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RUVBL2 Regulates Microglia Metabolic Reprogramming to Mediate Stress Granules Aggregation Exacerbating Postoperative Delirium in Aged Mild Cognitive Impairment Rats

12 hours 36 minutes ago
Postoperative delirium (POD) accelerates the transition from mild cognitive impairment (MCI) to Alzheimer's disease (AD) in elderly patients. Microglial metabolic reprogramming, a pivotal aspect of the immune-inflammatory response, modulates microglia-neuron interactions and postoperative cognitive function through microenvironmental alterations. Aberrant overexpression of RUVBL2 disrupts metabolic homeostasis, leading to stress granule (SG) aggregation and fibrosis. This study investigated the...
Lin Zhang

Deletion of SPI1 in microglia exacerbates amyloid pathology by impairing microglial response in Alzheimer's disease models

12 hours 36 minutes ago
Recent human genetic studies have highlighted the potential role of microglial genes and their regulatory functions in the pathogenesis of Alzheimer's disease (AD). The transcription factor PU.1 (encoded by SPI1) is expressed mainly in microglia in the central nervous system and has been reported to be a genetic risk factor for AD. However, the role of microglial SPI1 in AD etiology is still poorly understood. Here, we demonstrate that the selective deletion of Spi1 in microglia exacerbates...
Byungwook Kim

Identifying maximally informative signal-aware representations of single-cell data using the information bottleneck

12 hours 36 minutes ago
Rapid advancements in single-cell RNA sequencing (scRNA-seq) technologies revealed the richness of myriad attributes encompassing cell identity. However, the complexity of the data hinders tasks focusing on a specific biological signal. To address this challenge, we introduce bioIB, a framework based on the information bottleneck method, designed to extract an interpretable compressed representation of scRNA-seq data, optimally informative with respect to a specific biological signal, such as...
Serafima Dubnov

Urogenital dysfunction in neurological diseases

1 day 12 hours ago
Neural damage at any level of the neuraxis can lead to urogenital dysfunction, involving the lower urinary tract (LUT) and/or the sexual organs. The LUT consists of the bladder and the urethra (plus the prostate in males); LUT dysfunction can manifest as an underactive bladder, leading to urinary retention, or as an overactive bladder, leading to urinary incontinence. Manifestations of sexual dysfunction include loss of libido and dysfunction of erection, ejaculation and orgasm. In this Review,...
Ryuji Sakakibara

ss-adrenergic-like signalling engages CrebB in Drosophila gut to promote female longevity

1 day 12 hours ago
Adrenergic signalling is heavily implicated in human age-related disease and yet the potential for this neuroendocrine signalling pathway to modulate ageing has received little attention. Here, we use Drosophila melanogaster to test if adrenergic-like signalling can promote longevity by manipulating tyramine (TA) or octopamine (OA), the invertebrate equivalents of adrenergic hormones. Increased neuronal synthesis of TA boosts health and longevity in both sexes, whereas OA is marginally...
Ahmed F Sumit

Harnessing viral strategies to reverse cognitive dysfunction through the integrated stress response

1 day 12 hours ago
The integrated stress response (ISR) is essential for cellular homeostasis and cognitive function. We investigated how persistent ISR activation affects cognitive performance by studying the PPP1R15B^(R658C) genetic variant associated with intellectual disability. To model this condition, we generated a mouse line with the pathogenic allele inserted. This variant destabilized the PPP1R15B•PP1 phosphatase complex, causing persistent ISR activation, impaired protein synthesis, and long-term memory...
Lucas C Reineke

Siah-1 is Critical for Hypoxia-Induced Lifespan Extension in Caenorhabditis elegans by Regulating the Expression of SKN-1

1 day 12 hours ago
CONCLUSION: The present study identifies Siah-1 as a novel mediator linking hypoxic signaling to SKN-1-dependent transcriptional programs, providing insights into conserved mechanisms of stress adaptation and aging. This work underscores the importance of ubiquitin-mediated regulatory nodes in coordinating longevity pathways under environmental stressors.
Ferbian Milas Siswanto

Harnessing viral strategies to reverse cognitive dysfunction through the integrated stress response

1 day 12 hours ago
The integrated stress response (ISR) is essential for cellular homeostasis and cognitive function. We investigated how persistent ISR activation affects cognitive performance by studying the PPP1R15B^(R658C) genetic variant associated with intellectual disability. To model this condition, we generated a mouse line with the pathogenic allele inserted. This variant destabilized the PPP1R15B•PP1 phosphatase complex, causing persistent ISR activation, impaired protein synthesis, and long-term memory...
Lucas C Reineke