The stellar populations of early-type galaxies -- II. The effects of environment and mass

The degree of influence that environment and mass have on the stellar populations of early-type galaxies is uncertain. In this paper we present the results of a spectroscopic analysis of the stellar populations of early-type galaxies aimed at addressing this question. The sample of galaxies is drawn from four clusters, with =0.04, and their surrounding structure extending to ~10R_{vir}. We find that the distributions of the absorption-line strengths and the stellar population parameters age, metallicity and alpha-element abundance ratio do not differ significantly between the clusters and their outskirts, but the tight correlations found between these quantities and velocity dispersion within the clusters are weaker in their outskirts. All three stellar population parameters of cluster galaxies are positively correlated with velocity dispersion. Galaxies in clusters form a homogeneous class of objects that have similar distributions of line-strengths and stellar population parameters, and follow similar scaling relations regardless of cluster richness or morphology. We estimate the intrinsic scatter of the Gaussian distribution of metallicities to be 0.3 dex, while that of the alpha-element abundance ratio is 0.07 dex. The e-folding time of the exponential distribution of galaxy ages is estimated to be 900 Myr. The intrinsic scatters of the metallicity and alpha-element abundance ratio distributions can almost entirely be accounted for by the correlations with velocity dispersion and the intrinsic scatter about these relations. This implies that a galaxies mass plays the major role in determining its stellar population.Comment: 20 pages, 12 figures, 5 tables, accepted by MNRA

Convergent genetic and expression data implicate immunity in Alzheimer's disease

Background Late–onset Alzheimer's disease (AD) is heritable with 20 genes showing genome wide association in the International Genomics of Alzheimer's Project (IGAP). To identify the biology underlying the disease we extended these genetic data in a pathway analysis. Methods The ALIGATOR and GSEA algorithms were used in the IGAP data to identify associated functional pathways and correlated gene expression networks in human brain. Results ALIGATOR identified an excess of curated biological pathways showing enrichment of association. Enriched areas of biology included the immune response (p = 3.27×10-12 after multiple testing correction for pathways), regulation of endocytosis (p = 1.31×10-11), cholesterol transport (p = 2.96 × 10-9) and proteasome-ubiquitin activity (p = 1.34×10-6). Correlated gene expression analysis identified four significant network modules, all related to the immune response (corrected p 0.002 – 0.05). Conclusions The immune response, regulation of endocytosis, cholesterol transport and protein ubiquitination represent prime targets for AD therapeutics

Rare coding variants in PLCG2, ABI3, and TREM2 implicate microglial-mediated innate immunity in Alzheimer's disease

We identified rare coding variants associated with Alzheimer’s disease (AD) in a 3-stage case-control study of 85,133 subjects. In stage 1, 34,174 samples were genotyped using a whole-exome microarray. In stage 2, we tested associated variants (P<1×10-4) in 35,962 independent samples using de novo genotyping and imputed genotypes. In stage 3, an additional 14,997 samples were used to test the most significant stage 2 associations (P<5×10-8) using imputed genotypes. We observed 3 novel genome-wide significant (GWS) AD associated non-synonymous variants; a protective variant in PLCG2 (rs72824905/p.P522R, P=5.38×10-10, OR=0.68, MAFcases=0.0059, MAFcontrols=0.0093), a risk variant in ABI3 (rs616338/p.S209F, P=4.56×10-10, OR=1.43, MAFcases=0.011, MAFcontrols=0.008), and a novel GWS variant in TREM2 (rs143332484/p.R62H, P=1.55×10-14, OR=1.67, MAFcases=0.0143, MAFcontrols=0.0089), a known AD susceptibility gene. These protein-coding changes are in genes highly expressed in microglia and highlight an immune-related protein-protein interaction network enriched for previously identified AD risk genes. These genetic findings provide additional evidence that the microglia-mediated innate immune response contributes directly to AD development

New insights into the genetic etiology of Alzheimer's disease and related dementias

Characterization of the genetic landscape of Alzheimer's disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/'proxy' AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele

Design and baseline characteristics of the finerenone in reducing cardiovascular mortality and morbidity in diabetic kidney disease trial

Background: Among people with diabetes, those with kidney disease have exceptionally high rates of cardiovascular (CV) morbidity and mortality and progression of their underlying kidney disease. Finerenone is a novel, nonsteroidal, selective mineralocorticoid receptor antagonist that has shown to reduce albuminuria in type 2 diabetes (T2D) patients with chronic kidney disease (CKD) while revealing only a low risk of hyperkalemia. However, the effect of finerenone on CV and renal outcomes has not yet been investigated in long-term trials. Patients and Methods: The Finerenone in Reducing CV Mortality and Morbidity in Diabetic Kidney Disease (FIGARO-DKD) trial aims to assess the efficacy and safety of finerenone compared to placebo at reducing clinically important CV and renal outcomes in T2D patients with CKD. FIGARO-DKD is a randomized, double-blind, placebo-controlled, parallel-group, event-driven trial running in 47 countries with an expected duration of approximately 6 years. FIGARO-DKD randomized 7,437 patients with an estimated glomerular filtration rate >= 25 mL/min/1.73 m(2) and albuminuria (urinary albumin-to-creatinine ratio >= 30 to <= 5,000 mg/g). The study has at least 90% power to detect a 20% reduction in the risk of the primary outcome (overall two-sided significance level alpha = 0.05), the composite of time to first occurrence of CV death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure. Conclusions: FIGARO-DKD will determine whether an optimally treated cohort of T2D patients with CKD at high risk of CV and renal events will experience cardiorenal benefits with the addition of finerenone to their treatment regimen. Trial Registration: EudraCT number: 2015-000950-39; ClinicalTrials.gov identifier: NCT02545049

Fournier's gangrene as first presentation of promyelocytic leukemia

A 50-year-old male is described who presented with Fournier's gangrene as what is probably the first manifestation of a newly diagnosed acute myelogenous leukemia (AML), promyelocytic type or variant type M3 according to the FAB classification. Despite aggressive fluid resuscitation, tuned infusion of vasoactive drugs, appropriate antibiotics and extensive surgical debridement, the patient died within 24 h as a result of irreversible septic shock

Compressive strength and elastic modulus at Agilkia on comet 67P/Churyumov-Gerasimenko derived from the SESAME/CASSE touchdown signals

We report an analysis of the Comet Acoustic Surface Sounding Experiment (CASSE) acceleration signals at Philae's first touchdown site Agilkia on comet 67P/Churyumov-Gerasimenko. The signals yield the forces in the contact zone foot-sole and comet surface, and from these forces a compression strength of approximately 10 kPa can be derived. The sole's contact-resonances provide an elastic modulus of the order of 10 MPa. Our results are partially based on calibration experiments, which are described in the appendix of the current paper. Relations known in material science, linking porosity to elasticity and fracture energy, allow one to check the interdependence between compression strength and elasticity. (C) 2017 The Authors. Published by Elsevier Inc