Antibody class switching in activated B cells uses class switch recombination (CSR), which joins activation-induced cytidine deaminase (AID)-dependent double-strand breaks (DSBs) within two large immunoglobulin heavy chain (IgH) locus switch (S) regions that lie up to 200 kilobases apart. To test postulated roles of S regions and AID in CSR, we generated mutant B cells in which donor Smu and accepter Sgamma1 regions were replaced with yeast I-SceI endonuclease sites. We found that site-specific I-SceI DSBs mediate recombinational IgH locus class switching from IgM to IgG1 without S regions or AID. We propose that CSR evolved to exploit a general DNA repair process that promotes joining of widely separated DSBs within a chromosome.
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http://dx.doi.org/10.1126/science.1136386 | DOI Listing |
Chaos
January 2025
School of Mathematics and Statistics, University of Hyderabad, Hyderabad 500046, India.
The differential equations involving two discrete delays are helpful in modeling two different processes in one model. We provide the stability and bifurcation analysis in the fractional order delay differential equation Dαx(t)=ax(t)+bx(t-τ)-bx(t-2τ) in the ab-plane. Various regions of stability include stable, unstable, single stable region (SSR), and stability switch (SS).
View Article and Find Full Text PDFAngew Chem Int Ed Engl
January 2025
University of Regensburg, Faculty of Chemistry and Pharmacy, Institute of Inorganic Chemistry, Universitätsstraße 31, D-93053, Regensburg, GERMANY.
Aminophosphates are the focus of research on prebiotic phosphorylation chemistry. Their bifunctional nature also makes them a powerful class of organocatalysts. However, the structural chemistry and dynamics of proton-binding in phosphorylation and organocatalytic mechanisms are still not fully understood.
View Article and Find Full Text PDFTalanta
January 2025
School of Life Sciences, Faculty of Science, The University of Technology Sydney, Sydney, NSW, Australia.
Metabolomics analyses enable the examination and identification of endogenous biochemical reaction products, revealing information on the metabolic pathways and processes active within a living cell or organism. Determination of metabolic shifts can provide important information on a treatment or disease. Unlike other omics fields that typically have analytes of the same chemical class with common building blocks, those that fall under the nomenclature of metabolites encompass a wide array of different compounds with very diverse physiochemical properties.
View Article and Find Full Text PDFJ Clin Immunol
January 2025
Research Center for Immunodeficiencies, Pediatrics Center of Excellence, Children´s Medical Center, Tehran University of Medical Sciences, 62 Qarib St., Keshavarz Blvd, Tehran, 14194, Iran.
Background: Ataxia telangiectasia mutated (ATM) kinase plays a critical role in DNA double-strand break (DSB) repair. Ataxia telangiectasia (A-T) patients exhibit abnormalities in immunoglobulin isotype expression and class switch recombination (CSR). This study investigates the role of residual ATM kinase expression and activity in the severity of A-T disease.
View Article and Find Full Text PDFISA Trans
January 2025
School of Mathematics and Physics, Qingdao University of Science and Technology, Qingdao 266061, China; Qingdao Innovation Center of Artificial Intelligence Ocean Technology, Qingdao 266061, China; The Research Institute for Mathematics and Interdisciplinary Sciences, Qingdao University of Science and Technology, Qingdao 266061, China. Electronic address:
This paper considers the event-triggered adaptive fault-tolerant control (FTC) problem for a class of stochastic nonlinear systems suffering from finite number of actuator failures and abrupt system external failure. Unlike existing event-triggered mechanisms (ETMs), this paper proposes an improved switching threshold mechanism (STM) that effectively addresses the potential system security hazards caused by large signal impulses when both the magnitude size of the controller and its rate of change are too large, while also saving energy consumption. Especially, when the occurrence of both actuator failure and system external failure may lead to over-change rate of the controller, by using the multi-dimensional Taylor network (MTN) approximation technique, the adaptive fault-tolerant control scheme designed based on the improved STM not only has lower resource consumption, but also indirectly improves the control performance of the system by ensuring the system security operation.
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