141 research outputs found

    Olfactory bulbectomy in infant rats: Survival, growth and ingestive behaviors

    Full text link
    Growth and ingestive behaviors were measured for rats sustaining bilateral olfactory bulbectomies at 1 or 10 days of age. Tests designed to examine nipple-attachment capabilities were accomplished before weaning, and tests designed to examine drinking (e.g., water-deprivation), feeding (e.g., amphetamine-anorexia), and taste-related behaviors (e.g., quinine finickiness) were conducted from 35-150 days of age. Pups bulbectomized at 1 day of age displayed less severe nipple-attachment deficits than pups bulbectomized at 10 days of age; however, body weights of both bulbectomized groups were significantly below that of controls from the first day postsurgery through 150 days of age. Bulbectomized rats differed from controls on some drinking, feeding, and taste-related measures; deficits occurred most consistently on taste-related measures. The results are discussed in terms of neural and behavioral plasticity of developing animals sustaining neural damage.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/24223/1/0000482.pd

    Prioritizing individual genetic variants after kernel machine testing using variable selection: He et al.

    Get PDF
    Kernel machine learning methods, such as the SNP-set kernel association test (SKAT), have been widely used to test associations between traits and genetic polymorphisms. In contrast to traditional single-SNP analysis methods, these methods are designed to examine the joint effect of a set of related SNPs (such as a group of SNPs within a gene or a pathway) and are able to identify sets of SNPs that are associated with the trait of interest. However, as with many multi-SNP testing approaches, kernel machine testing can draw conclusion only at the SNP-set level, and do not directly inform on which one(s) of the identified SNP set is actually driving the associations. A recently proposed procedure, KerNel Iterative Feature Extraction (KNIFE), provides a general framework for incorporating variable selection into kernel machine methods. In this article, we focus on quantitative traits and relatively common SNPs, and adapt the KNIFE procedure to genetic association studies and propose an approach to identify driver SNPs after the application of SKAT to gene set analysis. Our approach accommodates several kernels that are widely used in SNP analysis, such as the linear kernel and the Identity By State (IBS) kernel. The proposed approach provides practically useful utilities to prioritize SNPs, and fills the gap between SNP set analysis and biological functional studies. Both simulation studies and real data application are used to demonstrate the proposed approach

    Maternal occupational exposure to solvents and gastroschisis in offspring-National Birth Defects Prevention Study 1997-2011

    Get PDF
    Objectives: The aim of this study was to assess the association between maternal occupational exposure to solvents and gastroschisis in offspring. Methods: We used data from the National Birth Defects Prevention Study, a large population-based case-control study of major birth defects conducted in 10 US states from 1997 to 2011. Infants with gastroschisis were ascertained by active birth defects surveillance systems. Control infants without major birth defects were selected from vital records or birth hospital records. Self-reported maternal occupational histories were collected by telephone interview. Industrial hygienists reviewed this information to estimate exposure to aromatic, chlorinated and petroleum-based solvents from 1 month before conception through the first trimester of pregnancy. Cumulative exposure to solvents was estimated for the same period accounting for estimated exposure intensity and frequency, job duration and hours worked per week. ORs and 95% CIs were estimated to assess the association between exposure to any solvents or solvent classes, and gastroschisis risk. Results: Among 879 cases and 7817 controls, the overall prevalence of periconceptional solvent exposure was 7.3% and 7.4%, respectively. Exposure to any solvent versus no exposure to solvents was not associated with gastroschisis after adjusting for maternal age (OR 1.00, 95% CI 0.75 to 1.32), nor was an association noted for solvent classes. There was no exposure-response relationship between estimated cumulative solvent exposure and gastroschisis after adjusting for maternal age. Conclusion: Our study found no association between maternal occupational solvent exposure and gastroschisis in offspring. Further research is needed to understand risk factors for gastroschisis

    Individual differences in texture preferences among European children: Development and validation of the Child Food Texture Preference Questionnaire (CFTPQ)

    Get PDF
    Texture has an important role in children's acceptance and rejection of food. However, little is known about individual differences in texture preference. The aim of this study was to develop and validate a child-friendly tool to explore individual differences in texture preferences in school-aged children from six European countries (Austria, Finland, Italy, Spain, Sweden and United Kingdom). Six hundred and ten children aged 9-12 years and their parents participated in a cross-sectional study. Children completed the Child Food Texture Preference Questionnaire (CFTPQ) and a Food Neophobia Scale (FNS). The CFTPQ consisted in asking children to choose the preferred item within 17 pairs of pictures of food varying in texture (hard vs. soft or smooth vs. lumpy). Children also evaluated all food items for familiarity. Parents completed the CFTPQ regarding their preferred items, a food frequency questionnaire for their child, and provided background information. For a subset of children, a re-test was done for the CFTPQ and FNS to assess reliability. The results showed that the tool was child-friendly, had high test-retest reliability, and identified country-related differences as well as segments of children with different texture preferences (hard- vs. soft-likers). These segments differed in consumption frequency of healthy foods, and in food neophobia

