Longitudinal associations between television in the bedroom and body fatness in a UK cohort study.

OBJECTIVE: To assess longitudinal associations between screen-based media use (television (TV) and computer hours, having a TV in the bedroom) and body fatness among UK children. METHODS: Participants were 12 556 children from the UK Millennium Cohort Study who were followed from age 7 to age 11 years. Associations were assessed between screen-based media use and the following outcomes: body mass index (BMI), fat mass index (FMI), and overweight. RESULTS: In fully adjusted models, having a bedroom TV at age 7 years was associated with significantly higher BMI and FMI (excess BMI for boys=0.29, 95% confidence interval (CI) 0.06-0.52; excess BMI for girls=0.57, 95% CI 0.31-0.84; excess FMI for boys=0.20, 95% CI 0.04-0.37; excess FMI for girls=0.39, 95% CI 0.21-0.57) and increased risk of being overweight (relative risk (RR) for boys=1.21, 95% CI 1.07-1.36; RR for girls=1.31, 95% CI 1.15-1.48) at age 11 years, compared with having no bedroom TV. Hours spent watching TV or digital versatile disks were associated with increased risk of overweight among girls only. Computer use at age 7 years was not related to later body fatness for either gender. CONCLUSION: Having a TV in the child's bedroom was an independent risk factor for overweight and increased body fatness in this nationally representative sample of UK children. Childhood obesity prevention strategies should consider TVs in children's bedrooms as a risk factor for obesity.International Journal of Obesity advance online publication, 27 June 2017; doi:10.1038/ijo.2017.129

Effect of dietary restriction and subsequent re-alimentation on the transcriptional profile of bovine ruminal epithelium

peer-reviewedCompensatory growth (CG) is utilised worldwide in beef production systems as a management approach to reduce feed costs. However the underlying biology regulating the expression of CG remains to be fully elucidated. The objective of this study was to examine the effect of dietary restriction and subsequent re-alimentation induced CG on the global gene expression profile of ruminal epithelial papillae. Holstein Friesian bulls (n = 60) were assigned to one of two groups: restricted feed allowance (RES; n = 30) for 125 days (Period 1) followed by ad libitum access to feed for 55 days (Period 2) or (ii) ad libitum access to feed throughout (ADLIB; n = 30). At the end of each period, 15 animals from each treatment were slaughtered and rumen papillae harvested. mRNA was isolated from all papillae samples collected. cDNA libraries were then prepared and sequenced. Resultant reads were subsequently analysed bioinformatically and differentially expressed genes (DEGs) are defined as having a Benjamini-Hochberg P value of <0.05. During re-alimentation in Period 2, RES animals displayed CG, growing at 1.8 times the rate of their ADLIB contemporary animals in Period 2 (P < 0.001). At the end of Period 1, 64 DEGs were identified between RES and ADLIB, with only one DEG identified at the end of Period 2. When analysed within RES treatment (RES, Period 2 v Period 1), 411 DEGs were evident. Genes identified as differentially expressed in response to both dietary restriction and subsequent CG included those involved in processes such as cellular interactions and transport, protein folding and gene expression, as well as immune response. This study provides an insight into the molecular mechanisms underlying the expression of CG in rumen papillae of cattle; however the results suggest that the role of the ruminal epithelium in supporting overall animal CG may have declined by day 55 of re-alimentation.SMW received financial assistance from Science Foundation Ireland (SFI) contract no 09/ RFP/GEN2447

