1,454 research outputs found
Candidate gene resequencing to identify rare, pedigree-specific variants influencing healthy aging phenotypes in the long life family study
Background: The Long Life Family Study (LLFS) is an international study to identify the genetic components of various healthy aging phenotypes. We hypothesized that pedigree-specific rare variants at longevity-associated genes could have a similar functional impact on healthy phenotypes. Methods: We performed custom hybridization capture sequencing to identify the functional variants in 464 candidate genes for longevity or the major diseases of aging in 615 pedigrees (4,953 individuals) from the LLFS, using a multiplexed, custom hybridization capture. Variants were analyzed individually or as a group across an entire gene for association to aging phenotypes using family based tests. Results: We found significant associations to three genes and nine single variants. Most notably, we found a novel variant significantly associated with exceptional survival in the 3' UTR OBFC1 in 13 individuals from six pedigrees. OBFC1 (chromosome 10) is involved in telomere maintenance, and falls within a linkage peak recently reported from an analysis of telomere length in LLFS families. Two different algorithms for single gene associations identified three genes with an enrichment of variation that was significantly associated with three phenotypes (GSK3B with the Healthy Aging Index, NOTCH1 with diastolic blood pressure and TP53 with serum HDL). Conclusions: Sequencing analysis of family-based associations for age-related phenotypes can identify rare or novel variants
Co-evolution of density and topology in a simple model of city formation
We study the influence that population density and the road network have on
each others' growth and evolution. We use a simple model of formation and
evolution of city roads which reproduces the most important empirical features
of street networks in cities. Within this framework, we explicitely introduce
the topology of the road network and analyze how it evolves and interact with
the evolution of population density. We show that accessibility issues -pushing
individuals to get closer to high centrality nodes- lead to high density
regions and the appearance of densely populated centers. In particular, this
model reproduces the empirical fact that the density profile decreases
exponentially from a core district. In this simplified model, the size of the
core district depends on the relative importance of transportation and rent
costs.Comment: 13 pages, 13 figure
Fortnightly changes in water transport direction across the mouth of a narrow estuary
This research investigates the dynamics of the axial
tidal flow and residual circulation at the lower Guadiana
Estuary, south Portugal, a narrow mesotidal estuary with low
freshwater inputs. Current data were collected near the deepest
part of the channel for 21 months and across the channel
during two (spring and neap) tidal cycles. Results indicate
that at the deep channel, depth-averaged currents are stronger
and longer during the ebb at spring and during the flood at
neap, resulting in opposite water transport directions at a
fortnightly time scale. The net water transport across the entire
channel is up-estuary at spring and down-estuary at neap, i.e.,
opposite to the one at the deep channel. At spring tide, when
the estuary is considered to be well mixed, the observed
pattern of circulation (outflow in the deep channel, inflow
over the shoals) results from the combination of the Stokes
transport and compensating return flow, which varies laterally
with the bathymetry. At neap tide (in particular for those of
lowest amplitude each month), inflows at the deep channel are
consistently associated with the development of gravitational
circulation. Comparisons with previous studies suggest that
the baroclinic pressure gradient (rather than internal tidal
asymmetries) is the main driver of the residual water transport.
Our observations also indicate that the flushing out of the
water accumulated up-estuary (at spring) may also produce
strong unidirectional barotropic outflow across the entire
channel around neap tide.info:eu-repo/semantics/publishedVersio
Radio Remnants of Compact Binary Mergers - the Electromagnetic Signal that will follow the Gravitational Waves
The question "what is the observable electromagnetic (EM) signature of a
compact binary merger?" is an intriguing one with crucial consequences to the
quest for gravitational waves (GW). Compact binary mergers are prime sources of
GW, targeted by current and next generation detectors. Numerical simulations
have demonstrated that these mergers eject energetic sub-relativistic (or even
relativistic) outflows. This is certainly the case if the mergers produce short
GRBs, but even if not, significant outflows are expected. The interaction of
such outflows with the surround matter inevitably leads to a long lasting radio
signal. We calculate the expected signal from these outflows (our calculations
are also applicable to short GRB orphan afterglows) and we discuss their
detectability. We show that the optimal search for such signal should,
conveniently, take place around 1.4 GHz. Realistic estimates of the outflow
parameters yield signals of a few hundred Jy, lasting a few weeks, from
sources at the detection horizon of advanced GW detectors. Followup radio
observations, triggered by GW detection, could reveal the radio remnant even
under unfavorable conditions. Upcoming all sky surveys can detect a few dozen,
and possibly even thousands, merger remnants at any give time, thereby
providing robust merger rate estimates even before the advanced GW detectors
become operational. In fact, the radio transient RT 19870422 fits well the
overall properties predicted by our model and we suggest that its most probable
origin is a compact binary merger radio remnant
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Using time perception to explore implicit sensitivity to emotional stimuli in autism spectrum disorder
