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DNA analysis of more than 15,500 people with the debilitating condition identifies eight tentative “genetic signals”

Farming and draft animals didn’t stratify societies in Carpathian Basin

Researchers now know why the caged bird dances: a form of mentally enriching play

Steve Gschmeissner’s electron microscope image of liver cholesterol won a Wellcome Photography Prize this year

The renin-angiotensin system (RAS), an important regulator of body fluid and cardiovascular homeostasis, is gradually implicated in the pathogenesis of neurological diseases due to its dysregulation. In addition to their traditional functions, components of the RAS, especially angiotensin-II (Ang-II), enhance neuroinflammation, oxidative stress, and neuronal injury. Ang-II exacerbates blood-brain barrier (BBB) disruption, promotes glial activation, and contributes to neurodegeneration via the...

Cerebrospinal fluid (CSF) α-synuclein (α-syn) seed amplification assays (SAAs) can detect Lewy body pathology (LBP) with high accuracy but are invasive and costly. To address these challenges, this study evaluated a two-step workflow combining prescreening via smell-function testing with confirmatory CSF α-syn SAA testing only in individuals with reduced smell, for predicting postmortem LBP status. Among 358 autopsied participants, the two-step workflow predicted brain LBP with high accuracy...

Leucine-rich repeat kinase 2 (LRRK2) is an essential regulator in cellular signaling and a major contributor to Parkinson's disease (PD) pathogenesis. 14-3-3 proteins are critical modulators of LRRK2 activity, yet the structural basis of their interaction has remained unclear. Here, we present the cryo-electron microscopy structure of the LRRK2:14-3-3(2) autoinhibitory complex, revealing how a 14-3-3 dimer stabilizes an autoinhibited LRRK2 monomer through dual-site anchoring. The dimer engages...

The three-dimensional (3D) genome structure is essential for gene regulation and various genomic functions. CTCF plays a key role in organizing Topologically Associated Domains (TADs) and promoter-enhancer loops, contributing to proper cell differentiation and development. Although CTCF binds the genome with high sequence specificity, its binding sites are dynamically regulated during development, and aberrant CTCF binding is linked to diseases such as cancer and neurological disorders, and...

State-of-the-art membranes derived from polymers of intrinsic microporosity offer promising alternatives to energy-intensive, thermally driven separation techniques but often suffer from reduced performance under condensable gases or physical aging. Here, extrinsically microporous polymer membranes (EMPMs) are introduced as a distinct class of microporous membranes, fabricated from perfluorinated aryl-ether-free aromatic polymers via defluorination-induced thermal cross-linking. This process...

Multi-organ biological aging clocks derived from clinical phenotypes and neuroimaging data have emerged as valuable tools for studying human aging and disease. Plasma proteomics provides an additional molecular dimension to enrich these clocks. In this study, I developed 11 multi-organ proteome-based biological age gaps (ProtBAGs) using 2,448 plasma proteins from 43,498 participants in the UK Biobank. Here I highlight methodological and clinical considerations for developing and using these...

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Older adults are the primary population for cell-based therapies for age-related diseases, but the efficacy of administering autologous mesenchymal stem cells (MSCs) is impaired due to biological aging. In the present study, we cultured aging adipose (AD)-derived MSCs from > 65-year-old donors on extracellular matrix (ECM) synthesized by human amniotic fluid-derived pluripotent stem cells (ECM Plus) versus tissue culture plastic (TCP) and hypothesized that ECM Plus provided an ideal "young"...

This systematic review aims to investigate the moderating effects of cognitive reserve (CR) on the relationships between cognitive function and multimodal Alzheimer's disease (AD)-signatured brain changes, measured by positron emission tomography (PET), structural magnetic resonance imaging (sMRI) and functional MRI (fMRI). Through a comprehensive search of PubMed, Scopus, and Web of Science, we identified 55 eligible studies examining the moderating effect of CR on the relationship between...

Accumulation of amyloid-β (Aβ) peptides and hyperphosphorylated tau proteins in the hippocampus triggers cognitive memory decline in Alzheimer's disease (AD). The incidence and mortality of sporadic AD were tightly associated with diabetes and hyperlipidemia, while the exact linked molecular mechanism is uncertain. Here, the present investigation identified significantly elevated serum Kallistatin levels in AD patients concomitant with hyperglycemia and hypertriglyceridemia, suggesting potential...

Aging is a process of gradual decline in physical and cognitive function and is a major risk factor for mortality. Despite the increasing number of relevant studies, the mechanisms regulating the aging process have not been fully elucidated. Genetic factors have long been recognized as key factors in controlling the rate of aging. Testes-specific protease 50 (TSP50) has been shown to be involved in the regulation of embryonic development and intestinal homeostasis, but its role in the regulation...