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Executive order on gain-of-function experiments could chill research on infectious diseases, scientists say

Internal emails from 2021 reveal tensions among researchers hunting for elusive Majorana particle

The mitochondrial deubiquitinase ubiquitin-specific protease (USP) 30 negatively regulates PINK1-parkin-driven mitophagy. Whether enhanced mitochondrial quality control through inhibition of USP30 can protect dopaminergic neurons is currently being explored in a clinical trial for Parkinson's disease. However, the molecular basis for specific inhibition of USP30 by small molecules has remained elusive. Here we report the crystal structure of human USP30 in complex with a specific inhibitor,...

Alzheimer's disease (AD) and age-related macular degeneration (AMD) represent the leading causes of dementia and vision impairment in the elderly, respectively. The retina is an extension of the brain, yet these two central nervous system (CNS) compartments are often studied separately. Despite affecting cognition vs. vision, AD and AMD share neuroinflammatory pathways. By comparing these diseases, we can identify converging immune mechanisms and potential cross-applicable therapies. Here, we...

Self-replicating amyloid beta (Aβ) oligomers are considered as one of the major drivers for disrupted synaptic function and plasticity, leading to impaired neuronal viability and progression of Alzheimer's disease (AD). Here, we investigated the safety, tolerability and pharmacokinetics of the anti-oligomeric peptide PRI-002, which was developed to disassemble toxic Aβ oligomers into non-toxic monomers. In a randomized, double-blind, single-center phase 1b trial, 20 patients aged between 50 and...

The central nervous system (CNS) was once perceived as entirely shielded from the immune system, protected behind the blood-brain barrier and thought to lack lymphatic drainage. However, recent evidence has challenged many dogmas in neuroimmunology. Indeed, by means of glymphatics, brain-derived "waste" from deep within the CNS mobilizes toward immunologically active brain borders, where meningeal lymphatic vessels are appropriately positioned to drain antigens from the brain to the periphery....

From the migration of precursor cells to the refinement of neural circuits, the immune system plays a critical role in the development of the central nervous system. As the brain resident macrophages, microglia are integral to these processes, influencing key developmental stages and contributing to circuit remodeling. Recent years have brought a wealth of new insights into how microglia regulate key stages of brain development, particularly through their continuous crosstalk with various brain...

Excessive levels of oncogenic RAS expression in normal cells trigger reactive cellular senescence, known as oncogene-induced senescence (OIS)-a putative autonomous tumor-suppressive mechanism. However, the monoallelic expression of oncogenic RAS from the endogenous locus often fails to induce senescence, at least in the short term. Consequently, whether robust senescence characterizes the preneoplasia driven by oncogenic RAS under physiological conditions has been debated. A key challenge is the...

Record power conversion efficiencies (PCEs) of perovskite solar cells (PSCs) are usually achieved using organic spiro-OMeTAD. However, conventional doping with hygroscopic dopants (LiTFSI and tBP) leads to compromised device stability. We introduce a synergistic mixed doping strategy that utilizes a combination of metal-TFSI dopants-LiTFSI, KTFSI, NaTFSI, Ca(TFSI)(2), and Mg(TFSI)(2)-to enhance doping efficiency while effectively removing hygroscopic contaminants from the Spiro-OMeTAD solution....

Aging is associated with the accumulation of senescent cells, which are triggered by tissue injury response and often escape clearance by the immune system. The specific traits and diversity of these cells in aged tissues, along with their effects on the tissue microenvironment, remain largely unexplored. Despite the advances in single-cell and spatial omics technologies to understand complex tissue architecture, senescent cell populations are often neglected in general analysis pipelines due to...