Recover Alaska: Healing Alaska's Alcohol Problems

This article provides an overview of the strategies being implemented by the Recover Alaska initiative in its mission to reduce excessive alcohol use and related harm in Alaska by influencing social norms and perceptions about alcohol use and abuse. Includes a list of online resources.[Introduction] Working with the Media / Alcohol Treatment Resources / Alcohol Policy Advocacy / Evaluation and Measuring Impact / Conclusion / Resource

Burnout: Why are teacher educators reaching their limits?

Burnout among our P-12 teachers has been well documented throughout the years. Yet, little research has been conducted into the burnout of higher education professionals in general. Lackritz (2004) found that emotional exhaustion is significantly and positively related to teaching load, grading, office hours, grant money, service time, and number of service activities. This research looks further into the variables that may impact burnout for higher education faculty, specifically in teacher education, seeking to answer the questions: Are teacher educators in NY experiencing stress/burnout? If so, what internal and/or external factors/conditions are contributing to their burnout? And are specific groups of teacher educators more at-risk for developing burnout more so than others. Survey results reveal that teacher educators have a very low to moderate chance of burnout, but experience many of the stressors that can lead to burnout. The findings build on and extend beyond Maslach, Schaufeli and Leiter’s (2001) framework which includes factors of workload, control, reward, community, fairness, and values

Impacto de las políticas públicas y normativas locales sobre el espacio público. Casos de estudio: Manizales, Medellín y Quito

Urban public space not only articulates various uses and activities within cities, it is also one of the most relevant elements for contemporary cities to be able to ensure  areas of socialization, recreation and expression for their inhabitants, which result in both the creation of citizenship and a better life quality for the population. Nevertheless, the recognition of the importance of regulations and public policies at both the national and local levels is not enough to achieve the goals set. This study examines two Colombian cities, as well as Quito, Ecuador, which, in addition to restrictions on growth due to the geographical features of their appropriate territories. We compared both the regulations and the public policies from the last ten years, as well as the public spaces in all three cities. This examination shows a number of differences in the implementation of policies between the two countries, as well as in the indicators of total public-space areas. Moreover, we found similarities in the unequal distribution of public spaces and existing green areas: Many neighborhoods have few or none, while other locations have a large number of such areas.El espacio público urbano no solo articula los diversos usos y actividades en las ciudades, es también, uno de los elementos más relevantes para las ciudades contemporáneas, que deben garantizar a sus habitantes espacios de socialización, recreación y expresión que redunden en una construcción de ciudadanía y en una mejor calidad de vida para la población. No obstante, el reconocimiento de su importancia en las normas y en las políticas públicas de orden nacional y local, no es suficiente para materializar las metas trazadas. Este trabajo analiza dos ciudades colombianas y a Quito, las cuales tienen, además, limitaciones para su crecimiento dadas por el relieve del territorio en el que se asientan. Se contrastaron las normas y políticas públicas de los últimos diez años, y los espacios públicos en las tres ciudades, lo que permitió evidenciar diferencias en la ejecución de las políticas entre los dos países y en los indicadores que dan cuenta de los espacios públicos totales. Por otro lado, se encontraron similitudes en la distribución desigual e inequitativa de los espacios públicos y zonas verdes existentes, de los cuales muchos barrios aún carecen o tienen muy pocos, mientras otros concentran gran cantidad de área

Investigating the Interplay between Glucose Regulation, Neural Activity, and Motivation: A Novel Approach Utilizing Vibration Stimulation

This research explores the intricate relationship between glucose regulation, neural activity, and motivation in key brain regions, including the hypothalamus, basal ganglia, ventral tegmental area (VTA), and nucleus accumbens (NA). We aim to unravel the potential relationship of these factors on dopamine (DA) release and the broader implications for mental health, glucose regulation, well-being, and overall health. Our innovative approach involves using a chair that causes heterodyned whole-body vibration designed to stimulate DA release from the VTA and NA, areas associated with motivation and rewards

