Additional Sex Combs-Like 2 (ASXL2): a Psychological Stress-related Gene in a Chicken Stress Model

Chronic stress is a problem not only in terms of its psychological effects but also due to the harmful physiological changes induced in the individual. Although chronic stress is recognized as detrimental and rampant throughout society, the stress system itself remains poorly understood in terms of comprehending which genes are involved in regulating and carrying out stress-induced signals. In a previous study, 57 candidate genes in the stress pathway had been identified based on the presence of stress-associated single nucleotide polymorphisms (SNPs) and differential expression from microarray data. The objective of this study was to investigate Additional Sex Combs-Like 2 (ASXL2), one of those 57 candidate genes, and to determine if it was part of the stress pathway through SNP identification and Real Time-Polymerase Chain Reaction (RT-PCR). Utilizing sequencing data of ASXL2 from Pubmed as well as SNP locations generated from DNASTAR’s SeqMan Ngen Assembly, SNPs were identified within the actual reference genome verifying the normal and mutant base pair for each SNP. After identifying SNPs of ASXL2 within the low stress line of Japanese quail, RT-PCR was performed in order to determine if mRNA expression for ASXL2 would change under acute and chronic stress. In order to perform RT-PCR, primers were designed and then tested utilizing gel electrophoresis in order to ensure optimization of the PCR product. ΔΔCT methodology was then used to determine the veracity of the mean fold expression changes found for ASXL2 under acute and chronic stress. As part of the experiment to determine the potential role of ASXL2 in the stress pathway, four SNPs were identified with high SNP rates in the low stress line of Japanese quail within ASXL2. After performing RT-PCR, it was found that ASXL2 was up regulated by 14% under acute stress and down regulated by 24% under chronic stress in comparison to the acute control group and chronic control group respectively. P-values of 0.0013 and 0.0004 for acute and chronic stress respectively indicate that the data are statistically significant. β-Actin was set at a value of 1.0 as an internal control in order to determine mean fold expression changes for ASXL2 under differing stress conditions by using ΔΔCT methodology. Based on the high SNP rate as well as the differential expression of ASXL2 under acute and chronic stress, ASXL2 has been directly implicated as a stress-related gene. Although ASXL2’s exact role within the stress pathway is unknown, its interactions with trithorax and Polycomb group genes as an epigenetic modifier make it an interesting candidate for further research to determine its possible role in the epigenetic effects of acute and chronic stress

Carbon Sequestration in Tidal Salt Marsh Restoration Projects in Northern Humboldt Bay, California

We provide here a literature review and methodology for quantifying carbon sequestration associated with the restoration of tidal salt marshes and construction of a proposed living shoreline structure in Humboldt Bay, California. The rate of carbon sequestration can be used by the City of Arcata to quantify the benefits of restored tidal wetlands and for the City’s own carbon balance documentation. This work scope focused on a) gathering and analyzing existing data sets to estimate carbon sequestration in restoring local tidal salt marshes, b) assessing existing carbon sequestration models to quantify carbon sequestration rates; and c) performing a literature search to inform approaches to quantify carbon sequestration and identify key factors that affect rates. This memo summarizes the results of our review in two sections: Section (1) presents estimates of carbon sequestered for two restoring salt marshes and a proposed Living Shoreline project in Humboldt Bay; Section (2) utilizes the Marsh Equilibrium Model (MEMIII) to quantify carbon sequestration rates in evolving tidal salt marshes coordinately with sea level rise scenarios. Further analysis is presented in Appendix 1 with discussion and literature review of factors that may improve predictive power of current carbon sequestration modeling and a summary of published carbon sequestration values; Appendix 2 presents a parameter sensitivity analysis for the Marsh Equilibrium Model (MEMIII) to illustrate which parameters exert the most influence on calculated carbon sequestration rates using this model. We conclude that upon restoration of the two tidal salt marshes and proposed living shoreline in Humboldt Bay to mature salt marsh vegetation, approximately 100 metric Tons per year of carbon will be sequestered above current condition

Investigational drugs for the treatment of AD: what can we learn from negative trials?

