Immunoglobulin (Ig) class switch recombination (CSR) is responsible for diversification of antibody effector function during an immune response. This region-specific recombination event, between repetitive switch (S) DNA elements, is unique to B lymphocytes and is induced by activationinduced deaminase (AID). CSR is critically dependent on transcription of noncoding RNAs across S regions. However, mechanistic insight regarding this process has remained unclear. New studies indicate that long-range intrachromosomal interactions among IgH transcriptional elements organize the formation of the S/S synaptosome, as a prerequisite for CSR. This three-dimensional chromatin architecture simultaneously brings promoters and enhancers into close proximity to facilitate transcription. Here, we recount how transcription across S DNA promotes accumulation of RNA polymerase II, leading to the introduction of activating chromatin modifications and hyperaccessible chromatin that is amenable to AID activity.
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http://dx.doi.org/10.1111/j.1749-6632.2012.06604.x | DOI Listing |
Nat Commun
December 2024
Oncology Bioinformatics, Genentech, South San Francisco, CA, USA.
Based on the success of cancer immunotherapy, personalized cancer vaccines have emerged as a leading oncology treatment. Antigen presentation on MHC class I (MHC-I) is crucial for the adaptive immune response to cancer cells, necessitating highly predictive computational methods to model this phenomenon. Here, we introduce HLApollo, a transformer-based model for peptide-MHC-I (pMHC-I) presentation prediction, leveraging the language of peptides, MHC, and source proteins.
View Article and Find Full Text PDFBMC Med Inform Decis Mak
December 2024
Department of Respiration, Peking Union Medical College Hospital, No.1, Shuaifuyuan, Dongcheng District, Beijing, 100730, China.
Background: Inpatients with high risk of venous thromboembolism (VTE) usually face serious threats to their health and economic conditions. Many studies using machine learning (ML) models to predict VTE risk overlook the impact of class-imbalance problem due to the low incidence rate of VTE, resulting in inferior and unstable model performance, which hinders their ability to replace the Padua model, a widely used linear weighted model in clinic. Our study aims to develop a new VTE risk assessment model suitable for Chinese medical inpatients.
View Article and Find Full Text PDFPulm Circ
October 2024
UK Service for Pulmonary Hypertension in Children, Great Ormond Street Hospital for Children London UK.
The aim of this single-centre retrospective observational study was to evaluate the safety, tolerability, and efficacy of an in-class combination therapy switch from bosentan plus sildenafil to ambrisentan plus tadalafil in children with pulmonary arterial hypertension. Children aged over 5 years who were established on sildenafil plus bosentan were offered to undergo a therapy switch from May 2014 to May 2021 and, if remaining in the service, followed up to May 2024. Children with Eisenmenger syndrome, open intra or extra-cardiac shunt, or with pulmonary hypertension-associated lung disease were excluded.
View Article and Find Full Text PDFCell Death Discov
December 2024
Pole of Pharmacology and Therapeutics, Institut de Recherche Expérimentale et Clinique (IREC), Université catholique de Louvain (UCLouvain), Brussels, Belgium.
Hypoxic tumors are radioresistant stemming from the fact that oxygen promotes reactive oxygen species (ROS) propagation after water radiolysis and stabilizes irradiation-induced DNA damage. Therefore, an attractive strategy to radiosensitize solid tumors is to increase tumor oxygenation at the time of irradiation, ideally above a partial pressure of 10 mm-Hg at which full radiosensitization can be reached. Historically, the many attempts to increase vascular O delivery have had limited efficacy, but mathematical models predicted that inhibiting cancer cell respiration would be more effective.
View Article and Find Full Text PDFJ Pers Med
December 2024
Dermatology Unit "Daniele Innocenzi", ASL Latina, Department of Medico-Surgical Sciences and Biotechnologies, Sapienza University of Rome, 04100 Latina, Italy.
the present multicenter retrospective study aimed to evaluate the efficacy and safety of intra-class switching between interleukin-17A (IL-17A) inhibitors, specifically from ixekizumab to secukinumab, in patients with plaque psoriasis. this study included 11 patients (6 male, 5 female) who had previously received ixekizumab and then were switched to secukinumab. Patients' PASI, DLQI, and pain VAS (in those with psoriatic arthritis) were evaluated at weeks 16, 24, 54, and 98.
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