Addiction-related genes in gambling disorders:new insights from parallel human and pre-clinical models

Neurobiological research supports the characterization of disordered gambling (DG) as a behavioral addiction. Recently, an animal model of gambling behavior was developed (rat gambling task, rGT), expanding the available tools to investigate DG neurobiology. We investigated whether rGT performance and associated risk gene expression in the rat's brain could provide cross-translational understanding of the neuromolecular mechanisms of addiction in DG. We genotyped tagSNPs (single-nucleotide polymorphisms) in 38 addiction-related genes in 400 DG and 345 non-DG subjects. Genes with P<0.1 in the human association analyses were selected to be investigated in the animal arm to determine whether their mRNA expression in rats was associated with the rat's performance on the rGT. In humans, DG was significantly associated with tagSNPs in DRD3 (rs167771) and CAMK2D (rs3815072). Our results suggest that age and gender might moderate the association between CAMK2D and DG. Moderation effects could not be investigated due to sample power. In the animal arm, only the association between rGT performance and Drd3 expression remained significant after Bonferroni correction for 59 brain regions. As male rats were used, gender effects could not be investigated. Our results corroborate previous findings reporting the involvement of DRD3 receptor in addictions. To our knowledge, the use of human genetics, pre-clinical models and gene expression as a cross-translation paradigm has not previously been attempted in the field of addictions. The cross-validation of human findings in animal models is crucial for improving the translation of basic research into clinical treatments, which could accelerate neurobiological and pharmacological investigations in addictions

By design : negotiating flexible learning in the built environment discipline

The term &lsquo;flexible education&rsquo; is now firmly entrenched within Australian higher education discourse, yet the term is a contested one imbued with a multiplicity of meanings. This paper describes a process designed to elucidate how the idea of flexible education can be translated into teaching models that are informed by the specific demands of disciplinary contexts. The process uses a flexible learning &lsquo;matching&rsquo; tool to articulate the understandings and preferences of students and academics of the Built Environment to bridge the gap between student expectations of flexibility and their teacher&rsquo;s willingness and ability to provide that flexibility within the limits of the pedagogical context and teaching resources. The findings suggest an informed starting point for educators in the Built Environment and other creative disciplines from which to traverse the complexities inherent in negotiating flexibility in an increasingly digital world

Schizophrenia-risk variant rs6994992 in the neuregulin-1 gene on brain developmental trajectories in typically developing children

The neuregulin-1 (NRG1) gene is one of the best-validated risk genes for schizophrenia, and psychotic and bipolar disorders. The rs6994992 variant in the NRG1 promoter (SNP8NRG243177) is associated with altered frontal and temporal brain macrostructures and/or altered white matter density and integrity in schizophrenic adults, as well as healthy adults and neonates. However, the ages when these changes begin and whether neuroimaging phenotypes are associated with cognitive performance are not fully understood. Therefore, we investigated the association of the rs6994992 variant on developmental trajectories of brain macro- and microstructures, and their relationship with cognitive performance. A total of 972 healthy children aged 3–20 years had the genotype available for the NRG1-rs6994992 variant, and were evaluated with magnetic resonance imaging (MRI) and neuropsychological tests. Age-by-NRG1-rs6994992 interactions and genotype effects were assessed using a general additive model regression methodology, covaried for scanner type, socioeconomic status, sex and genetic ancestry factors. Compared with the C-carriers, children with the TT-risk-alleles had subtle microscopic and macroscopic changes in brain development that emerge or reverse during adolescence, a period when many psychiatric disorders are manifested. TT-children at late adolescence showed a lower age-dependent forniceal volume and lower fractional anisotropy; however, both measures were associated with better episodic memory performance. To our knowledge, we provide the first multimodal imaging evidence that genetic variation in NRG1 is associated with age-related changes on brain development during typical childhood and adolescence, and delineated the altered patterns of development in multiple brain regions in children with the T-risk allele(s)

Genome-wide association study of shared components of reading disability and language impairment