Given the level of interest and activity in the race to find a treatment for Alzheimer's disease, it is expected that a reasonably safe and effective drug will be identified within the next decade. It may be worthwhile to pause periodically during the course of this race to take stock of what we have learned. Over the past few years, a number of trials have been conducted with promising new compounds (including some with novel mechanisms of action) that failed to meet primary endpoints and so were discontinued from clinical development. This article reviews a set of molecules with a range of mechanisms that have been trialed but with negative results. This article also examines the reasons for the negative findings and summarizes some of what we have learned from these experiences

Probable Early-Onset Alzheimer's Disease in an Apolipoprotein E2 Homozygote

Objective: To describe a case of early-onset Alzheimer's disease (AD) in an apolipoprotein (Apo) epsilon 2/epsilon 2 homozygote. Background: Apo epsilon 2/epsilon 2 is the rarest of the ApoE genotypes, representing only 1.4% of the population. Cognitive decline in ApoE epsilon 2 homozygotes has rarely been reported. Case Report/Methods: We report a 58-year-old Apo epsilon 2/epsilon 2 female who meets clinical criteria for probable AD as confirmed by neuropsychological testing, positron emission/computed tomography scan, CSF analysis and genetic screening for known mutations. Results: The clinical course is typical of AD, with progressive cognitive and functional decline. Conclusion: Clinically confirmed early-onset AD is atypical in ApoE2 homozygotes but can occur. Copyright (C) 2010 S. Karger AG, Base

Mediating and Moderating Effects of Iron Homeostasis Alterations on Fetal Alcohol-Related Growth and Neurobehavioral Deficits

We have previously demonstrated prenatal alcohol exposure (PAE)-related alterations in maternal and infant iron homeostasis. Given that early iron deficiency and PAE both lead to growth restriction and deficits in recognition memory and processing speed, we hypothesized that PAE-related iron homeostasis alterations may mediate and/or moderate effects of PAE on growth and neurobehavior. We examined this hypothesis in a prenatally recruited, prospective longitudinal birth cohort [87 mother-infant pairs with heavy prenatal alcohol exposure (mean = 7.2 drinks/occasion on 1.4 days/week); 71 controls], with serial growth measures and infant neurobehavioral assessments. PAE was related to growth restriction at 2 weeks and 5 years, and, in infancy, poorer visual recognition memory, slower processing speed, lower complexity of symbolic play, and higher emotionality and shyness on a parental report temperament scale. Lower maternal hemoglobin-to-log(ferritin) ratio, which we have shown to be associated with PAE, appeared to exacerbate PAE-related 2-week head circumference reductions, and elevated maternal ferritin, which we have shown to be associated with PAE, appeared to exacerbate PAE-related visual recognition memory deficits. In causal inference analyses, PAE-related elevations in maternal ferritin and hemoglobin:log(ferritin) appeared to statistically mediate 22.6–82.3% of PAE-related growth restriction. These findings support potential mechanistic roles of iron homeostasis alterations in fetal alcohol spectrum disorders (FASD)

A multi-objective, hub-and-spoke model to design and manage biofuel supply chains

In this paper we propose a multi-objective, mixed integer linear programming model to design and manage the supply chain for biofuels. This model captures the trade-offs that exist between costs, environmental and social impacts of delivering biofuels. The in-bound supply chain for biofuel plants relies on a hub-and-spoke structure which optimizes transportation costs of biomass. The model proposed optimizes the CO2 style= position: relative; tabindex= 0 id= MathJax-Element-1-Frame \u3eCO2 emissions due to transportation-related activities in the supply chain. The model also optimizes the social impact of biofuels. The social impacts are evaluated by the number of jobs created. The multi-objective optimization model is solved using an augmented ϵ style= position: relative; tabindex= 0 id= MathJax-Element-2-Frame \u3eϵ-constraint method. The method provides a set of Pareto optimal solutions. We develop a case study using data from the Midwest region of the USA. The numerical analyses estimates the quantity and cost of cellulosic ethanol delivered under different scenarios generated. The insights we provide will help policy makers design policies which encourage and support renewable energy production

