116 research outputs found

    Predicting Weight Outcomes in Preadolescence: The Role of Toddlers? Self-regulation Skills and the Temperament Dimension of Pleasure

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    Objective To investigate the role of toddlers? self-regulation skills and temperament in predicting weight outcomes in preadolescence. Method Participants for this study included 195 children (114 girls) obtained from three different cohorts participating in a larger ongoing longitudinal study. At 2 years of age, participants participated in several laboratory tasks designed to assess their self-regulation abilities, including emotion regulation, sustained attention, and delay of gratification, while parents filled out a temperament questionnaire to assess toddlers? pleasure expression. Height and weight measures were collected when children were 4, 5, 7, and 10 years of age. Children also filled out a body image and eating questionnaire at the 10 year visit. Results Self-regulation skills in toddlers were associated with both BMI development, pediatric obesity, and body image/eating concerns. The temperament dimension of pleasure was also associated with BMI development and pediatric obesity but not body image/eating concerns. Conclusion Self-regulation difficulties across domains as well as temperament based pleasure in toddlers represented significant individual risk factors for the development of pediatric obesity eight years later. Early self-regulation difficulties also contributed to body image and eating concerns that typically accompanied overweight children. The mechanisms by which early self-regulation skills and temperament based pleasure may contribute to the development of pediatric obesity and associated weight concerns are discussed

    A prospective multi-center cohort study of acute non-displaced fractures of the scaphoid: operative versus non-operative treatment [NCT00205985]

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    BACKGROUND: Acute scaphoid fractures are common in active adults and do lead to reasonable time lost to work. One important goal of treatment is early return to work or sport. On this background, the adequate treatment of non-displaced acute scaphoid fractures is still under discussion. The aim of this study is to compare time to return to previous activity level comparing surgical versus non-surgical treatment of non-displaced acute scaphoid fractures. METHODS/DESIGN: The study is designed as a non-randomized multiple center cohort study including 12 sites in Germany and Austria. The inclusion period is planned to be 12 months with a follow up of 6 months. Allocation to operative or non-operative treatment is choosen by the patient together with his treating surgeon. The primary outcome is time to return to previous activity level adapted for loading of the wrist in daily life as measured by a newly developed questionnaire (PLDL-wrist). Factors identified a priori to be associated with the outcome, e.g., poverty status, age, education, smoking status, gender, and occupation, are measured to ensure adequate control for their potential confounding effects. DISCUSSION: The rationale and the design of a multiple center cohort study are presented. As it is not considered feasible to randomize patients in this study, potential confounding effects need to be controlled adequately

    Interaction between genetic and epigenetic variation defines gene expression patterns at the asthma-associated locus 17q12-q21 in lymphoblastoid cell lines

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    Phenotypic variation results from variation in gene expression, which is modulated by genetic and/or epigenetic factors. To understand the molecular basis of human disease, interaction between genetic and epigenetic factors needs to be taken into account. The asthma-associated region 17q12-q21 harbors three genes, the zona pellucida binding protein 2 (ZPBP2), gasdermin B (GSDMB) and ORM1-like 3 (ORMDL3), that show allele-specific differences in expression levels in lymphoblastoid cell lines (LCLs) and CD4+ T cells. Here, we report a molecular dissection of allele-specific transcriptional regulation of the genes within the chromosomal region 17q12-q21 combining in vitro transfection, formaldehyde-assisted isolation of regulatory elements, chromatin immunoprecipitation and DNA methylation assays in LCLs. We found that a single nucleotide polymorphism rs4795397 influences the activity of ZPBP2 promoter in vitro in an allele-dependent fashion, and also leads to nucleosome repositioning on the asthma-associated allele. However, variable methylation of exon 1 of ZPBP2 masks the strong genetic effect on ZPBP2 promoter activity in LCLs. In contrast, the ORMDL3 promoter is fully unmethylated, which allows detection of genetic effects on its transcription. We conclude that the cis-regulatory effects on 17q12-q21 gene expression result from interaction between several regulatory polymorphisms and epigenetic factors within the cis-regulatory haplotype region

    An NF-Y-Dependent Switch of Positive and Negative Histone Methyl Marks on CCAAT Promoters

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    Background: Histone tails have a plethora of different post-translational modifications, which are located differently in ‘‘open’ ’ and ‘‘closed’ ’ parts of genomes. H3K4me3/H3K79me2 and H4K20me3 are among the histone marks associated with the early establishment of active and inactive chromatin, respectively. One of the most widespread promoter elements is the CCAAT box, bound by the NF-Y trimer. Two of NF-Y subunits have an H2A-H2B-like structure. Principal findings: We established the causal relationship between NF-Y binding and positioning of methyl marks, by ChIP analysis of mouse and human cells infected with a dominant negative NF-YA: a parallel decrease in NF-Y binding, H3K4me3, H3K79me2 and transcription was observed in promoters that are dependent upon NF-Y. On the contrary, changes in the levels of H3K9-14ac were more subtle. Components of the H3K4 methylating MLL complex are not recruited in the absence of NF-Y. As for repressed promoters, NF-Y removal leads to a decrease in the H4K20me3 mark and deposition of H3K4me3. Conclusions: Two relevant findings are reported: (i) NF-Y gains access to its genomic locations independently from the presence of methyl histone marks, either positive or negative; (ii) NF-Y binding has profound positive or negative consequences on the deposition of histone methyl marks. Therefore NF-Y is a fundamental switch at the heart of decisio

