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Uracil-induced replication stress drives mutations, genome instability, anti-cancer treatment efficacy, and resistance
Uracil incorporation into DNA, as a result of nucleotide pool imbalances or cytosine deamination (e.g., through APOBEC3A/3B), can result in replication stress and is the most common source of mutations in cancer and aging. Despite the critical role of uracil in genome instability, cancer development, and cancer therapy, only now is there emerging data on its impact on fundamental processes such as DNA replication and genome stability. Removal of uracil from DNA by base excision repair (BER) can...
Cross-regulation between the nervous system and type 2 immunity
Interactions between the nervous and immune systems are critical to healthy physiology and are altered in many human diseases. Many of the major players in type 2 immune responses, including type 2 lymphocytes and cytokines, mast cells, and immunoglobulin E, have been implicated in neuronal function and behavior. Conversely, neurons in both the central and peripheral nervous systems can affect type 2 immune responses and behaviors relevant to allergy, such as food avoidance. Defining this...
Epilepsy and autophagy modulators: a therapeutic split
Epilepsy is a neurological disease characterized by repeated unprovoked seizure. Epilepsy is controlled by anti-epileptic drugs (AEDs); however, one third of epileptic patients have symptoms that are not controlled by AEDs in a condition called refractory epilepsy. Dysregulation of macroautophagy/autophagy is involved in the pathogenesis of epilepsy. Autophagy prevents the development and progression of epilepsy through regulating the balance between inhibitory and excitatory neurotransmitters....
Quercetin Reduces Vascular Senescence and Inflammation in Symptomatic Male but Not Female Coronary Artery Disease Patients
Recent studies suggest that vascular senescence and its associated inflammation fuel the inflammaging to favor atherogenesis; whether these pathways can be therapeutically targeted in coronary artery disease (CAD) patients remains unknown. In a randomized, double-blind trial, 97 patients (78 men) undergoing coronary artery bypass graft surgery were treated with either quercetin (500 mg twice daily, 47 patients) or placebo (50 patients) for two days pre-surgery through hospital discharge. Primary...
Changes in Home Care Clients' Sensory Impairment Status and Its Association With Functioning Over 18 Months: A Longitudinal Register-Based Study
We investigated the changes in home care clients' vision and hearing over 18 months and examined the role of sensory impairments in maintaining their functioning. We used data from the Finnish Resident Assessment Instrument (RAI) database (n = 7013). Sensory impairment status was categorized by type (single or dual) and severity (mild or moderate/severe). The association between sensory impairment and functioning over 18 months was examined using binary logistic regression analysis with...
Nuclear Import Defects Drive Cell Cycle Dysregulation in Neurodegeneration
Neurodegenerative diseases (NDDs) and other age-related disorders have been classically defined by a set of key pathological hallmarks. Two of these hallmarks, cell cycle dysregulation (CCD) and nucleocytoplasmic transport (NCT) defects, have long been debated as being either causal or consequential in the pathology of accelerated aging. Specifically, aberrant cell cycle activation in post-mitotic neurons has been shown to trigger neuronal cell death pathways and cellular senescence....
Effect of the 2018 Japan floods and COVID-19 pandemic on cognitive decline among atomic bomb survivors in Hiroshima, Japan: a retrospective cohort study
CONCLUSIONS: ABSs had a reduced risk of cognitive decline during the pandemic compared with that of the other groups.
The association between the number of teeth and frailty among older adults: a systematic review and meta-analysis
CONCLUSIONS: There is a significant association between tooth count and frailty, particularly in those with 20 or fewer teeth. Policymakers should prioritize oral health within aging populations by promoting early preventive care and education to mitigate frailty risk. Robust, large-scale studies are needed to guide evidence-based interventions and public health policy.
Longitudinal effects of diet quality on healthy aging - Focus on cardiometabolic health: findings from the Canadian longitudinal study on aging (CLSA)
BACKGROUND: Hypertension, a major concern for older adults, contributes to morbidity and mortality by increasing the risk of cardiovascular disease, stroke, kidney dysfunction, and cognitive decline. A healthy diet plays a vital role in limiting chronic disease progression in aging populations.
Daily briefing: Meet the baby who received the world’s first personalized CRISPR therapy
Single particle acts as a quantum computer to simulate molecules
Can AI help us talk to dolphins? The race is now on
US brain drain: <i>Nature</i>’s guide to the initiatives drawing scientists abroad
Can NIH-funded research on racism and health survive Trump’s cuts?
Atacama sunshine helps to pull water from thin air
Large-scale network analysis of the cerebrospinal fluid proteome identifies molecular signatures of frontotemporal lobar degeneration
NSF’s grant cuts fall heaviest on scientists from underrepresented groups
Projects to broaden participation were cut disproportionately—and were often led by Black scientists, women, and those with disabilities
This mass of amber traps evidence of an ancient tsunami
Deep-sea rocks suggest giant waves pounded modern-day Japan 115 million years ago
Microglial TMEM119 binds to amyloid-beta to promote its clearance in an Abeta-depositing mouse model of Alzheimer's disease
The progression of Alzheimer's disease (AD) involves temporal dynamics of microglial activation. Restoring or maintaining microglial homeostasis has emerged as a promising therapeutic strategy to combat AD. Transmembrane protein 119 (TMEM119) is a homeostatic marker of microglia but has not been fully studied under AD pathological conditions. Here, we observed that amyloid-beta (Aβ) induced a decrease in TMEM119 expression in microglia, and TMEM119 deficiency increased AD progression in the...
The genetic risk factors, molecular pathways, microRNAs, and the gut microbiome in Alzheimer's disease
Alzheimer's disease (AD) is the most prevalent form of dementia worldwide. It is a multifaceted condition resulting from interplay of genetic mutations (e.g., APP, PSEN1, PSEN2) that account for less than 5% of cases, several genetic risk variants such as APOE4, TREM2, CD33, CLU, SORL1, and CR1 contribute to disease susceptibility and epigenetic factors, which may mediate the influence of environmental and lifestyle factors over time. Other critical contributors such as aging, protein misfolding...