Identification of Carnitine Transporter CT1 Binding Protein Lin-7 in Nervous System

_L-Carnitine is an essential component of mitochondrial fatty acid b-oxidation in the muscle and may control the acetyl moiety levels in the brain for acetylcholine synthesis. Carnitine transporter 1(CT1)is the high affinity _L-carnitine transporter whose localization was observed in the kidney, testis, liver, skeletal muscle and brain. To clarify the molecular mechanism of carnitine transport, we sought to find the interacting protein that may be related to the transport function of CT1. Using the intracellular C-terminal region of rat CT1 containing PDZ(PSD95/DLG/ZO-1)motif as bait, we performed the yeast two-hybrid screening against rat brain cDNA library. Thirty two positive clones were obtained from the 2.7×10^7 clones screened. One of them was PDZ domain-containing protein Lin-7. We found that Lin-7 interacts specifically with C-termini of CT1:deletion and mutation of the CT1 C-terminal PDZ-motif abolished the interaction with Lin-7 in the yeast two-hybrid assay. In addition, a PDZ domain within Lin-7 associates with the CT1 C-terminal. The association of CT1 with Lin-7 enhanced _L-carnitine transport activities in HEK293 cells although there is no statistical significance. Coexpression of Lin-7 and CT1 is identified in motor neurons of the spinal cord ventral horn together with Lin-2, a binding partner of Lin-7 known to assemble proteins involved in synaptic vesicle exocytosis and synaptic junctions. Therefore, Lin-7 interacts with CT1 and may regulate their subcellular distribution or function in central nervous system

Social Value of Marine and Coastal Protected Areas in England and Wales.

The U.K. government is committed to establishing a coherent network of marine protected areas by 2012 and the recentMarine and Coastal Access Act, 2009 will designate marine conservation zones and provide wider access rights to the coast. To fulfill these goals, this article argues the need for a clearer, shared understanding of the social value of protected areas in creating new designations and managing existing ones. Although marine and coastal environments attract many people and are vitally important in terms of realized and potential social value, the majority of the public in the United Kingdom lacks understanding and awareness regarding them. Combined with this, the social value of marine and coastal protected areas (MCPAs) have been largely ignored relative to conservation and economics, with the latter invariably taking precedence in environmental policymaking. Social value reflects the complex, individual responses that people experience in a given place. Many reasons determine why one area is valued above another, and this research investigates the social value of MCPAs from a practitioner’s perspective through a series of interviews. Understanding why we “socially” value MCPAs will ultimately equip managers with an informed understanding of these spaces, influence management decisions, and, potentially, policymaking. This article defines social value in the context of MCPAs in England and Wales from a practitioner perspective, explores key concepts, and suggests possible improvements in decision-making

The international society for traumatic stress studies new guidelines for the prevention and treatment of Posttraumatic Stress Disorder: methodology and development process

Over the last two decades, treatment guidelines have become major aids in the delivery of evidence‐based care and improvement of clinical outcomes. The International Society for Traumatic Stress Studies (ISTSS) produced the first guidelines for the prevention and treatment of posttraumatic stress disorder (PTSD) in 2000 and published its latest recommendations, along with position papers on complex PTSD (CPTSD), in November 2018. A rigorous methodology was developed and followed; scoping questions were posed, systematic reviews were undertaken, and 361 randomized controlled trials were included according to the a priori agreed inclusion criteria. In total, 208 meta‐analyses were conducted and used to generate 125 recommendations (101 for adults and 24 for children and adolescents) for specific prevention and treatment interventions, using an agreed definition of clinical importance and recommendation setting algorithm. There were eight strong, eight standard, five low effect, 26 emerging evidence, and 78 insufficient evidence to recommend recommendations. The inclusion of separate scoping questions on treatments for complex presentations of PTSD was considered but decided against due to definitional issues and the virtual absence of studies specifically designed to clearly answer possible scoping questions in this area. Narrative reviews were undertaken and position papers prepared (one for adults and one for children and adolescents) to consider the current issues around CPTSD and make recommendations to facilitate further research. This paper describes the methodology and results of the ISTSS Guideline process and considers the interpretation and implementation of the recommendations

Cancer Incidence among Pesticide Applicators Exposed to Permethrin in the Agricultural Health Study

