Sex differences in epigenetic age in Mediterranean high longevity regions

Sex differences in aging manifest in disparities in disease prevalence, physical health, and lifespan, where women tend to have greater longevity relative to men. However, in the Mediterranean Blue Zones of Sardinia (Italy) and Ikaria (Greece) are regions of centenarian abundance, male-female centenarian ratios are approximately one, diverging from the typical trend and making these useful regions in which to study sex differences of the oldest old. Additionally, these regions can be investigated as examples of healthy aging relative to other populations. DNA methylation (DNAm)-based predictors have been developed to assess various health biomarkers, including biological age, Pace of Aging, serum interleukin-6 (IL-6), and telomere length. Epigenetic clocks are biological age predictors whose deviation from chronological age has been indicative of relative health differences between individuals, making these useful tools for interrogating these differences in aging. We assessed sex differences between the Horvath, Hannum, GrimAge, PhenoAge, Skin and Blood, and Pace of Aging predictors from individuals in two Mediterranean Blue Zones and found that men displayed positive epigenetic age acceleration (EAA) compared to women according to all clocks, with significantly greater rates according to GrimAge (β = 3.55; p = 1.22 × 10-12), Horvath (β = 1.07; p = 0.00378) and the Pace of Aging (β = 0.0344; p = 1.77 × 10-08). Other DNAm-based biomarkers findings indicated that men had lower DNAm-predicted serum IL-6 scores (β = -0.00301, p = 2.84 × 10-12), while women displayed higher DNAm-predicted proportions of regulatory T cells than men from the Blue Zone (p = 0.0150, 95% Confidence Interval [0.00131, 0.0117], Cohen's d = 0.517). All clocks showed better correlations with chronological age in women from the Blue Zones than men, but all clocks showed large mean absolute errors (MAE >30 years) in both sexes, except for PhenoAge (MAE <5 years). Thus, despite their equal survival to older ages in these Mediterranean Blue Zones, men in these regions remain biologically older by most measured DNAm-derived metrics than women, with the exception of the IL-6 score and proportion of regulatory T cells

Major improvements to the Heliconius melpomene genome assembly used to confirm 10 chromosome fusion events in 6 million years of butterfly evolution

The Heliconius butterflies are a widely studied adaptive radiation of 46 species spread across Central and South America, several of which are known to hybridize in the wild. Here, we present a substantially improved assembly of the Heliconius melpomene genome, developed using novel methods that should be applicable to improving other genome assemblies produced using short read sequencing. First, we whole-genome-sequenced a pedigree to produce a linkage map incorporating 99% of the genome. Second, we incorporated haplotype scaffolds extensively to produce a more complete haploid version of the draft genome. Third, we incorporated ~20x coverage of Pacific Biosciences sequencing, and scaffolded the haploid genome using an assembly of this long-read sequence. These improvements result in a genome of 795 scaffolds, 275 Mb in length, with an N50 length of 2.1 Mb, an N50 number of 34, and with 99% of the genome placed, and 84% anchored on chromosomes. We use the new genome assembly to confirm that the Heliconius genome underwent 10 chromosome fusions since the split with its sister genus Eueides, over a period of about 6 million yr

Migrant African women: tales of agency and belonging

This paper explores issues of belonging and agency among asylum seekers and refugee women of African origin in the UK. It discusses the ways these women engendered resistance in their everyday life to destitution, lack of cultural recognition, and gender inequality through the foundation of their own non-governmental organization, African Women’s Empowerment Forum, AWEF, a collective ‘home’ space. The focus of this account is on migrant women’s agency and self-determination for the exercise of choice to be active actors in society. It points to what might be an important phenomenon on how local grassroots movements are challenging the invisibility of asylum seekers’ and refugees’ lives and expanding the notion of politics to embrace a wider notion of community politics with solidarity. AWEF is the embodiment of a social space that resonates the ‘in-between’ experience of migrant life providing stability to the women members regarding political and community identification

No evidence for maintenance of a sympatric Heliconius species barrier by chromosomal inversions.

