-timescale approach

Hazards threaten coastal communities and ecosystems over a wide range of spatiotemporal scales. One of the most pressing concerns for coastal property owners, decision makers, and researchers is the uncertain role that a changing climate will have on the intensity and frequency of these hazards. The significant uncertainties associated with both projected rates of global sea level rise (SLR) and the potential for continued trends of increasing wave heights and changes to storm tracks has made the task of incorporating the impacts of climate change into coastal vulnerability assessments challenging. Within this context of this uncertainty, we present a methodology to directly incorporate the impacts of climate change and variability into coastal vulnerability assessments via an integrated multi-scale, multi-hazard approach. Our quasi-probabilistic technique integrates two coastal hazards (dune overtopping and coastal erosion) over a time scales ranging from individual storm events to multidecadal trends influenced by a variety of climate change scenarios. Since both SLR and changes in storminess have the potential to exacerbate the extent of vulnerable stretches along a coast, these two climate controlled factors are integrated into projections of local total water levels (wave runup plus tides) to assess the relative strengths of their influence on flood and erosion hazards. Despite underlying uncertainties associated with future climate conditions, coastal decision makers need to begin planning for a changing climate now. Therefore, we use a suite of recently published semi-empirical global SLR predictions to develop scenarios of future conditions. The potential for continued changes in storminess is accounted for by developing a range of wave climate scenarios based on decadal observations from regional wave buoys. While this approach has been developed for dune backed coastlines in general, discussed here is application of the technique to a 14 kilometer stretch of the dynamic Northern Oregon coast along which significant coastal erosion and flood hazards are currently perceived. By using simple models to predict the possibility of coastal dune overtopping and the extent of coastal erosion from storm events we can quantitatively assess the relative influence of climate change trends based on projections at various future planning horizons. Incorporation of these future hazard probabilities into the development of coastal hazard maps can provide science-based support to allow prioritization of resource allocation to best prepare coastal communities, fragile ecosystems, and jeopardized infrastructure which are likely to experience accelerated vulnerability due to a changing climate.Keywords: coastal, natural hazard

A bone-specific adipogenesis pathway in fat-free mice defines key origins and adaptations of bone marrow adipocytes with age and disease

Bone marrow adipocytes accumulate with age and in diverse disease states. However, their origins and adaptations in these conditions remain unclear, impairing our understanding of their context-specific endocrine functions and relationship with surrounding tissues. In this study, by analyzing bone and adipose tissues in the lipodystrophic \u27fat-free\u27 mouse, we define a novel, secondary adipogenesis pathway that relies on the recruitment of adiponectin-negative stromal progenitors. This pathway is unique to the bone marrow and is activated with age and in states of metabolic stress in the fat-free mouse model, resulting in the expansion of bone marrow adipocytes specialized for lipid storage with compromised lipid mobilization and cytokine expression within regions traditionally devoted to hematopoiesis. This finding further distinguishes bone marrow from peripheral adipocytes and contributes to our understanding of bone marrow adipocyte origins, adaptations, and relationships with surrounding tissues with age and disease

Drought at a coastal wetland affects refuelling and migration strategies of shorebirds

Droughts can affect invertebrate communities in wetlands, which can have bottom-up effects on the condition and survival of top predators. Shorebirds, key predators at coastal wetlands, have experienced widespread population declines and could be negatively affected by droughts. We explored, in detail, the effects of drought on multiple aspects of shorebird stopover and migration ecology by contrasting a year with average wet/dry conditions (2016) with a year with moderate drought (2017) at a major subarctic stopover site on southbound migration. We also examined the effects of drought on shorebird body mass during stopover across 14 years (historical: 1974–1982 and present-day: 2014–2018). For the detailed comparison of two years, in the year with moderate drought we documented lower invertebrate abundance at some sites, higher prey family richness in shorebird faecal samples, lower shorebird refuelling rates, shorter stopover durations for juveniles, and, for most species, a higher probability of making a subsequent stopover in North America after departing the subarctic, compared to the year with average wet/dry conditions. In the 14-year dataset, shorebird body mass tended to be lower in drier years. We show that even short-term, moderate drought conditions can negatively affect shorebird refuelling performance at coastal wetlands, which may carry-over to affect subsequent stopover decisions. Given shorebird population declines and predicted changes in the severity and duration of droughts with climate change, researchers should prioritize a better understanding of how droughts affect shorebird refuelling performance and survival

Incorporating climate change and morphological uncertainty into coastal change hazard assessments

Documented and forecasted trends in rising sea levels and changes in storminess patterns have the potential to increase the frequency, magnitude, and spatial extent of coastal change hazards. To develop realistic adaptation strategies, coastal planners need information about coastal change hazards that recognizes the dynamic temporal and spatial scales of beach morphology, the climate controls on coastal change hazards, and the uncertainties surrounding the drivers and impacts of climate change. We present a probabilistic approach for quantifying and mapping coastal change hazards that incorporates the uncertainty associated with both climate change and morphological variability. To demonstrate the approach, coastal change hazard zones of arbitrary confidence levels are developed for the Tillamook County (State of Oregon, USA) coastline using a suite of simple models and a range of possible climate futures related to wave climate, sea-level rise projections, and the frequency of major El Niño events. Extreme total water levels are more influenced by wave height variability, whereas the magnitude of erosion is more influenced by sea-level rise scenarios. Morphological variability has a stronger influence on the width of coastal hazard zones than the uncertainty associated with the range of climate change scenarios.Keywords: Climate change, Uncertainty, Exposure, El Niño, Probabilistic coastal hazard zones, Sea-level rise, Increasing stormines

Characterization of Antibodies against Receptor Activity-Modifying Protein 1 (RAMP1): A Cautionary Tale

Calcitonin gene-related peptide (CGRP) is a key component of migraine pathophysiology, yielding effective migraine therapeutics. CGRP receptors contain a core accessory protein subunit: receptor activity-modifying protein 1 (RAMP1). Understanding of RAMP1 expression is incomplete, partly due to the challenges in identifying specific and validated antibody tools. We profiled antibodies for immunodetection of RAMP1 using Western blotting, immunocytochemistry and immunohistochemistry, including using RAMP1 knockout mouse tissue. Most antibodies could detect RAMP1 in Western blotting and immunocytochemistry using transfected cells. Two antibodies (844, ab256575) could detect a RAMP1-like band in Western blots of rodent brain but not RAMP1 knockout mice. However, cross-reactivity with other proteins was evident for all antibodies. This cross-reactivity prevented clear conclusions about RAMP1 anatomical localization, as each antibody detected a distinct pattern of immunoreactivity in rodent brain. We cannot confidently attribute immunoreactivity produced by RAMP1 antibodies (including 844) to the presence of RAMP1 protein in immunohistochemical applications in brain tissue. RAMP1 expression in brain and other tissues therefore needs to be revisited using RAMP1 antibodies that have been comprehensively validated using multiple strategies to establish multiple lines of convincing evidence. As RAMP1 is important for other GPCR/ligand pairings, our results have broader significance beyond the CGRP field

Homogeneous low-molecular-weight heparins with reversible anticoagulant activity

Low-molecular-weight heparins (LMWHs) are carbohydrate-based anticoagulants clinically used to treat thrombotic disorders, but impurities, structural heterogeneity or functional irreversibility can limit treatment options. We report a series of synthetic LMWHs prepared by cost-effective chemoenzymatic methods. The high activity of one defined synthetic LMWH against human factor Xa (FXa) was reversible in vitro and in vivo using protamine, demonstrating that synthetically accessible constructs can have a critical role in the next generation of LMWHs