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Imaging the neurohiv brain in animal models: past, present, and future-toward longitudinal, whole-brain aging phenotypes

7 hours 4 minutes ago
Animal models are essential for defining mechanisms of HIV-associated brain injury in the antiretroviral therapy era, where neurocognitive impairment and brain aging have replaced opportunistic infections as dominant clinical concerns. Humanized mice, EcoHIV murine systems, and SIV or SHIV nonhuman primates now enable increasingly sophisticated brain imaging across in vivo and ex vivo scales. Structural and diffusion MRI, perfusion imaging, manganese-enhanced MRI, and multiphoton and endoscopic...
Paddy Ssentongo

The Construct Validity of the Life-Space Assessment in the Canadian Longitudinal Study on Aging (CLSA)

7 hours 4 minutes ago
CONCLUSION: The LSA can be used to differentiate between known groups. However, there is limited evidence of its convergent validity as its relationship with other measures of actual mobility, perceived mobility, and locomotor capacity for mobility was weak. Future studies need to assess the convergent validity of the LSA against different comparator measures before its use among community-dwelling Canadians.
Selina Malouka

Scientists finally solved how a common gut bacterium triggers colon cancer

11 hours 26 minutes ago
Researchers solved a long-standing mystery behind how a bacterial toxin associated with colorectal cancer damages the colon. The toxin first binds to a receptor called claudin-4, giving it access to attack the cells' protective barrier. After identifying this weak point, the team designed a decoy protein that successfully blocked the toxin in mice. The discovery could pave the way for new therapies to prevent inflammation and colon tumors.

Common constipation drug may help clear depression brain fog

16 hours 14 minutes ago
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

1 day 2 hours ago
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.

Development of an RNA aptamer as a therapeutic agent for synucleinopathies

1 day 7 hours ago
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...
Kazuma Murakami

Cell-type signatures of Alzheimer's disease shared across population groups

1 day 7 hours ago
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...
Tain Luquez

Immunotherapy with a short-lived anti-PD-L1 antibody in Alzheimer's disease: a phase 1b, randomized, double-blind trial

1 day 7 hours ago
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...
Tommaso Croese

Chronological age as a major determinant of systemic metabolic remodeling in women

1 day 7 hours ago
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...
S Serafini

The SIRT5-SUCLG2 desuccinylation axis delays ovarian aging via a mitochondrial-epigenetic regulatory mechanism

1 day 7 hours ago
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...
Dejun Xu

Oncogene inactivation-induced senescence facilitates tumor relapse

1 day 7 hours ago
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...
Philipp Schmitt