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Category: sex

One DNA letter can trigger complete sex reversal

Researchers at Bar-Ilan University have discovered that changing just one letter in DNA can completely alter sex development in mice. In the new study, published in Nature Communications, a single-letter insertion in a non-coding regulatory region caused XX mice, which would normally develop as females, to develop instead as males with testis and male genitalia.

The finding is especially striking because the mutation was not made in a gene itself, but in a distant stretch of DNA that helps control a key developmental gene. The study highlights the major role of the non-coding genome —the 98% of DNA that does not make proteins but helps regulate when and how genes are turned on and off.

“This is a remarkable finding because such a tiny change—just one DNA letter out of approximately 2.8 billion—was enough to produce a dramatic developmental outcome,” said Dr. Nitzan Gonen, from the Goodman Faculty of Life Sciences and Institute of Nanotechnology and Advanced Materials at Bar-Ilan University. “It shows that non-coding DNA can have a profound effect on development and disease.”

Exercise induces sex-specific assembly of mitochondrial supercomplexes

Mitochondrial supercomplexes assembly in exercise.

The function of supercomplexes (SCs) formed from mitochondrial electron transport chain (ETC) is not well understood.

The researchers demonstrate that exercise dynamically modulates the assembly of mitochondrial respiratory complexes into supercomplexes (SCs) in human skeletal muscle, with this remodeling being sex dependent.

The authors found that males increased the assembly of complex III (CIII) into SCs, particularly high molecular weight SCs (HMWSCs), in an intensity-dependent manner within skeletal muscle. Females showed a stable content of both HMWSCs and I+III2 SCs during exercise.

This highlights the importance of accounting for biological sex when studying mitochondrial adaptations to exercise. sciencenewshighlights ScienceMission https://sciencemission.com/mitochondrial-supercomplexes-and-exercise

Huertas et al. demonstrate that exercise dynamically modulates the assembly of mitochondrial respiratory complexes into supercomplexes in human skeletal muscle, with this remodeling being sex dependent. This highlights the importance of accounting for biological sex when studying mitochondrial adaptations to exercise.

Continue reading “Exercise induces sex-specific assembly of mitochondrial supercomplexes” | >

Validation of the MOG-AR ScoreA Retrospective Multicenter Study

Validation of the MOG-AR score: a retrospective multicenter study.

Recently, a simple score (the MOG-AR Score), including onset age, sex, onset attack phenotype, use of immunosuppressive therapy, and duration of oral glucocorticoids treatment, has been proposed to identify patients at high relapse risk since onset.11

The aim of this study was to provide the first validation of the MOG-AR Score in a national multicenter cohort and to assess other factors associated with a relapsing disease.

A direct auditory subcortical route to the amygdala associated with fear in humans

New in JNeurosci from Kosteletou-Kassotaki et al: A white matter tract connecting the inferior colliculus to the basolateral amygdala via the MGB of the thalamus is linked to better hearing ability and higher self-reported fearfulness in people.

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Rapid and efficient fear processing is essential for survival. In vision, this function is supported by a well-characterized subcortical pathway consisting of direct projections from the pulvinar of the thalamus to the amygdala in the human brain. In contrast, the existence of an analogous shortcut for fear in audition has been demonstrated in non-human animals, but remains unconfirmed in humans. To address this question, we used probabilistic streamline tractography and fixel-based analysis on diffusion-weighted images from Human Connectome Project participants of either sex, to reconstruct candidate auditory subcortical pathways and examine their associations with affective and auditory behavioral measures. Our findings revealed a robust white matter tract connecting the inferior colliculus to basolateral amygdala via the medial geniculate body (MGB) of the thalamus. Remarkably, higher fiber density in this tract was associated with better hearing ability in noise and increased self-reported fearfulness, supporting its role in auditory and affective function. Conversely, a control analysis of the core thalamocortical pathway from ventral MGB to primary auditory cortex (PAC), representing the main route for auditory processing, was associated with auditory ability but not with affective measures. These findings provide previously unreported evidence for an auditory colliculo-geniculo-amygdala “low road” in humans, aligning with evolutionarily conserved pathways for fear described in non-human species.

Significance Statement Rapid fear processing is crucial for survival. While a visual subcortical “low road” for fear is well characterized in humans, the existence of an analogous human auditory shortcut remains undetermined. Using diffusion magnetic resonance imaging tractography, we provide evidence for a white matter tract connecting the inferior colliculus to basolateral amygdala via the medial geniculate body of the thalamus, which is associated with hearing ability and self-reported fearfulness. Our findings provide novel evidence for an auditory colliculo-geniculo-amygdala direct route in humans, revealing an evolutionarily conserved pathway for fear previously described in non-human species.

Targeted Remediation of the Ipsilesional Arm in Chronic Stroke: A Randomized Clinical Trial

Among patients with chronic stroke and severe contralesional impairment, targeted ipsilesional arm training supported significant and sustained improvements in ipsilesional motor performance vs best practice therapy.

Importance Ipsilesional upper-limb motor deficits after stroke are functionally important yet largely neglected in rehabilitation. Remediation may improve motor outcomes in individuals with severe contralesional arm hemiparesis.

Objective To determine whether training of the ipsilesional arm improves motor performance in chronic stroke with severe contralesional impairment and significant ipsilesional arm motor deficits.

Design, Setting, and Participants This 2-site, parallel-group randomized clinical trial with blinded outcome assessment was conducted from February 2019 to August 2024, with follow-up through 6 months posttreatment. Data analysis was performed from August 2024 through August 2025. The trial was conducted at outpatient research laboratories at Penn State College of Medicine and the University of Southern California among adults with radiologically confirmed unilateral middle cerebral artery stroke, severe contralesional upper-extremity impairment (Fugl-Meyer score ≤28), and ipsilesional motor deficits. Participants were randomly assigned with equal probability to 2 treatment groups and stratified by sex.

