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Experiments implementing small commuting models lack gravitational features
Pre-rRNA spatial distribution and functional organization of the nucleolus
There’s a new acid in our rain — should we be worried?
Protect the integrity of the US National Institutes of Health
Ageing stem cells in the knees drive arthritis damage
Rumble in the Miocene: terror bird versus caiman
Trump’s plan to slash global health spending rejected by key spending panel
House of Representatives committee signals support for HIV/AIDS and other funding
Cheap drug could fight malaria by spoiling mosquitoes’ blood meal
Field study in Kenya suggests innovative strategy has promise—but some researchers question its viability
Songbirds play optical tricks to make their feather colors ‘pop’
Concealed black or white bands on feathers boost the vibrancy of bird plumage
Can portable headsets peer into the minds of hunter-gatherers and other understudied populations?
Science chats with health economist Shailender Swaminathan about how compact EEGs could reveal the impact of culture and environment on the brain
Employees’ protests against Trump science policies spread to NSF
Letter to key House Democrat follows declarations by scientists at NIH, EPA, and NASA
Watch an earthquake split a hillside in two
Footage of massive Myanmar temblor provides the first video evidence of earthquake ruptures
Molecular Function of Midnolin and Its Relevance to Parkinson's Disease
Midnolin (Midn) was originally discovered as a gene expressed specifically in the mouse midbrain at the embryonic developmental stage; MIDN was localized in the nucleus/nucleolus. Although the pathophysiological roles of MIDN remained largely unknown for many years after its discovery, its molecular functions and relevance to diseases have gradually become clearer. In PC12 cells, a rat neuronal model cell line, liquidity factors that are necessary for neurite outgrowth are reported to induce...
Cell-type-directed network-correcting combination therapy for Alzheimer's disease
Alzheimer's disease (AD) is a multifactorial neurodegenerative disorder characterized by heterogeneous molecular changes across diverse cell types, posing significant challenges for treatment development. To address this, we introduced a cell-type-specific, multi-target drug discovery strategy grounded in human data and real-world evidence. This approach integrates single-cell transcriptomics, drug perturbation databases, and clinical records. Using this framework, letrozole and irinotecan were...
Spatial proteomics of Alzheimer's disease-specific human microglial states
Microglia are implicated in aging, neurodegeneration and Alzheimer's disease (AD). Low-plex protein imaging does not capture cellular states and interactions in the human brain, which differs from rodent models. Here we used multiplexed ion beam imaging to spatially map cellular states and niches in cognitively normal human brains, identifying a spectrum of proteomic microglial profiles. Defined by immune activation states that were skewed across brain regions and compartmentalized according to...
Combined single-cell profiling of chromatin-transcriptome and splicing across brain cell types, regions and disease state
Measuring splicing and chromatin accessibility simultaneously in frozen tissues remains challenging. Here we combined single-cell isoform RNA sequencing and assay for transposase accessible chromatin (ScISOr-ATAC) to interrogate the correlation between these modalities in single cells in human and rhesus macaque frozen cortical tissue samples. Applying a previous definition of four 'cell states' in which the transcriptome and chromatin accessibility are coupled or decoupled for each gene, we...
A genome-wide association study implicates the olfactory system in Drosophila melanogaster diapause-associated lifespan extension and fecundity
The effects of environmental stress on animal life are gaining importance with climate change. Diapause is a dormancy program that occurs in response to an adverse environment, followed by resumption of development and reproduction upon the return of favorable conditions. Diapause is a complex trait, so we leveraged the Drosophila Genetic Reference Panel (DGRP) lines and conducted a genome-wide association study (GWAS) to characterize the genetic basis of diapause. We assessed post-diapause and...
Variations in perfusion detectable in advance of microstructure in white matter aging
One of the most promising interventional targets for brain health is cerebral perfusion, but its link to white matter (WM) aging remains unclear. Motivated by existing literature demonstrating links between declining cortical perfusion and the development of WM hyperintensities, we posit that regional WM hypoperfusion precedes deteriorating WM integrity. Using the Human Connectome Project Aging (HCP-A) data set, we examine tract-wise associations between WM microstructural integrity (i.e....
Central memory T cells with key TCR repertoires and gene expression profiles dominate influenza CD8+ T cell pools across the human lifespan
Central memory CD8^(+) T cells (T(cm)) represent the prominent memory T cell subset in human blood, yet the persistence of T cell receptor (TCR) clonotypic and transcriptional features of epitope-specific T(cm) pools across the human lifespan remains unknown. We analyzed T(cm) CD8^(+) T cells specific for HLA-A*02:01-M1(58-66) (A2/M1(58); a prominent influenza epitope) in newborns, children, adults, and older adults directly ex vivo. Our data provide evidence that epitope-specific T(cm) CD8^(+)...
In vivo prime editing rescues alternating hemiplegia of childhood in mice
Alternating hemiplegia of childhood (AHC) is a neurodevelopmental disorder with no disease-modifying treatment. Mutations in ATP1A3, encoding an Na^(+)/K^(+) ATPase subunit, cause 70% of AHC cases. Here, we present prime editing (PE) and base editing (BE) strategies to correct ATP1A3 and Atp1a3 mutations in human cells and in two AHC mouse models. We used PE and BE to correct five prevalent ATP1A3 mutations with 43%-90% efficiency. AAV9-mediated in vivo PE corrects Atp1a3 D801N and E815K in the...