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Microscopic spikes on snakeskin block bacterial buildup
Structures on python scales could inspire chemical-free antimicrobial designs
First science from private Moon lander challenges lunar divide
Blue Ghost data suggest NASA’s growing commercial Moon program can deliver results
Energy Department merges nuclear and particle physics programs, unsettling researchers
In spite of synergies, physicists worry both fields are being sidelined in favor of AI
Impact of P-glycoprotein substrates on transendothelial transport of amyloid-β peptide in an in vitro model
Alzheimer's disease (AD) is a pervasive neurodegenerative disorder and the leading cause of dementia, strongly associated with amyloid β-peptide (Aβ) accumulation in the cerebrum. In most cases, this aggregation is primarily due to inefficiencies in the degradation and clearance of Aβ, notably its transport across the blood-brain barrier (BBB) into the bloodstream. This study investigates the role of P-glycoprotein (P-gp), a key transporter in transporting Aβ across endothelial-cell monolayers,...
Subtyping based on hippocampal cryptic exon burden reveals proteome-wide changes associated with TDP-43 and Alzheimer's disease pathology
TDP-43 pathology defines limbic-predominant age-related TDP-43 encephalopathy (LATE-NC) and frequently co-occurs with Alzheimer's disease neuropathologic change (ADNC), yet the molecular consequences of overlapping pathology remain unclear. We performed biochemical and proteomic analyses of postmortem hippocampal tissue from 90 individuals spanning control, LATE-NC, ADNC, and ADNC+LATE-NC groups. Cryptic exon (CE) inclusion was quantified across eight TDP-43-regulated transcripts and related to...
What percentage of neuromuscular strength reduction in older adults determines the decline in walking speed?
CONCLUSION: Losing 15% or more of neuromuscular strength reduces walking speed over time. Therefore, monitoring the percentage change in NS can serve as a useful tool for early detection of the risk of WS decline, allowing for more personalised clinical investigations and timely neuromuscular strengthening interventions to minimise adverse effects on mobility in older adults.
IFN-β as a therapeutic agent for influenza A virus infection in old mice
CONCLUSIONS: IFN-β administration to IAV-infected old mice improved overall outcome without worsening lung damage and inhibited neuroinflammatory and brain damage-associated pathways. These results suggest IFN-β warrants further investigation as adjunctive treatment for severe viral infections in select hosts.
A parsimonious six-predictor model for memory decline: cross-population validation in Chinese and Japanese aging cohorts
To develop and validate a parsimonious risk model for short-term memory decline in older adults and to evaluate its cross-population transportability between Chinese and Japanese cohorts. The model was developed in 5985 cognitively normal older adults from the China Health and Retirement Longitudinal Study (CHARLS, 2011-2015). Seven machine learning algorithms were compared, and a Cox proportional hazards (CoxPH) model was selected for its optimal balance between performance and parsimony. The...
FGF21-Mediated Upregulation of SIRT1 Delays Intervertebral Disc Degeneration by Promoting PINK1/Parkin Dependent Mitophagy Through Deacetylation of FOXO3
Intervertebral Disc Degeneration (IDD) is a common degenerative spinal disease and a leading cause of low back pain and disability. The senescence of nucleus pulposus cells (NPCs) is a central mechanism driving the pathological progression of IDD, though its regulatory mechanisms remain unclear. Bioinformatic analysis identified FGF21 as a key gene regulating NPCs senescence. In both human and rat degenerated intervertebral discs, FGF21 expression was significantly downregulated and closely...
Age-Like Methylation Changes of HSCs in GADD45B Knockout Mice Define Methylation Sites Associated With Loss of Function
Hematopoietic stem cells (HSCs) self-renew and differentiate into all blood cells maintaining the hematopoietic system. Age-related HSC dysfunction impacts all of hematopoiesis, with DNA methylation alterations in aged HSCs contributing to altered function. Growth Arrest and DNA Damage-inducible proteins (Gadd45a, Gadd45b, and Gadd45g) are expressed in HSC activation, and Gadd45b has been reported to induce DNA demethylation. Thus, we explored the relationship between Gadd45b, DNA methylation...
