A Genetic Locus Regulates the Expression of Tissue-Specific mRNAs from Multiple Transcription Units

129 GIX- mice, unlike animals of the congeneic partner strain GIX+, do not express significant amounts of the retroviral antigens gp70 and p30. Evidence is presented indicating that the GIX phenotype is specified by a distinct regulatory gene acting on multiple transcription units to control the levels of accumulation of specific mRNA species. The steady-state levels of retroviral-homologous mRNA from the tissues of GIX+ and GIX- mice were examined by blot hybridization using as probes DNA fragments from cloned murine leukemia viruses. RNA potentially encoding viral antigens was reduced or absent in GIX- mice, even though no differences in integrated viral genomes were detected between these congeneic strains by DNA blotting. Tissue-specific patterns of accumulation of these RNA species were detected in brain, epididymis, liver, spleen, and thymus, and several distinct RNA species were found to be coordinately regulated with the GIX phenotype. Measurements of RNA synthesis suggest a major role for transcriptional control in the regulation of some retroviral messages

Protein Structure Prediction Using Basin-Hopping

Associative memory Hamiltonian structure prediction potentials are not overly rugged, thereby suggesting their landscapes are like those of actual proteins. In the present contribution we show how basin-hopping global optimization can identify low-lying minima for the corresponding mildly frustrated energy landscapes. For small systems the basin-hopping algorithm succeeds in locating both lower minima and conformations closer to the experimental structure than does molecular dynamics with simulated annealing. For large systems the efficiency of basin-hopping decreases for our initial implementation, where the steps consist of random perturbations to the Cartesian coordinates. We implemented umbrella sampling using basin-hopping to further confirm when the global minima are reached. We have also improved the energy surface by employing bioinformatic techniques for reducing the roughness or variance of the energy surface. Finally, the basin-hopping calculations have guided improvements in the excluded volume of the Hamiltonian, producing better structures. These results suggest a novel and transferable optimization scheme for future energy function development

A comparison of cognitive restructuring and thought listing for excessive acquiring in hoarding disorder

Excessive acquiring is a common symptom of hoarding disorder (HD). Little is known about subjective distress associated with acquiring in HD. The present study examined acquiring- related distress and reactions to cognitive restructuring (CR) in 92 individuals with HD and 66 community control (CC) participants. All participants identified an item of interest at a high-risk acquiring location and then decided whether or not to acquire the item. HD participants completed the acquiring task while receiving a CR-based intervention or a thought-listing (TL) control condition. Results showed that HD participants reported more severe distress and greater urges to acquire the item of interest than did CC participants. Nevertheless, subjective distress decreased in both groups following the acquiring task. There were no differences in acquiring- related distress between the CR and TL conditions. The findings indicate that subjective distress may decrease after relatively short periods of time in individuals with HD, but that a single session of CR may not alleviate acquiring-related distress in HD participants.R01 MH068007 - NIMH NIH HHS; R01 MH068008 - NIMH NIH HHSAccepted manuscrip

A Comparison of Cognitive Restructuring And Thought Listing For Excessive Acquiring In Hoarding Disorder

Excessive acquiring is a common symptom of hoarding disorder (HD). Little is known about subjective distress associated with acquiring in HD. The present study examined acquiring-related distress and reactions to cognitive restructuring (CR) in 92 individuals with HD and 66 community control (CC) participants. All participants identified an item of interest at a high-risk acquiring location and then decided whether or not to acquire the item. HD participants completed the acquiring task while receiving a CR-based intervention or a thought-listing (TL) control condition. Results showed that HD participants reported more severe distress and greater urges to acquire the item of interest than did CC participants. Nevertheless, subjective distress decreased in both groups following the acquiring task. There were no differences in acquiring-related distress between the CR and TL conditions. The findings indicate that subjective distress may decrease after relatively short periods of time in individuals with HD, but that a single session of CR may not alleviate acquiring-related distress in HD participants

Severity scoring of manganese health effects for categorical regression

Characterizing the U-shaped exposure response relationship for manganese (Mn) is necessary for estimating the risk of adverse health from Mn toxicity due to excess or deficiency. Categorical regression has emerged as a powerful tool for exposure-response analysis because of its ability to synthesize relevant information across multiple studies and species into a single integrated analysis of all relevant data. This paper documents the development of a database on Mn toxicity designed to support the application of categorical regression techniques. Specifically, we describe (i) the conduct of a systematic search of the literature on Mn toxicity to gather data appropriate for dose-response assessment; (ii) the establishment of inclusion/exclusion criteria for data to be included in the categorical regression modeling database; (iii) the development of a categorical severity scoring matrix for Mn health effects to permit the inclusion of diverse health outcomes in a single categorical regression analysis using the severity score as the outcome variable; and (iv) the convening of an international expert panel to both review the severity scoring matrix and assign severity scores to health outcomes observed in studies (including case reports, epidemiological investigations, and in vivo experimental studies) selected for inclusion in the categorical regression database. Exposure information including route, concentration, duration, health endpoint(s), and characteristics of the exposed population was abstracted from included studies and stored in a computerized manganese database (MnDB), providing a comprehensive repository of exposure-response information with the ability to support categorical regression modeling of oral exposure data

The effect of tobacco control policies on smoking prevalence and smoking-attributable deaths. Findings from the Netherlands SimSmoke Tobacco Control Policy Simulation Model

Aim To develop a simulation model projecting the effect of tobacco control policies in the Netherlands on smoking prevalence and smoking-attributable deaths. Design, setting and participants Netherlands SimSmoke-an adapted version of the SimSmoke simulation model of tobacco control policy-uses population, smoking rates and tobacco control policy data for the Netherlands to predict the effect of seven types of policies: taxes, smoke-free legislation, mass media, advertising bans, health warnings, cessation treatment and youth access policies. Measurements Outcome measures were smoking prevalence and smoking-attributable deaths. Findings With a comprehensive set of policies, as recommended by MPOWER, smoking prevalence can be decreased by asmuch as 21% in the first year, increasing to a 35% reduction in the next 20 years and almost 40% by 30 years. By 2040, 7706 deaths can be averted in that year alone with the stronger set of policies. Without effective tobacco control policies, almost a million lives will be lost to tobacco-related diseases between 2011 and 2040. Of those, 145 000 can be saved with a comprehensive tobacco control package. Conclusions Smoking prevalence and smoking-attributable deaths in the Netherlands can be reduced substantially through tax increases, smoke-free legislation, high-intensity media campaigns, stronger advertising bans and health warnings, comprehensive cessation treatment and youth access laws. The implementation of these FCTC/ MPOWER recommended policies could be expected to show similar or even larger relative reductions in smoking prevalence in other countries which currently have weak policies