Establishing whether implicit responses to emotional cues are intact in autism spectrum disorder (ASD) is fundamental to ascertaining why their emotional understanding is compromised. We used a temporal bisection task to assess for responsiveness to face and wildlife images that varied in emotional salience. There were no significant differences between an adult ASD and comparison group, with both showing implicit overestimation of emotional stimuli. Further, there was no correlation between overestimation of emotional stimuli and autistic traits in undergraduate students. These data do not suggest a fundamental insensitivity to the arousing content of emotional images in ASD, or in individuals with a high degree of autistic traits. The findings have implications for understanding how emotional stimuli are processed in ASD
Hundreds of variants clustered in genomic loci and biological pathways affect human height
Most common human traits and diseases have a polygenic pattern of inheritance: DNA sequence variants at many genetic loci influence the phenotype. Genome-wide association (GWA) studies have identified more than 600 variants associated with human traits, but these typically explain small fractions of phenotypic variation, raising questions about the use of further studies. Here, using 183,727 individuals, we show that hundreds of genetic variants, in at least 180 loci, influence adult height, a highly heritable and classic polygenic trait. The large number of loci reveals patterns with important implications for genetic studies of common human diseases and traits. First, the 180 loci are not random, but instead are enriched for genes that are connected in biological pathways (P = 0.016) and that underlie skeletal growth defects (P < 0.001). Second, the likely causal gene is often located near the most strongly associated variant: in 13 of 21 loci containing a known skeletal growth gene, that gene was closest to the associated variant. Third, at least 19 loci have multiple independently associated variants, suggesting that allelic heterogeneity is a frequent feature of polygenic traits, that comprehensive explorations of already-discovered loci should discover additional variants and that an appreciable fraction of associated loci may have been identified. Fourth, associated variants are enriched for likely functional effects on genes, being over-represented among variants that alter amino-acid structure of proteins and expression levels of nearby genes. Our data explain approximately 10% of the phenotypic variation in height, and we estimate that unidentified common variants of similar effect sizes would increase this figure to approximately 16% of phenotypic variation (approximately 20% of heritable variation). Although additional approaches are needed to dissect the genetic architecture of polygenic human traits fully, our findings indicate that GWA studies can identify large numbers of loci that implicate biologically relevant genes and pathways.
Pharmacotherapy of Schizophrenic Patients: Preponderance of Off-Label Drug Use
Multiple drug class combinations are often prescribed for the treatment of schizophrenia, although antipsychotic monotherapy reflects FDA labeling and scientific justification for combinations is highly variable. This study was performed to gain current data regarding drug treatment of schizophrenia as practiced in the community and to assess the frequencies of off-label drug class combinations. 200 DSM IV-diagnosed schizophrenic patients recruited from community treatment sources participated in this cross-sectional study of community based schizophrenic patients. Drug class categories include First and Second Generation Antipsychotic drugs (FGA and SGA, respectively), mood stabilizers, antidepressants and anti-anxiety drugs. 25.5% of patients received antipsychotic monotherapy; 70% of patients received an antipsychotic and another drug class. A total of 42.5% of patients received more than one antipsychotic drug. The most common drug class combination was antipsychotic and a mood stabilizer. Stepwise linear discriminant function analysis identified the diagnosis of schizoaffective schizophrenia, history of having physically hurt someone and high scores on the General Portion of the PANSS rating scale predicted the combined use of an antipsychotic drug and a mood stabilizer. “Real world” pharmacotherapy of schizophrenia has developed its own established practice that is predominantly off-label and may have outstripped current data support. The economic implications for public sector payers are substantial as well as for the revenue of the pharmaceutical industry, whose promotion of off-label drug use is an increasingly problematic. These data are consistent with the recognition of the therapeutic limitations of both first and second generation antipsychotic drugs
Which patient will feel down, which will be happy? The need to study the genetic disposition of emotional states
Purpose In quality-of-life (QL) research, the genetic susceptibility of negative and positive emotions is frequently ignored, taken for granted, or treated as noise. The objectives are to describe: (1) the major findings of studies addressing the heritable and environmental causes of variation in negative and positive emotional states and (2) the major biological pathways of and genetic variants involved in these emotional states
Search for new phenomena in final states with an energetic jet and large missing transverse momentum in pp collisions at √ s = 8 TeV with the ATLAS detector
Results of a search for new phenomena in final states with an energetic jet and large missing transverse momentum are reported. The search uses 20.3 fb−1 of √ s = 8 TeV data collected in 2012 with the ATLAS detector at the LHC. Events are required to have at least one jet with pT > 120 GeV and no leptons. Nine signal regions are considered with increasing missing transverse momentum requirements between Emiss T > 150 GeV and Emiss T > 700 GeV. Good agreement is observed between the number of events in data and Standard Model expectations. The results are translated into exclusion limits on models with either large extra spatial dimensions, pair production of weakly interacting dark matter candidates, or production of very light gravitinos in a gauge-mediated supersymmetric model. In addition, limits on the production of an invisibly decaying Higgs-like boson leading to similar topologies in the final state are presente
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