R Coronae Borealis Stars are Viable Factories of Pre-solar Grains

We present a new theoretical estimate for the birthrate of R Coronae Borealis (RCB) stars that is in agreement with recent observational data. We find the current Galactic birthrate of RCB stars to be $\approx$ 25% of the Galactic rate of Type Ia supernovae, assuming that RCB stars are formed through the merger of carbon-oxygen and helium-rich white dwarfs. Our new RCB birthrate ($1.8 \times 10^{-3}$ yr$^{-1}$) is a factor of 10 lower than previous theoretical estimates. This results in roughly 180--540 RCB stars in the Galaxy, depending on the RCB lifetime. From the theoretical and observational estimates, we calculate the total dust production from RCB stars and compare this rate to dust production from novae and born-again asymptotic giant branch (AGB) stars. We find that the amount of dust produced by RCB stars is comparable to the amounts produced by novae or born-again post-AGB stars, indicating that these merger objects are a viable source of carbonaceous pre-solar grains in the Galaxy. There are graphite grains with carbon and oxygen isotopic ratios consistent with the observed composition of RCB stars, adding weight to the suggestion that these rare objects are a source of stardust grains.Comment: Accepted for publication in The Astrophysical Journal, 7 page

Learning about the intermediate neutron-capture process from lead abundances

Lead (Pb) is predominantly produced by the slow neutron-capture process (s process) in asymptotic giant branch (AGB) stars. In contrast t metallicity AGB-models, observations of Magellanic post-AGB stars sho poor (CEMP) stars whose s-process enrichments are accompanied by heav elements traditionally associated with the rapid neutron-capture proces (r process) have raised the need for a neutron-capture process operatin at neutron densities intermediate to the s and r process: the so-calle network calculations. Our i-process models can explain the heavy-elemen abundance patterns measured in Magellanic post-AGB stars including thei puzzlingly low Pb abundances. Furthermore, the heavy-elemen enhancements in the post-AGB and CEMP-i stars, particularly their P abundance, allow us to characterise the neutron densities and exposure of the i process that produced the observed abundance patterns. We fin that the lower-metallicity CEMP-i stars ($\\left[ \\mathrm{Fe} \\mathrm{H} \\right] \\approx -2.5$) have heavy-element abundances bes matched by models with higher neutron densities and exposures ($\\ta > 2.0 \\, \\mathrm{mbarn}^{-1}$) compared to the higher-metallicit post-AGB stars ($\\left[ \\mathrm{Fe} / \\mathrm{H} \\right] \\approx -1.3$ $\\tau < 1.3 \\, \\mathrm{mbarn}^{-1}$). This offers new constraints an insights regarding the properties of i-process sites and demonstrate that the responsible process operates on time scales of the order of few years or les

Learning about the intermediate neutron-capture process from lead abundances

Lead (Pb) is predominantly produced by the slow neutron-capture process (s process) in asymptotic giant branch (AGB) stars. In contrast t metallicity AGB-models, observations of Magellanic post-AGB stars sho poor (CEMP) stars whose s-process enrichments are accompanied by heav elements traditionally associated with the rapid neutron-capture proces (r process) have raised the need for a neutron-capture process operatin at neutron densities intermediate to the s and r process: the so-calle network calculations. Our i-process models can explain the heavy-elemen abundance patterns measured in Magellanic post-AGB stars including thei puzzlingly low Pb abundances. Furthermore, the heavy-elemen enhancements in the post-AGB and CEMP-i stars, particularly their P abundance, allow us to characterise the neutron densities and exposure of the i process that produced the observed abundance patterns. We fin that the lower-metallicity CEMP-i stars ($\\left[ \\mathrm{Fe} \\mathrm{H} \\right] \\approx -2.5$) have heavy-element abundances bes matched by models with higher neutron densities and exposures ($\\ta > 2.0 \\, \\mathrm{mbarn}^{-1}$) compared to the higher-metallicit post-AGB stars ($\\left[ \\mathrm{Fe} / \\mathrm{H} \\right] \\approx -1.3$ $\\tau < 1.3 \\, \\mathrm{mbarn}^{-1}$). This offers new constraints an insights regarding the properties of i-process sites and demonstrate that the responsible process operates on time scales of the order of few years or les

MLH1-methylated endometrial cancer under 60 years of age as the “sentinel” cancer in female carriers of high-risk constitutional MLH1 epimutation

