716 research outputs found
What Is a Schizophrenic Mouse?
In this issue of Neuron, Clapcote et al. examine mice containing missense mutations of the DISC1 gene, a locus associated with major mental illness in at least one large Scottish family. Genetic manipulation of mouse homologs of genes implicated in the etiology of psychiatric disorders is a promising avenue of research, but also one that is fraught with interpretative difficulties
Genetic variants and early cigarette smoking and nicotine dependence phenotypes in adolescents
Background: While the heritability of cigarette smoking and nicotine dependence
(ND) is well-documented, the contribution of specific genetic variants to specific
phenotypes has not been closely examined. The objectives of this study were to
test the associations between 321 tagging single-nucleotide polymorphisms
(SNPs) that capture common genetic variation in 24 genes, and early smoking and
ND phenotypes in novice adolescent smokers, and to assess if genetic predictors
differ across these phenotypes.
Methods: In a prospective study of 1294 adolescents aged 12–13 years recruited
from ten Montreal-area secondary schools, 544 participants who had smoked at
least once during the 7–8 year follow-up provided DNA. 321 single-nucleotide
polymorphisms (SNPs) in 24 candidate genes were tested for an association with
number of cigarettes smoked in the past 3 months, and with five ND phenotypes (a
modified version of the Fagerstrom Tolerance Questionnaire, the ICD-10 and three
clusters of ND symptoms representing withdrawal symptoms, use of nicotine for
self-medication, and a general ND/craving symptom indicator).
Results: The pattern of SNP-gene associations differed across phenotypes.
Sixteen SNPs in seven genes (ANKK1, CHRNA7, DDC, DRD2, COMT, OPRM1,
SLC6A3 (also known as DAT1)) were associated with at least one phenotype with a
p-value ,0.01 using linear mixed models. After permutation and FDR adjustment, none of the associations remained statistically significant, although the p-values for
the association between rs557748 in OPRM1 and the ND/craving and selfmedication phenotypes were both 0.076.
Conclusions: Because the genetic predictors differ, specific cigarette smoking and
ND phenotypes should be distinguished in genetic studies in adolescents. Fifteen
of the 16 top-ranked SNPs identified in this study were from loci involved in
dopaminergic pathways (ANKK1/DRD2, DDC, COMT, OPRM1, and SLC6A3).
Impact: Dopaminergic pathways may be salient during early smoking and the
development of ND
Scaling Up Towards International Targets for AIDS, Tuberculosis, and Malaria: Contribution of Global Fund-Supported Programs in 2011–2015
OBJECTIVE: The paper projects the contribution to 2011-2015 international targets of three major pandemics by programs in 140 countries funded by the Global Fund to Fight AIDS, Tuberculosis and Malaria, the largest external financier of tuberculosis and malaria programs and a major external funder of HIV programs in low and middle income countries. DESIGN: Estimates, using past trends, for the period 2011-2015 of the number of persons receiving antiretroviral (ARV) treatment, tuberculosis case detection using the internationally approved DOTS strategy, and insecticide-treated nets (ITNs) to be delivered by programs in low and middle income countries supported by the Global Fund compared to international targets established by UNAIDS, Stop TB Partnership, Roll Back Malaria Partnership and the World Health Organisation. RESULTS: Global Fund-supported programs are projected to provide ARV treatment to 5.5-5.8 million people, providing 30%-31% of the 2015 international target. Investments in tuberculosis and malaria control will enable reaching in 2015 60%-63% of the international target for tuberculosis case detection and 30%-35% of the ITN distribution target in sub-Saharan Africa. CONCLUSION: Global Fund investments will substantially contribute to the achievement by 2015 of international targets for HIV, TB and malaria. However, additional large scale international and domestic financing is needed if these targets are to be reached by 2015
Reduction Algorithms for the Multiband Imaging Photometer for Spitzer
We describe the data reduction algorithms for the Multiband Imaging
Photometer for Spitzer (MIPS) instrument. These algorithms were based on
extensive preflight testing and modeling of the Si:As (24 micron) and Ge:Ga (70
and 160 micron) arrays in MIPS and have been refined based on initial flight
data. The behaviors we describe are typical of state-of-the-art infrared focal
planes operated in the low backgrounds of space. The Ge arrays are bulk
photoconductors and therefore show a variety of artifacts that must be removed
to calibrate the data. The Si array, while better behaved than the Ge arrays,
does show a handful of artifacts that also must be removed to calibrate the
data. The data reduction to remove these effects is divided into three parts.