Written and verbal languages are neurobehavioral traits vital to the development of communication skills. Unfortunately, disorders involving these traits—specifically reading disability (RD) and language impairment (LI)—are common and prevent affected individuals from developing adequate communication skills, leaving them at risk for adverse academic, socioeconomic and psychiatric outcomes. Both RD and LI are complex traits that frequently co-occur, leading us to hypothesize that these disorders share genetic etiologies. To test this, we performed a genome-wide association study on individuals affected with both RD and LI in the Avon Longitudinal Study of Parents and Children. The strongest associations were seen with markers in ZNF385D (OR = 1.81, P = 5.45 × 10−7) and COL4A2 (OR = 1.71, P = 7.59 × 10−7). Markers within NDST4 showed the strongest associations with LI individually (OR = 1.827, P = 1.40 × 10−7). We replicated association of ZNF385D using receptive vocabulary measures in the Pediatric Imaging Neurocognitive Genetics study (P = 0.00245). We then used diffusion tensor imaging fiber tract volume data on 16 fiber tracts to examine the implications of replicated markers. ZNF385D was a predictor of overall fiber tract volumes in both hemispheres, as well as global brain volume. Here, we present evidence for ZNF385D as a candidate gene for RD and LI. The implication of transcription factor ZNF385D in RD and LI underscores the importance of transcriptional regulation in the development of higher order neurocognitive traits. Further study is necessary to discern target genes of ZNF385D and how it functions within neural development of fluent language

Patterns of local and nonlocal water resource use across the western U.S. determined via stable isotope intercomparisons

In the western U.S., the mismatch between public water demands and natural water availability necessitates large interbasin transfers of water as well as groundwater mining of fossil aquifers. Here we identify probable situations of nonlocal water use in both space and time based on isotopic comparisons between tap waters and potential water resources within hydrologic basins. Our approach, which considers evaporative enrichment of heavy isotopes during storage and distribution, is used to determine the likelihood of local origin for 612 tap water samples collected from across the western U.S. We find that 64% of samples are isotopically distinct from precipitation falling within the local hydrologic basin, a proxy for groundwater with modern recharge, and 31% of samples are isotopically distinct from estimated surface water found within the local basin. Those samples inconsistent with local water sources, which we suggest are likely derived from water imported from other basins or extracted from fossil aquifers, are primarily clustered in southern California, the San Francisco Bay area, and central Arizona. Our isotope-based estimates of nonlocal water use are correlated with both hydrogeomorphic and socioeconomic properties of basins, suggesting that these factors exert a predictable influence on the likelihood that nonlocal waters are used to supply tap water. We use these basin properties to develop a regional model of nonlocal water resource use that predicts (r2 = 0.64) isotopically inferred patterns and allows assessment of total interbasin transfer and/or fossil aquifer extraction volumes across the western U.S.Fil: Good, Stephen P.. University of Utah; Estados UnidosFil: Kennedy, Casey D.. United States Department Of Agriculture. Agriculture Research Service; Estados UnidosFil: Stalker Jeremy C.. Jacksonville University; Estados UnidosFil: Chesson, Lesley A.. IsoForensics; Estados UnidosFil: Valenzuela, Luciano Oscar. Universidad Nacional del Centro de la Provincia de Buenos Aires. Facultad de Ciencias Sociales. Departamento de Arqueología. Laboratorio de Ecología Evolutiva Humana (Sede Quequén); Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. University of Utah; Estados UnidosFil: Beasley, Melanie M.. University of California at San Diego; Estados UnidosFil: Ehleringer, James R. University of Utah; Estados UnidosFil: Bowen, Gabriel J.. University of Utah; Estados Unido

Accretion-related properties of Herbig Ae/Be stars. Comparison with T Tauris

We look for trends relating the mass accretion rate (Macc) and the stellar ages (t), spectral energy distributions (SEDs), and disk masses (Mdisk) for a sample of 38 HAeBe stars, comparing them to analogous correlations found for classical T Tauri stars. Our goal is to shed light on the timescale and physical processes that drive evolution of intermediate-mass pre-main sequence objects. Macc shows a dissipation timescale \tau = 1.3^{+1.0}_{-0.5} Myr from an exponential law fit, while a power law yields Macc(t) \propto t^{-\eta}, with \eta = 1.8^{+1.4}_{-0.7}. This result is based on our whole HAeBe sample (1-6 Msun), but the accretion rate decline most probably depends on smaller stellar mass bins. The near-IR excess is higher and starts at shorter wavelengths (J and H bands) for the strongest accretors. Active and passive disks are roughly divided by 2 x 10^{-7} Msun/yr. The mid-IR excess and the SED shape from the Meeus et al. classification are not correlated with Macc. We find Macc \propto Mdisk^{1.1 +- 0.3}. Most stars in our sample with signs of inner dust dissipation typically show accretion rates ten times lower and disk masses three times smaller than the remaining objects. The trends relating Macc with the near-IR excess and Mdisk extend those for T Tauri stars, and are consistent with viscous disk models. The differences in the inner gas dissipation timescale, and the relative position of the stars with signs of inner dust clearing in the Macc-Mdisk plane, could be suggesting a slightly faster evolution, and that a different process - such as photoevaporation - plays a more relevant role in dissipating disks in the HAeBe regime compared to T Tauri stars. Our conclusions must consider the mismatch between the disk mass estimates from mm fluxes and the disk mass estimates from accretion, which we also find in HAeBe stars.Comment: 11 pages, 7 figures, 1 appendix. Accepted in A&

