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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...

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...

Although recent advances in treatment of traumatic olfactory dysfunction, which had a low rate of improvement through treatment, have increased the improvement rate in younger patients, it remains low in middle-aged and older patients. Although olfactory function declines with age, its impact on traumatic dysfunction recovery remains unclear. This study was conducted to investigate the effects of aging on olfactory nerve regeneration and olfactory function recovery in an animal model of...

Medical practice mainly addresses single diseases, neglecting multimorbidity as a heterogeneous health decline across organ systems. Aging is a multidimensional process and cannot be captured by a single metric. Therefore, we assessed global health in longitudinal studies, BLSA (n = 907), InCHIANTI (n = 986), and NHANES (n = 40,790), by examining disease severities in 13 bodily systems, generating the Body Organ Disease Number (BODN), reflecting progressive system morbidities. We used Bayesian...

Electrochemical conversion of CO(2) into fuels represents an important pathway for addressing the challenges of climate change and energy storage. However, large-scale applications remain hindered by the instability and inefficiency of CO(2) reduction systems, particularly under highly alkaline electrolytes and high current densities. One primary obstacle is the cathodic salt precipitation, which hinders mass transfer and blocks active sites limiting the lifespan of these systems. Here, we...

The protective role of dietary vitamin D intake on cognitive function is of interest, but evidence remains inconsistent. We aimed to evaluate the association between dietary vitamin D intake and 2-year cognitive changes in older adults at risk of cognitive decline. This longitudinal study comprised 5454 individuals (aged 55-75 years in men and 60-75 years in women) who exhibited overweight/obesity and metabolic syndrome. Data on dietary vitamin D intake was assessed using a validated 143-item...

Evidence across a broad range of disciplines has demonstrated how individuals' social environments can impact their health, lifespan, reproduction, and ultimately their evolutionary fitness. Past research has primarily focused on either traits specific to individuals or wider traits of social groups, linking these with a component of fitness. In this study, we examined how both individual- and group-level social traits in 164 wild mountain gorillas combine to influence multiple pathways...

How central and peripheral circadian clocks regulate protein metabolism and affect tissue mass homeostasis has been unclear. Circadian shifts in the balance between anabolism and catabolism control muscle growth rate in young zebrafish independent of behavioral cycles. Here, we show that the ubiquitin-proteasome system (UPS) and autophagy, which mediate muscle protein degradation, are each upregulated at night under the control of the muscle peripheral clock. Perturbation of the muscle...

Cerebral small vessel disease (cSVD) refers to all pathologies of the brain's arterioles, capillaries, and venules. cSVD is highly prevalent with ageing and is diagnosed by its characteristic neuro-imaging features. Emerging evidence suggests that circulating immune cells play an important role in cSVD's pathology. However, the specific immune cell populations involved remain poorly understood. This systematic review synthesizes current evidence on circulating immune cells in cSVD and their...

Despite significant advances in aging research, translating these findings into clinical practice remains a challenge. Aging is a complex, multifactorial process shaped by many factors including genetic, metabolic, and environmental factors. While medical advancements have extended lifespan, healthspan remains constrained by cellular senescence, telomere attrition, and systemic inflammation-core hallmarks of biological aging. However, emerging evidence suggests that telomere dynamic is not...