391 research outputs found

    Longitudinal stability of genetic and environmental influences on the association between diurnal preference and sleep quality in young adult twins and siblings

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    Overlapping genetic influences have been implicated in diurnal preference and subjective sleep quality. Our overall aim was to examine overlapping concurrent and longitudinal genetic and environmental effects on diurnal preference and sleep quality over ~5 years. Behavioural genetic analyses were performed on data from the longitudinal British G1219 study of young adult twins and non-twin siblings. 1556 twins and siblings provided data on diurnal preference (Morningness-Eveningness Questionnaire) and sleep quality (Pittsburgh Sleep Quality Index) at time 1 (mean age=20.30 years, SD=1.76; 62% female); and 862 participated at time 2 (mean age=25.30 years, SD=1.81; 66% female). Preference for eveningness was associated with poorer sleep quality at both time-points (r=.25[95% confidence intervals, (CI)=.20-.30], and r=.21[CI=.15-.28]). There was substantial overlap in the genetic influences on diurnal preference and sleep quality individually, across time (genetic correlations [rA’s]: .64[95% CI = .59-.67] and .48[95% CI = .42-.53]). There were moderate genetic correlations between diurnal preference and sleep quality concurrently and longitudinally (rAs=.29-.60). Non-shared environmental overlap was substantially smaller for all cross-phenotype associations (non-shared environmental correlations [rE’s]=-.02-.08). All concurrent and longitudinal associations within and between phenotypes were largely accounted for by genetic factors (explaining between 60%-100% of the associations). All shared environmental effects were non-significant. Non-shared environmental influences played a smaller role on the associations between phenotypes (explaining between -.06%-40% of the associations). These results suggest that to some extent similar genes contribute to the stability of diurnal preference and sleep quality throughout young adulthood, but also that different genes play a part over this relatively short time-frame. While there was evidence of genetic overlap between phenotypes concurrently and longitudinally, the possible emergence of new genetic factors (or decline of previously associated factors) suggests that molecular genetic studies focussing on young adults should consider more tightly specified age-groups, given that genetic effects may be time-specific

    Extraction of the D13(1520) photon-decay couplings from pion- and eta-photoproduction data

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    We compare results for the D13(1520) photon-decay amplitudes determined in analyses of eta- and pion-photoproduction data. The ratio of helicity amplitudes (A_3/2 / A_1/2), determined from eta-photoproduction data, is quite different from that determined in previous analyses of pion-photoproduction data. We consider how strongly the existing pion-photoproduction data constrain both this ratio and the individual photon-decay amplitudes.Comment: 7 pages, 2 figure

    Estimating the bispectrum of the Very Small Array data

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    We estimate the bispectrum of the Very Small Array data from the compact and extended configuration observations released in December 2002, and compare our results to those obtained from Gaussian simulations. There is a slight excess of large bispectrum values for two individual fields, but this does not appear when the fields are combined. Given our expected level of residual point sources, we do not expect these to be the source of the discrepancy. Using the compact configuration data, we put an upper limit of 5400 on the value of f_NL, the non-linear coupling parameter, at 95 per cent confidence. We test our bispectrum estimator using non-Gaussian simulations with a known bispectrum, and recover the input values.Comment: 17 pages, 16 figures, replaced with version accepted by MNRAS. Primordial bispectrum recalculated and figure 11 change

    The moon as a recorder of organic evolution in the early solar system: a lunar regolith analog study

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    The organic record of Earth older than ∼3.8 Ga has been effectively erased. Some insight is provided to us by meteorites as well as remote and direct observations of asteroids and comets left over from the formation of the Solar System. These primitive objects provide a record of early chemical evolution and a sample of material that has been delivered to Earth's surface throughout the past 4.5 billion years. Yet an effective chronicle of organic evolution on all Solar System objects, including that on planetary surfaces, is more difficult to find. Fortunately, early Earth would not have been the only recipient of organic matter–containing objects in the early Solar System. For example, a recently proposed model suggests the possibility that volatiles, including organic material, remain archived in buried paleoregolith deposits intercalated with lava flows on the Moon. Where asteroids and comets allow the study of processes before planet formation, the lunar record could extend that chronicle to early biological evolution on the planets. In this study, we use selected free and polymeric organic materials to assess the hypothesis that organic matter can survive the effects of heating in the lunar regolith by overlying lava flows. Results indicate that the presence of lunar regolith simulant appears to promote polymerization and, therefore, preservation of organic matter. Once polymerized, the mineral-hosted newly formed organic network is relatively protected from further thermal degradation. Our findings reveal the thermal conditions under which preservation of organic matter on the Moon is viable

    Spontaneous HIV expression during suppressive ART is associated with the magnitude and function of HIV-specific CD4+ and CD8+ T cells.

