HSPH

The excitement over findings from Genome-Wide Association Studies (GWASs) has been tempered by the difficulty in finding the location of the true causal disease susceptibility loci (DSLs), rather than markers that are correlated with the causal variants. In addition, many recent GWASs have studied multiple phenotypes--often highly correlated--making it difficult to understand which associations are causal and which are seemingly causal, induced by phenotypic correlations. In order to identify DSLs, which are required to understand the genetic etiology of the observed associations, statistical methodology has been proposed that distinguishes between a direct effect of a genetic locus on the primary phenotype and an indirect effect induced by the association with the intermediate phenotype that is also correlated with the primary phenotype...

The effort to vaccinate the US population against the 2009 H1N1 influenza virus hinged, in part, on public confidence in vaccine safety. Early in the vaccine program, >20% of parents reported that they would not vaccinate their children. Concerns about the safety of the vaccines were reported by many parents as a factor that contributed to their intention to forgo vaccination (see www.hsph.harvard.edu/news/press-releases/2009-releases/survey-40-adults-absolutely-certain-h1n1-vaccine.html and www.med.umich...

The pathology of many neurodegenerative diseases is characterized by the accumulation of misfolded and aggregated proteins in various cell types and regional substructures throughout the central and peripheral nervous systems. The accumulation of these aggregated proteins signals dysfunction of cellular protein homeostatic mechanisms such as the ubiquitin/proteasome system, autophagy, and the chaperone network. Although there are several published studies in which transcriptional profiling has been used to examine gene expression in various tissues, including tissues of neurodegenerative disease models, there has not been a report that focuses exclusively on expression of the chaperone network...

The highly conserved heat-shock proteins (HSPs) from mammals and microbial reagents are among the immunogenic proteins. Their expression is induced in response to a wide variety of physiological and environmental insults. Their functions as molecular chaperones allow cells to adapt to gradual changes in their environment and to survive in otherwise lethal conditions. Although the role of HSPs in atherosclerosis remains controversial, HSPs were thought to act as autoantigens, and trigger both cell- and antibody-mediated immune responses...

This study examined the outcome of a cohort of 72 patients from a high secure psychiatric hospital (HSPH) who were admitted to and discharged from the Edenfield Centre over a 16-year period. The sample was predominately male and mentally ill and the majority was subject to restriction orders. Compared with two similar studies focusing specifically on the outcomes of HSPH patients in medium security, our sample had fewer women and the group had more extensive criminal and psychiatric histories. None of our cohort was discharged to the community via district services or transferred to other hospitals...

Existing study design formulas for longitudinal studies have assumed that the exposure is time-invariant. We derived sample size formulas for studies comparing rates of change by exposure when the exposure varies with time within a subject, focusing on observational studies where this variation is not controlled by the investigator. Two scenarios are considered, one assuming that the effect of exposure on the response is acute and the other assuming that it is cumulative. We show that accurate calculations can often be obtained by providing the intraclass correlation of exposure and the exposure prevalence at each time point...

MOTIVATION: Pathway and gene set-based approaches for the analysis of gene expression profiling experiments have become increasingly popular for addressing problems associated with individual gene analysis. Since most genes are not differently expressed, existing gene set tests, which consider all the genes within a gene set, are subject to considerable noise and power loss, a concern exacerbated in studies in which the degree of differential expression is moderate for truly differentially expressed genes...

In this manuscript, we describe the generation of a gene library for the expression of HSP110/HSPH, HSP70/HSPA and HSP40/DNAJ members. First, the heat shock protein (HSP) genes were collected from the gene databases and the gene families were analyzed for expression patterns, heat inducibility, subcellular localization, and protein homology using several bioinformatics approaches. These results can be used as a working draft model until data are confirmed by experimental approaches. In addition, we describe the generation of a HSPA/DNAJ overexpression library and tested the effect of different fusion tags on HSPA and DNAJ members using different techniques for measuring chaperone activity...

The expanding number of members in the various human heat shock protein (HSP) families and the inconsistencies in their nomenclature have often led to confusion. Here, we propose new guidelines for the nomenclature of the human HSP families, HSPH (HSP110), HSPC (HSP90), HSPA (HSP70), DNAJ (HSP40), and HSPB (small HSP) as well as for the human chaperonin families HSPD/E (HSP60/HSP10) and CCT (TRiC). The nomenclature is based largely on the more consistent nomenclature assigned by the HUGO Gene Nomenclature Committee and used in the National Center of Biotechnology Information Entrez Gene database for the heat shock genes...

Heat shock proteins (HSPs) were originally identified as stress-responsive proteins required to deal with proteotoxic stresses. Besides being stress-protective and possible targets for delaying progression of protein folding diseases, mutations in chaperones also have been shown to cause disease (chaperonopathies). The mechanism of action of the "classical", stress-inducible HSPs in serving as molecular chaperones preventing the irreversible aggregation of stress-unfolded or disease-related misfolded proteins is beginning to emerge...

Though there is an increasing support for an important contribution of copy number variation (CNV) to the genetic architecture of complex disease, few methods have been developed for the analysis of such variation in the context of genetic association studies. In this paper, we propose a generalization of family-based association tests (FBATs) to allow for the analysis of CNVs at a genome-wide level. We translate the popular FBAT approach so that, instead of genotypes, raw intensity values that reflect copy number are used directly in the test statistic, thereby bypassing the need for a CNV genotyping algorithm...