Objective. Universal screening of endometrial carcinoma (EC) for mismatch repair deficiency (MMRd) and Lynch syndrome uses presence of MLH1 methylation to omit common sporadic cases from follow-up germline testing. However, this overlooks rare cases with high-risk constitutional MLH1 methylation (epimutation), a poorly-recognized mechanism that predisposes to Lynch-type cancers with MLH1 methylation. We aimed to de-termine the role and frequency of constitutional MLH1 methylation among EC cases with MMRd, MLH1- methylated tumors.Methods. We screened blood for constitutional MLH1 methylation using pyrosequencing and real-time methylation-specific PCR in patients with MMRd, MLH1-methylated EC ascertained from (i) cancer clinics (n = 4, <60 years), and (ii) two population-based cohorts; Columbus-area (n = 68, all ages) and Ohio Colo-rectal Cancer Prevention Initiative (OCCPI) (n = 24, <60 years).Results. Constitutional MLH1 methylation was identified in three out of four patients diagnosed between 36 and 59 years from cancer clinics. Two had mono-/hemiallelic epimutation (similar to 50% alleles methylated). One with multiple primaries had low-level mosaicism in normal tissues and somatic second-hits affecting the unmethylated allele in all tumors, demonstrating causation. In the population-based cohorts, all 68 cases from the Columbus-area cohort were negative and low-level mosaic constitutional MLH1 methylation was identified in one patient aged 36 years out of 24 from the OCCPI cohort, representing one of six (similar to 17%) patients <50 years and one of 45 patients (similar to 2%) <60 years in the combined cohorts. EC was the first/dual-first cancer in three pa-tients with underlying constitutional MLH1 methylation.Conclusions. A correct diagnosis at first presentation of cancer is important as it will significantly alter clinical management. Screening for constitutional MLH1 methylation is warranted in patients with early-onset EC or syn-chronous/metachronous tumors (any age) displaying MLH1 methylation.(c) 2023 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license (http:// creativecommons.org/licenses/by-nc-nd/4.0/)

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

Unusual neutron-capture nucleosynthesis in a carbon-rich Galactic bulge star

Metal-poor stars in the Galactic halo often show strong enhancements in carbon and/or neutron-capture elements. However, the Galactic bulge is notable for its paucity of these carbon-enhanced metal-poor (CEMP) and/or CH-stars, with only two such objects known to date. This begs the question whether the processes that produced their abundance distribution were governed by a comparable nucleosynthesis in similar stellar sites as for their more numerous counterparts in the halo. Recently, two contenders of these classes of stars were discovered in the bulge, at [Fe/H] = −1.5 and −2.5 dex, both of which show enhancements in [C/Fe] of 0.4 and 1.4 dex (respectively), [Ba/Fe] in excess of 1.3 dex, and also elevated nitrogen. The more metal-poor of the stars can be well matched by standard s-process nucleosynthesis in low-mass asymptotic giant branch (AGB) polluters. The other star shows an abnormally high [Rb/Fe] ratio. Here, we further investigate the origin of the abundance peculiarities in the Rb-rich star by new, detailed measurements of heavy element abundances and by comparing the chemical element ratios of 36 species to several models of neutron-capture nucleosynthesis. The i-process with intermediate neutron densities between those of the slow (s-) and rapid (r)-neutron-capture processes has been previously found to provide good matches of CEMP stars with enhancements in both r- and s-process elements (class CEMP-r/s), rather than invoking a superposition of yields from the respective individual processes. However, the peculiar bulge star is incompatible with a pure i-process from a single ingestion event. Instead, it can, statistically, be better reproduced by more convoluted models accounting for two proton ingestion events, or by an i-process component in combination with s-process nucleosynthesis in low-to-intermediate mass (2–3 M⊙) AGB stars, indicating multiple polluters. Finally, we discuss the impact of mixing during stellar evolution on the observed abundance peculiarities

Deep‐Sea Wooden Shipwrecks Influence Sediment Microbiome Diversity

Historic shipwrecks function as habitats for benthic organisms by providing food, refuge, and structure. They also form islands of biodiversity on the seabed, shaping microbial ecology and ecosystem processes. This study examined two wooden deep-sea shipwrecks at 525 and 1800 m water depth and probed their influence on sediment microbiomes and geochemistry. Microbiomes were investigated with 16S rRNA gene amplicon sequencing along 60 m transects extending in four directions from the hulls of the shipwrecks. Distance from shipwrecks and sediment depth both shaped microbiome structure. Archaeal alpha diversity was significantly and positively correlated with proximity to the deeper shipwreck while bacterial diversity was not to either. Archaeal community structure differed at both sites; the deeper site had a higher proportion of Bathyarchaeia and Lokiarchaeia proximate to shipwreck compared to the shallow location. Major bacterial communities were consistent at both sites, however, at the deeper site had higher abundance of Bacteroidetes, Chloroflexi, Desulfofarculales, and Desulfobacteriales. Core microbiome and differential abundance analyses revealed unique taxa nearest the shipwrecks compared to the surrounding seabed including organoheterotrophs, and cellulolytic and sulfur cycling taxa. Sediment carbon content influenced microbiome structure near the shipwrecks (5–10 m). We show that shipwrecks have a distinct sediment microbiome and form unique habitat patches on seabed, resembling those surrounding organic falls. The shipwreck influence was more pronounced at the deeper site, further from terrestrial influences signaling shipwrecks may be a significant source of organic matter in far-shore oligotrophic settings