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Strongest Candidates (strongest + candidate)
Selected AbstractsFurther genetic evidence implicates the vasopressin system in childhood-onset mood disordersEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 8 2009Emma L. Dempster Abstract Studies in both animals and humans advocate a role for the vasopressin (AVP) system in the aetiology of depressive symptoms. Attention has particularly focused on the role of AVP in the overactivation of the hypothalamic-pituitary-adrenal (HPA)-axis in mood disorders. Elevated AVP plasma levels have been found in mood disorder patients, which are often positively correlated with the severity of symptoms. We recently reported an association between childhood-onset mood disorders (COMD) and polymorphisms in the receptor responsible for the AVP-mediated activation of the HPA-axis (AVPR1B). As genetic variation in the vasopressinergic system could provide a mechanism to explain the endocrine alterations observed in mood disorders, we investigated other genes in this system. The gene encoding AVP is the strongest candidate, particularly as genetic variation in this gene in rodents is associated with anxiety-related behaviours. Six single-nucleotide polymorphisms (SNPs) were genotyped across the AVP gene in a sample comprised of 586 Hungarian nuclear families ascertained through affected probands with a diagnosis of COMD. In addition, AVP coding and putative regulatory regions were screened for mutations using denaturing high-performance liquid chromatography. One SNP, 3, to the AVP, gene reached significance (P = 0.03), as did the overtransmission of a five-marker haplotype with a frequency of 22% (P = 0.0001). The subsequent mutation screen failed to identify any putative functional polymorphisms. The outcome of this study, combined with our previous association between COMD and AVPR1B, implicates genetic variation in vasopressinergic genes in mediating vulnerability to COMD. [source] The ultraluminous X-ray source in M82: an intermediate-mass black hole with a giant companionMONTHLY NOTICES OF THE ROYAL ASTRONOMICAL SOCIETY: LETTERS (ELECTRONIC), Issue 1 2006A. Patruno ABSTRACT The starburst galaxy M82, at a distance of 12 million light years, is the host of an unusually bright 2.4,16 × 1040 erg s,1 X-ray point source, which is best explained by an accreting black hole 102 to 104 times more massive than the Sun. Though the strongest candidate for a so-called intermediate-mass black hole, the only support stems from the observed luminosity and the 0.05,0.1 Hz quasi-periodicity in its signal. Interestingly, the 7,12 Myr old star cluster MGG-11 which has been associated with the X-ray source is sufficiently dense that an intermediate mass black hole could have been produced in the cluster core via collision runaway. The recently discovered 62.0 ± 2.5 d periodicity in the X-ray source X-1 further supports the hypothesis that this source is powered by a black hole several hundred times more massive than the Sun. We perform detailed binary evolution simulations with an accreting compact object of 10,5000 M, and find that the X-ray luminosity, the age of the cluster, the observed quasi-periodic oscillations and the now observed orbital period are explained best by a black hole of 200,5000 M, that accretes material from a 22,25 M, giant companion in a state of Roche-lobe contact. Interestingly, such a companion star is consistent with the expectation based on the tidal capture in a young and dense star cluster such as MGG-11, making the picture self-consistent. [source] Genome-Wide Association Study of Alcohol Dependence Implicates a Region on Chromosome 11ALCOHOLISM, Issue 5 2010Howard J. Edenberg Background:, Alcohol dependence is a complex disease, and although linkage and candidate gene studies have identified several genes associated with the risk for alcoholism, these explain only a portion of the risk. Methods:, We carried out a genome-wide association study (GWAS) on a case,control sample drawn from the families in the Collaborative Study on the Genetics of Alcoholism. The cases all met diagnostic criteria for alcohol dependence according to the Diagnostic and Statistical Manual of Mental Disorders,Fourth Edition; controls all consumed alcohol but were not dependent on alcohol or