Dia2 Controls Transcription by Mediating Assembly of the RSC Complex

Background: Dia2 is an F-box protein found in the budding yeast, S. cerevisiae. Together with Skp1 and Cul1, Dia2 forms the substrate-determining part of an E3 ubiquitin ligase complex, otherwise known as the SCF. Dia2 has previously been implicated in the control of replication and genome stability via its interaction with the replisome progression complex. Principal Findings: We identified components of the RSC chromatin remodelling complex as genetic interactors with Dia2, suggesting an additional role for Dia2 in the regulation of transcription. We show that Dia2 is involved in controlling assembly of the RSC complex. RSC belongs to a group of ATP-dependent nucleosome-remodelling complexes that controls the repositioning of nucleosomes. The RSC complex is expressed abundantly and its 17 subunits are recruited to chromatin in response to both transcription activation and repression. In the absence of Dia2, RSC-mediated transcription regulation was impaired, with concomitant abnormalities in nucleosome positioning. Conclusions: Our findings imply that Dia2 is required for the correct assembly and function of the RSC complex. Dia2, by controlling the RSC chromatin remodeller, fine-tunes transcription by controlling nucleosome positioning during transcriptional activation and repression

Five insights from the Global Burden of Disease Study 2019

The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019 provides a rules-based synthesis of the available evidence on levels and trends in health outcomes, a diverse set of risk factors, and health system responses. GBD 2019 covered 204 countries and territories, as well as first administrative level disaggregations for 22 countries, from 1990 to 2019. Because GBD is highly standardised and comprehensive, spanning both fatal and non-fatal outcomes, and uses a mutually exclusive and collectively exhaustive list of hierarchical disease and injury causes, the study provides a powerful basis for detailed and broad insights on global health trends and emerging challenges. GBD 2019 incorporates data from 281 586 sources and provides more than 3.5 billion estimates of health outcome and health system measures of interest for global, national, and subnational policy dialogue. All GBD estimates are publicly available and adhere to the Guidelines on Accurate and Transparent Health Estimate Reporting. From this vast amount of information, five key insights that are important for health, social, and economic development strategies have been distilled. These insights are subject to the many limitations outlined in each of the component GBD capstone papers.Peer reviewe

Population-level risks of alcohol consumption by amount, geography, age, sex, and year: a systematic analysis for the Global Burden of Disease Study 2020

Background The health risks associated with moderate alcohol consumption continue to be debated. Small amounts of alcohol might lower the risk of some health outcomes but increase the risk of others, suggesting that the overall risk depends, in part, on background disease rates, which vary by region, age, sex, and year. Methods For this analysis, we constructed burden-weighted dose–response relative risk curves across 22 health outcomes to estimate the theoretical minimum risk exposure level (TMREL) and non-drinker equivalence (NDE), the consumption level at which the health risk is equivalent to that of a non-drinker, using disease rates from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2020 for 21 regions, including 204 countries and territories, by 5-year age group, sex, and year for individuals aged 15–95 years and older from 1990 to 2020. Based on the NDE, we quantified the population consuming harmful amounts of alcohol. Findings The burden-weighted relative risk curves for alcohol use varied by region and age. Among individuals aged 15–39 years in 2020, the TMREL varied between 0 (95% uncertainty interval 0–0) and 0·603 (0·400–1·00) standard drinks per day, and the NDE varied between 0·002 (0–0) and 1·75 (0·698–4·30) standard drinks per day. Among individuals aged 40 years and older, the burden-weighted relative risk curve was J-shaped for all regions, with a 2020 TMREL that ranged from 0·114 (0–0·403) to 1·87 (0·500–3·30) standard drinks per day and an NDE that ranged between 0·193 (0–0·900) and 6·94 (3·40–8·30) standard drinks per day. Among individuals consuming harmful amounts of alcohol in 2020, 59·1% (54·3–65·4) were aged 15–39 years and 76·9% (73·0–81·3) were male. Interpretation There is strong evidence to support recommendations on alcohol consumption varying by age and location. Stronger interventions, particularly those tailored towards younger individuals, are needed to reduce the substantial global health loss attributable to alcohol. Funding Bill & Melinda Gates Foundation

Reporter gene assay with chimeric promoter and 5' untranslated region (UTR) with A or G at the -26 position (upper panel) and the effect of increasing the dose of adriamycin (0, 1, and 2

<p><b>Copyright information:</b></p><p>Taken from "Implication of -26G>A 5' untranslated region polymorphism in susceptibility to sporadic breast cancer and its modulation by codon 72 Arg>Pro polymorphism"</p><p>http://breast-cancer-research.com/content/9/5/R71</p><p>Breast cancer research : BCR 2007;9(5):R71-R71.</p><p>Published online 18 Oct 2007</p><p>PMCID:PMC2242669.</p><p></p>5 μM) (lower panel)

Effect of -26 G/A polymorphism on the 5' untranslated region secondary structure of RNA and stability analyzed by the RNAstructure program (version 4

<p><b>Copyright information:</b></p><p>Taken from "Implication of -26G>A 5' untranslated region polymorphism in susceptibility to sporadic breast cancer and its modulation by codon 72 Arg>Pro polymorphism"</p><p>http://breast-cancer-research.com/content/9/5/R71</p><p>Breast cancer research : BCR 2007;9(5):R71-R71.</p><p>Published online 18 Oct 2007</p><p>PMCID:PMC2242669.</p><p></p>3) and VRNAAFOLD (The European Molecular Biology Open Software Suite). The -26 position with G or A is indicated by arrows

Comparison of allelic imbalance in chromosomes 16 and 17 along with mutation in with -26 GA polymorphism background

<p><b>Copyright information:</b></p><p>Taken from "Implication of -26G>A 5' untranslated region polymorphism in susceptibility to sporadic breast cancer and its modulation by codon 72 Arg>Pro polymorphism"</p><p>http://breast-cancer-research.com/content/9/5/R71</p><p>Breast cancer research : BCR 2007;9(5):R71-R71.</p><p>Published online 18 Oct 2007</p><p>PMCID:PMC2242669.</p><p></p> values given are for overall distribution, G/G versus G/A, and A/A versus G/A

Epigenetic regulation of the X-chromosomal macrosatellite repeat encoding for the cancer/testis gene CT47

Genomics, epigenetics, population genetics and bioinformatic