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Ancient Rapanui genomes reveal resilience and pre-European contact with the Americas
Decoding drivers of carbon flux attenuation in the oceanic biological pump
Multi-pass, single-molecule nanopore reading of long protein strands
Linear symmetric self-selecting 14-bit kinetic molecular memristors
Molecular programs guiding arealization of descending cortical pathways
Mechanism of BRCA1–BARD1 function in DNA end resection and DNA protection
Two-axis twisting using Floquet-engineered XYZ spin models with polar molecules
Two-dimensional-lattice-confined single-molecule-like aggregates
One month convection timescale on the surface of a giant evolved star
Heteromeric amyloid filaments of ANXA11 and TDP-43 in FTLD-TDP Type C
Structure of human TIP60-C histone exchange and acetyltransferase complex
Gasdermin D-mediated metabolic crosstalk promotes tissue repair
Plasma proteomics for risk prediction of Alzheimer's disease in the general population
We aimed to develop and validate a protein risk score for predicting Alzheimer's disease (AD) and compare its performance with a validated clinical risk model (Cognitive Health and Dementia Risk Index for AD [CogDrisk-AD]) and apolipoprotein E (APOE) genotypes. The development cohort, consisting of 35,547 participants from England in the UK Biobank, was randomly divided into a 7:3 training-testing ratio. The validation cohort included 4667 participants from Scotland and Wales in the UK Biobank....
Mechanical force of uterine occupation enables large vesicle extrusion from proteostressed maternal neurons
Large vesicle extrusion from neurons may contribute to spreading pathogenic protein aggregates and promoting inflammatory responses, two mechanisms leading to neurodegenerative disease. Factors that regulate the extrusion of large vesicles, such as exophers produced by proteostressed C. elegans touch neurons, are poorly understood. Here, we document that mechanical force can significantly potentiate exopher extrusion from proteostressed neurons. Exopher production from the C. elegans ALMR neuron...
Speech-induced suppression and vocal feedback sensitivity in human cortex
Across the animal kingdom, neural responses in the auditory cortex are suppressed during vocalization, and humans are no exception. A common hypothesis is that suppression increases sensitivity to auditory feedback, enabling the detection of vocalization errors. This hypothesis has been previously confirmed in non-human primates, however a direct link between auditory suppression and sensitivity in human speech monitoring remains elusive. To address this issue, we obtained intracranial...
Entorhinal cortex vulnerability to human APP expression promotes hyperexcitability and tau pathology
Preventative treatment for Alzheimer's Disease (AD) is dire, yet mechanisms underlying early regional vulnerability remain unknown. In AD, one of the earliest pathophysiological correlates to cognitive decline is hyperexcitability, which is observed first in the entorhinal cortex. Why hyperexcitability preferentially emerges in specific regions in AD is unclear. Using regional, cell-type-specific proteomics and electrophysiology in wild-type mice, we uncovered a unique susceptibility of the...
Europe sidelines Alzheimer's drug: lessons must be learnt
No abstract
Publisher Correction: A plasma protein-based risk score to predict hip fractures
Intracerebroventricular injection of α-synuclein preformed fibrils do not induce motor and olfactory impairment in C57BL/6 mice
CONCLUSION: The intraventricular injection of αSyn PFFs does not induce synucleinopathy or behavioral symptoms. These findings have implications that CSF αSyn aggregates may not necessarily contribute to the onset or progression in PD.
Genetic, transcriptomic, histological, and biochemical analysis of progressive supranuclear palsy implicates glial activation and novel risk genes
Progressive supranuclear palsy (PSP), a rare Parkinsonian disorder, is characterized by problems with movement, balance, and cognition. PSP differs from Alzheimer's disease (AD) and other diseases, displaying abnormal microtubule-associated protein tau by both neuronal and glial cell pathologies. Genetic contributors may mediate these differences; however, the genetics of PSP remain underexplored. Here we conduct the largest genome-wide association study (GWAS) of PSP which includes 2779 cases...