Onset of Type 2 diabetes in adults aged 50 and older in Europe: an intersectional multilevel analysis of individual heterogeneity and discriminatory accuracy.

Background: Disparities in the development of Type 2 Diabetes (T2D) are associated with various social determinants, including sex/gender, migration background, living arrangement, education, and household income. This study applied an intersectional perspective to map social disparities and investigate intersectional effects regarding the onset of T2D among older adults across Europe.

Methods: We used data from the Survey of Health and Retirement in Europe (SHARE) to conduct an Intersectional Multilevel Analysis of Individual Heterogeneity and Discriminatory Accuracy (I-MAIHDA) of T2D onset.

Prevention of frailty in relation with social out-of-home activities in older adults: results from the Survey of Health, Ageing, and Retirement in Europe.

Out-of-home mobility and social participation have been identified as resources to postpone frailty. We aim to examine the mediating role and specific contribution of social out-of-home activities in frailty prevention. Data from the Survey of Health, Ageing, and Retirement in Europe (SHARE) waves six (w6), seven (w7), and eight (w8) were used.

Depressive symptoms among individuals identifying as asexual: a cross-sectional study.

Although asexuality became a growing research subject over the last decade, data on the mental health of individuals identifying as asexual is still rare. The key objective of the present study was to examine depressive symptoms among individuals identifying as asexual. Data of LGBTQIA+ (Lesbian, Gay, Bi-sexual, Trans*, Queer, Inter*, Asexual and/or + indicating others within the community) and cisgender heterosexual individuals was collected through an online survey during the COVID-19 lockdowns in Germany.

Psychosocial and biological pathways to aging : The role(s) of the behavioral and social sciences in geroscience.

While the biological hallmarks of aging are widely recognized as fundamental mechanisms of biological aging, more recently, there have been calls within geroscience to understand the aging process more comprehensively by adding a perspective of the social hallmarks of aging. Social and behavioral factors, such as socioeconomic status, life events or behavior and beliefs can alter the aging process per se and act in complex interactions with biological pathways. In addition, underlying biological pathways have been proposed for various psychosocial concepts, such as views on age and relationship quality.

Intersectional Inequalities in the Transition to Grandparenthood and Cognitive Functioning: A Longitudinal Multilevel Analysis of Individual Heterogeneity and Discriminatory Accuracy.

Objectives: In aging societies, more people become vulnerable to experiencing cognitive decline. Simultaneously, the role of grandparenthood is central for older adults and their families. Our study investigates inequalities in the level and trajectories of cognitive functioning among older adults, focusing on possible intersectional effects of social determinants and grandparenthood as a life course transition that may contribute to delaying cognitive decline.

Intersectional inequalities in the transition to grandparenthood and cognitive functioning: A longitudinal Multilevel Analysis of Individual Heterogeneity and Discriminatory Accuracy (MAIHDA).

Objectives: With aging societies, more people become vulnerable to experiencing cognitive decline. While normal aging is associated with a deterioration in certain cognitive abilities, little is known about how social determinants intersect to create late-life cognitive functioning inequalities. Simultaneously, the role of grandparenthood is central for older adults and their families.

Family Structure and Family Climate in Relation to Health and Socioeconomic Status for Older Adults: A Longitudinal Moderated Mediation Analysis.

Family characteristics are associated with individuals' health and wellbeing. However, the link between family structure (e.g.

S. cerevisiae Cells Can Grow without the Pds5 Cohesin Subunit.

During DNA replication, the newly created sister chromatids are held together until their separation at anaphase. The cohesin complex is in charge of creating and maintaining sister chromatid cohesion (SCC) in all eukaryotes. In Saccharomyces cerevisiae cells, cohesin is composed of two elongated proteins, Smc1 and Smc3, bridged by the kleisin Mcd1/Scc1.

Health Care Costs in Patients with and without Secondary Hyperparathyroidism in Spain.

Objective: To analyze the economic burden of secondary hyperparathyroidism (sHPT) in Spain by quantifying differences in costs of pharmacological treatments and associated cardiovascular events (CVE) between renal patients with and without sHPT.

Methods: We used data collected in the NEFRONA cohort study and obtained treatment and CVE costs from the BOT PLUS database and Hospital Discharge Records in the Spanish Health System (CMBD-H), respectively. We examined data from 2445 renal patients followed during 2 years for chronic kidney disease (CKD) progression and 4 years for CVE, stratifying by presence of sHPT.

Characterization of the Pharmaceutical Risk-Sharing Arrangement Process in Catalonia.

Pharmaceutical risk-sharing arrangements have emerged as a reasonable tool to promote sustainable access to innovative medicines with uncertain clinical evidence and/or economic impact from the payer perspective. These funding mechanisms pose an alternative option to the traditional fixed-price methods and are intended to align the price of medication with the value delivered in treating patients, balancing clinical need with affordability in the face of increasing therapeutic innovation and ever-tight budgets. The Catalan Health Service (CatSalut) has set up a systematic, traceable, and transparent methodology for the design and implementation of risk-sharing arrangements and 15 of such access schemes have been successfully implemented until December 2019.

Mutagenic mechanisms of cancer-associated DNA polymerase ϵ alleles.