Mortalidade cerebrovascular: tendência e sazonalidade nas capitais brasileiras, 2000–2019

OBJETIVO: Avaliar a tendência e a sazonalidade das taxas de mortalidade cerebrovascular na população adulta das capitais brasileiras de 2000 a 2019. MÉTODOS: Estudo ecológico e descritivo de séries temporais de mortalidade por causas cerebrovasculares em adultos (≥ 18 anos) residentes nas capitais do Brasil no período 2000–2019, obtidas do Sistema de Informações sobre Mortalidade. Técnicas de estatística descritiva foram aplicadas na análise exploratória dos dados e no resumo de taxas específicas, padronizadas e razões por características sociodemográficas. A regressão de pontos de junção ( jointpoint regression model) e stimou a t endência d as t axas d e m ortalidade c erebrovascular p or s exo, grupos etários e regiões geográficas. A variabilidade sazonal por regiões geográficas das taxas foi estimada utilizando o modelo aditivo generalizado por meio de splines de suavização cúbica. RESULTADOS: As pessoas maiores de 60 anos representaram 77% dos óbitos cerebrovasculares. Predominaram o sexo feminino (52%), a raça branca (47%), os solteiros (59%) e a baixa escolaridade (57%, ensino fundamental). As capitais Recife (20/1.000 hab.) e Vitória (16/1.000 hab.) apresentaram as maiores taxas brutas de mortalidade. Aplicando as taxas padronizadas Recife (49/10.000 hab.) e Palmas (47/10.000 hab.) prevaleceram. As taxas de mortalidade cerebrovascular no Brasil apresentam uma tendência favorável ao declínio em ambos os sexos e em adultos. A sazonalidade mostrou influenciar na elevação das taxas entre os meses de julho a agosto em quase todas as capitais das regiões, exceto na Norte, que se elevaram nos meses de março, abril e maio. CONCLUSÕES: Os óbitos por causa cerebrovascular prevaleceram em pessoas idosas, solteiras e com baixa escolaridade. A tendência foi favorável ao declínio, sendo o inverno o período de maior risco. As diferenças regionais permitem subsidiar os tomadores de decisões em relação à implementação de políticas públicas para reduzir a mortalidade cerebrovascular.OBJECTIVE: To evaluate the trend and seasonality of cerebrovascular mortality rates in the adult population of Brazilian capitals from 2000 to 2019. METHODS: This is an ecological and descriptive study of a time series of mortality due to cerebrovascular causes in adults (≥ 18 years) living in Brazilian capitals from 2000 to 2019, based on the Brazilian Mortality Information System. Descriptive statistical techniques were applied in the exploratory analysis of data and in the summary of specific, standardized rates and ratios by sociodemographic characteristics. The jointpoint regression model was used to estimate the trend of cerebrovascular mortality rates by gender, age groups, and geographic regions. The seasonal variability of rates by geographic regions was estimated using the generalized additive model by smoothing cubic splines. RESULTS: People aged over 60 years comprised 77% of all cerebrovascular deaths. Women (52%), white individuals (47%), single people (59%), and those with low schooling (57%, elementary school) predominated in our sample. Recife (20/1,000 inhab.) and Vitória (16/1,000 inhab.) showed the highest crude mortality rates. Recife (49/10,000 inhab.) and Palmas (47/10,000 inhab.) prevailed after we applied standardized rates. Cerebrovascular mortality rates in Brazil show a favorable declining trend for adults of all genders. Seasonality influenced rate increase from July to August in almost all region capitals, except in the North, which rose in March, April, and May. CONCLUSIONS: Deaths due to cerebrovascular causes prevailed in older single adults with low schooling. The trend showed a tendency to decline and winter, the greatest risk. Regional differences can support decision-makers in implementing public policies to reduce cerebrovascular mortality