Project description:Abstract: C. elegans SIR-2.1, a member of the Sir-2 family of NAD(+)-dependent protein deacetylases, has been shown to regulate nematode aging via the insulin/IGF pathway transcription factor daf-16. Treatment of C. elegans with the small molecule resveratrol, however, extends life span in a manner fully dependent upon sir-2.1, but independent of daf-16. Microarray analysis of worms treated with resveratrol demonstrates the transcriptional induction of a family of genes encoding prion-like glutamine/asparagine-rich proteins involved in endoplasmic reticulum (ER) stress response to unfolded proteins. RNA interference of abu-11, a member of this ER stress gene family, abolishes resveratrol-mediated life span extension, and overexpression of abu-11 extends the life span of transgenic animals. Furthermore, SIR-2.1 normally represses transcription of abu-11 and other ER stress gene family members, indicating that resveratrol extends life span by inhibiting sir-2.1-mediated repression of ER stress genes. Our findings demonstrate that abu-11 and other members of its ER stress gene family are positive determinants of C. elegans life span. This SuperSeries is composed of the SubSeries listed below.
Project description:This SuperSeries is composed of the following subset Series: GSE4093: Resveratrol treatment of daf-16 mutant C. elegans GSE4094: N2 worms treated with Resveratrol GSE4095: Sir-2.1 low copy transgenic Abstract: C. elegans SIR-2.1, a member of the Sir-2 family of NAD(+)-dependent protein deacetylases, has been shown to regulate nematode aging via the insulin/IGF pathway transcription factor daf-16. Treatment of C. elegans with the small molecule resveratrol, however, extends life span in a manner fully dependent upon sir-2.1, but independent of daf-16. Microarray analysis of worms treated with resveratrol demonstrates the transcriptional induction of a family of genes encoding prion-like glutamine/asparagine-rich proteins involved in endoplasmic reticulum (ER) stress response to unfolded proteins. RNA interference of abu-11, a member of this ER stress gene family, abolishes resveratrol-mediated life span extension, and overexpression of abu-11 extends the life span of transgenic animals. Furthermore, SIR-2.1 normally represses transcription of abu-11 and other ER stress gene family members, indicating that resveratrol extends life span by inhibiting sir-2.1-mediated repression of ER stress genes. Our findings demonstrate that abu-11 and other members of its ER stress gene family are positive determinants of C. elegans life span. Refer to individual Series
Project description:Candida albicans repetitive elements display epigenetic diversity and plasticity. This experiment inspects RNA levels on both wild- type (BWP17 strain) and sir double deletion mutant strain in order to detect changes in gene expression associated with SIR2-dependent heterochromatin patterns.
Project description:In the UK10K project we propose a series of complementary genetic approaches to find new low frequency/rare variants contributing to disease phenotypes. These will be based on obtaining the genome wide sequence of 4000 samples from the TwinsUK and ALSPAC cohorts (at 6x sequence coverage), and the exome sequence (protein coding regions and related conserved sequence) of 6000 samples selected for extreme phenotypes.
Our studies will focus primarily on cardiovascular-related quantitative traits, obesity and related metabolic traits, neurodevelopmental disorders and a limited number of extreme clinical phenotypes that will provide proof-of-concept for future familial trait sequencing.
We will analyse directly quantitative traits in the cohorts and the selected traits in the extreme samples, and also use imputation down to 0.1% allele frequency to extend the analyses to further sample sets with genome wide genotype data. In each case we will investigate indels and larger structural variants as well as SNPs, and use statistical methods that combine rare variants in a locus or pathway as well as single-variant approaches.
The SIR (Severe Insulin Resistance) samples are part of the “rare disease” group, and will undergo exome sequencing. For further information with regard to this cohort please contact Robert Semple (rks16@cam.ac.uk).
Project description:The purpose of this study is to determine the safety of regorafenib, an antiangiogenic drug, when combined with radioembolization using SIR-Spheres microspheres in the treatment of colorectal cancer (CRC) that has spread to the liver.
Project description:Hai-Feng Huo, Peng Yang & Hong Xiang. Stability and bifurcation for an SEIS epidemic model with the impact of media. Physica A: Statistical Mechanics and its Applications 490 (2018).
A novel SEIS epidemic model with the impact of media is introduced. By analyzing the characteristic equation of equilibrium, the basic reproduction number is obtained and the stability of the steady states is proved. The occurrence of a forward, backward and Hopf bifurcation is derived. Numerical simulations and sensitivity analysis are performed. Our results manifest that media can regard as a good indicator in controlling the emergence and spread of the epidemic disease.
Project description:The aim of this article is to understand the extreme variability in estimates of the reproduction ratio R0 observed in practice. For expository purposes, we consider a discrete-time, stochastic version of the susceptible-infected-recovered model and introduce different approximate maximum likelihood estimators of R0. We carefully discuss the properties of these estimators and illustrate, by a Monte Carlo study, the widths of confidence intervals for R0.