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More than 400 sick as CDC searches for the source of a mystery outbreak
A growing Cyclospora outbreak has sickened more than 400 people in four states, and investigators are still searching for the contaminated food responsible. The CDC warns the actual number of cases is likely much higher and urges anyone with symptoms to seek medical care.
Common constipation drug may help clear depression brain fog
An existing constipation drug may have an unexpected new use: helping clear the "brain fog" that often lingers after depression. In a small clinical trial, people with a history of depression who took the medication prucalopride for about a week performed better on tests of memory, attention, and thinking speed than those who received a placebo. The drug targets a serotonin receptor found in both the gut and the brain, and researchers saw no significant side effects.
The hidden skeleton “gatekeeper” inside brain cells could help fight Alzheimer's
Researchers have discovered that a microscopic skeleton inside neurons does much more than hold cells together. It acts as a gatekeeper that controls what brain cells absorb and when they absorb it. When this protective structure weakens, neurons rapidly take in harmful proteins associated with Alzheimer's disease, suggesting that stabilizing it could become a promising new strategy for preventing brain cell damage.
This pet gecko could help scientists unlock the secrets of cancer
An unusual leopard gecko that naturally develops aggressive tumors may become an important new model for cancer research. Scientists found its tumors share key genetic changes with human cancers, offering a rare opportunity to study the disease as it develops naturally.
Tree-killing beetle is spreading to urban forests around the world
As researchers piece together the pest’s global trek, countries are working to contain the growing threat
Did U.S. scrutiny of foreign research drive prominent geneticist to decline authorship?
George Church moved to paper’s acknowledgements section, triggering exodus
Development of an RNA aptamer as a therapeutic agent for synucleinopathies
The aggregation of α-synuclein (αSyn), a 140-mer protein, has been implicated in the pathogenesis of Parkinson's disease, multiple system atrophy, and dementia with Lewy bodies. KTKEGV pseudo-repeats (KRs) in the sequence of αSyn are key mediators of its prion-like propagation and neurodegeneration. Despite the availability of symptomatic treatments, no current therapy effectively delays disease progression. Here we report a 77-nucleotide RNA aptamer called 1R6, obtained through in vitro...
Cell-type signatures of Alzheimer's disease shared across population groups
Genomic studies at single-cell resolution have identified several cell types associated with clinical and pathological traits in Alzheimer's disease^(1-9), but have not examined associations that are shared across populations. To bridge this gap, here we use single-nucleus RNA sequencing and assay for transposase-accessible chromatin with sequencing to profile cortical and subcortical regions in post-mortem brain-tissue samples from Latin, white (excluding Latin) and African American (excluding...
Immunotherapy with a short-lived anti-PD-L1 antibody in Alzheimer's disease: a phase 1b, randomized, double-blind trial
While Alzheimer's disease (AD) is initiated by amyloid plaque accumulation, its progression involves local neuroinflammation that the brain cannot resolve when age-related dysfunction of the systemic immune system limits peripheral immune support. Preclinical studies using rodent models showed that transient systemic blockade of programmed death-ligand 1 is associated with reduced neuroinflammation, neuroprotection and attenuation of disease progression. Based on the underlying mechanism, a new...
Chronological age as a major determinant of systemic metabolic remodeling in women
Chronological aging is a major source of interindividual biological variability, yet the metabolic background that accompanies aging in women remains incompletely defined. Using large-scale plasma metabolomic and lipidomic profiling across the adult female lifespan, this study identifies coordinated metabolic signatures that progressively emerge with aging and dominate systemic metabolic variability independently of body mass index and estradiol status. Aging was associated with consistent...
