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Stimulating the regenerative capacity of the human retina with proneural transcription factors in 3D cultures.
Proc Natl Acad Sci U S A
January 2025
Department of Biological Structure, University of Washington, Seattle, WA 98125.
Retinal diseases often lead to degeneration of specific retinal cell types with currently limited therapeutic options to replace the lost neurons. Previous studies have reported that overexpression of or combinations of proneural factors in Müller glia (MG) induce regeneration of functional neurons in the adult mouse retina. Recently, we applied the same strategy in dissociated cultures of fetal human MG and although we stimulated neurogenesis from MG, our effect in 2D cultures was modest and our analysis of newborn neurons was limited.
View Article and Find Full Text PDFDetailed Structural Elucidation of Antibody-Drug Conjugate Biotransformation Species Using High Resolution Multiple Reaction Monitoring Mass Spectrometry with Orthogonal Dissociation Methods.
ACS Pharmacol Transl Sci
January 2025
Integrated Bioanalysis, Clinical Pharmacology and Safety Sciences, R&D, AstraZeneca, 121 Oyster Point Blvd, South San Francisco, California 94080, United States.
Antibody-drug conjugates (ADCs) are a promising drug modality substantially expanding in both the discovery space and clinical development. Assessing the biotransformation of ADCs and is important in understanding their stability and pharmacokinetic properties. We previously reported biotransformation pathways for the anti-B7H4 topoisomerase I inhibitor ADC, AZD8205, puxitatug samrotecan, that underpin its structural stability using an intact protein liquid chromatography-high resolution mass spectrometry (LC-HRMS) approach.
View Article and Find Full Text PDFRegulatory dynamics of Sch9 in response to cytosolic acidification: From spatial reconfiguration to cellular adaptation to stresses.
iScience
January 2025
Department of Biology, Graduate School of Science, Chiba University, Chiba 263-8522, Japan.
The regulation of cellular metabolism is crucial for cell survival, with Sch9 in serving a key role as a substrate of TORC1. Sch9 localizes to the vacuolar membrane through binding to PI(3,5)P, which is necessary for TORC1-dependent phosphorylation. This study demonstrates that cytosolic pH regulates Sch9 localization.
View Article and Find Full Text PDFIsolation of Quick-Response High-Affinity Aptamers for Continuous and Reagentless Detection of Thrombin.
Anal Chem
January 2025
Department of Chemistry, Capital Normal University, Xisanhuan North Road. 105, Beijing 100048, China.
Continuous and reagentless biomolecular detection technologies are bringing an evolutionary influence on disease diagnostics and treatment. Aptamers are attractive as specific recognition probes because they are capable of regeneration without washing. Unfortunately, the affinity and dissociation kinetics of the aptamers developed to date show an inverse relationship, preventing continuous and reagentless detection of protein targets due to their low dissociation rates.
View Article and Find Full Text PDFNegative DNA supercoiling enhances DARS2 binding of DNA-bending protein IHF in the activation of Fis-dependent ATP-DnaA production.
Nucleic Acids Res
January 2025
Department of Molecular Biology, Graduate School of Pharmaceutical Sciences, Kyushu University, Fukuoka 812-8582, Japan.
Oscillation of the active form of the initiator protein DnaA (ATP-DnaA) allows for the timely regulation for chromosome replication. After initiation, DnaA-bound ATP is hydrolyzed, producing inactive ADP-DnaA. For the next round of initiation, ADP-DnaA interacts with the chromosomal locus DARS2 bearing binding sites for DnaA, a DNA-bending protein IHF, and a transcription activator Fis.
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