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GABAergic Progenitor Cell Graft Rescues Cognitive Deficits in Fragile X Syndrome Mice.
Adv Sci (Weinh)
January 2025
Department of Neurology, Institute of Neuroscience, Key Laboratory of Neurogenetics and Channelopathies of Guangdong Province and the Ministry of Education of China, The Second Affiliated Hospital, Guangzhou Medical University, Guangzhou, 510260, China.
Fragile X syndrome (FXS) is an inherited neurodevelopmental disorder characterized by a range of clinical manifestations with no effective treatment strategy to date. Here, transplantation of GABAergic precursor cells from the medial ganglionic eminence (MGE) is demonstrated to significantly improve cognitive performance in Fmr1 knockout (KO) mice. Within the hippocampus of Fmr1-KO mice, MGE-derived cells from wild-type donor mice survive, migrate, differentiate into functionally mature interneurons, and form inhibitory synaptic connections with host pyramidal neurons.
View Article and Find Full Text PDFControl of striatal circuit development by the chromatin regulator .
Sci Adv
January 2025
Department of Neuroscience, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
The pathophysiology of neurodevelopmental disorders involves vulnerable neural populations, including striatal circuitry, and convergent molecular nodes, including chromatin regulation and synapse function. Despite this, how epigenetic regulation regulates striatal development is understudied. Recurrent de novo mutations in are associated with intellectual disability and autism.
View Article and Find Full Text PDFPrecision data-driven modeling of cortical dynamics reveals person-specific mechanisms underpinning brain electrophysiology.
Proc Natl Acad Sci U S A
January 2025
Department of Electrical & Systems Engineering, Washington University in St. Louis, St. Louis, MO 63130.
Task-free brain activity affords unique insight into the functional structure of brain network dynamics and has been used to identify neural markers of individual differences. In this work, we present an algorithmic optimization framework that directly inverts and parameterizes brain-wide dynamical-systems models involving hundreds of interacting neural populations, from single-subject M/EEG time-series recordings. This technique provides a powerful neurocomputational tool for interrogating mechanisms underlying individual brain dynamics ("precision brain models") and making quantitative predictions.
View Article and Find Full Text PDFChemical Constituents of the Deep-Sea-Derived Penicillium citrinum W22 and Their Ferroptosis Inhibitory Activity.
Chem Biodivers
January 2025
Hainan Pharmaceutical Research and Development Science Park, Hainan Academy of Medical Sciences, Hainan Medical University, Haikou, China.
One new monomeric citrinin analog (1) and 42 known compounds (2-43) were isolated from Penicillium citrinum W22. The structure of 1 was determined by detailed analysis of the 1D and 2D nuclear magnetic resonance (NMR), HRESIMS, and time-dependent density functional theory (TD-DFT)-based electronic circular dichroism (ECD) calculation. Penicitrinol A (2) and methyl 2-(2-acetyl-3,5-dihydroxy-4,6-dimethylphenyl) acetate (11) significantly inhibited renin-angiotensin system-selective lethal 3 (RSL3)-induced ferroptosis with half maximal effective concentration (EC) values of 1.
View Article and Find Full Text PDFMetabolically Stable Adenylation Inhibitors of Biotin Protein Ligase as Antibacterial Agents.
J Med Chem
January 2025
Department of Medicinal Chemistry, University of Minnesota, 308 Harvard Street SE, Minneapolis, Minnesota 55455, United States.
The antibacterial agent Bio-AMS is metabolized in vivo through hydrolysis of the central acyl-sulfamide linker leading to high clearance and release of a moderately cytotoxic metabolite . Herein, we disclose analogues designed to prevent the metabolism of the central acyl-sulfamide moiety through steric hindrance or attenuation of the acyl-sulfamide electrophilicity. was identified as a metabolically stable analogue with a single-digit nanomolar dissociation constant for biotin protein ligase (BPL) and minimum inhibitory concentrations (MICs) against and ranging from 0.
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