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After years of delay and political wrangling, DOE’s Hanford site opens vitrification plant

Iconic amphibians took an unexpected path across the globe, study finds—with toxins as a “game changer”

Modern humans’ tolerance for the toxic metal may have helped them outcompete our closest evolutionary cousins

Parkinson's disease (PD) has long been considered an appropriate candidate for cell replacement therapy. We generated high-purity dopaminergic progenitors (A9-DPCs) from human embryonic stem cells and evaluated their safety and exploratory efficacy in a single-center, open-label, dose-escalation phase 1/2a trial (NCT05887466) for PD patients. Twelve patients with moderate-to-severe PD received bilateral putamen transplantation of low-dose (3.15 million cells; n = 6) or high-dose (6.30 million...

Galactocerebrosidase (GALC) is a lysosomal enzyme crucially involved in the catabolism of galactosphingolipids. Among galactosphingolipids, galactosylceramide and sulfatide are crucial determinants for oligodendrocyte differentiation, as well as myelin stability and structure. Homozygous or compound heterozygous inherited mutations leading to a severe decrease in GALC enzymatic activity have been associated with the onset of Krabbe disease, also known as "globoid cell leukodystrophy". Extensive...

The sensory motor cortex (SMC) plays a crucial role in motor function and is implicated in the pathophysiology of idiopathic Parkinson's disease (iPD). Asymmetric motor symptomatology in iPD suggests lateralized neurochemical alterations that may underlie disease progression and severity. Single-voxel in vivo proton magnetic resonance spectroscopy using PRESS (20 × 20 × 20 mm³) and MEGA-PRESS (30 × 30 × 30 mm3) sequences were performed on bilateral SMC in 25 iPD patients and 23 healthy controls...

Biological phenotypes emerge from complex interactions across molecular layers. Yet, data-driven approaches to infer these regulatory networks have primarily focused on single-omic studies, overlooking inter-layer regulatory relationships. To address these limitations, we developed MINIE, a computational method that integrates multi-omic data from bulk metabolomics and single-cell transcriptomics through a Bayesian regression approach that explicitly models the timescale separation between...

Chaperone-mediated autophagy (CMA) declines in ageing and neurodegenerative diseases. Loss of CMA in neurons leads to neurodegeneration and behavioural changes in mice but the role of CMA in neuronal physiology is largely unknown. Here we show that CMA deficiency causes neuronal hyperactivity, increased seizure susceptibility and disrupted calcium homeostasis. Pre-synaptic neurotransmitter release and NMDA receptor-mediated transmission were enhanced in CMA-deficient females, whereas males...

Liquid-liquid phase separation (LLPS) and subsequent liquid-gel/solid transition are considered common aggregation mechanisms of proteins linked to neurodegenerative diseases. α-synuclein (α-syn), the main factor in Parkinson's disease pathology, has been reported to undergo LLPS, thereby accelerating aggregate formation. However, the precise molecular events involved in the early stages of α-syn aggregation remain controversial. In this study, we show that α-syn aggregation is promoted by...

Age and APOE ε4 are major risk factors for Alzheimer's disease (AD), while sex differences exist in disease prevalence and progression. Cerebrospinal fluid (CSF) proteomics can provide additional insights into brain aging and AD. To examine proteomic changes due to age, sex and apolipoprotein E (APOE) ε4 along with amyloid status before clinical AD occurs, we profiled 6,175 proteins in the CSF from 994 cognitively normal individuals aged 43-91 years. We identified and replicated 2,172...