    A DNA Methylation Biomarker of Alcohol Consumption

    Get PDF
    The lack of reliable measures of alcohol intake is a major obstacle to the diagnosis and treatment of alcohol-related diseases. Epigenetic modifications such as DNA methylation may provide novel biomarkers of alcohol use. To examine this possibility, we performed an epigenome-wide association study of methylation of cytosine-phosphate-guanine dinucleotide (CpG) sites in relation to alcohol intake in 13 population-based cohorts (ntotal=13 317; 54% women; mean age across cohorts 42–76 years) using whole blood (9643 European and 2423 African ancestries) or monocyte-derived DNA (588 European, 263 African and 400 Hispanic ancestry) samples. We performed meta-analysis and variable selection in whole-blood samples of people of European ancestry (n=6926) and identified 144 CpGs that provided substantial discrimination (area under the curve=0.90–0.99) for current heavy alcohol intake (≥ 42 g per day in men and ≥ 28 g per day in women) in four replication cohorts. The ancestry-stratified meta-analysis in whole blood identified 328 (9643 European ancestry samples) and 165 (2423 African ancestry samples) alcohol-related CpGs at Bonferroni-adjusted P \u3c 1 × 10−7. Analysis of the monocyte-derived DNA (n = 1251) identified 62 alcohol-related CpGs at P \u3c 1 × 10-7. In whole-blood samples of people of European ancestry, we detected differential methylation in two neurotransmitter receptor genes, the γ-Aminobutyric acid-A receptor delta and γ-aminobutyric acid B receptor subunit 1; their differential methylation was associated with expression levels of a number of genes involved in immune function. In conclusion, we have identified a robust alcohol-related DNA methylation signature and shown the potential utility of DNA methylation as a clinically useful diagnostic test to detect current heavy alcohol consumption

    Largest GWAS of PTSD (N=20 070) yields genetic overlap with schizophrenia and sex differences in heritability

    Get PDF
    The Psychiatric Genomics Consortium-Posttraumatic Stress Disorder group (PGC- PTSD) combined genome-wide case–control molecular genetic data across 11 multiethnic studies to quantify PTSD heritability, to examine potential shared genetic risk with schizophrenia, bipolar disorder, and major depressive disorder and to identify risk loci for PTSD. Examining 20 730 individuals, we report a molecular genetics-based heritability estimate (h2SNP) for European- American females of 29% that is similar to h2SNP for schizophrenia and is substantially higher than h2SNP in European-American males (estimate not distinguishable from zero). We found strong evidence of overlapping genetic risk between PTSD and schizophrenia along with more modest evidence of overlap with bipolar and major depressive disorder. No single-nucleotide polymorphisms (SNPs) exceeded genome-wide significance in the transethnic (overall) meta- analysis and we do not replicate previously reported associations. Still, SNP- level summary statistics made available here afford the best-available molecular genetic index of PTSD—for both European- and African-American individuals—and can be used in polygenic risk prediction and genetic correlation studies of diverse phenotypes. Publication of summary statistics for ∼10 000 African Americans contributes to the broader goal of increased ancestral diversity in genomic data resources. In sum, the results demonstrate genetic influences on the development of PTSD, identify shared genetic risk between PTSD and other psychiatric disorders and highlight the importance of multiethnic/racial samples. As has been the case with schizophrenia and other complex genetic disorders, larger sample sizes are needed to identify specific risk loci

    Frequency of alcohol consumption in humans; the role of metabotropic glutamate receptors and downstream signaling pathways

    Get PDF
    Rodent models implicate metabotropic glutamate receptors (mGluRs) and downstream signaling pathways in addictive behaviors through metaplasticity. One way mGluRs can influence synaptic plasticity is by regulating the local translation of AMPA receptor trafficking proteins via eukaryotic elongation factor 2 (eEF2). However, genetic variation in this pathway has not been examined with human alcohol use phenotypes. Among a sample of adults living in Detroit, Michigan (Detroit Neighborhood Health Study; n=788; 83% African American), 206 genetic variants across the mGluR–eEF2–AMPAR pathway (including GRM1, GRM5, HOMER1, HOMER2, EEF2K, MTOR, EIF4E, EEF2, CAMK2A, ARC, GRIA1 and GRIA4) were found to predict number of drinking days per month (corrected P-value <0.01) when considered as a set (set-based linear regression conducted in PLINK). In addition, a CpG site located in the 3′-untranslated region on the north shore of EEF2 (cg12255298) was hypermethylated in those who drank more frequently (P<0.05). Importantly, the association between several genetic variants within the mGluR–eEF2–AMPAR pathway and alcohol use behavior (i.e., consumption and alcohol-related problems) replicated in the Grady Trauma Project (GTP), an independent sample of adults living in Atlanta, Georgia (n=1034; 95% African American), including individual variants in GRM1, GRM5, EEF2, MTOR, GRIA1, GRIA4 and HOMER2 (P<0.05). Gene-based analyses conducted in the GTP indicated that GRM1 (empirical P<0.05) and EEF2 (empirical P<0.01) withstood multiple test corrections and predicted increased alcohol consumption and related problems. In conclusion, insights from rodent studies enabled the identification of novel human alcohol candidate genes within the mGluR–eEF2–AMPAR pathway
    • …
    corecore