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Affinity maturation

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https://www.readbyqxmd.com/read/28935768/the-microanatomic-segregation-of-selection-by-apoptosis-in-the-germinal-center
#1
Christian T Mayer, Anna Gazumyan, Ervin E Kara, Alexander D Gitlin, Jovana Golijanin, Charlotte Viant, Joy Pai, Thiago Y Oliveira, Qiao Wang, Amelia Escolano, Max Medina-Ramirez, Rogier W Sanders, Michel C Nussenzweig
B cells undergo rapid cell division and affinity maturation in anatomically distinct sites in lymphoid organs called germinal centers (GCs). Homeostasis is maintained in part by B cell apoptosis. However, the precise contribution of apoptosis to GC biology and selection is not well defined. We developed apoptosis-indicator mice and used them to visualize, purify, and characterize dying GC B cells. Apoptosis is prevalent in the GC with up to half of all GC B cells dying every 6 hours. Moreover, programmed cell death is differentially regulated in the light zone (LZ) and the dark zone (DZ): LZ B cells die by default if they are not positively selected, whereas DZ cells die when their antigen receptors are damaged by activation-induced cytidine deaminase (AID)...
September 21, 2017: Science
https://www.readbyqxmd.com/read/28933967/aid-biology-a-pathological-and-clinical-perspective
#2
Meenal Choudhary, Anubhav Tamrakar, Amit Kumar Singh, Monika Jain, Ankit Jaiswal, Prashant Kodgire
Activation-induced cytidine deaminase (AID), primarily expressed in activated mature B lymphocytes in germinal centers, is the key factor in adaptive immune response against foreign antigens. AID is responsible for producing high-affinity and high-specificity antibodies against an infectious agent, through the physiological DNA alteration processes of antibody genes by somatic hypermutation (SHM) and class-switch recombination (CSR) and functions by deaminating deoxycytidines (dC) to deoxyuridines (dU), thereby introducing point mutations and double-stranded chromosomal breaks (DSBs)...
September 21, 2017: International Reviews of Immunology
https://www.readbyqxmd.com/read/28928732/facile-affinity-maturation-of-antibody-variable-domains-using-natural-diversity-mutagenesis
#3
Kathryn E Tiller, Ratul Chowdhury, Tong Li, Seth D Ludwig, Sabyasachi Sen, Costas D Maranas, Peter M Tessier
The identification of mutations that enhance antibody affinity while maintaining high antibody specificity and stability is a time-consuming and laborious process. Here, we report an efficient methodology for systematically and rapidly enhancing the affinity of antibody variable domains while maximizing specificity and stability using novel synthetic antibody libraries. Our approach first uses computational and experimental alanine scanning mutagenesis to identify sites in the complementarity-determining regions (CDRs) that are permissive to mutagenesis while maintaining antigen binding...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28923704/cloning-characterisation-docking-and-expression-analysis-of-3-beta-hydroxysteroid-dehydrogenase-during-ontogenetic-development-and-annual-reproductive-cycles-in-catfish-clarias-batrachus
#4
Irfan Ahmad Bhat, Mohd Ashraf Rather, Mir Ishfaq Nazir, Gireesh-Babu Pathakota, Mukunda Goswami, J K Sundaray, Rupam Sharma
Fish like higher animals, have a well-defined mechanism to produce sex steroids that play a critical role in gonadal development and maturation. In this study, we aimed to analyse the expression pattern of 3β-HSD in different tissues, during ontogenetic development and gonadal recrudescence of Clarias batrachus. A full-length cDNA of 1617 bp including an open reading frame (ORF) of 1125 bp encoding 374 amino acids was isolated from testes of C. batrachus. The docking analysis between C. batrachus 3β-HSD protein and eurycomanone exhibited high binding affinity toward each other with total energy of -108...
September 11, 2017: Theriogenology
https://www.readbyqxmd.com/read/28923420/high-doses-of-lipid-core-nanocapsules-do-not-affect-bovine-embryonic-development-in-vitro
#5
Caroline Lucas, Mariana Remião, Franciele Bruinsmann, Isadora Lopes, Morgana Borges, Ana Laura Feijó, Andrea Cristina Basso, Adriana Pohlmann, Silvia Guterres, Vinicius Campos, Fabiana Seixas, Tiago Collares
The improvement of in vitro embryo production by culture media supplementation has been a potential tool to increase blastocyst quality and development. Recently, lipid-core nanocapsules (LNC), which were developed for biomedical applications as a drug-delivery system, have demonstrated beneficial effects on in vitro embryo production studies. LNCs have a core composed of sorbitan monostearate dispersed in capric/caprylic triglyceride. Based on that, we firstly investigated if LNCs supplemented during in vitro oocyte maturation had affinity to the mineral oil placed over the top of the IVM media...
