Project description:<p>This study includes SSADDA (Semi Structured Assessment for Drug Dependence and Alcoholism) assessed subjects (mostly unrelated, but including some affected sibling pairs) recruited in the course of several substance dependence genetics projects. The sample includes 1889 African-American (AA) subjects and 1020 European-American (EA) subjects. Among the AAs, 1397 meet DSM-IV criteria for alcohol dependence and 491 are controls. Among the EAs, 1010 meet the criteria for alcohol dependence and 9 are controls. (One in each population meets criteria for alcohol abuse and not dependence, and is therefore counted in neither category.) Although alcohol dependence is the major focus, the sample is informative also for cocaine, nicotine, and opioid dependence.</p>
Project description:Short bowel syndrome (SBS) is a rare condition resulting from the loss of portions of the small intestine, and can cause a spectrum of metabolic and physiologic disturbances.The objective of this study was to determine the longterm survival and parenteral nutrition dependence of adult patients with SBS.
Project description:<p>This collaboration of Australian and American investigators aims to identify genes associated with liability for heroin dependence. The project uses a case-control design in which cases met lifetime DSM-IV criteria for heroin dependence. Controls included assessed individuals who did not meet DSM-IV heroin dependence criteria and unassessed general population controls. Cases and controls were obtained from the several large investigations including: The Comorbidity and Trauma Study, Heroin Dependence in Western Australia, the OZ-ALC Study, a Twin Study of Mole Development in Adolescence, and ongoing genetic studies of substance dependence conducted by investigators at Yale and collaborating institutions. These projects are briefly described below.</p> <p>The Comorbidity and Trauma Study (PI: Elliot Nelson), a retrospective case-control study examining genetic and environmental factors contributing to heroin dependence liability. The study was funded by the National Institute on Drug Abuse (NIDA), and was run in collaboration with Washington University, the Queensland Institute of Medical Research (QIMR), and the National Drug and Alcohol Research Centre (NDARC), University of New South Wales. Case participants were recruited from maintenance clinics in the greater Sydney area. Control participants were recruited from employment centres and community centres, open street malls, and local press servicing the same geographical area as the opioid maintenance treatment clinics and either denied recreational use of opioids or had used these drugs recreationally fewer than 11 times lifetime. The prevalence in these individuals of non-opioid licit drug dependence and illicit drug dependence as well as childhood trauma exposure and other psychiatric disorders is elevated considerably versus estimates of similar measures in Australian general population samples. Participants provided blood samples as a source of DNA and completed a comprehensive psychiatric diagnostic interview based on the Semi-Structured Assessment of the Genetics of Alcoholism - Australia (SSAGA-OZ) augmented with sections drawn from other instruments assessing childhood trauma exposure, family history, and screening for borderline personality disorder.</p> <p>Heroin Dependence in Western Australia (PI: Sybille Schwab) is a study focusing both on genetic contributions to heroin dependence and response to naltrexone treatment of the disorder. Participants completed a clinical assessment and provided blood samples during their treatment at the Perth Naltrexone Clinic now name as the Fresh Start Recovery Programme. Funding for the project was provided by the Australia Government's National Health and Medical Research Council (Grant # 513862; PI: Sybille Schwab)</p> <p>Affected subjects from ongoing genetic studies of substance dependence conducted by investigators at Yale (PI: Joel Gelernter) and collaborating institutions were collected in the course of several NIDA-funded studies. Those included in the current set were assessed by means of the SSADDA (Semi-Structured Assessment for Drug Dependence and Alcoholism). All are opioid dependent European-Americans, and all list heroin as the opioid must used. Most were collected at Yale University School of Medicine or University of CT School of Medicine under the supervision of Drs Joel Gelernter and Henry Kranzler. Control subjects were also collected in the course of several NIDA- and NIAAA-funded studies. Those included in the current set were assessed by means of the SSADDA (Semi-structured Assessment for Drug Dependence and Alcoholism). Most were collected at Yale University School of Medicine or University of Connecticut School of Medicine under the supervision of Drs Joel Gelernter and Henry Kranzler.</p> <p>The OZ-ALC Study (PI: Andrew Heath) consists of a large group of twins and their family members ascertained from the general population Australian Twin Registry who have participated in ongoing research projects. For the control investigation, we have selected individuals who do meet criteria for illicit drug dependence who have had GWAS genotyping with the Illumina Human CNV370-Quad. Inclusion of individuals with alcohol dependence or nicotine dependence was minimized. For a more detailed description of the study, please see this <a href="./study.cgi?study_id=phs000181">link</a>.</p> <p>The Twin Study of Mole Development in Adolescence (PI: Nick Martin) is an ongoing investigation of melanocytic naevi funded by the Australian Government's National Health and Medical Research Council (Grant # 389891; PI: Nick Martin). For the current project, unassessed parents of these twins will serve as a control group. These individuals will either have been previously genotyped with the Illumina Human 610-Quad BeadChip or will be genotyped as part of the current project. Parents have largely survived the period of risk for heroin dependence, and by virtue of their participation in this research, are very likely to have a prevalence of heroin dependence lower than that in the general population (i.e., <0.7%).</p>
Project description:Here we investigated colistin effects on A. baumannii, employing a Mass spectrometry approach and comparing a colistin-susceptible multidrug-resistantclinical isolate to its colistin-dependent subpopulation obtained by subsequent passages in moderate colistin concentrations. Colistin dependence might represent a stepping-stone to resistance, but the mechanisms of colistin dependence are far from clear.
Project description:Accumulating evidence indicates adaptive cellular reprogramming is a major contributor to disease recurrence and acquired drug resistance in cancer. Here we show that chronic drug exposure results in a multi-state metabolic and epigenetic adaption that allows cancer cells to regain proliferative capacity and eventually develop permanent drug resistance. Specifically, the escape from the previously described slow cycling induced drug tolerant cell state is driven by transiently increased expression of O-GlcNAc transferase (OGT) linking metabolic to epigenetic changes by facilitating global H3K4me3 remodeling. This adaptive process can be blocked by genetic or pharmacological inhibition of OGT or concurrent activation of AMPK to prevent metabolic adaption, subsequent epigenetic remodeling and permanent acquired drug resistance. This novel metabolic and epigenetic remodeling process is also observed following oncogene induced stress and the OGT dependence of this adaptive process uncovered promising targets for combination therapy with current standard of care drugs that could significantly increase response duration and patient outcomes.
Project description:The mechanism of nicotine dependence and nicotine related pain remains unclear. tRNAs, a major source of small noncoding RNAs (ncRNA), are the immediate areas of research focus, which have an important role in many pathophysiological processes. However, the role of tRNAs on nicotine dependence and related pain hasn’t been explored yet. In this study, our results indicated that the expression profiles of tRNAs have changed in nicotine treated rats as compared with normal rats, and among those, some differentially expressed tRNAs might be novel targets for nicotine dependence or nicotine related pain.