Studying genetic determinants of intermediate phenotypes is a powerful tool to increase our understanding of genotype-phenotype correlations. Metabolic traits pertinent to the central nervous system ...(CNS) constitute a potentially informative target for genetic studies of intermediate phenotypes as their genetic underpinnings may elucidate etiological mechanisms. We therefore conducted a genome-wide association study (GWAS) of monoamine metabolite (MM) levels in cerebrospinal fluid (CSF) of 414 human subjects from the general population. In a linear model correcting for covariates, we identified one locus associated with MMs at a genome-wide significant level (standardized β=0.32, P=4.92 × 10(-8)), located 20 kb from SSTR1, a gene involved with brain signal transduction and glutamate receptor signaling. By subsequent whole-genome expression quantitative trait locus (eQTL) analysis, we provide evidence that this variant controls expression of PDE9A (β=0.21; P unadjusted=5.6 × 10(-7); P corrected=0.014), a gene previously implicated in monoaminergic transmission, major depressive disorder and antidepressant response. A post hoc analysis of loci significantly associated with psychiatric disorders suggested that genetic variation at CSMD1, a schizophrenia susceptibility locus, plays a role in the ratio between dopamine and serotonin metabolites in CSF. The presented DNA and mRNA analyses yielded genome-wide and suggestive associations in biologically plausible genes, two of which encode proteins involved with glutamate receptor functionality. These findings will hopefully contribute to an exploration of the functional impact of the highlighted genes on monoaminergic transmission and neuropsychiatric phenotypes.
Single phase polycrystalline Sn-doped CuInO2 thin films are prepared by the oxygen plasma enhanced reactive evaporation method. X-ray diffraction indicates a preferential orientation of crystallites ...along the (006) plane on doping while energy dispersive analysis of X-rays and atomic force microscopy are employed to appraise the composition and morphology of the films, respectively. Remarkably, about 2-3 orders of magnitude enhancement in their electrical conductivity than that reported till date is observed. Further, the Sn-doped thin films possess 2-3 orders of magnitude higher carrier concentration (1018-1019/cm3) than undoped films that is associated with a drastic reduction in mobility. Moreover, different conduction mechanisms possible at different temperature regions ranging from around 55 K–450 K are studied in detail. While the transparency of the films is increased from 43% to 85% on doping, the optical band gap decreases from 3.83 eV to 3.5 eV.
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•2-3 orders of magnitude increase in electrical conductivity by tin doping in CuInO2.•First report on analysis of electrical transport mechanisms in the range 55–450 K.•Reorientation of crystallites along (006) plane by tin incorporation in CuInO2.•Optical transparency doubles without adversely affecting electrical conductivity.
High demand for nuclear reaction cross-section measurements relevant for astrophysical processes requires the development of new experimental techniques that allow for investigation of, often very ...low, cross-sections. For this purpose, a new 4πSumming NaI(Tl) detector (SuN) has been constructed, which is an 8-fold segmented NaI(Tl) barrel read by 24 photomultipliers. The design of the detector will be presented and detailed results of the commissioning experiments utilizing standard calibration sources and known Al27(p,γ)Si28 resonances will be discussed.
Women with atypical hyperplasia (AH) or lobular carcinoma in situ (LCIS) have a significantly increased risk of breast cancer, which can be substantially reduced with antiestrogen therapy for ...chemoprevention. However, antiestrogen therapy for breast cancer risk reduction remains underutilized. Improving knowledge about breast cancer risk and chemoprevention among high-risk patients and their healthcare providers may enhance informed decision-making about this critical breast cancer risk reduction strategy.
We are conducting a cluster randomized controlled trial to evaluate the effectiveness and implementation of patient and provider decision support tools to improve informed choice about chemoprevention among women with AH or LCIS. We have cluster randomized 26 sites across the U.S. through the SWOG Cancer Research Network. A total of 415 patients and 200 healthcare providers are being recruited. They are assigned to standard educational materials alone or combined with the web-based decision support tools. Patient-reported and clinical outcomes are assessed at baseline, after a follow-up visit at 6 months, and yearly for 5 years. The primary outcome is chemoprevention informed choice after the follow-up visit. Secondary endpoints include other patient-reported outcomes, such as chemoprevention knowledge, decision conflict and regret, and self-reported chemoprevention usage. Barriers and facilitators to implementing decision support into clinic workflow are assessed through patient and provider interviews at baseline and mid-implementation.
With this hybrid effectiveness/implementation study, we seek to evaluate if a multi-level intervention effectively promotes informed decision-making about chemoprevention and provide valuable insights on how the intervention is implemented in U.S. clinical settings.
