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Wobble-board instability re-orthogonalizes postural geometry in older adults through exogenous constraint
Postural control is expressed as intermittent organization of center-of-pressure (CoP) motion on a saddle-shaped manifold typically aligned with the anteroposterior (AP) and mediolateral (ML) axes. When task demands reorient postural focus, this saddle rotates away from the AP-ML alignment yet preserves orthogonal axes that indicate directions of greatest and least fractal temporal correlations in sway. Preserved orthogonality appears to reflect a balance between endogenous fractal fluctuations...
Identifying a cancer therapeutic target: Cell-SELEX identifies a membrane protein for aptamer-mediated growth suppression
The identification of functional ligand-membrane protein interactions under native conditions remains a major challenge in cancer biology. Using cell-systematic evolution of ligands by exponential enrichment, we identified a high-affinity DNA aptamer, CW06, against breast cancer cells. To precisely identify its native membrane target, we developed Aptamer-mediated Metabolic Glycan-labeling Proximity Hybridization (Apt-MGPH), which revealed the mitochondrial solute carrier SLC25A24 as the...
Unveiling the developmental and tumor-suppressive roles of the p53 variant p53psi
Through alternative splicing, the TP53 gene can generate multiple protein isoforms with distinct biochemical properties. The p53psi isoform has been identified as a shorter variant than full-length p53 as it lacks nuclear localization, oligomerization, and part of the DNA binding domains due to the use of an alternative 3' splice site in intron 6. Several TP53-truncating mutations, including those producing p53psi, have been detected in a significant proportion of human tumors. However, the...
Social Return on Investment of Interventions Supporting Aging in Place: A Systematic Review
CONCLUSIONS AND IMPLICATIONS: Despite methodological variation, community-based programs that reduce loneliness, social isolation, and support aging in place consistently generate positive SROI ratios, benefiting participants, families, and volunteers while reducing health care use. Collaboration among researchers, communities, and policymakers is essential to translate findings into community actions that enable older adults to age in place.
Coevolution of Cognitive and Health Trajectories Among US Older Adults With Cognitive Impairment
CONCLUSIONS AND IMPLICATIONS: Stable health trajectories are strongly linked to better cognitive outcomes, whereas sharp health declines predict poorer cognition. Our findings highlight the interconnected biological and behavioral pathways through which health changes may accelerate or mitigate cognitive deterioration, offering insights for targeted interventions and holistic care for persons with cognitive impairment.
Diverse mitochondrial stresses activate PINK1-PRKN/parkin mitophagy by a unified mechanism
Mutations in PINK1 and PRKN/parkin are the leading recessive causes of Parkinson disease (PD). Together PINK1 and PRKN form a mitophagy pathway for clearing damaged mitochondria from the cell. It was unclear, however, whether diverse forms of mitochondrial damage activate the PINK1-PRKN pathway through a unified mechanism. Recently, we demonstrated that loss of mitochondrial membrane potential (MMP) leads to the stabilization and activation of PINK1 under a wide range of mitochondrial stressors,...
RF-SIRF reveals a replication stress-specific epigenetic code by spatio-temporal mapping of reversed forks
DNA replication stress responses are guardians of genomic stability critical during development, hematopoiesis, cancer therapy response, aging and disease suppression. Central to these responses are reversed forks (RF), which are distinct four-way DNA structures formed during DNA replication stalling to protect against toxic DNA lesions. Historically, RF detection relies on specialized electron microscopy, precluding studies within their native cellular context. By harnessing intrinsic...
Age-related directional asymmetry in the rod-and-frame test
CONCLUSIONS: We propose that aging affects RFT performance through two dissociable mechanisms. A general decline in multisensory integration increases overall errors symmetrically across tilt angles. The clockwise-specific asymmetry, by contrast, may reflect age-related changes in lateralized visuospatial attention-specifically, the well-documented rightward attentional shift that accompanies healthy aging-which differentially affects the weighting of visual cues for clockwise vs....
Telomere dysfunction is associated with exacerbated intermittent hypoxia-induced cognitive deficits and nerve damage
Cognitive impairment associated with obstructive sleep apnea (OSA) is more prevalent and severe in the elderly, possibly due to age-related increases in neuronal susceptibility to intermittent hypoxia (IH). As telomere dysfunction is a key driver of cellular aging, this study aimed to characterize the interaction between telomere dysfunction and IH, and to explore the associated molecular alterations. Using telomere-damaged PC12 cells and G3 Tert^(-/-) progeria mice exposed to IH, we assessed...
Serum proteomics reveals biomarkers for diagnosis, stratification, and mechanistic insights into cerebral microbleeds
OBJECTIVE: Cerebral microbleeds (CMBs) are small vascular lesions detectable on MRI and are associated with increased stroke risk and cognitive decline. However, imaging-based diagnosis is limited by cost and accessibility. This study aimed to identify serum protein biomarkers for early CMB diagnosis and to elucidate molecular mechanisms underlying CMB subtypes.
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