BACKGROUND: 1) To elicit the opinions of the Public Health alumni of the MPH program; 2) To assess the applicability of the knowledge and skills acquired; 3) To identify the frequency of the public health competencies that the alumni performed. METHODS: We requested 187 graduates to complete a self-administered questionnaire and conducted in-depth interviews with 8 alumni as well as a focus group discussion with 14 alumni. RESULTS: In total 79...

The phosphide-bridged dimolybdenum complexes (H-DBU)[Mo2Cp2(mu-PR2)(CO)4] (R= Cy, Ph; DBU = 1,8-diazabicyclo[5.4.0.]undec-7-ene) react with p-benzoquinone to give the hemiquinone complexes [Mo(2)Cp2(OC6H4OH)(mu-PR2)(CO)4]. The latter experience facile homolytic cleavage of the corresponding Mo-O bonds and react readily at room temperature with HSPh or S2Ph2 to give the thiolate complexes [Mo2Cp2(mu-PCy2)(mu-SPh)(CO)4] or [Mo2Cp2(mu-PR2)(mu-SPh)(CO)2]. In contrast, PRH-bridged substrates experience overall insertion of quinone into the P-H bond to give the anionic compounds (H-DBU)[Mo(2)Cp2{mu-PR(OC6H4OH)}(CO)4], which upon acidification yield the corresponding neutral hydrides...

OBJECTIVE: The Panel on Cost-Effectiveness in Health and Medicine recommended the compilation of a catalog of health state utility weights for use in cost-utility analyses (CUAs), and has given methodological recommendations. This study presents an update, through 2001, to our current registry of utility weights (available at https://www.tufts-nemc.org/cearegistry; previously at https://www.hsph.harvard.edu/cearegistry), and documents recent changes in methods used for utility weight elicitation...

The reaction of [(TMS)2N]3La(mu-Cl)Li(THF)3 (1) and HSPh produced a bimetallic complex [{(TMS)2N}2La(THF)]2(mu-SPh)(mu-Cl)] (2). Compound [{(TMS)2N}2La5O(SPh)10LiCl2(THF)6] (3) was prepared by control of the hydrolysis of 2 and LiCl or 1 and HSPh with the proper amount of water. 1 was treated first with 1/6 equiv of H2O and then with equimolar HSPh; a polymeric complex [{(TMS)2N}2(mu-SPh)La(mu-SPh)Li(THF)2](infinity) (4) was isolated. 3 contains a central [(mu-SPh)4(mu3-SPh)2{La(THF)}4(mu3-O)]4+ tetrahedral fragment in which two La atoms are linked by a pair of mu-SPh- and mu3-Cl- ligands to a [{(TMS)2N}2La]+ fragment, while the other two are bridged by two mu-SPh- ligands to a [Li(THF)2]+ fragment, forming a bee-shaped structure...

Historically, a substantial proportion of women have been unduly detained in conditions of high security in England due to the lack of suitable alternative facilities. There have been no studies that have comprehensively examined the individual needs of these women in relation to their placement needs. A cross sectional survey was undertaken of the individual and placement needs of all females detained in the three high security psychiatric hospitals (HSPHs) in England on 18th October 1999. Whilst there are clearly differences in accommodation needs among the women, those requiring lower secure services are significantly less likely to have needs in relation to violence (OR 0...

BACKGROUND: In US colleges, alcohol and tobacco pose substantial health risks but little is known about their co-occurrence, limiting development and use of appropriately targeted prevention efforts. METHODS: Data from the 2001 HSPH College Alcohol Study (student n = 10,924; college n = 120) were analyzed using multivariate logistic regression. Co-occurring smoking/drinking risks were examined in aggregate, by gender, and by age of onset of regular drinking and smoking across 10 measures of drinking style, three categories of transitional drinking behavior, and by treatment behavior...

The kinetics of the oxidative addition of PhSeSePh and PhTeTePh to the stable 17-electron complex *Cr(CO)3C5Me5 have been studied utilizing stopped-flow techniques. The rates of reaction are first-order in each reactant, and the enthalpy of activation decreases in going from Se (deltaH(double dagger) = 7.0 +/- 0.5 kcal/mol, deltaS(double dagger) = -22 +/- 3 eu) to Te (deltaH(double dagger) = 4.0 +/- 0.5 kcal/mol, deltaS(double dagger) = -26 +/- 3 eu). The kinetics of the oxidative addition of PhSeH and *Cr(CO)3C5Me5 show a change in mechanism in going from low (overall third-order) to high (overall second-order) temperatures...

BACKGROUND: Single nucleotide polymorphisms (SNPs) provide an important tool in pinpointing susceptibility genes for complex diseases and in unveiling human molecular evolution. Selection and retrieval of an optimal SNP set from publicly available databases have emerged as the foremost bottlenecks in designing large-scale linkage disequilibrium studies, particularly in case-control settings. RESULTS: We describe the architectural structure and implementations of a novel software program, SNPHunter, which allows for both ad hoc-mode and batch-mode SNP search, automatic SNP filtering, and retrieval of SNP data, including physical position, function class, flanking sequences at user-defined lengths, and heterozygosity from NCBI dbSNP...

The complex [{(TMS)2N}4(mu4-Cl)Sm4(mu-SPh)4(mu3-Cl)Li(THF)] has been formed by protonolysis of [(Me3Si)2N]3Sm(mu-Cl)Li(THF)3 with 1 equiv of HSPh, which contains a square array of Sm(III) ions connected by a central mu4-Cl ligand. The edges of the square Sm4 array are bridged by four mu3-Cl and four mu-SPh ligands. The four Sm atoms and Li atom are connected by four mu3-Cl ligands.