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Science, Volume 387, Issue 6741, March 2025.

Science, Volume 387, Issue 6741, March 2025.

Science, Volume 387, Issue 6741, March 2025.

Science, Volume 387, Issue 6741, March 2025.

Science, Volume 387, Issue 6741, March 2025.

Science, Volume 387, Issue 6741, March 2025.

Particles loaded with RNA reverse symptoms of respiratory failure and atherosclerosis in mice

Hunter-gatherers in what today is Turkey may have smelted copper more than 10,000 years ago

Studies examining the interplay between chronic pain, cognitive function, and functional brain abnormalities in older adults are scarce. To address this gap, we administered a series of neuropsychological tests and recorded electroencephalography (EEG) data during resting-state conditions in 26 older adults with chronic pain (CPOA), 30 pain-free older adults (OA), and 31 younger adults (YA). CPOA demonstrated poorer performance compared to OA on the Stroop test, the Wisconsin Card Sorting Test...

Collagen loss is one of the major contributor to signs of skin aging such as dryness, roughness, and wrinkle formation, which is closely linked to a decline in the amount of proline produced in mitochondria. Melatonin has been shown to improve several clinical signs of skin aging, while the mechanism is unclear. In our study, we found that mitophagy, proline synthesis key enzyme NADK2 and proline and collagen levels were significantly reduced, while oxidative stress levels increased in aging...

Parkinson's disease (PD) is a neurodegenerative disorder characterized by the progressive loss of dopaminergic neurons in the Substantia Nigra, leading to motor impairment. A hallmark of PD is the presence of misfolded α-synuclein (α-syn) proteins and their neurotoxic accumulations, contributing to neuronal loss. Additionally, the inflammatory response plays a critical role in modulating the neurodegeneration process in PD. Moreover, peripheral macrophages recognize α-syn, triggering chronic...

Synapses represent a fundamental unit of information transfer during cognition via presynaptic vesicle exocytosis. It has been established that evoked release is probabilistic, but the mechanisms behind spontaneous release are less clear. Understanding spontaneous release is vital, as it plays a key role in maintaining synaptic connections. We propose a model framework for spontaneous release where the reserve pool geometrically constrains recycling pool vesicles, creating an entropic force that...

Finely tuned gamma (FTG) oscillations from the subthalamic nucleus (STN) and cortex in Parkinson's disease (PD) patients undergoing deep brain stimulation (DBS) are often associated with dyskinesia. Recently it was shown that DBS entrains gamma activity at 1:2 of the stimulation frequency; however, the functional role of this signal is not yet fully understood. We recorded local field potentials from the STN in 19 chronically implanted PD patients on dopaminergic medication during DBS, at rest,...

No abstract

Ageing is the most prominent risk factor for Alzheimer's disease (AD). However, the cellular mechanisms linking neuronal proteostasis decline to the characteristic aberrant protein deposits in the brains of patients with AD remain elusive. Here we develop transdifferentiated neurons (tNeurons) from human dermal fibroblasts as a neuronal model that retains ageing hallmarks and exhibits AD-linked vulnerabilities. Remarkably, AD tNeurons accumulate proteotoxic deposits, including phospho-tau and...

No abstract

Evidence regarding the clinical validity of blood biomarkers of Alzheimer's disease (AD) in the general population is limited. We estimated the hazard and predictive performance of six AD blood biomarkers for incident all-cause and AD dementia-the ratio of amyloid-β 42 to amyloid-β 40 and levels of tau phosphorylated at T217 (p-tau217), tau phosphorylated at T181 (p-tau181), total tau, neurofilament light chain (NfL), and glial fibrillary acidic protein (GFAP)-in a cohort of 2,148 dementia-free...

The presence of neuronal Lewy bodies mainly composed of SNCA/α-synuclein aggregations is a pathological feature of Parkinson disease (PD), whereas reducing SNCA protein levels may slow the progression of this disease. We hypothesized that compounds enhancing SNCA's interaction with MAP1LC3/LC3 May increase its macroautophagic/autophagic degradation. Here, we conducted small molecule microarray (SMM)-based screening to identify such compounds and revealed that the compound R406 could decrease...

Ames dwarf mice (df/df) live 50% longer than normal littermates due to a genetic defect in growth hormone (GH) signaling. The enhanced longevity of Ames dwarfs has been studied extensively in an endocrinological context of cellular metabolism and increased resistance to oxidative stress (Bartke. World J Mens Health 37(1):19, 8; Bartke 2; BartkeJ Am Aging Assoc 23(4):219, 10; Bartke. World J Mens Health 39(3):454-465, 11; Brown-Borg et al. Nature 384(6604):33-33, 1; Masternak et al. 2018)....

The human Fallopian tube (FT) is an important organ in the female reproductive system and has been implicated as a site of origin for pelvic serous cancers, including high-grade serous tubo-ovarian carcinoma (HGSC). We have generated comprehensive whole-genome bisulfite sequencing, RNA-seq, and proteomic data of over 100 human FTs, with detailed clinical covariate annotations. Our results challenge existing paradigms that extensive epigenetic, transcriptomic and proteomic alterations exist in...