CRISPR-enhanced human adipocyte \u27browning\u27 as cell therapy for metabolic disease [preprint]

Obesity and type 2 diabetes (T2D) are associated with poor tissue responses to insulin [1,2], disturbances in glucose and lipid fluxes [3-5] and comorbidities including steatohepatitis [6] and cardiovascular disease [7,8]. Despite extensive efforts at prevention and treatment [9,10], diabetes afflicts over 400 million people worldwide [11]. Whole body metabolism is regulated by adipose tissue depots [12-14], which include both lipid-storing white adipocytes and less abundant \u27brown\u27 and \u27brite/beige\u27 adipocytes that express thermogenic uncoupling protein UCP1 and secrete factors favorable to metabolic health [15-18]. Application of clustered regularly interspaced short palindromic repeats (CRISPR) gene editing [19,20] to enhance \u27browning\u27 of white adipose tissue is an attractive therapeutic approach to T2D. However, the problems of cell-selective delivery, immunogenicity of CRISPR reagents and long term stability of the modified adipocytes are formidable. To overcome these issues, we developed methods that deliver complexes of SpyCas9 protein and sgRNA ex vivo to disrupt the thermogenesis suppressor gene NRIP1 [21,22] with near 100% efficiency in human or mouse adipocytes. NRIP1 gene disruption at discrete loci strongly ablated NRIP1 protein and upregulated expression of UCP1 and beneficial secreted factors, while residual Cas9 protein and sgRNA were rapidly degraded. Implantation of the CRISPR-enhanced human or mouse brown-like adipocytes into high fat diet fed mice decreased adiposity and liver triglycerides while enhancing glucose tolerance compared to mice implanted with unmodified adipocytes. These findings advance a therapeutic strategy to improve metabolic homeostasis through CRISPR-based genetic modification of human adipocytes without exposure of the recipient to immunogenic Cas9 or delivery vectors

Integrated Carbon Budget Models for the Everglades Terrestrial-Coastal-Oceanic Gradient: Current Status and Needs for Inter-Site Comparisons

Recent studies suggest that coastal ecosystems can bury significantly more C than tropical forests, indicating that continued coastal development and exposure to sea level rise and storms will have global biogeochemical consequences. The Florida Coastal Everglades Long Term Ecological Research (FCE LTER) site provides an excellent subtropical system for examining carbon (C) balance because of its exposure to historical changes in freshwater distribution and sea level rise and its history of significant long-term carbon-cycling studies. FCE LTER scientists used net ecosystem C balance and net ecosystem exchange data to estimate C budgets for riverine mangrove, freshwater marsh, and seagrass meadows, providing insights into the magnitude of C accumulation and lateral aquatic C transport. Rates of net C production in the riverine mangrove forest exceeded those reported for many tropical systems, including terrestrial forests, but there are considerable uncertainties around those estimates due to the high potential for gain and loss of C through aquatic fluxes. C production was approximately balanced between gain and loss in Everglades marshes; however, the contribution of periphyton increases uncertainty in these estimates. Moreover, while the approaches used for these initial estimates were informative, a resolved approach for addressing areas of uncertainty is critically needed for coastal wetland ecosystems. Once resolved, these C balance estimates, in conjunction with an understanding of drivers and key ecosystem feedbacks, can inform cross-system studies of ecosystem response to long-term changes in climate, hydrologic management, and other land use along coastlines