BACKGROUND: Permethrin is a synthetic pyrethroid insecticide widely used in agriculture, in public health, and in many U.S. homes and gardens. OBJECTIVE: In this study we evaluated the incidence of cancer among pesticide applicators exposed to permethrin in the Agricultural Health Study (AHS). METHODS: A total of 49,093 pesticide applicators were included in this analysis of the AHS, a prospective cohort study of licensed pesticide applicators in Iowa and North Carolina. Detailed information on pesticide exposure and lifestyle factors was obtained from self-administered questionnaires completed in 1993-1997. Average length of follow-up since applicator enrollment in the cohort was 9.14 years. We used two permethrin exposure metrics: a) lifetime days applicators personally mixed or applied permethrin and b) intensity-weighted lifetime days (lifetime days weighted by estimated intensity of exposure). We used Poisson regression analysis to estimate relative risks (RRs) and 95% confidence intervals (CIs) for malignancies by tertiles of exposure. RESULTS: We found no associations between permethrin and all malignant neoplasms combined, or between permethrin and melanoma, non-Hodgkin lymphoma, leukemia, or cancers of the colon, rectum, lung, or prostate. We found elevated and statistically significant risks for multiple myeloma in the highest tertiles of both lifetime exposure-days (RR = 5.72; 95% CI, 2.76-11.87) and intensity-weighted lifetime exposure-days (RR = 5.01; 95% CI, 2.41-10.42), compared with applicators reporting they never used permethrin; these results are based on only 15 exposed cases. These findings were similar across a variety of alternative exposure metrics, exposure categories, and reference groups. CONCLUSIONS: This study found no association with most cancers analyzed. Although the suggested association with multiple myeloma was based on a small number of cases, it warrants further evaluation

A transatlantic perspective on 20 emerging issues in biological engineering

Advances in biological engineering are likely to have substantial impacts on global society. To explore these potential impacts we ran a horizon scanning exercise to capture a range of perspectives on the opportunities and risks presented by biological engineering. We first identified 70 potential issues, and then used an iterative process to prioritise 20 issues that we considered to be emerging, to have potential global impact, and to be relatively unknown outside the field of biological engineering. The issues identified may be of interest to researchers, businesses and policy makers in sectors such as health, energy, agriculture and the environment

Source reduction for prevention of methylene chloride hazards: cases from four industrial sectors

BACKGROUND: Source reduction, defined as chemical, equipment and process changes that intervene in an industrial process to eliminate or reduce hazards, has not figured as a front-line strategy for the protection of workers' health. Such initiatives are popular for environmental protection, but their feasibility and effectiveness as an industrial hygiene approach have not been well described. METHODS: We investigated four cases of source reduction as a hazard prevention strategy in Massachusetts companies that had used methylene chloride, an occupational carcinogen, for cleaning and adhesive thinning. Three cases were retrospective and one was prospective, where the researchers assisted with the source reduction process change. Data were collected using qualitative research methods, including in-depth interviews and site visits. RESULTS: Motivated by environmental restrictions, a new worker health standard, and opportunity for productivity improvements, three companies eliminated their use of methylene chloride by utilizing available technologies and drop-in substitutes. Aided by technical assistance from the investigators, a fourth case dramatically reduced its use of methylene chloride via process and chemistry changes. While the companies' evaluations of potential work environment impacts of substitutes were not extensive, and in two cases new potential hazards were introduced, the overall impact of the source reduction strategy was deemed beneficial, both from a worker health and a production standpoint. CONCLUSION: The findings from these four cases suggest that source reduction should be considered potentially feasible and effective for reducing or eliminating the potential hazards of methylene chloride exposure. Especially when faced with a hazard that is both an environmental and worker health concern, companies may chose to change their processes rather than rely on local exhaust ventilation equipment or personal protective equipment that might not be as effective, might transfer risk and/or not be integrated with financial goals. However, technical assistance sensitive to environmental and health and safety impacts as well as production issues should be provided to guide companies' source reduction efforts

Comment letters to the National Commission on Commission on Fraudulent Financial Reporting, 1987 (Treadway Commission) Vol. 1

https://egrove.olemiss.edu/aicpa_sop/1661/thumbnail.jp