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Analytical Characterization of Aberrant Trisulfide Bond Formation in Therapeutic Proteins and Their Impact on Product Quality.
J Pharm Sci
January 2025
Laboratory of Applied Biochemistry, Division of Biotechnology Review and Research III, Office of Biotechnology Products, Center for Drug Evaluation and Research, Food and Drug Administration, Silver Spring, MD, USA.. Electronic address:
Post translational modifications (PTMs) of proteins play an integral role in maintaining the overall structure and function of proteins including their proper folding, binding, and potency. However, not all PTMs play a positive role in protein drugs as some can lead to product-related impurities that negatively impact protein function. One example of a PTM is trisulfide formation, which appears as a product related species in multiple biologic drug products.
View Article and Find Full Text PDFProper names-expressions such as "Barack Obama" or "New York"-play a crucial role in the philosophical debate on reference, that is, the relation that allows words to stand for entities of the world. In an elicited production test, Devitt and Porot prompt participants to use proper names to compare the Descriptivist Theory and the Causal-Historical Theory on proper names' reference. According to the Descriptivist Theory, names refer to the entity that fulfills the description that speakers associate with them.
View Article and Find Full Text PDFTranscriptional dynamics during karyogamy in rice zygotes.
Development
January 2025
Department of Biological Sciences, Tokyo Metropolitan University, Hachioji, Tokyo, Japan.
Upon fertilization, male and female nuclei fuse to form the zygotic nucleus in angiosperms. Karyogamy is considered to be essential for proper embryogenesis; however, the transcriptional dynamics during karyogamy in plant zygotes remain unclear. In this study, we performed a single-cell transcriptome analysis of rice zygotes at six early developmental stages (15 min, 30 min, 1 h, 2 h, 4 h, and 6 h after gamete fusion) to reveal gene expression profiles during karyogamy in plant zygotes.
View Article and Find Full Text PDFDecoding the Torsional Dynamics of Main-Chain Atoms Within CαNN Motif Facilitating Specific Anion Recognition.
Proteins
January 2025
Department of Biotechnology, Maulana Abul Kalam Azad University of Technology, Haringhata, India.
The structural plasticity of proteins at the molecular level is largely dictated by backbone torsion angles, which play a critical role in ligand recognition and binding. To establish the anion-induced cooperative arrangement of the main-chain (mc) torsion, herein, we analyzed a set of naturally occurring CαNN motifs as "static models" for their anion-binding competence through docking and molecular dynamics simulations and decoded its torsion angle influenced mc-driven anion recognition potential. By comparing a pool of 20 distinct sets of CαNN motif with identical sequences in their "anion bound/present, aP" and "anion free/absent, aA" versions, we could discern that there exists a positive correlation between the "difference of anion residence time (ΔR)" and "difference among the main-chain torsion angle" of the aP and aA population.
View Article and Find Full Text PDFInvestigating the role of GPR39 in treatment of stress-induced depression and anxiety.
Psychopharmacology (Berl)
January 2025
Department of Pharmacobiology, Jagiellonian University Medical College, Medyczna 9, 30-688, Kraków, Poland.
Rationale: Chronic stress is one of the leading causes of depression. Yet, knowledge of the pathomechanism of this process still eludes us. Chronic unpredictable mild stress (CUMS) model of depression enables researchers to look for a root cause of the disease in mice by mimicking a stressful human environment.
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