Perinatal arsenic exposure inhibits binding ability of glucocorticoid receptors to nuclear response elements altering gene expression and affecting learning behavior

Learning deficits in children following arsenic (As) exposure via drinking water have been epidemiologically described in the last decade. Arsenic is a persistent environmental toxin and exposure has been shown to perturb the hypothalamic-pituitary-adrenal (HPA) stress axis. The glucocorticoid receptors (GR) are an integral part of the HPA axis and are found throughout the central nervous system, particularly in the hippocampus, an area of the brain important in learning and memory. The mitogen-activated protein kinase (MAPK) pathway is involved in learning and two kinases of the MAPK pathway, Ras and Raf are transcriptionally regulated by GRs. In the studies detailed in this dissertation the impact of perinatal exposure to 50 parts per billion (ppb) sodium arsenate on learning behavior, GRs and MAPK pathway genes in the C57BL/6J adolescent mouse were examined. Hippocampal-sensitive learning was assessed using a novel object task and eight-way radial arm maze (RAM). Arsenic-exposed offspring showed increased latency to the novel object and increased number of entry errors in the RAM compared to controls. Immunoblotting revealed that arsenic-exposed offspring had significantly lower levels of both GR and mineralocorticoid receptors in the activated nuclear subcellular fraction than controls. As-exposed mice also showed significantly lower Ras and Raf-1 mRNA levels, assessed by real-time RT-PCR, compared to controls. Binding of the glucocorticoid receptor (GR) to glucocorticoid response elements (GREs) in Ras and Raf genes was measured by chromatin immunoprecipitation (ChIP). ChIP revealed reduced binding of the GR to GREs in target genes in the As group. Electrophoretic mobility shift assay (EMSA) revealed intact binding ability in both control and arsenic-exposed offspring to a synthetic GRE. Results suggest that moderate exposures to As can significantly reduce GR levels in the hippocampus, affecting expression of genes that are under the control of the GR and impacting learning behavior. Overall, these data suggest that moderate levels of perinatal As can have a lasting impact on the brain and HPA axis of offspring

Revelations from the Nematode Caenorhabditis elegans on the Complex Interplay of Metal Toxicological Mechanisms

Metals have been definitively linked to a number of disease states. Due to the widespread existence of metals in our environment from both natural and anthropogenic sources, understanding the mechanisms of their cellular detoxification is of upmost importance. Organisms have evolved cellular detoxification systems including glutathione, metallothioneins, pumps and transporters, and heat shock proteins to regulate intracellular metal levels. The model organism, Caenorhabditis elegans (C. elegans), contains these systems and provides several advantages for deciphering the mechanisms of metal detoxification. This review provides a brief summary of contemporary literature on the various mechanisms involved in the cellular detoxification of metals, specifically, antimony, arsenic, cadmium, copper, manganese, mercury, and depleted uranium using the C. elegans model system for investigation and analysis

Revelations from the Nematode Caenorhabditis elegans on the Complex Interplay of Metal Toxicological Mechanisms

Metals have been definitively linked to a number of disease states. Due to the widespread existence of metals in our environment from both natural and anthropogenic sources, understanding the mechanisms of their cellular detoxification is of upmost importance. Organisms have evolved cellular detoxification systems including glutathione, metallothioneins, pumps and transporters, and heat shock proteins to regulate intracellular metal levels. The model organism, Caenorhabditis elegans (C. elegans), contains these systems and provides several advantages for deciphering the mechanisms of metal detoxification. This review provides a brief summary of contemporary literature on the various mechanisms involved in the cellular detoxification of metals, specifically, antimony, arsenic, cadmium, copper, manganese, mercury, and depleted uranium using the C. elegans model system for investigation and analysis

