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Long-overlooked Kepler signal discovered by citizen scientists reveals promising world worth a closer look

Blood-brain barrier (BBB) dysfunction is a hallmark of many diseases of the brain, including those that represent the largest healthcare burden (for example, Alzheimer disease and stroke). Despite this, rejuvenation and repair of the BBB is not a mainstream concept. During life, the BBB is subjected to perturbations and stresses from a wide range of endogenous or exogenous sources, which can promote brain health or can lead to brain pathologies. The BBB supports many functions that are critical...

Emerging evidence suggests that Parkinson's disease (PD) may have its origin in the enteric nervous system (ENS), from where α-synuclein (αS) pathology spreads to the brain^(1-4). Decades before the onset of motor symptoms, patients with PD suffer from constipation and present with circulating T cells responsive to αS, suggesting that peripheral immune responses initiated in the ENS may be involved in the early stages of PD^(1,5-7). However, cellular mechanisms that trigger αS pathology in the...

Blood-brain barrier (BBB) dysfunction is a hallmark of many diseases of the brain, including those that represent the largest healthcare burden (for example, Alzheimer disease and stroke). Despite this, rejuvenation and repair of the BBB is not a mainstream concept. During life, the BBB is subjected to perturbations and stresses from a wide range of endogenous or exogenous sources, which can promote brain health or can lead to brain pathologies. The BBB supports many functions that are critical...

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Spatiotemporal changes in the nuclear lamina and cell metabolism shape cell fate, yet their interplay is poorly understood. Here we identify lamin A/C as a key regulator of cysteine catabolic flux essential for proper cell fate and longevity. Its loss in naive mouse pluripotent stem cells leads to upregulation of the cysteine-generating and catabolizing enzymes, cystathionine γ-lyase (CTH) and cystathionine β-synthase (CBS), thereby promoting de novo cysteine synthesis. Increased cysteine flux...

Integrated circuits for communications play an enabling role when it comes to outer-space exploration thanks to their small footprint and low weight^(1-3). However, owing to the severe irradiation effects of space energetic particles, the implementation of radiation-tolerant electronic circuits remains a challenge^(4-6). Here we report the observation of the space radiation effect on a satellite-based device and find that atomically thin materials are expected to accumulate minimal...

CONCLUSION: This claims-based frailty prediction model showed reasonable performance and prognostic value. It may support efficient, population-level frailty screenings where questionnaire-based assessments are impractical.

Serial multi-omic analysis of proteome, phosphoproteome, and glycoproteome is pivotal for elucidating drug mechanisms, discovering biomarkers, and identifying therapeutic targets. However, simultaneous multi-level post-translational modifications (PTMs) analysis via parallel processing is hampered by laborious, time-consuming procedures and inconsistent reproducibility. We present an integrated Multi-level PTMs-Proteomic Enrichment platform (MuPPE), enabling sequential glycoproteome,...

Environmental differences in genetic effect sizes, namely, gene-environment interactions, may uncover the genetic encoding of phenotypic plasticity^(1-3). We provide a cross-population atlas of gene-environment interactions comprising 440,210 individuals from European and Japanese populations, with replication in 539,794 individuals from diverse populations. By decomposing the contributions from age, sex and lifestyles, we delineate the aetiology of these gene-environment interactions, including...

α-Synuclein (αSyn) is a presynaptic protein of unestablished physiological function that plays a central role in Parkinson's disease neuropathology. To date, the reported effects of αSyn expression on the kinetics of axonal synaptic vesicle exocytosis and membrane cycling have been relatively small. In contrast, we report that αSyn is the major modulator of substantia nigra somatodendritic dopamine release, a little-understood form of neurotransmission that is central to sensorimotor and basal...

Alzheimer's disease (AD) risk is strongly influenced by genetic variants that converge on pathways regulating endosomal homeostasis. Among these, BIN1 and RIN3 have emerged as susceptibility genes, yet their functional relationship in AD remains largely unknown. Here, we investigated how BIN1 and RIN3 interaction regulates RAB5 activity and endosomal pathology. RIN3 has been shown to bind BIN1, and we previously reported that this interaction modulates amyloid-β (Aβ) precursor protein (APP)...

512-million-year-old marine fossils highlight life and death at the Cambrian explosion’s close

Heart disease is the leading cause of death in the elderly population. Age-related heart failure is frequently associated with energy deficits in cardiomyocytes. These cells rely on their abundant, cristae-rich mitochondria for ATP production. ATP synthase, localized along the cristae rims, is central to this process. It is presumed that its function is tightly bound to its spatial organization, but details remain unclear. Here, we explored the spatiotemporal organization of ATP synthase in...

Aging is a dominant risk factor for chronic diseases characterized by the functional decline of tissues and organs. During aging, the hematopoietic system declines in regenerative capacity-seemingly attributable to increases in DNA damage, replicative stress, and autophagic flux-resulting in skewing towards a myeloid lineage and away from a lymphoid lineage. Here, we characterized the transcriptomic and cellular landscape of the aged C57Bl/6J mouse hematopoietic system using a combination of...

Humans routinely anticipate upcoming language, but whether such predictions come at a cognitive cost remains debated. In this study, we demonstrate the resource-dependent nature of predictive mechanisms in language comprehension across the lifespan: Experimentally limiting executive resources through a concurrent task reduces the effect of language predictability on reading time. Participants (N = 175, replication N = 96) read short articles presented word-by-word while completing a secondary...

Ribosomes are central to protein synthesis in all organisms. In mammals, the ribosome functional core is highly conserved. Remarkably, two rodent species, the naked mole-rat (NMR) and tuco-tuco, display fragmented 28S ribosomal RNA (rRNA), coupled with high translational fidelity and long lifespan. The unusual ribosomal architecture in the NMR and tuco-tuco has been speculated to be linked to high translational fidelity. Here, we show, by single-particle cryo-electron microscopy, that despite...

Phenotypic age, an aging indicator derived from clinical biomarkers, is associated with morbidities and mortality. However, a liver-specific phenotypic aging indicator is still lacking, and its longitudinal associations with liver-related outcomes, as well as the underlying biological mechanisms, remain elusive. We developed a liver-specific phenotypic age using 11 selected clinical blood markers within the England-White cohort of the UK Biobank and validated this metric in both the...

Mitochondrial function is important to healthy aging, as it influences energy metabolism, oxidative stress, and physical performance. With age, mitochondrial function and biosynthesis of coenzyme Q10 (CoQ10) may change. CoQ10 serves as a key antioxidant and component of the electron transport system. Supplementation with CoQ10 may help preserve mitochondrial function and support healthy aging. Forty older community-dwelling adults (74 ± 4 years) received either daily oral CoQ10 supplementation...