NETosis in Alzheimer's Disease

Alzheimer's disease (AD) is a neurodegenerative disorder characterized by the progressive deterioration of cognitive functions. Its neuropathological features include amyloid-\u3b2 (A\u3b2) accumulation, the formation of neurofibrillary tangles, and the loss of neurons and synapses. Neuroinflammation is a well-established feature of AD pathogenesis, and a better understanding of its mechanisms could facilitate the development of new therapeutic approaches. Recent studies in transgenic mouse models of AD have shown that neutrophils adhere to blood vessels and migrate inside the parenchyma. Moreover, studies in human AD subjects have also shown that neutrophils adhere and spread inside brain vessels and invade the parenchyma, suggesting these cells play a role in AD pathogenesis. Indeed, neutrophil depletion and the therapeutic inhibition of neutrophil trafficking, achieved by blocking LFA-1 integrin in AD mouse models, significantly reduced memory loss and the neuropathological features of AD. We observed that neutrophils release neutrophil extracellular traps (NETs) inside blood vessels and in the parenchyma of AD mice, potentially harming the blood-brain barrier and neural cells. Furthermore, confocal microscopy confirmed the presence of NETs inside the cortical vessels and parenchyma of subjects with AD, providing more evidence that neutrophils and NETs play a role in AD-related tissue destruction. The discovery of NETs inside the AD brain suggests that these formations may exacerbate neuro-inflammatory processes, promoting vascular and parenchymal damage during AD. The inhibition of NET formation has achieved therapeutic benefits in several models of chronic inflammatory diseases, including autoimmune diseases affecting the brain. Therefore, the targeting of NETs may delay AD pathogenesis and offer a novel approach for the treatment of this increasingly prevalent disease

Mapping genomic loci implicates genes and synaptic biology in schizophrenia

Schizophrenia has a heritability of 60-80%1, much of which is attributable to common risk alleles. Here, in a two-stage genome-wide association study of up to 76,755 individuals with schizophrenia and 243,649 control individuals, we report common variant associations at 287 distinct genomic loci. Associations were concentrated in genes that are expressed in excitatory and inhibitory neurons of the central nervous system, but not in other tissues or cell types. Using fine-mapping and functional genomic data, we identify 120 genes (106 protein-coding) that are likely to underpin associations at some of these loci, including 16 genes with credible causal non-synonymous or untranslated region variation. We also implicate fundamental processes related to neuronal function, including synaptic organization, differentiation and transmission. Fine-mapped candidates were enriched for genes associated with rare disruptive coding variants in people with schizophrenia, including the glutamate receptor subunit GRIN2A and transcription factor SP4, and were also enriched for genes implicated by such variants in neurodevelopmental disorders. We identify biological processes relevant to schizophrenia pathophysiology; show convergence of common and rare variant associations in schizophrenia and neurodevelopmental disorders; and provide a resource of prioritized genes and variants to advance mechanistic studies

Dissecting the Shared Genetic Architecture of Suicide Attempt, Psychiatric Disorders, and Known Risk Factors

Background Suicide is a leading cause of death worldwide, and nonfatal suicide attempts, which occur far more frequently, are a major source of disability and social and economic burden. Both have substantial genetic etiology, which is partially shared and partially distinct from that of related psychiatric disorders. Methods We conducted a genome-wide association study (GWAS) of 29,782 suicide attempt (SA) cases and 519,961 controls in the International Suicide Genetics Consortium (ISGC). The GWAS of SA was conditioned on psychiatric disorders using GWAS summary statistics via multitrait-based conditional and joint analysis, to remove genetic effects on SA mediated by psychiatric disorders. We investigated the shared and divergent genetic architectures of SA, psychiatric disorders, and other known risk factors. Results Two loci reached genome-wide significance for SA: the major histocompatibility complex and an intergenic locus on chromosome 7, the latter of which remained associated with SA after conditioning on psychiatric disorders and replicated in an independent cohort from the Million Veteran Program. This locus has been implicated in risk-taking behavior, smoking, and insomnia. SA showed strong genetic correlation with psychiatric disorders, particularly major depression, and also with smoking, pain, risk-taking behavior, sleep disturbances, lower educational attainment, reproductive traits, lower socioeconomic status, and poorer general health. After conditioning on psychiatric disorders, the genetic correlations between SA and psychiatric disorders decreased, whereas those with nonpsychiatric traits remained largely unchanged. Conclusions Our results identify a risk locus that contributes more strongly to SA than other phenotypes and suggest a shared underlying biology between SA and known risk factors that is not mediated by psychiatric disorders.Peer reviewe