Gene expression during normal and FSHD myogenesis

<p>Abstract</p> <p>Background</p> <p>Facioscapulohumeral muscular dystrophy (FSHD) is a dominant disease linked to contraction of an array of tandem 3.3-kb repeats (D4Z4) at 4q35. Within each repeat unit is a gene, <it>DUX4</it>, that can encode a protein containing two homeodomains. A <it>DUX4 </it>transcript derived from the last repeat unit in a contracted array is associated with pathogenesis but it is unclear how.</p> <p>Methods</p> <p>Using exon-based microarrays, the expression profiles of myogenic precursor cells were determined. Both undifferentiated myoblasts and myoblasts differentiated to myotubes derived from FSHD patients and controls were studied after immunocytochemical verification of the quality of the cultures. To further our understanding of FSHD and normal myogenesis, the expression profiles obtained were compared to those of 19 non-muscle cell types analyzed by identical methods.</p> <p>Results</p> <p>Many of the ~17,000 examined genes were differentially expressed (> 2-fold, <it>p </it>< 0.01) in control myoblasts or myotubes vs. non-muscle cells (2185 and 3006, respectively) or in FSHD vs. control myoblasts or myotubes (295 and 797, respectively). Surprisingly, despite the morphologically normal differentiation of FSHD myoblasts to myotubes, most of the disease-related dysregulation was seen as dampening of normal myogenesis-specific expression changes, including in genes for muscle structure, mitochondrial function, stress responses, and signal transduction. Other classes of genes, including those encoding extracellular matrix or pro-inflammatory proteins, were upregulated in FSHD myogenic cells independent of an inverse myogenesis association. Importantly, the disease-linked <it>DUX4 </it>RNA isoform was detected by RT-PCR in FSHD myoblast and myotube preparations only at extremely low levels. Unique insights into myogenesis-specific gene expression were also obtained. For example, all four Argonaute genes involved in RNA-silencing were significantly upregulated during normal (but not FSHD) myogenesis relative to non-muscle cell types.</p> <p>Conclusions</p> <p><it>DUX4</it>'s pathogenic effect in FSHD may occur transiently at or before the stage of myoblast formation to establish a cascade of gene dysregulation. This contrasts with the current emphasis on toxic effects of experimentally upregulated <it>DUX4 </it>expression at the myoblast or myotube stages. Our model could explain why <it>DUX4</it>'s inappropriate expression was barely detectable in myoblasts and myotubes but nonetheless linked to FSHD.</p

Real-time visualization of heterotrimeric G protein Gq activation in living cells

Contains fulltext : 97296.pdf (publisher's version ) (Open Access)BACKGROUND: Gq is a heterotrimeric G protein that plays an important role in numerous physiological processes. To delineate the molecular mechanisms and kinetics of signalling through this protein, its activation should be measurable in single living cells. Recently, fluorescence resonance energy transfer (FRET) sensors have been developed for this purpose. RESULTS: In this paper, we describe the development of an improved FRET-based Gq activity sensor that consists of a yellow fluorescent protein (YFP)-tagged Ggamma2 subunit and a Galphaq subunit with an inserted monomeric Turquoise (mTurquoise), the best cyan fluorescent protein variant currently available. This sensor enabled us to determine, for the first time, the kon (2/s) of Gq activation. In addition, we found that the guanine nucleotide exchange factor p63RhoGEF has a profound effect on the number of Gq proteins that become active upon stimulation of endogenous histamine H1 receptors. The sensor was also used to measure ligand-independent activation of the histamine H1 receptor (H1R) upon addition of a hypotonic stimulus. CONCLUSIONS: Our observations reveal that the application of a truncated mTurquoise as donor and a YFP-tagged Ggamma2 as acceptor in FRET-based Gq activity sensors substantially improves their dynamic range. This optimization enables the real-time single cell quantification of Gq signalling dynamics, the influence of accessory proteins and allows future drug screening applications by virtue of its sensitivity

Behavioral genetics and taste

This review focuses on behavioral genetic studies of sweet, umami, bitter and salt taste responses in mammals. Studies involving mouse inbred strain comparisons and genetic analyses, and their impact on elucidation of taste receptors and transduction mechanisms are discussed. Finally, the effect of genetic variation in taste responsiveness on complex traits such as drug intake is considered. Recent advances in development of genomic resources make behavioral genetics a powerful approach for understanding mechanisms of taste

Study of the influence of nifedipine on the pharmacokinetics and pharmacodynamics of propranolol, metoprolol and atenolol

The influence of chronic therapy with nifedipine on the pharmacokinetics of propranolol 80 mg twice daily, metoprolol 100 mg twice daily and atenolol 100 mg once daily was investigated in eight healthy volunteers. Nifedipine 10 mg three times daily did not affect the pharmacokinetics of metoprolol and atenolol whereas nifedipine shortened the time to peak plasma concentration for propranolol by about 1 h. Propranolol, metoprolol and atenolol provoked comparable decreases in heart rate measured at rest and during exercise. The beta-adrenoceptor blocking properties of propranolol, metoprolol and atenolol were not affected by concomitant therapy with nifedipine. The present study did not show significant pharmacokinetic and pharmacodynamic interactions between nifedipine and lipophilic beta-adrenoceptor blockers.Journal ArticleResearch Support, Non-U.S. Gov'tSCOPUS: ar.jFLWINinfo:eu-repo/semantics/publishe