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    Spontaneous transcription and translation of HIV can persist during suppressive antiretroviral therapy (ART). The quantity, phenotype, and biological relevance of this spontaneously "active" reservoir remain unclear. Using multiplexed single-cell RNAflow-fluorescence in situ hybridization (FISH), we detect active HIV transcription in 14/18 people with HIV on suppressive ART, with a median of 28/million CD4 <sup>+</sup> T cells. While these cells predominantly exhibit abortive transcription, p24-expressing cells are evident in 39% of participants. Phenotypically diverse, active reservoirs are enriched in central memory T cells and CCR6- and activation-marker-expressing cells. The magnitude of the active reservoir positively correlates with total HIV-specific CD4 <sup>+</sup> and CD8 <sup>+</sup> T cell responses and with multiple HIV-specific T cell clusters identified by unsupervised analysis. These associations are particularly strong with p24-expressing active reservoir cells. Single-cell vDNA sequencing shows that active reservoirs are largely dominated by defective proviruses. Our data suggest that these reservoirs maintain HIV-specific CD4 <sup>+</sup> and CD8 <sup>+</sup> T responses during suppressive ART

    How spiking neurons give rise to a temporal-feature map

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    A temporal-feature map is a topographic neuronal representation of temporal attributes of phenomena or objects that occur in the outside world. We explain the evolution of such maps by means of a spike-based Hebbian learning rule in conjunction with a presynaptically unspecific contribution in that, if a synapse changes, then all other synapses connected to the same axon change by a small fraction as well. The learning equation is solved for the case of an array of Poisson neurons. We discuss the evolution of a temporal-feature map and the synchronization of the single cells’ synaptic structures, in dependence upon the strength of presynaptic unspecific learning. We also give an upper bound for the magnitude of the presynaptic interaction by estimating its impact on the noise level of synaptic growth. Finally, we compare the results with those obtained from a learning equation for nonlinear neurons and show that synaptic structure formation may profit from the nonlinearity

    Congenital diaphragmatic hernia: To repair on or off extracorporeal membrane oxygenation?

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    Background: Congenital diaphragmatic hernia (CDH) can be repaired on or off extracorporeal membrane oxygenation (ECMO). In many centers, operating off ECMO is advocated to prevent bleeding complications. We aimed to compare surgery-related bleeding complications between repair on or off ECMO. Methods: All patients with CDH repair and ECMO treatment between January 1, 1995, and May 31, 2008, were retrospectively reviewed. Tranexamic acid was routinely given to all patients repaired on ECMO for 24 hours perioperatively after 2003. Extra-fluid expansion, transfusion, or relaparotomy caused by postoperative bleeding were scored as surgery-related bleeding complications and were related to the Extracorporeal Life Support Organization (ELSO) registry. We used χ 2 test and t test for statistics. Results: Demographic data and surgery-related bleeding complications in the on-ECMO group were not significantly different compared with the off-ECMO group (P =.331) in our institute. In contrast, more surgery-related bleeding complications were reported by ELSO in their on-ECMO group (P <.0001). Conclusion: In contrast to the data from the ELSO registry, we did not observe significantly more surgery-related bleeding complications after CDH repair on ECMO. Using a specific perioperative hemostatic treatment enabled us to perform CDH repair on ECMO with a low frequency of bleeding complications, thereby taking advantage of having the physiologic benefits of ECMO available perioperatively

    Identification and characterization of mechanistically distinct inducers of gamma-globin transcription

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    Inhibition of HbS polymerization is a major target for therapeutic approaches in sickle cell anemia. Toward this goal, initial efforts at pharmacological elevation of fetal hemoglobin (HbF) has shown therapeutic efficacy. In order to identify well-tolerated, novel agents that induce HbF in patients, we developed a high-throughput screening approach based on induction of gamma-globin gene expression in erythroid cells. We measured gamma-globin transcription in K562 cells transfected with either gamma promoter elements fused with the locus control region hypersensitivity site 2 and luciferase reporter gene (HS2 gamma) or a beta-yeast artificial chromosome in which the luciferase reporter gene was recombined into the gamma-globin coding sequences (gamma YAC). Corresponding pharmacological increases in HbF protein were confirmed in both K562 cells and in human primary erythroid progenitor cells. Approximately 186,000 defined chemicals and fungal extracts were evaluated for their ability to increase gamma gene transcription in either HS2 gamma or gamma YAC models. Eleven distinct classes of compounds were identified, the majority of which were active within 24-48 hr. The short chain hydroxamate-containing class generally exhibited delayed maximal activity, which continued to increase transcription up to 120 hr. The cyclic tetrapeptide OSI-2040 and the hydroxamates were shown to have histone deacetylase inhibitory activity. In primary hematopoietic progenitor cell cultures, OSI-2040 increased HbF by 4.5-fold at a concentration of only 40 nM, comparable to the effects of hydroxyurea at 100 microM. This screening methodology successfully identifies active compounds for further mec
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