    Sex Reversal in Zebrafish fancl Mutants Is Caused by Tp53-Mediated Germ Cell Apoptosis

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    The molecular genetic mechanisms of sex determination are not known for most vertebrates, including zebrafish. We identified a mutation in the zebrafish fancl gene that causes homozygous mutants to develop as fertile males due to female-to-male sex reversal. Fancl is a member of the Fanconi Anemia/BRCA DNA repair pathway. Experiments showed that zebrafish fancl was expressed in developing germ cells in bipotential gonads at the critical time of sexual fate determination. Caspase-3 immunoassays revealed increased germ cell apoptosis in fancl mutants that compromised oocyte survival. In the absence of oocytes surviving through meiosis, somatic cells of mutant gonads did not maintain expression of the ovary gene cyp19a1a and did not down-regulate expression of the early testis gene amh; consequently, gonads masculinized and became testes. Remarkably, results showed that the introduction of a tp53 (p53) mutation into fancl mutants rescued the sex-reversal phenotype by reducing germ cell apoptosis and, thus, allowed fancl mutants to become fertile females. Our results show that Fancl function is not essential for spermatogonia and oogonia to become sperm or mature oocytes, but instead suggest that Fancl function is involved in the survival of developing oocytes through meiosis. This work reveals that Tp53-mediated germ cell apoptosis induces sex reversal after the mutation of a DNA–repair pathway gene by compromising the survival of oocytes and suggests the existence of an oocyte-derived signal that biases gonad fate towards the female developmental pathway and thereby controls zebrafish sex determination

    Short Term Effects of Gossip Behavior on Self-Esteem

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    Gossip is a frequent social activity, yet there is little research on the experience of providing gossip and how it impacts upon well-being of the gossiper. The present research aimed to investigate the effect of gossip behavior on the self-esteem of the gossiper. In Study 1, 140 participants were asked to write either a positive or negative description of a target person. Self-esteem was significantly reduced after providing a negative description but there was no effect of providing a positive one. In Study 2, 112 participants were asked to share information about someone they knew. Self-esteem decreased significantly regardless of the valence of the information. This research suggests that the act of gossiping is one which leads to self‐criticism regardless of valence

    DRD4 Polymorphism Moderates the Effect of Alcohol Consumption on Social Bonding

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    Development of interpersonal relationships is a fundamental human motivation, and behaviors facilitating social bonding are prized. Some individuals experience enhanced reward from alcohol in social contexts and may be at heightened risk for developing and maintaining problematic drinking. We employed a 3 (group beverage condition) ×2 (genotype) design (N = 422) to test the moderating influence of the dopamine D4 receptor gene (DRD4 VNTR) polymorphism on the effects of alcohol on social bonding. A significant gene x environment interaction showed that carriers of at least one copy of the 7-repeat allele reported higher social bonding in the alcohol, relative to placebo or control conditions, whereas alcohol did not affect ratings of 7-absent allele carriers. Carriers of the 7-repeat allele were especially sensitive to alcohol's effects on social bonding. These data converge with other recent gene-environment interaction findings implicating the DRD4 polymorphism in the development of alcohol use disorders, and results suggest a specific pathway by which social factors may increase risk for problematic drinking among 7-repeat carriers. More generally, our findings highlight the potential utility of employing transdisciplinary methods that integrate genetic methodologies, social psychology, and addiction theory to improve theories of alcohol use and abuse

    Noise Contributions in an Inducible Genetic Switch: A Whole-Cell Simulation Study

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    Stochastic expression of genes produces heterogeneity in clonal populations of bacteria under identical conditions. We analyze and compare the behavior of the inducible lac genetic switch using well-stirred and spatially resolved simulations for Escherichia coli cells modeled under fast and slow-growth conditions. Our new kinetic model describing the switching of the lac operon from one phenotype to the other incorporates parameters obtained from recently published in vivo single-molecule fluorescence experiments along with in vitro rate constants. For the well-stirred system, investigation of the intrinsic noise in the circuit as a function of the inducer concentration and in the presence/absence of the feedback mechanism reveals that the noise peaks near the switching threshold. Applying maximum likelihood estimation, we show that the analytic two-state model of gene expression can be used to extract stochastic rates from the simulation data. The simulations also provide mRNA–protein probability landscapes, which demonstrate that switching is the result of crossing both mRNA and protein thresholds. Using cryoelectron tomography of an E. coli cell and data from proteomics studies, we construct spatial in vivo models of cells and quantify the noise contributions and effects on repressor rebinding due to cell structure and crowding in the cytoplasm. Compared to systems without spatial heterogeneity, the model for the fast-growth cells predicts a slight decrease in the overall noise and an increase in the repressors rebinding rate due to anomalous subdiffusion. The tomograms for E. coli grown under slow-growth conditions identify the positions of the ribosomes and the condensed nucleoid. The smaller slow-growth cells have increased mRNA localization and a larger internal inducer concentration, leading to a significant decrease in the lifetime of the repressor–operator complex and an increase in the frequency of transcriptional bursts
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