The SIRT5-SUCLG2 desuccinylation axis delays ovarian aging via a mitochondrial-epigenetic regulatory mechanism
Mitochondrial dysfunction and epigenetic alterations play critical roles in aging-related diseases, yet the molecular mechanisms linking mito-nuclear crosstalk to ovarian aging remain poorly understood. Here, single-cell transcriptome analysis of aging ovaries revealed senescence-associated hallmark alterations, including abnormally elevated mitochondrial metabolism, disrupted histone modification patterns, and enrichment of the senescence-associated secretory phenotype (SASP). We demonstrated...
Oncogene inactivation-induced senescence facilitates tumor relapse
Oncogene-directed therapies can induce profound tumor regression in oncogene-addicted cancers, but their long-term benefit is often limited by resistance and relapse. Here we show that oncogene inactivation rapidly induces senescence and a pro-inflammatory senescence-associated secretory phenotype (SASP). In vivo, oncogene inactivation-induced senescence (OIIS) predisposes tumors to relapse, accompanied by polyploidy, chromosomal instability, acquisition of alternative oncogenic pathways...
Cellular hallmarks and aging clock of the human lung parenchyma
Aging affects lung function, predisposing older adults to respiratory diseases; however, the cellular and molecular mechanisms of lung aging are not fully understood. Leveraging single-cell and spatial transcriptomics data from 184 and 70 lung parenchyma samples, respectively, we present an analytical platform to dissect the cell composition, gene expression modules, and regulatory changes linked to multiple hallmarks of lung aging. Our findings show cell type-specific age-association of...
A unified catalytic mechanism in bifunctional DNA glycosylases with an evolutionarily conserved aspartate-lysine dyad
Bifunctional glycosylases, OGG1 for purines and NTH1 for pyrimidines, repair oxidized DNA bases via consecutive glycosylase and AP-lyase reactions, yet their catalytic relationships and lyase activity's biological relevance remain unresolved. Here, we solved crystal structures of archaeal and human Ogg1 and Nth1 captured in key damage-recognition and catalysis-ready states, complemented by ab initio molecular dynamics simulations of their complete reaction trajectories. We thereby define a...
Lysosomes and lysosomal dysfunction in ageing biology
Lysosomes are essential regulators of cellular homeostasis. Emerging evidence positions lysosomes as both vulnerable targets and active drivers of ageing biology. During ageing, lysosomes exhibit impaired biogenesis, defective acidification, reduced hydrolytic activity and compromised membrane integrity. These defects impair the clearance of damaged organelles and macromolecules and promote cellular stress responses, inflammageing and senescence, causing age-dependent functional decline across...
Daily briefing: Can regrowing the thymus slow down ageing?
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Increased DNA methylation linked to aging phenotypes in a progeria syndrome
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Developing a contextually relevant framework for assessing older adults' access to primary healthcare in Iran: an expert-based qualitative study
CONCLUSION: The contextually relevant framework derived from this study can help identify reasons for older adults' reluctance or inability to access elderly care services at health centers. Future studies can apply the proposed framework to thoroughly examine the challenges of implementing the national aging care program across various universities of medical sciences in Iran.
A small molecule reduces both parkinsonism and l-dopa-induced dyskinesia in animal models of Parkinson's disease
Maximizing clinical benefits of therapeutics while minimizing adverse effects is a central challenge in drug development. For Parkinson's disease (PD), l-3,4-dihydroxyphenylalanine (l-dopa) is the most effective treatment available, but chronic use is associated with periods of reduced efficacy (motor fluctuations) and the debilitating on-target side effect of l-dopa-induced dyskinesia. To disentangle the molecular mechanisms underlying l-dopa's antiparkinsonian effects versus its dyskinetic...
Functional segregation in Parkinson's disease
The basal ganglia are characterized by somatotopic representation and are organized in parallel, functionally segregated corticostriatal circuits, but the impact of Parkinson's disease (PD) on this architecture is unknown. We mapped task-evoked dopamine release using [^(11)C]raclopride positron emission tomography/magnetic resonance in 13 early PD and 15 healthy control (HC) subjects during the performance of motor, cognitive, and reward tasks. In PD, motor tasks elicited decreased relative...