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Development and applications of a machine learning model for an in-depth analysis of pentylenetetrazol-induced seizure-like behaviors in adult zebrafish.
Neuroscience
January 2025
Laboratory of Experimental Neuropsychobiology, Department of Biochemistry and Molecular Biology, Federal University of Santa Maria, Santa Maria, RS, Brazil; Graduate Program in Biological Sciences: Toxicological Biochemistry, Federal University of Santa Maria, Santa Maria, RS, Brazil; The International Zebrafish Neuroscience Research Consortium (ZNRC), Slidell, LA, United States. Electronic address:
Epilepsy, a neurological disorder causing recurring seizures, is often studied in zebrafish by exposing animals to pentylenetetrazol (PTZ), which induces clonic- and tonic-like behaviors. While adult zebrafish seizure-like behaviors are well characterized, manual assessment remains challenging due to its time-consuming nature, potential for human error/bias, and the risk of overlooking subtle behaviors. Aiming to circumvent these issues, we developed a machine learning model for automating the analysis of subtle abnormal and seizure-like behaviors in PTZ-exposed adult zebrafish.
View Article and Find Full Text PDFDiscovery of novel benzo[b][1,4]oxazine derivatives as ferroptosis inhibitors.
Bioorg Chem
January 2025
Basic Medicine Research and Innovation Center for Novel Target and Therapeutic Intervention (Ministry of Education), Department of Urology and Department of Cancer Center of the Second Affiliated Hospital, College of Pharmacy, Chongqing Medical University, Chongqing 400016, China; The Fifth People's Hospital of Shanghai, Molecular and Cell Biology Laboratory, Institutes of Biomedical Sciences, Fudan University, Shanghai 200032, China. Electronic address:
Ferroptosis is a novel type of programmed cell death characterized by radical-driven lipid peroxidation accumulation, which is involved in various diseases, including acute organ injury and neurodegenerative disorders. Pharmacological inhibition of ferroptosis is a promising strategy for treating these diseases. In this study, 16 benzo[b][1,4]oxazine derivatives were synthesized and assayed for their antiferroptotic activity.
View Article and Find Full Text PDFIdentification of a 7H-pyrrolo[2,3-d]pyrimidin derivatives as selective type II c-Met/Axl inhibitors with potent antitumor efficacy.
Bioorg Chem
January 2025
Center for Preclinical Safety Evaluation of Drugs, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu 610041, China. Electronic address:
In this study, we reported the discovery of a novel type II c-Met/Axl inhibitor, characterized by using 4-amino-7H-pyrrolo[2,3-d]pyrimidine as a hinge region binder. Through a systematic exploration of the structure-activity relationship, based on the clinically reported c-Met inhibitor BMS-777607, we identified the optimized compound 22a. 22a exhibited remarkable potency against c-Met and Axl kinases, with IC values of 1 nM and 10 nM, respectively, and demonstrated over 100-fold selectivity to other members of the TAM subfamily.
View Article and Find Full Text PDFLight and dark biofilm adaptation impacts larval settlement in diverse coral species.
Environ Microbiome
January 2025
Australian Centre for Ecogenomics, School of Chemistry and Molecular Biosciences, The University of Queensland, St Lucia, QLD, Australia.
Background: Recovery of degraded coral reefs is reliant upon the recruitment of coral larvae, yet the mechanisms behind coral larval settlement are not well understood, especially for non-acroporid species. Biofilms associated with reef substrates, such as coral rubble or crustose coralline algae, can induce coral larval settlement; however, the specific biochemical cues and the microorganisms that produce them remain largely unknown. Here, we assessed larval settlement responses in five non-acroporid broadcast-spawning coral species in the families Merulinidae, Lobophyllidae and Poritidae to biofilms developed in aquaria for either one or two months under light and dark treatments.
View Article and Find Full Text PDFEvaluating polyglutamine protein aggregation and toxicity in transgenic Caenorhabditis elegans models of Huntington's disease.
Methods Cell Biol
January 2025
State University of Minas Gerais, Department of Biomedical Sciences and Health, Passos, MG, Brazil. Electronic address:
Huntington's disease (HD) is an autosomal dominant neurodegenerative disorder characterized by a repeat of the cytosine-adenine-guanine trinucleotide (CAG) in the huntingtin gene (HTT). This results in the translation of a mutant huntingtin (mHTT) protein with an abnormally long polyglutamine (polyQ) repeat. The pathology of HD leads to neuronal cell loss, motor abnormalities, and dementia.
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