illicit drugs. To prioritize among the strongest candidates, we genotyped most of the top 199 single nucleotide polymorphisms (SNPs) (p , 2.1 × 10,4) in a sample of alcohol-dependent families and performed pedigree-based association analysis. We also examined whether the genes harboring the top SNPs were expressed in human brain or were differentially expressed in the presence of ethanol in lymphoblastoid cells. Results:, Although no single SNP met genome-wide criteria for significance, there were several clusters of SNPs that provided mutual support. Combining evidence from the case,control study, the follow-up in families, and gene expression provided strongest support for the association of a cluster of genes on chromosome 11 (SLC22A18, PHLDA2, NAP1L4, SNORA54, CARS, and OSBPL5) with alcohol dependence. Several SNPs nominated as candidates in earlier GWAS studies replicated in ours, including CPE, DNASE2B, SLC10A2, ARL6IP5, ID4, GATA4, SYNE1, and ADCY3. Conclusions:, We have identified several promising associations that warrant further examination in independent samples. [source] Insurance for Good Losers and the Survival of Chile's ConcertaciónLATIN AMERICAN POLITICS AND SOCIETY, Issue 2 2005John M. Carey ABSTRACT In the transition from military rule to democracy, the government of Augusto Pinochet bequeathed to Chile a unique electoral law by which all legislative seats are contested in two-member districts. A key implication of this rule is that in order to secure legislative majorities, coalitions have to put their strongest candidates in the most precarious electoral list positions. This generates a divergence of interests between coalitions and politicians. Chile's largest coalition, the Concertación, has resolved the dilemma by providing appointed posts to unsuccessful congressional candidates who accept personal political risk on the coalition's behalf. This study argues that this insurance system has provided the critical glue to hold the coalition together since Chile's transition to democracy in 1990. Recent changes in the electoral environment could threaten the Concertación's control over the appointed posts that have sustained this informal institution. This could jeopardize the Concertación's cohesion during the process of negotiating coalition candidate lists for the 2005 legislative elections. [source] Reciprocal regulation of the mouse protamine genes by the orphan nuclear receptor germ cell nuclear factor and CREM,MOLECULAR REPRODUCTION & DEVELOPMENT, Issue 4 2004Geoffrey C. Hummelke Abstract Germ cell nuclear factor (GCNF) is a member of the nuclear receptor superfamily, which is expressed in the adult predominantly in the male and female germ cells. In the male, GCNF is expressed in spermatogenic cells. GCNF binds as a homodimer to direct repeat response elements of the consensus half-site sequence, AGGTCA, with 0 bp spacing (DR0). Using this information, a search of genomic databases was performed to identify candidate GCNF responsive, spermatogenic-specific, genes that contain DR0 sequences. The mouse protamine genes are the strongest candidates identified to date, as they are post-meiotically expressed in round spermatids and contain DR0 elements in their proximal promoters. Previous work has shown that both recombinant and endogenous GCNF bind to DR0 elements in the mouse protamine 1 and 2 (Prm 1 and Prm 2) promoters with high affinity and specificity. The present work shows that in transient transfection assays in GC-1 and JEG-3 cells, co-transfection of a GCNF-VP16 expression plasmid with reporter plasmids containing either the wild type Prm 1 or Prm 2 promoter established that GCNF-VP16 is able to regulate transcription from both promoters in a DR0-dependent manner. Wild type GCNF, in contrast, acts as a repressor of basal transcription on both the Prm 1 and Prm 2 promoters in a DR0-dependent manner. Furthermore, CREM, activation of these promoters is also repressed by wild-type GCNF, indicating that GCNF also acts as a repressor of activated transcription. GCNF therefore defines a novel nuclear receptor-signaling pathway that may regulate a subset of genes involved in the terminal differentiation process of spermatogenesis, exemplified by the protamines. Mol. Reprod. Dev. 68: 394,407, 2004. © 2004 Wiley-Liss, Inc. [source] | ||||||||||