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Politics and environmental concerns imperil plans to divert the Mississippi River to build new land

Current Aβ-targeting therapeutics for Alzheimer's disease (AD) only slow cognitive decline due to poor understanding of AD pathogenesis. Here we describe a mechanism of AD pathogenesis in which the histone methyltransferase G9a noncanonically regulates translation of hippocampal proteins associated with AD pathology. Correspondingly, we developed a brain-penetrant inhibitor of G9a, MS1262, which restored both age-related learning & memory and noncognitive functions in multiple AD mouse models....

The dopamine transporter (DAT) is linked to neuropsychiatric disorders including ADHD, Parkinson's disease, and substance use disorders. Accordingly, DAT is the target of illicit drugs and clinically important medicines. However, the number and function of ligand binding sites in DAT is enigmatic due to conflicting data from available structures and molecular pharmacology. Herein, we design force sensors with DAT ligands and measure their interaction forces with wild-type and mutated DATs, from...

Cortical circuit activity is controlled by GABA-mediated inhibition in a spatiotemporally restricted manner. GABA(B) receptor (GABA(B)R) signalling exerts powerful slow inhibition that controls synaptic, dendritic and neuronal activity. But, how GABA(B)Rs contribute to circuit-level inhibition over the lifespan of rodents and humans is poorly understood. In this study, we quantitatively determined the functional contribution of GABA(B)R signalling to pre- and postsynaptic domains in rat and...

Testicular aging commonly leads to testosterone deficiency and impaired spermatogenesis, yet the underlying mechanisms remain elusive. Here, we show that Leydig cells are particularly vulnerable to aging processes in testis. Single-cell RNA sequencing identifies the expression of Hmgcs2, the gene encoding rate-limiting enzyme of ketogenesis, decreases significantly in Leydig cells from aged mice. Additionally, the concentrations of ketone bodies β-hydroxybutyric acid and acetoacetic acid in...

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On September 11, 2023, Storm Daniel unleashed unprecedented rainfall over the Wadi Derna watershed, triggering one of the most devastating floods in modern history, striking Derna, a coastal city in Libya. This study reconstructs the disaster using an integrated modeling approach that combines satellite imagery, hydrologic, hydraulic, and geotechnical simulations, machine learning, eyewitness accounts, and digital elevation data to assess the impact of cascading dam failures. Our findings reveal...

CONCLUSION: According to the relatively high prevalence of mild cognitive impairment in geriatric population, determination of proper health strategies seems necessary for diagnosis and treatment of mild cognitive impairment along with awareness and management of associated consequences in geriatric population.

CONCLUSION: The LC9 score represents an important advancement in assessing mortality risk among frail older adults. This study highlights the need for holistic approaches in aging health assessments and suggests that integrating mental health within cardiovascular metrics may enhance the accuracy of risk predictions.

Specialized intramembrane proteases, known as iCLiPs, regulate the processing of transmembrane proteins by releasing intracellular domains, which can function as transcriptional regulators. The signal peptide peptidase-like (SPPL) family of iCLiPs, particularly SPPL2b, has roles in immune regulation, neuronal function, and disease pathogenesis. In the brain, SPPL2b localizes mainly in the plasma membrane of neurons and microglia and is abundant in the cortex and hippocampus. Its known substrates...

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