Genome-wide association study of shared components of reading disability and language impairment

Written and verbal languages are neurobehavioral traits vital to the development of communication skills. Unfortunately, disorders involving these traits-specifically reading disability (RD) and language impairment (LI)-are common and prevent affected individuals from developing adequate communication skills, leaving them at risk for adverse academic, socioeconomic and psychiatric outcomes. Both RD and LI are complex traits that frequently co-occur, leading us to hypothesize that these disorders share genetic etiologies. To test this, we performed a genome-wide association study on individuals affected with both RD and LI in the Avon Longitudinal Study of Parents and Children. The strongest associations were seen with markers in ZNF385D (OR = 1.81, P = 5.45 × 10(-7) ) and COL4A2 (OR = 1.71, P = 7.59 × 10(-7) ). Markers within NDST4 showed the strongest associations with LI individually (OR = 1.827, P = 1.40 × 10(-7) ). We replicated association of ZNF385D using receptive vocabulary measures in the Pediatric Imaging Neurocognitive Genetics study (P = 0.00245). We then used diffusion tensor imaging fiber tract volume data on 16 fiber tracts to examine the implications of replicated markers. ZNF385D was a predictor of overall fiber tract volumes in both hemispheres, as well as global brain volume. Here, we present evidence for ZNF385D as a candidate gene for RD and LI. The implication of transcription factor ZNF385D in RD and LI underscores the importance of transcriptional regulation in the development of higher order neurocognitive traits. Further study is necessary to discern target genes of ZNF385D and how it functions within neural development of fluent language

Search for the standard model Higgs boson decaying to a bb pair in events with one charged lepton and large missing transverse energy using the full CDF data set

We present a search for the standard model Higgs boson produced in association with a W boson in sqrt(s) = 1.96 TeV p-pbar collision data collected with the CDF II detector at the Tevatron corresponding to an integrated luminosity of 9.45 fb-1. In events consistent with the decay of the Higgs boson to a bottom-quark pair and the W boson to an electron or muon and a neutrino, we set 95% credibility level upper limits on the WH production cross section times the H->bb branching ratio as a function of Higgs boson mass. At a Higgs boson mass of 125 GeV/c2 we observe (expect) a limit of 4.9 (2.8) times the standard model value.Comment: Submitted to Phys. Rev. Lett (v2 contains clarifications suggested by PRL

Search for the standard model Higgs boson decaying to a bbˉb\bar{b} pair in events with no charged leptons and large missing transverse energy using the full CDF data set

We report on a search for the standard model Higgs boson produced in association with a vector boson in the full data set of proton-antiproton collisions at $\sqrt{s} = 1.96$ TeV recorded by the CDF II detector at the Tevatron, corresponding to an integrated luminosity of 9.45 fb$^{-1}$. We consider events having no identified charged lepton, a transverse energy imbalance, and two or three jets, of which at least one is consistent with originating from the decay of a $b$ quark. We place 95% credibility level upper limits on the production cross section times standard model branching fraction for several mass hypotheses between 90 and $150 \mathrm{GeV}/c^2$. For a Higgs boson mass of $125 \mathrm{GeV}/c^2$, the observed (expected) limit is 6.7 (3.6) times the standard model prediction.Comment: Accepted by Phys. Rev. Let

Search for the standard model Higgs boson decaying to a bb pair in events with two oppositely-charged leptons using the full CDF data set

We present a search for the standard model Higgs boson produced in association with a Z boson in data collected with the CDF II detector at the Tevatron, corresponding to an integrated luminosity of 9.45/fb. In events consistent with the decay of the Higgs boson to a bottom-quark pair and the Z boson to electron or muon pairs, we set 95% credibility level upper limits on the ZH production cross section times the H -> bb branching ratio as a function of Higgs boson mass. At a Higgs boson mass of 125 GeV/c^2 we observe (expect) a limit of 7.1 (3.9) times the standard model value.Comment: To be submitted to Phys. Rev. Let