The first part converts the non-destructively read data ramps into slopes while
removing artifacts with time constants of the order of the exposure time. The
second part calibrates the slope measurements while removing artifacts with
time constants longer than the exposure time. The third part uses the
redundancy inherit in the MIPS observing modes to improve the artifact removal
iteratively. For each of these steps, we illustrate the relevant laboratory
experiments or theoretical arguments along with the mathematical approaches
taken to calibrate the data. Finally, we describe how these preflight
algorithms have performed on actual flight data.Comment: 21 pages, 16 figures, PASP accepted (May 2005 issue), version of
paper with full resolution images is available at
http://dirty.as.arizona.edu/~kgordon/papers/PS_files/mips_dra.pd
Genome Sequence of a Lancefield Group C Streptococcus zooepidemicus Strain Causing Epidemic Nephritis: New Information about an Old Disease
Outbreaks of disease attributable to human error or natural causes can provide unique opportunities to gain new information about host-pathogen interactions and new leads for pathogenesis research. Poststreptococcal glomerulonephritis (PSGN), a sequela of infection with pathogenic streptococci, is a common cause of preventable kidney disease worldwide. Although PSGN usually occurs after infection with group A streptococci, organisms of Lancefield group C and G also can be responsible. Despite decades of study, the molecular pathogenesis of PSGN is poorly understood. As a first step toward gaining new information about PSGN pathogenesis, we sequenced the genome of Streptococcus equi subsp. zooepidemicus strain MGCS10565, a group C organism that caused a very large and unusually severe epidemic of nephritis in Brazil. The genome is a circular chromosome of 2,024,171 bp. The genome shares extensive gene content, including many virulence factors, with genetically related group A streptococci, but unexpectedly lacks prophages. The genome contains many apparently foreign genes interspersed around the chromosome, consistent with the presence of a full array of genes required for natural competence. An inordinately large family of genes encodes secreted extracellular collagen-like proteins with multiple integrin-binding motifs. The absence of a gene related to speB rules out the long-held belief that streptococcal pyrogenic exotoxin B or antibodies reacting with it singularly cause PSGN. Many proteins previously implicated in GAS PSGN, such as streptokinase, are either highly divergent in strain MGCS10565 or are not more closely related between these species than to orthologs present in other streptococci that do not commonly cause PSGN. Our analysis provides a comparative genomics framework for renewed appraisal of molecular events underlying APSGN pathogenesis
Supplement: "Localization and broadband follow-up of the gravitational-wave transient GW150914" (2016, ApJL, 826, L13)
This Supplement provides supporting material for Abbott et al. (2016a). We briefly summarize past electromagnetic (EM) follow-up efforts as well as the organization and policy of the current EM follow-up program. We compare the four probability sky maps produced for the gravitational-wave transient GW150914, and provide additional details of the EM follow-up observations that were performed in the different bands
Physiological Correlates of Volunteering
We review research on physiological correlates of volunteering, a neglected but promising research field. Some of these correlates seem to be causal factors influencing volunteering. Volunteers tend to have better physical health, both self-reported and expert-assessed, better mental health, and perform better on cognitive tasks. Research thus far has rarely examined neurological, neurochemical, hormonal, and genetic correlates of volunteering to any significant extent, especially controlling for other factors as potential confounds. Evolutionary theory and behavioral genetic research suggest the importance of such physiological factors in humans. Basically, many aspects of social relationships and social activities have effects on health (e.g., Newman and Roberts 2013; Uchino 2004), as the widely used biopsychosocial (BPS) model suggests (Institute of Medicine 2001). Studies of formal volunteering (FV), charitable giving, and altruistic behavior suggest that physiological characteristics are related to volunteering, including specific genes (such as oxytocin receptor [OXTR] genes, Arginine vasopressin receptor [AVPR] genes, dopamine D4 receptor [DRD4] genes, and 5-HTTLPR). We recommend that future research on physiological factors be extended to non-Western populations, focusing specifically on volunteering, and differentiating between different forms and types of volunteering and civic participation
Large-scale analyses of common and rare variants identify 12 new loci associated with atrial fibrillation
Atrial fibrillation affects more than 33 million people worldwide and increases the risk of stroke, heart failure, and death. Fourteen genetic loci have been associated with atrial fibrillation in European and Asian ancestry groups. To further define the genetic basis of atrial fibrillation, we performed large-scale, trans-ancestry meta-analyses of common and rare variant association studies. The genome-wide association studies (GWAS) included 17,931 individuals with atrial fibrillation and 115,142 referents; the exome-wide association studies (ExWAS) and rare variant association studies (RVAS) involved 22,346 cases and 132,086 referents. We identified 12 new genetic loci that exceeded genome-wide significance, implicating genes involved in cardiac electrical and structural remodeling. Our results nearly double the number of known genetic loci for atrial fibrillation, provide insights into the molecular basis of atrial fibrillation, and may facilitate the identification of new potential targets for drug discovery
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