Parkinson's disease-associated PLA2G6 protects IP3R1 protein to control ER-mitochondria tethering and Ca(2+) transfer
Mutations in the phospholipase A2 group VI (PLA2G6) gene have been linked to autosomal recessive Parkinson's disease (PD), yet the molecular mechanisms remain poorly understood. This study provides the in vitro and in vivo evidence, specifically in dopaminergic neurons derived from patients with PD, that PLA2G6 loss-of-function disrupts the mitochondria-associated endoplasmic reticulum (ER) membrane (MAM), a critical regulator of Ca^(2+) transfer and energy homeostasis. This study demonstrates...
Membrane interfacial potential governs surface condensation and fibrillation of α-Synuclein in neurons
Biomolecular condensates formed via liquid-liquid phase separation (LLPS) are essential for cellular organization. α-Synuclein, an amyloidogenic protein linked to Parkinson's Disease (PD), undergoes phase separation at high concentrations, but the influence of lipid membranes on this process remains unclear. Here, combining in vitro reconstitution, cell biology, and simulations, we show that membranous interfaces promote α-Synuclein condensation at physiologically relevant sub-critical...
A biomarker of Alzheimer's disease could be a useful diagnostic tool for other amyloidoses
No abstract
StrucGAP: a modular, streamlined and traceable data mining platform for structural and site-specific glycoproteomics
The rapidly developing search engines for glycopeptide identification and accumulated high-resolution glycoproteomic data underscore the need for robust downstream data mining platforms towards subsequently functional and mechanistic studies. Here, we introduce StrucGAP, a Structural Glycoproteomics Analysis Platform for scalable downstream data mining of site-specific N-glycoproteomics. It integrates modules for data quality control, overall glycan structural characterization, altered glycan...
IVNS1ABP mutation drives cellular senescence in newly identified progeroid neuropathy
We identified a new progeroid syndrome with severe neuropathy and intellectual deficits but its underlying cellular and molecular mechanism is unknown. Exome sequencing revealed a homozygous mutation in the IVNS1ABP gene, which encodes IVNS1ABP, an influenza virus non-structural protein-1 binding protein. To investigate disease mechanisms, we generated isogenic induced pluripotent stem cells (iPSCs) from patient fibroblasts and differentiated them into neural progenitor cells (NPCs). Mutant...
Faster ticking of 'biological clock' predicts shorter lifespan
No abstract
The brain-gut-muscle axis: a mechanism for exercise-mediated protection in brain aging
The global challenge of population aging underscores the critical need to delay brain aging and cognitive decline, a pressing public health issue. The brain-gut-muscle axis is a complex regulatory network connecting skeletal muscle, gut microbiota, and the brain. It has received considerable research attention for its crucial role in maintaining brain health and counteracting aging. As a safe and effective non-pharmacological intervention, exercise modulates gut microbiota composition and...
TAS2R38 taster variants-linked MGAM expression in Alzheimer's disease: a novel target for precision drug repurposing
INTRODUCTION: TAS2R38 is a taste receptor gene located on human chromosome 7 that influences sensitivity to bitter tastes and has been implicated in innate immunity, glucose level, and human longevity. However, its potential association with Alzheimer's Disease (AD) has not been explored. Identifying such a genetic connection could support developing new drugs or repurposing existing ones for AD treatment.
Diet, gut microbiome, and cognition in neurodegeneration: a review and methodological framework
The gut microbiome influences brain function through the gut-brain axis via synthesis of neurotransmitters, production of metabolites affecting epithelial barrier integrity and immune modulation and signaling through the vagus nerve. In humans, microbiome diversity reflects healthy aging and predicts survival, while dysbiosis is increasingly implicated in neurodegenerative conditions including Alzheimer's disease, Parkinson's disease, multiple sclerosis, and ALS. Fecal transplant studies in...
Age-related changes in static and dynamic postural balance performance
CONCLUSION: Age-related changes in balance control are task dependent. Older adults preserved static balance performance but demonstrated impaired reactive balance responses in dynamic tasks. Furthermore, static and dynamic balance rely on distinct control mechanisms, highlighting the need for separate assessments.