Aggregator

Mary Brunkow, Fred Ramsdell, and Shimon Sakaguchi revealed how regulatory T cells prevent autoimmune disease

Cascadia and San Andreas fault zones appear to generate synchronized earthquakes

We investigated the roles of Rac guanine-nucleotide exchange factor (Rac-GEF) P-Rex1 in glucose homeostasis using Prex1^(-/-) and catalytically inactive Prex1^(GD) mice. P-Rex1 maintains fasting blood glucose levels and insulin sensitivity through its Rac-GEF activity but limits glucose clearance independently of its catalytic activity, throughout aging. Prex1^(-/-) mice on a high-fat diet are protected from diabetes. The increased glucose clearance in Prex1^(-/-) mice may stem in part from...

While progressive cognitive decline is the defining feature of Alzheimer's disease (AD), many patients also develop prominent neuropsychiatric symptoms, including anxiety and depression. The circuit-level mechanisms underlying these distinct symptom domains remain poorly understood, and treatments that address both cognitive and noncognitive aspects of AD are limited. Here, we identify anatomically, molecularly, and functionally distinct subpopulations of supramammillary (SuM) neurons that...

Zinc plays a critical role in memory, learning, and neuronal function, with dysregulation increasingly implicated in neurodegenerative diseases such as Alzheimer's disease (AD). This study aimed to investigate whether changes in the expression of zinc transporter proteins, ZnT3 and ZIP3, in the retina mirror those in the brain, and to explore their potential as non-invasive biomarkers for early AD detection. Immunofluorescence and Western blotting were used to assess ZnT3 and ZIP3 expression in...

Predictors of immune checkpoint inhibitor response in cancer remain elusive. From a previous phase 2 neoadjuvant immunotherapy window-of-opportunity study, we present the single-cell RNA and T cell receptor (TCR) sequencing analysis of 57 pre- and post-treatment tumor biopsies from head and neck cancer patients treated with durvalumab (anti-PD-L1) alone or with tremelimumab (anti-CTLA-4), identifying key cellular and molecular predictors of immune checkpoint inhibitor (ICI) response. Malignant...

BACKGROUND: Despite the success of immune modulation in the treatment of relapsing multiple sclerosis, disability progression is a major problem driven by multiple mechanisms. Comorbidities (eg, vascular risk) and ageing are thought to augment these neurodegenerative pathologies. In the phase 2b MS-STAT trial of simvastatin (80 mg) versus placebo in secondary progressive multiple sclerosis (SPMS), the adjusted difference in brain atrophy rate between groups was -0·254% per year: a 43% reduction....

CONCLUSION: The ABC community program might be a scalable collaborative dementia care model targeting socially vulnerable people living with dementia.

As government websites go dark, some nonprofits are trying to fill the void

Alzheimer's disease (AD) has long resisted effective treatments due to its pathological heterogeneity and cell-type-specific regulatory changes. In this issue of Cell, Li et al. leverage single-cell RNA sequencing and drug repurposing to propose a promising combination therapy, validated through real-world evidence and mouse models, that targets multiple AD-relevant cell types.