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Mulberry may reshape gut bacteria and influence metabolism

1 day 1 hour ago
Mulberry compounds may reshape the gut microbiome in ways that support intestinal health and metabolism, with some combinations showing especially strong effects in animal studies. However, the results vary depending on the plant part and processing method, and the benefits have yet to be confirmed in humans.

The default mode network exhibits circuit-specific selective vulnerability despite widespread amyloid burden in an animal model of Alzheimer's disease

1 day 3 hours ago
In Alzheimer's Disease (AD) the default mode network (DMN) exhibits selective vulnerability to functional decline and amyloid beta (Aβ) plaques in early AD. DMN vulnerability may simply be the result of Aβ accumulation. Alternately, Aβ may unmask an intrinsic susceptibility of DMN circuits. Should DMN vulnerability persist amidst global Aβ deposition, this would support the latter hypothesis. We tested this using long-term, multi-region recordings of single units in mice characterized by...
Samuel J Brunwasser

Single-cell profiling and genetic regulation of alternative polyadenylation in the human brain

1 day 3 hours ago
Alternative polyadenylation (APA) has a central role in regulation of the fate of mRNA and exhibits high variability in the brain and in neurons. However, brain APA regulation has not been mapped at cell type resolution, and the genetic control of APA in brain cell types and its contribution to genetic disease have remained unclear. Here we report a single-cell atlas of APA of the aged human brain across 2 million cells from 379 human postmortem brains across individuals with and without...
Jiuhong Nan

Prion-like transmission of human tau strains in the mouse brain

1 day 3 hours ago
Most neurodegenerative diseases are thought to spread through the brain by prion-like mechanisms, in which filamentous protein assemblies self-propagate by templated seeding¹. Distinct conformations of amyloid filaments may provide the physical basis for the strains that lead to different diseases². However, a central pillar of the prion hypothesis, that strains retain their structural identity upon transmission, has not been demonstrated. Here we show that the injection of tau filaments from...
Sofia Lövestam

Mutation-agnostic base editing of the progerin farnesylation site rescues Hutchinson-Gilford progeria syndrome phenotypes in neuromuscular organoids

1 day 3 hours ago
Hutchinson Gilford progeria syndrome (HGPS) is a fatal premature aging disorder caused by pathogenic farnesylated lamin A variants that disrupt nuclear architecture and DNA repair. Current therapies, including farnesyltransferase inhibitors, provide only modest survival benefits and lack molecular specificity, while mutation-specific genome-editing strategies cannot address atypical laminopathies. Here, we develop Farnesylation Amino acid Targeted Editing (FATE), a mutation-agnostic base-editing...
Dong-Woo Kim

ERα Micromap (µMap) proximity labeling reveals fulvestrant mechanisms

1 day 3 hours ago
Estrogen Receptor alpha (ERα) is the primary driver in ER+ breast cancer and can be targeted using small molecules such as fulvestrant, a selective estrogen receptor degrader (SERD). Despite being approved over two decades ago and used regularly in post-menopausal women, its precise anti-tumor mechanism remains unclear, with several reports showing efficacy without the requirement for ERα degradation. To investigate the molecular basis of fulvestrant's action, we employed split intein-based µMap...
Chun Li

Written in development and lost in ageing: the grammar of cellular identity

1 day 3 hours ago
Ageing has been described through many theoretical frameworks, yet its mechanistic basis remains unresolved. Here we propose that ageing reflects progressive decanalization of mammalian cell identity, driven by erosion of a regulatory grammar written during development. Extending Waddington's epigenetic landscape, development canalizes cell fates through globally coordinated chromatin programs that establish identity constraints across multiple timescales. Subsequently, these constraints can...
A Doğa Yücel

Redox-Mitochondrial Crosstalk in Neurotoxicity: Regulated Cell Death Pathways and Neuroprotective Strategies

1 day 3 hours ago
Neurotoxicity refers to injury of the central or peripheral nervous system caused by harmful stimuli including environmental chemicals, disease-associated endogenous stressors and other exposures that disturb neuronal homeostasis. A common outcome of neurotoxic stress is progressive disruption of synaptic function, redox balance and energy metabolism which together increase vulnerability to regulated cell-death programs. This review focuses on oxidative stress as core driver that shift reactive...
Kunal Bhattacharya

Lifelong Epstein-Barr virus persistence as a stress test of ageing immune surveillance: from infectious mononucleosis to chronic active EBV disease and virus-associated malignancy

1 day 3 hours ago
Epstein-Barr virus (EBV) infects most humans and persists lifelong within a dynamic equilibrium maintained by B-cell latency, cytotoxic T-cell control, NK-cell surveillance and humoral immunity. Ageing can remodel this equilibrium through thymic involution, contraction of the naive T-cell pool, accumulation of late-differentiated or exhaustion-like T-cell states, altered NK-cell function, B-cell dysfunction and chronic low-grade inflammation. Although cytomegalovirus has dominated discussions of...
Yue Cao

Electronic profiling of neuronal extracellular vesicles enables early prediction of Parkinson's disease

1 day 3 hours ago
Misfolded alpha-Synuclein (α-Syn) accumulation is the defining molecular pathology of Parkinson's disease (PD), yet blood-based assays remain challenged by the high background of peripheral α-Syn originating mainly from red blood cells. Neuronal extracellular vesicles (EVs) circulating in blood offer a biologically enriched source of brain-derived α-Syn proteoforms, but their ultralow abundance has hindered reliable detection. Here, we introduce an organic electrochemical transistor-based...
Tianrui Chang

Speech clocks decode dementia phenotypes, social exposome, and biological aging

1 day 3 hours ago
Biological aging clocks offer estimations of aging and dementia, yet scalability is limited. We introduce a large-scale, cross-national speech clock derived from 2928 individuals across five Latin American countries, spanning healthy controls (HCs), mild cognitive impairment (MCI), Alzheimer's disease (AD), and non-language/language-dominant frontotemporal dementia (nldFTD/ldFTD). Multimodal acoustic and linguistic features were trained with supervised models to estimate chronological age,...
Hernan Hernandez