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OBJECTIVES/SPECIFIC AIMS: Long interspersed element-1s (L1s) are autonomous, mobile elements that are able to copy and insert themselves throughout the genome with their own reverse transcriptase and endonuclease. These elements make up 17% of the human genome with over 500,000 copies, though the vast majority of L1s are defective with only a few dozen potentially responsible for L1 activity. Full-length L1s have the potential to contribute to mutagenesis through random insertion and increased genetic instability. Here we set out to study L1 expression at the specific loci level in bone marrow-derived stem cells (bmSCs) and adipose-derived stem cells (ASCs) and compare the levels of expression from ASCs from donor patients who are young and lean, obese, and old. Our hypothesis is that L1-related damage may contribute to mutation and inflammation that alters the function of these stem cells throughout the life of an individual. METHODS/STUDY POPULATION: ASCs and bmSCs were isolated from patient donors. The following samples were collected: ASCs from 3 young (under the age of 59) and lean (BMI<30) patients, ASCs from 3 older patients (over the age of 59), ASCs from 3 patients with BMI>30, and bmSCs from 4 young and lean patients. Cytoplasmic RNA from the cell populations was isolated and sequenced by RNA-Seq from the cell populations. Using our recently developed bioinformatics pipeline, we set out to quantify L1 expression and identify the few culprit L1s at specific loci that are actively transcribing to RNA in the ASC and bmSC samples. RESULTS/ANTICIPATED RESULTS: Here we provide proof of concept with the application of this novel method in characterizing full-length expressed L1s at the specific loci level in ASCs and bmSCs. We identified L1 loci that are commonly expressed in these cell types and observed an increase in L1 expression in the obese and old ASC cells compared with the young, lean ASCs and bmSCs. DISCUSSION/SIGNIFICANCE OF IMPACT: ASCs hold the promise of broad application in the biomedical field including regenerative treatment. There are reports that ASCs cultivated from older and obese donors are less effective in regenerative treatments. By demonstrating an increased expression of the mutagenic L1 element in ASCs from obese and old donors, this study provides further evidence suggesting the preferable use of ASCs from young and lean donors for regenerative therapies. These studies will also help us to understand the potential contribution of L1 expression to loss of stem cell function during the aging process.
In substantial numbers of affected populations, disasters adversely affect well-being and influence the development of emotional problems and dysfunctional behaviors. Nowhere is the integration of mental and behavioral health into broader public health and medical preparedness and response activities more crucial than in disasters such as the 2009-2010 H1N1 influenza pandemic. The National Biodefense Science Board, recognizing that the mental and behavioral health responses to H1N1 were vital to preserving safety and health for the country, requested that the Disaster Mental Health Subcommittee recommend actions for public health officials to prevent and mitigate adverse behavioral health outcomes during the H1N1 pandemic. The subcommittee's recommendations emphasized vulnerable populations and concentrated on interventions, education and training, and communication and messaging. The subcommittee's H1N1 activities and recommendations provide an approach and template for identifying and addressing future efforts related to newly emerging public health and medical emergencies. The many emotional and behavioral health implications of the crisis and the importance of psychological factors in determining the behavior of members of the public argue for a programmatic integration of behavioral health and science expertise in a comprehensive public health response.
(Disaster Med Public Health Preparedness. 2012;6:67–71)
The close interplay between mental health and physical health makes it critical to integrate mental and behavioral health considerations into all aspects of public health and medical disaster management. Therefore, the National Biodefense Science Board (NBSB) convened the Disaster Mental Health Subcommittee to assess the progress of the US Department of Health and Human Services (HHS) in integrating mental and behavioral health into disaster and emergency preparedness and response activities. One vital opportunity to improve integration is the development of clear and directive national policy to firmly establish the role of mental and behavioral health as part of a unified public health and medical response to disasters. Integration of mental and behavioral health into disaster preparedness, response, and recovery requires it to be incorporated in assessments and services, addressed in education and training, and founded on and advanced through research. Integration must be supported in underlying policies and administration with clear lines of responsibility for formulating and implementing policy and practice.
(Disaster Med Public Health Preparedness. 2012;6:60–66)
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