NCT04496739
The N-methyl-D-aspartate receptor (NMDAR) coagonists glycine, D-serine and L-proline play crucial roles in NMDAR-dependent neurotransmission and are associated with a range of neuropsychiatric ...disorders. We conducted the first genome-wide association study of concentrations of these coagonists and their enantiomers in plasma and cerebrospinal fluid (CSF) of human subjects from the general population (N=414). Genetic variants at chromosome 22q11.2, located in and near PRODH (proline dehydrogenase), were associated with L-proline in plasma (β=0.29; P=6.38 × 10(-10)). The missense variant rs17279437 in the proline transporter SLC6A20 was associated with L-proline in CSF (β=0.28; P=9.68 × 10(-9)). Suggestive evidence of association was found for the D-serine plasma-CSF ratio at the D-amino-acid oxidase (DAO) gene (β=-0.28; P=9.08 × 10(-8)), whereas a variant in SRR (that encodes serine racemase and is associated with schizophrenia) constituted the most strongly associated locus for the L-serine to D-serine ratio in CSF. All these genes are highly expressed in rodent meninges and choroid plexus, anatomical regions relevant to CSF physiology. The enzymes and transporters they encode may be targeted to further construe the nature of NMDAR coagonist involvement in NMDAR gating. Furthermore, the highlighted genetic variants may be followed up in clinical populations, for example, schizophrenia and 22q11 deletion syndrome. Overall, this targeted metabolomics approach furthers the understanding of NMDAR coagonist concentration variability and sets the stage for non-targeted CSF metabolomics projects.
The neutron unbound ground state of (25)O (Z=8, N=17) was observed for the first time in a proton knockout reaction from a (26)F beam. A single resonance was found in the invariant mass spectrum ...corresponding to a neutron decay energy of 770_+20(-10) keV with a total width of 172(30) keV. The N=16 shell gap was established to be 4.86(13) MeV by the energy difference between the nu1s(1/2) and nu0d(3/2) orbitals. The neutron separation energies for (25)O agree with the calculations of the universal sd shell model interaction. This interaction incorrectly predicts an (26)O ground state that is bound to two-neutron decay by 1 MeV, leading to a discrepancy between the theoretical calculations and experiment as to the particle stability of (26)O. The observed decay width was found to be on the order of a factor of 2 larger than the calculated single-particle width using a Woods-Saxon potential.
White‐tailed deer (Odocoileus virginianus) were nearly extirpated from the southeastern USA during the late 19th and early 20th centuries. Recovery programmes, including protection of remnant native ...stocks and transplants from other parts of the species’ range, were initiated in the early 1900s. The recovery programmes were highly successful and deer are presently numerous and continuously distributed throughout the southeastern USA. However, the impact of the recovery programmes on the present genetic structure of white‐tailed deer remains to be thoroughly investigated. We used 17 microsatellite DNA loci to assess genetic differentiation and diversity for 543 white‐tailed deer representing 16 populations in Mississippi and three extra‐state reference populations. There was significant genetic differentiation among all populations and the majority of genetic variation (≥ 93%) was contained within populations. Patterns of genetic structure, genetic similarity and isolation by distance within Mississippi were not concordant with geographical proximity of populations or subspecies delineations. We detected evidence of past genetic bottlenecks in nine of the 19 populations examined. However, despite experiencing genetic bottlenecks or founder events, allelic diversity and heterozygosity were uniformly high in all populations. These exceeded reported values for other cervid species that experienced similar population declines within the past century. The recovery programme was successful in that deer were restored to their former range while maintaining high and uniform genetic variability. Our results seem to confirm the importance of rapid population expansion and habitat continuity in retaining genetic variation in restored populations. However, the use of diverse transplant stocks and the varied demographic histories of populations resulted in fine‐scale genetic structuring.
A Monte Carlo simulation of a large-area neutron time-of-flight detector, built on the Geant4 framework, has been compared with an experimental measurement of the B16→B15+n decay produced from a ...55MeV/u17C beam. The ability of the Monte Carlo simulation to reproduce the intermediate-energy neutron interactions within the detector has been explored using both the stock Geant4 physics processes and a custom neutron interaction model, menate_r. The stock Geant4 physics processes were unable to reproduce the experimental observables, while excellent agreement was obtained through the inclusion of the menate_r model within Geant4. The differences between the two approaches are shown to be related to the modeling of the neutron–carbon inelastic reactions. Additionally, the use of menate_r provided accurate reproduction of experimental signals associated with neutron scattering within the detector. These results provide validation of the Monte Carlo simulation for modeling measurements of multiple neutrons where the identification and removal of false neutron signals, due to multiple neutron scattering, are required.
The paper reports the fabrication of Zn-doped TiO2 nanotubes（Zn-TONT）/ZnO nanoflakes heterostructure for the first time,which shows improved performance as a photoanode in dye-sensitized solar ...cell（DSSC）.The layered structure of this novel nanoporous structure has been analyzed unambiguously by Rutherford backscattering spectroscopy,scanning electron microscopy,and X-ray diffractometer.The cell using the heterostructure as photoanode manifests an enhancement of about an order in the magnitude of the short circuit current and a seven-fold increase in efficiency,over pure TiO2 photoanodes.Characterizations further reveal that the Zn-TONT is preferentially oriented in 001 direction and there is a Ti metal-depleted interface layer which leads to better band alignment in DSSC.
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