Mechanisms that suppress recombination are known to help maintain species barriers by preventing the breakup of coadapted gene combinations. The sympatric butterfly species Heliconius melpomene and Heliconius cydno are separated by many strong barriers, but the species still hybridize infrequently in the wild, and around 40% of the genome is influenced by introgression. We tested the hypothesis that genetic barriers between the species are maintained by inversions or other mechanisms that reduce between-species recombination rate. We constructed fine-scale recombination maps for Panamanian populations of both species and their hybrids to directly measure recombination rate within and between species, and generated long sequence reads to detect inversions. We find no evidence for a systematic reduction in recombination rates in F1 hybrids, and also no evidence for inversions longer than 50 kb that might be involved in generating or maintaining species barriers. This suggests that mechanisms leading to global or local reduction in recombination do not play a significant role in the maintenance of species barriers between H. melpomene and H. cydno

American Society of Clinical Oncology Summit on Addressing Obesity Through Multidisciplinary Provider Collaboration: Key Findings and Recommendations for Action

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/139117/1/oby21987.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/139117/2/oby21987_am.pd

Sexual arousal: the correspondence of eyes and genitals.

Men's, more than women's, sexual responses may include a coordination of several physiological indices in order to build their sexual arousal to relevant targets. Here, for the first time, genital arousal and pupil dilation to sexual stimuli were simultaneously assessed. These measures corresponded more strongly with each other, subjective sexual arousal, and self-reported sexual orientation in men than women. Bisexual arousal is more prevalent in women than men. We therefore predicted that if bisexual-identified men show bisexual arousal, the correspondence of their arousal indices would be more female-typical, thus weaker, than for other men. Homosexual women show more male-typical arousal than other women; hence, their correspondence of arousal indices should be stronger than for other women. Findings, albeit weak in effect, supported these predictions. Thus, if sex-specific patterns are reversed within one sex, they might affect more than one aspect of sexual arousal. Because pupillary responses reflected sexual orientation similar to genital responses, they offer a less invasive alternative for the measurement of sexual arousal

Genome-Wide Discovery of Somatic Regulatory Variants in Diffuse Large B-Cell Lymphoma

Diffuse large B-cell lymphoma (DLBCL) is an aggressive cancer originating from mature B-cells. Prognosis is strongly associated with molecular subgroup, although the driver mutations that distinguish the two main subgroups remain poorly defined. Through an integrative analysis of whole genomes, exomes, and transcriptomes, we have uncovered genes and non-coding loci that are commonly mutated in DLBCL. Our analysis has identified novel cis-regulatory sites, and implicates recurrent mutations in the 3′ UTR of NFKBIZ as a novel mechanism of oncogene deregulation and NF-κB pathway activation in the activated B-cell (ABC) subgroup. Small amplifications associated with over-expression of FCGR2B (the Fcγ receptor protein IIB), primarily in the germinal centre B-cell (GCB) subgroup, correlate with poor patient outcomes suggestive of a novel oncogene. These results expand the list of subgroup driver mutations that may facilitate implementation of improved diagnostic assays and could offer new avenues for the development of targeted therapeutics.&nbsp

Risk entrepreneurship and the construction of healthcare deservingness for ‘desirable’, ‘acceptable’ and ‘disposable’ migrants in Malaysia

In recent years, scholars have focused on the concept of healthcare deservingness, observing that healthcare professionals, state authorities and the broader public make moral judgements about which migrants are deserving of health care and which are not. This literature tends to focus on migrants with irregular status. This article examines how state calculations of healthcare deservingness have also been applied to authorised migrants. Focusing on Malaysia, we examine the ways in which state authorities construct migrants as ‘desirable’, ‘acceptable’ and ‘disposable’, differentiated through calculations of their biological and economic risks and potential contribution to ‘the nation’. To do this, we analyse recent government and commercial policies, plans and practices to reflect on how such biopolitical orderings create the conditions for risk entrepreneurship – where public and private actors capitalise on profit-making opportunities that emerge from the construction of risky subjects and risky scenarios – while reinforcing hierarchies of healthcare deservingness that exacerbate health inequalities by privileging migrants with greater economic capital and legitimising the exclusion of poor migrants