A single amino acid residue change in the exonuclease domain of human DNA polymerase ϵ, P286R, is associated with the development of colorectal cancers, and has been shown to impart a mutator phenotype. The corresponding Pol ϵ allele in the yeast Saccharomyces cerevisiae (pol2-P301R), was found to drive greater mutagenesis than an entirely exonuclease-deficient Pol ϵ (pol2-4), an unexpected phenotype of ultra-mutagenesis. By studying the impact on mutation frequency, type, replication-strand bias, and sequence context, we show that ultra-mutagenesis is commonly observed in yeast cells carrying a range of cancer-associated Pol ϵ exonuclease domain alleles.

Telomeres and stress in yeast cells: When genes and environment interact.

Telomeres are structures composed of simple DNA repeats and specific proteins that protect the eukaryotic chromosomal ends from degradation, and facilitate the replication of the genome. They are central to the maintenance of the genome integrity, and play important roles in the development of cancer and in the process of aging in humans. The yeast Saccharomyces cerevisiae has greatly contributed to our understanding of basic telomere biology.

The Main Role of Srs2 in DNA Repair Depends on Its Helicase Activity, Rather than on Its Interactions with PCNA or Rad51.

Homologous recombination (HR) is a mechanism that repairs a variety of DNA lesions. Under certain circumstances, however, HR can generate intermediates that can interfere with other cellular processes such as DNA transcription or replication. Cells have therefore developed pathways that abolish undesirable HR intermediates.

Clonal Heterogeneity Influences the Fate of New Adaptive Mutations.

The joint contribution of pre-existing and de novo genetic variation to clonal adaptation is poorly understood but essential to designing successful antimicrobial or cancer therapies. To address this, we evolve genetically diverse populations of budding yeast, S. cerevisiae, consisting of diploid cells with unique haplotype combinations.

Disentangling genetic and epigenetic determinants of ultrafast adaptation.

A major rationale for the advocacy of epigenetically mediated adaptive responses is that they facilitate faster adaptation to environmental challenges. This motivated us to develop a theoretical-experimental framework for disclosing the presence of such adaptation-speeding mechanisms in an experimental evolution setting circumventing the need for pursuing costly mutation-accumulation experiments. To this end, we exposed clonal populations of budding yeast to a whole range of stressors.

Lack of replication of higher genetic risk load in men than in women with systemic lupus erythematosus.

Introduction: We aimed to replicate a recent study which showed higher genetic risk load at 15 loci in men than in women with systemic lupus erythematosus (SLE). This difference was very significant, and it was interpreted as indicating that men require more genetic susceptibility than women to develop SLE.

Methods: Nineteen SLE-associated loci (thirteen of which are shared with the previous study) were analyzed in 1,457 SLE patients and 1,728 healthy controls of European ancestry.

Influence of Atg5 mutation in SLE depends on functional IL-10 genotype.

Increasing evidence supports the involvement of autophagy in the etiopathology of autoimmune diseases. Despite the identification of autophagy-related protein (Atg)-5 as one of the susceptibility loci in systemic Lupus erythematosus (SLE), the consequences of the carriage of these mutations for patients remain unclear. The present work analyzed the association of Atg5 rs573775 single nucleotide polymorphism (SNP) with SLE susceptibility, IFNα, TNFα and IL-10 serum levels, and clinical features, in 115 patients and 170 healthy individuals.

Identification of three new cis-regulatory IRF5 polymorphisms: in vitro studies.

Background: Polymorphisms in the interferon regulatory factor 5 (IRF5) gene are associated with susceptibility to systemic lupus erythematosus, rheumatoid arthritis and other diseases through independent risk and protective haplotypes. Several functional polymorphisms are already known, but they do not account for the protective haplotypes that are tagged by the minor allele of rs729302.

Methods: Polymorphisms in linkage disequilibrium (LD) with rs729302 or particularly associated with IRF5 expression were selected for functional screening, which involved electrophoretic mobility shift assays (EMSAs) and reporter gene assays.

Further evidence of subphenotype association with systemic lupus erythematosus susceptibility loci: a European cases only study.

Introduction: Systemic Lupus Erythematosus (SLE) shows a spectrum of clinical manifestations that complicate its diagnosis, treatment and research. This variability is likely related with environmental exposures and genetic factors among which known SLE susceptibility loci are prime candidates. The first published analyses seem to indicate that this is the case for some of them, but results are still inconclusive and we aimed to further explore this question.

Bias in effect size of systemic lupus erythematosus susceptibility loci across Europe: a case-control study.

Introduction: We aimed to investigate whether the effect size of the systemic lupus erythematosus (SLE) risk alleles varies across European subpopulations.

Methods: European SLE patients (n = 1,742) and ethnically matched healthy controls (n = 2,101) were recruited at 17 centres from 10 different countries. Only individuals with self-reported ancestry from the country of origin were included.

Association of systemic lupus erythematosus clinical features with European population genetic substructure.

Systemic Lupus Erythematosus (SLE) is an autoimmune disease with a very varied spectrum of clinical manifestations that could be partly determined by genetic factors. We aimed to determine the relationship between prevalence of 11 clinical features and age of disease onset with European population genetic substructure. Data from 1413 patients of European ancestry recruited in nine countries was tested for association with genotypes of top ancestry informative markers.

Opposed independent effects and epistasis in the complex association of IRF5 to SLE.

Genetic variation in the interferon regulatory factor 5 (IRF5) gene affects systemic lupus erythematosus (SLE) susceptibility. However, association is complex and incompletely defined. We obtained fourteen European sample collections with a total of 1383 SLE patients and 1614 controls to better define the role of the different IRF5 variants.