Genome-Wide Analyses of Metal Responsive Genes in Caenorhabditis elegans

Metals are major contaminants that influence human health. Many metals have physiologic roles, but excessive levels can be harmful. Advances in technology have made toxicogenomic analyses possible to characterize the effects of metal exposure on the entire genome. Much of what is known about cellular responses to metals has come from mammalian systems; however the use of non-mammalian species is gaining wider attention. Caenorhabditis elegans is a small round worm whose genome has been fully sequenced and its development from egg to adult is well characterized. It is an attractive model for high throughput screens due to its short lifespan, ease of genetic mutability, low cost, and high homology with humans. Research performed in C. elegans has led to insights in apoptosis, gene expression, and neurodegeneration, all of which can be altered by metal exposure. Additionally, by using worms one can potentially study mechanisms that underline differential responses to metals in nematodes and humans, allowing for identification of novel pathways and therapeutic targets. In this review, toxicogenomic studies performed in C. elegans exposed to various metals will be discussed, highlighting how this non-mammalian system can be utilized to study cellular processes and pathways induced by metals. Recent work focusing on neurodegeneration in Parkinson’s disease will be discussed as an example of the usefulness of genetic screens in C. elegans and the novel findings that can be produced

Library Instruction and Information Literacy 2015

Purpose: This paper aims to highlight recent resources on information literacy (IL) and library instruction, providing an introductory overview and a selected annotated bibliography of publications covering all library types. Design/methodology/approach: This paper introduces and annotates English-language periodical articles, monographs, dissertations and other materials on library instruction and IL published in 2015. Findings: This paper provides information about each source, describes the characteristics of current scholarship and highlights sources that contain either unique or significant scholarly contributions. Originality/value: The information may be used by librarians and interested parties as a quick reference to literature on library instruction and IL

Chaperoning ribosome assembly

Chaperones help proteins fold in all cellular compartments, and many associate directly with ribosomes, capturing nascent chains to assist their folding and prevent aggregation. In this issue, new data from Koplin et al. (2010. J. Cell Biol. doi: 10.1083/jcb.200910074) and Albanèse et al. (2010. J. Cell Biol. doi: 10.1083/jcb.201001054) suggest that in addition to promoting protein folding, the chaperones ribosome-associated complex (RAC), nascent chain–associated complex (NAC), and Jjj1 also help in the assembly of ribosomes

Effects of selenium addition on minimally processed leafy vegetables grown in a floating system

BACKGROUND: In recent years the consumption ofminimally processed leafy vegetables has been increasing. At the same time food quality and its effects on human health have become crucial issues. Since selenium (Se) is an important microelement due to its ability to defend human organisms against free radicals, we investigated the effects of Se on chicory and lettuce production, and assessed the feasibility of a floating system as a method of producing Se-enriched vegetables. RESULTS: The addition of 0.5 and 1.0mg Se L−1 to the nutrient solution resulted in an increase in the selenium concentration in the leaves, which had a positive effect on the plant yield. Selenium was generally effective in decreasing the production of ethylene and phenylalanine ammonia lyase (PAL) activity, even though a seasonal effect seemed to be present, consequently improving the quality of leafy vegetables and the shelf life in both species. The amount of Se accumulated in plants grown in the nutrient solution containing 0.5 mgSe kg−1 could provide the rational Se intake for human nutrition in accordance with the recommended dietary allowance (RDA) guidelines. CONCLUSIONS: The addition of Se in a nutrient solution can be a useful system for providing enriched leafy vegetables. The floating system can be used to modulate the availability of Se in nutrient solutions and to grow vegetables with the optimal Se content for human healt

Assessment and management of pediatric pain based on the opinions of health professionals

The present study characterized the opinions of health professionals about strategies for assessing and managing pediatric pain in a public teaching hospital. The sample consisted of 92 health professionals who worked in pediatric wards, pediatric intensive care, and neonatal intensive care. The sample included 45 doctors, 18 nurses, 16 psychologists, eight physiotherapists, and five occupational therapists. Data were collected through a self-administered questionnaire that included 22 open questions on the following topics: pain assessment, pharmacological management, and non-pharmacological interventions. Each area was analyzed with regard to actions, resources, gaps, and needs. The questionnaire was developed based on the principles of Strategic Planning. Two trained researchers analyzed the thematic content of all of the responses. With regard to actions and resources, 33% of the respondents mentioned the use of instruments for pain assessment, 73% reported that they prescribed pharmacological treatments for symptoms of pain, and 26% reported the use of non-pharmacological interventions for the relief of pain. The professionals predominantly reported a lack of training for pain assessment and management, standardized protocols, and human and material resources. Consequently, 96% of the professionals reported the necessity for educational training and standardized implementation guidelines for pain assessment services. These findings provide a baseline of the health professional's opinions of pain issues, which are essential for implementing and increasing pain assessment and management policies institutionally