76 research outputs found
A role for CaV1 and calcineurin signalling to depolarization-induced changes in neuronal DNA methylation
Get PDFCopyright © 2015 The Authors Published by Elsevier Inc.Direct manipulations of neuronal activity have been shown to induce changes in DNA methylation (DNAm), although little is known about the cellular signaling pathways involved. Using reduced representation bisulfite sequencing, we identify DNAm changes associated with moderate chronic depolarization in dissociated rat hippocampal cultures. Consistent with previous findings, these changes occurred primarily in the vicinity of loci implicated in neuronal function, being enriched in intergenic regions and underrepresented in CpG-rich promoter regulatory regions. We subsequently used 2 pharmacological interventions (nifedipine and FK-506) to test whether the identified changes depended on 2 interrelated signaling pathways known to mediate multiple forms of neuronal plasticity. Both pharmacological manipulations had notable effects on the extent and magnitude of depolarization-induced DNAm changes indicating that a high proportion of activity-induced changes are likely to be mediated by calcium entry through L-type CaV1 channels and/or downstream signaling via the calcium-dependent phosphatase calcineurin.Wellcome TrustMRC 4-year PhD studentshipKCL CDN-SGDP collaborative seed fundin
Cancer control needs of 2-1-1 callers in Missouri, North Carolina, Texas, and Washington
Get PDFInnovative interventions are needed to connect underserved populations to cancer control services. With data from Missouri, North Carolina, Texas, and Washington this study a) estimated the cancer control needs of callers to 2-1-1, an information and referral system used by underserved populations, b) compared rates of need to state and national data, and c) examined receptiveness to needed referrals. From October 2009 to March 2010 callers’ (N = 1408) cancer control needs were assessed in six areas: breast, cervical, and colorectal cancer screening, HPV vaccination, smoking, and smoke-free homes using Behavioral Risk Factor Surveillance System (BRFSS) survey items. Standardized estimates were compared to state and national rates. Nearly 70% of the sample had at least one cancer control need. Needs were greater for 2-1-1 callers compared to state and national rates, and callers were receptive to referrals. 2-1-1 could potentially be a key partner in efforts to reduce cancer disparities
<html>Cancer Control Needs of <i>2-1-1</i> Callers in Missouri, North Carolina, Texas, and Washington</html>
Get PDFInnovative interventions are needed to connect underserved populations to cancer control services. With data from Missouri, North Carolina, Texas, and Washington this study a) estimated the cancer control needs of callers to 2-1-1, an information and referral system used by underserved populations, b) compared rates of need to state and national data, and c) examined receptiveness to needed referrals. From October 2009 to March 2010 callers’ (N = 1408) cancer control needs were assessed in six areas: breast, cervical, and colorectal cancer screening, HPV vaccination, smoking, and smoke-free homes using Behavioral Risk Factor Surveillance System (BRFSS) survey items. Standardized estimates were compared to state and national rates. Nearly 70% of the sample had at least one cancer control need. Needs were greater for 2-1-1 callers compared to state and national rates, and callers were receptive to referrals. 2-1-1 could potentially be a key partner in efforts to reduce cancer disparities
Structure and properties of densified silica glass: characterizing the order within disorder
Get PDF世界一構造秩序のあるガラスの合成と構造解析に成功 --ガラスの一見無秩序な構造の中に潜む秩序を抽出--. 京都大学プレスリリース. 2021-12-25.The broken symmetry in the atomic-scale ordering of glassy versus crystalline solids leads to a daunting challenge to provide suitable metrics for describing the order within disorder, especially on length scales beyond the nearest neighbor that are characterized by rich structural complexity. Here, we address this challenge for silica, a canonical network-forming glass, by using hot versus cold compression to (i) systematically increase the structural ordering after densification and (ii) prepare two glasses with the same high-density but contrasting structures. The structure was measured by high-energy X-ray and neutron diffraction, and atomistic models were generated that reproduce the experimental results. The vibrational and thermodynamic properties of the glasses were probed by using inelastic neutron scattering and calorimetry, respectively. Traditional measures of amorphous structures show relatively subtle changes upon compacting the glass. The method of persistent homology identifies, however, distinct features in the network topology that change as the initially open structure of the glass is collapsed. The results for the same high-density glasses show that the nature of structural disorder does impact the heat capacity and boson peak in the low-frequency dynamical spectra. Densification is discussed in terms of the loss of locally favored tetrahedral structures comprising oxygen-decorated SiSi4 tetrahedra
Cancer Control Plannersʼ Perceptions and Use of Evidence-Based Programs
Get PDFThe Cancer Prevention and Control Research Network (CPCRN) surveyed 282 cancer control planners to inform its efforts to increase the use of evidence-based cancer control programs (EBPs; programs that have been scientifically tested and successfully changed behavior). Respondents included planners from organizations in state Comprehensive Cancer Control coalitions as well as other governmental and non-governmental organizations, and community-based coalitions. Respondents provided information about personal and organizational characteristics, their cancer control programs, their attitudes toward EBPs, and their awareness and use of Web-based resources for EBPs. Although findings showed strong preferences for cancer control programs that have been shown to work, less than half of respondents (48%) had ever used EBP resources. Regardless of whether they had used EBP resources, almost all respondents (97%) indicated that further training would help them and their organization adopt and adapt EBPs for use in their communities. The most frequently endorsed training needs were finding and securing additional resources (such as funding and technical assistance), followed by adapting EBPs for cultural appropriateness. The CPCRN consortium is using these findings to develop a Web-based interactive training and decision support tool that is responsive to the needs identified by the survey respondents
Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial
Get PDFBackground
Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy
Expression quantitative trait loci in the developing human brain and their enrichment in neuropsychiatric disorders
Get PDFBACKGROUND: Genetic influences on gene expression in the human fetal brain plausibly impact upon a variety of postnatal brain-related traits, including susceptibility to neuropsychiatric disorders. However, to date, there have been no studies that have mapped genome-wide expression quantitative trait loci (eQTL) specifically in the human prenatal brain. RESULTS: We performed deep RNA sequencing and genome-wide genotyping on a unique collection of 120 human brains from the second trimester of gestation to provide the first eQTL dataset derived exclusively from the human fetal brain. We identify high confidence cis-acting eQTL at the individual transcript as well as whole gene level, including many mapping to a common inversion polymorphism on chromosome 17q21. Fetal brain eQTL are enriched among risk variants for postnatal conditions including attention deficit hyperactivity disorder, schizophrenia, and bipolar disorder. We further identify changes in gene expression within the prenatal brain that potentially mediate risk for neuropsychiatric traits, including increased expression of C4A in association with genetic risk for schizophrenia, increased expression of LRRC57 in association with genetic risk for bipolar disorder, and altered expression of multiple genes within the chromosome 17q21 inversion in association with variants influencing the personality trait of neuroticism. CONCLUSIONS: We have mapped eQTL operating in the human fetal brain, providing evidence that these confer risk to certain neuropsychiatric disorders, and identifying gene expression changes that potentially mediate susceptibility to these conditions
Machine learning uncovers the most robust self-report predictors of relationship quality across 43 longitudinal couples studies
Get PDFGiven the powerful implications of relationship quality for health and well-being, a central mission of relationship science is explaining why some romantic relationships thrive more than others. This large-scale project used machine learning (i.e., Random Forests) to 1) quantify the extent to which relationship quality is predictable and 2) identify which constructs reliably predict relationship quality. Across 43 dyadic longitudinal datasets from 29 laboratories, the top relationship-specific predictors of relationship quality were perceived-partner commitment, appreciation, sexual satisfaction, perceived-partner satisfaction, and conflict. The top individual-difference predictors were life satisfaction, negative affect, depression, attachment avoidance, and attachment anxiety. Overall, relationship-specific variables predicted up to 45% of variance at baseline, and up to 18% of variance at the end of each study. Individual differences also performed well (21% and 12%, respectively). Actor-reported variables (i.e., own relationship-specific and individual-difference variables) predicted two to four times more variance than partner-reported variables (i.e., the partner’s ratings on those variables). Importantly, individual differences and partner reports had no predictive effects beyond actor-reported relationship-specific variables alone. These findings imply that the sum of all individual differences and partner experiences exert their influence on relationship quality via a person’s own relationship-specific experiences, and effects due to moderation by individual differences and moderation by partner-reports may be quite small. Finally, relationship-quality change (i.e., increases or decreases in relationship quality over the course of a study) was largely unpredictable from any combination of self-report variables. This collective effort should guide future models of relationships
DNA methylation signatures of aggression and closely related constructs : A meta-analysis of epigenome-wide studies across the lifespan
Get PDFDNA methylation profiles of aggressive behavior may capture lifetime cumulative effects of genetic, stochastic, and environmental influences associated with aggression. Here, we report the first large meta-analysis of epigenome-wide association studies (EWAS) of aggressive behavior (N = 15,324 participants). In peripheral blood samples of 14,434 participants from 18 cohorts with mean ages ranging from 7 to 68 years, 13 methylation sites were significantly associated with aggression (alpha = 1.2 x 10(-7); Bonferroni correction). In cord blood samples of 2425 children from five cohorts with aggression assessed at mean ages ranging from 4 to 7 years, 83% of these sites showed the same direction of association with childhood aggression (r = 0.74, p = 0.006) but no epigenome-wide significant sites were found. Top-sites (48 at a false discovery rate of 5% in the peripheral blood meta-analysis or in a combined meta-analysis of peripheral blood and cord blood) have been associated with chemical exposures, smoking, cognition, metabolic traits, and genetic variation (mQTLs). Three genes whose expression levels were associated with top-sites were previously linked to schizophrenia and general risk tolerance. At six CpGs, DNA methylation variation in blood mirrors variation in the brain. On average 44% (range = 3-82%) of the aggression-methylation association was explained by current and former smoking and BMI. These findings point at loci that are sensitive to chemical exposures with potential implications for neuronal functions. We hope these results to be a starting point for studies leading to applications as peripheral biomarkers and to reveal causal relationships with aggression and related traits.Peer reviewe
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