Multi-tissue transcriptomic aging atlas reveals predictive aging biomarkers in the killifish

Characterizing molecular aging features is crucial for understanding systemic and local factors contributing to the aging process. Here Costa, Chen et al. performed RNA sequencing on 13 tissues across six ages in male and female African turquoise killifish. This sex-balanced killifish aging atlas provides a comprehensive resource for studying aging dynamics across tissues in the killifish—a powerful, short-lived vertebrate model of aging.

Persistent Sex Disparities in Pre‐Hospital Delay Among Patients With STEMI Despite Overall Improvements: Findings From the Chinese Cardiovascular Association Chest Pain Center Registry

Despite overall improvements, women with STEMI in China still face longer pre-hospital delays than men, especially in rural areas. The gap is driven mostly by delayed EMS calls. Cardiology.

HealthEquity STEMI

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Frontiers: Dietary restriction (DR)

Defined as reduced caloric intake or selective limitation of specific nutrients without malnutrition, is one of the most robust interventions known to extend lifespan and healthspan across species. Studies from yeast to mammals demonstrate that DR elicits conserved genetic, transcriptional, and epigenetic programs that promote cellular maintenance and stress resistance. At the molecular level, DR engages evolutionarily conserved nutrient-sensing pathways, including insulin/IGF-1 signaling (IIS), the mechanistic target of rapamycin (mTOR), AMP-activated protein kinase (AMPK), and NAD+-dependent sirtuins, which converge on key transcription factors (TFs) and transcriptional coactivators (TCs) to coordinate metabolic and longevity-associated gene expression. Downstream, these pathways enhance autophagy and proteostasis, remodel mitochondrial function and redox balance, reshape immune and inflammatory networks, and induce epigenetic and transcriptional reprogramming. Recent work further highlights amino acid–specific sensing mechanisms, endocrine mediators such as fibroblast growth factor 21 (FGF21), the gut microbiome, circadian regulators, and nuclear pore–associated transcriptional plasticity as integral components of DR responses. Importantly, the physiological outcomes of DR are context dependent and influenced by genetic background, sex, age at intervention, and the type and duration of restriction. In this review, we summarize current knowledge on the genetic and molecular architecture underlying DR-induced longevity and health benefits across species, discuss implications for aging-related diseases, and outline future directions toward precision nutrition and safe translational strategies.

Aging is characterized by a progressive decline in physiological integrity, reduced stress resilience, and increased susceptibility to chronic diseases (Lopez-Otin et al., 2023). Among numerous genetic, pharmacological, and lifestyle interventions examined over the past decades, dietary restriction (DR) remains the most robust and evolutionarily conserved strategy for extending lifespan and improving healthspan. Originally described in rodents nearly a century ago, the beneficial effects of reduced nutrient intake have since been validated in a wide range of organisms, including yeast, nematodes, flies, and mammals (Wu et al., 2022). While often used interchangeably, it is critical to distinguish between different nutritional interventions to avoid conceptual overlap. Caloric restriction (CR) typically refers to a chronic reduction in total calorie intake (usually 20%–40%) without malnutrition.

Heterogeneity of Treatment Effects of Glucagon-Like Peptide-1 Receptor Agonists

Among adults treated with glucagon-like peptide-1 receptor agonists (GLP-1 RAs) for weight loss, efficacy was greater in women than men, but similar across age, race, ethnicity, baseline body mass index, and hemoglobin A1c.

These findings indicate that GLP1RA therapy for weight loss is broadly effective across key patient characteristics, supporting inclusive clinical decision-making. GLP-1 RAs include semaglutide, liraglutide, exenatide, lixisenatide, and dulaglutide.

Question How heterogeneous are the treatment effects of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) on weight loss, by age, sex, race and ethnicity, baseline body mass index, and baseline hemoglobin A1c?

Findings In this systematic review and meta-analysis of 41 articles representing 64 randomized clinical trials, the efficacy of GLP-1 RAs was greater among women than men but did not otherwise differ by age, race and ethnicity, baseline body mass index, or baseline hemoglobin A1c.

Meaning Except for the difference by sex, the efficacy of GLP-1 RAs for weight loss appears to be consistent across many important subpopulations of patients who may be eligible for treatment.

Social Risk Prevalence in AYAs With and Without a History of Cancer

About one-third of adolescents and young adults, with or without Cancer, reported at least one social risk such as financial hardship or food insecurity, highlighting the need for routine screening.

This cross-sectional study used data from KPNW, an integrated health care system serving more than 620 000 members in northwest Oregon and southwest Washington, representing approximately 16% of the region’s population. The KPNW Institutional Review Board deemed the study exempt from review and informed consent under category 4 of the Common Rule, meaning that this research was determined to be low risk as it involves the use of secondary data. The study followed the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) reporting guideline for cross-sectional studies.

Members of KPNW are demographically similar to the surrounding community, with a broad age distribution (approximately 23% aged 18–35 years and 40% aged 36–64 years), a nearly equal sex distribution (52% female), and a racial and ethnic composition comparable to that of the regional population. Approximately 18% of members live below 200% of the federal poverty level, and approximately 80% receive coverage through employer-sponsored plans, contributing to high annual retention rates (approximately 88%). In early 2020, KPNW implemented a social risk screening tool via the EPIC-based (Epic Systems Corp) HealthConnect system. Full details of the screening process have been previously described.22,23

We included KPNW members aged 15 to 40 years who received care at KPNW; completed the social determinants of health screener between January 1, 2022, and December 31, 2024 (the first screening was defined as the index date); and had at least 6 months of follow-up data (eFigure 1 in Supplement 1).

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