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Deep learning-based design and experimental validation of a medicine-like human antibody library.
Brief Bioinform
November 2024
Biotherapeutics Molecule Discovery, Boehringer Ingelheim Pharmaceutical Inc., 900 Ridgebury Road, Ridgefield, CT 06877, United States.
Antibody generation requires the use of one or more time-consuming methods, namely animal immunization, and in vitro display technologies. However, the recent availability of large amounts of antibody sequence and structural data in the public domain along with the advent of generative deep learning algorithms raises the possibility of computationally generating novel antibody sequences with desirable developability attributes. Here, we describe a deep learning model for computationally generating libraries of highly human antibody variable regions whose intrinsic physicochemical properties resemble those of the variable regions of the marketed antibody-based biotherapeutics (medicine-likeness).
View Article and Find Full Text PDFAntibiotic-mediated dysbiosis leads to activation of inflammatory pathways.
Front Immunol
January 2025
Charles Perkins Centre, The University of Sydney, Sydney, NSW, Australia.
Introduction: The gut microbiota plays a pivotal role in influencing host health, through the production of metabolites and other key signalling molecules. While the impact of specific metabolites or taxa on host cells is well-documented, the broader impact of a disrupted microbiota on immune homeostasis is less understood, which is particularly important in the context of the increasing overuse of antibiotics.
Methods: Female C57BL/6 mice were gavaged twice daily for four weeks with Vancomycin, Polymyxin B, or PBS (control).
Recognition of by the pattern recognition molecules langerin, mannan-binding lectin, and surfactant protein D: the influence of capsular polysaccharides and wall teichoic acid.
Front Immunol
January 2025
Department of Biomedicine, Aarhus University, Aarhus, Denmark.
The innate immune system plays a critical role in the rapid recognition and elimination of pathogens through pattern recognition receptors (PRRs). Among these PRRs are the C-type lectins (CTLs) langerin, mannan-binding lectin (MBL), and surfactant protein D (SP-D), which recognize carbohydrate patterns on pathogens. Each represents proteins from different compartments of the body and employs separate effector mechanisms.
View Article and Find Full Text PDFGenetic determinants of COVID-19 severity and mortality: Alu 287 bp polymorphism and , , expression in hospitalized patients.
PeerJ
January 2025
Departamento de genética, ecologia e evolução, Laboratório de biologia integrativa, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
Background: The angiotensin-converting enzyme 2 (ACE2) and the transmembrane serine protease 2 (TMPRSS2) are central human molecules in the SARS-CoV-2 virus-host interaction. Evidence indicates that may influence expression. This study aims to determine whether ACE1, ACE2, and TMPRSS2 mRNA expression levels, along with the ACE1 Alu 287 bp polymorphism (rs4646994), contribute to the severity and mortality of COVID-19.
View Article and Find Full Text PDFTranscription factor specificity protein (SP) family in renal physiology and diseases.
PeerJ
January 2025
Department of Nephrology, Children's Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Hangzhou, Zhejiang, China.
Dysregulated specificity proteins (SPs), members of the C2H2 zinc-finger family, are crucial transcription factors (TFs) with implications for renal physiology and diseases. This comprehensive review focuses on the role of SP family members, particularly SP1 and SP3, in renal physiology and pathology. A detailed analysis of their expression and cellular localization in the healthy human kidney is presented, highlighting their involvement in fatty acid metabolism, electrolyte regulation, and the synthesis of important molecules.
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