September 15, 2017: Toxicology in Vitro: An International Journal Published in Association with BIBRA
https://www.readbyqxmd.com/read/28921439/purification-method-for-recombinant-hg-csf-by-affinity-chromatography
#6
Bruna Samham Archangelo, Elisa Maria de Sousa Russo
The human granulocytic colony-stimulating factor (hG-CSF) acts mainly by promoting the maturation of granulocytes and stimulating their phagocytic and chemotactic activity. It has been used in the treatment of many diseases, in particular in neutropenic conditions. Here, we describe the purification process of the recombinant protein hG-CSF expressed in Pichia pastoris. The protein purification proved to be efficient using the nickel affinity chromatography method described in this chapter.
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28919529/acetylation-of-lysine-residues-in-apomyoglobin-structural-changes-amyloid-fibrillation-and-role-of-surface-charge
#7
Mehrnaz Azami-Movahed, Ali Akbar Meratan, Atiyeh Ghasemi, Azadeh Ebrahim-Habibi, Mohsen Nemat-Gorgani
Post-translational modifications play important roles in conformational properties and aggregation propensities of different peptides and proteins. In the present study, we have investigated the effects of acetylation of lysine residues on the structure and aggregation properties of apomyoglobin (apoMb).All of the 19 lysine residues were modified. Far-, near-UV CD, intrinsic and acrylamide quenching fluorescence studies indicated that acetylation significantly influences conformation of apoMb by altering both its secondary and tertiary structures...
September 14, 2017: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/28911847/analysis-of-structural-features-contributing-to-weak-affinities-of-ubiquitin-protein-interactions
#8
REVIEW
Ariel Cohen, Eran Rosenthal, Julia M Shifman
Ubiquitin is a small protein that enables one of the most common post-translational modifications, where the whole ubiquitin molecule is attached to various target proteins, forming mono- or polyubiquitin conjugations. As a prototypical multispecific protein, ubiquitin interacts non-covalently with a variety of proteins in the cell, including ubiquitin modifying enzymes and ubiquitin receptors that recognize signals from ubiquitin-conjugated substrates. To enable recognition of multiple targets and to support fast dissociation from the ubiquitin modifying enzymes, ubiquitin/protein interactions are characterized with low affinities, frequently in the higher μM and lower mM range...
September 11, 2017: Journal of Molecular Biology
https://www.readbyqxmd.com/read/28900678/socs1-regulator-of-t-cells-in-autoimmunity-and-cancer
#9
Subburaj Ilangumaran, Diwakar Bobbala, Sheela Ramanathan
SOCS1 is a negative feedback regulator of cytokine and growth factor receptor signaling, and plays an indispensable role in attenuating interferon gamma signaling. Studies on SOCS1-deficient mice have established a crucial role for SOCS1 in regulating CD8(+) T cell homeostasis. In the thymus, SOCS1 prevents thymocytes that had failed positive selection from surviving and expanding, ensures negative selection and prevents inappropriate developmental skewing toward the CD8 lineage. In the periphery, SOCS1 not only controls production of T cell stimulatory cytokines but also attenuates the sensitivity of CD8(+) T cells to synergistic cytokine stimulation and antigen non-specific activation...
September 13, 2017: Current Topics in Microbiology and Immunology
https://www.readbyqxmd.com/read/28900542/mitochondrial-dna-haplotypes-induce-differential-patterns-of-dna-methylation-that-result-in-differential-chromosomal-gene-expression-patterns
#10
William T Lee, Xin Sun, Te-Sha Tsai, Jacqueline L Johnson, Jodee A Gould, Daniel J Garama, Daniel J Gough, Matthew McKenzie, Ian A Trounce, Justin C St John
Mitochondrial DNA copy number is strictly regulated during development as naive cells differentiate into mature cells to ensure that specific cell types have sufficient copies of mitochondrial DNA to perform their specialised functions. Mitochondrial DNA haplotypes are defined as specific regions of mitochondrial DNA that cluster with other mitochondrial sequences to show the phylogenetic origins of maternal lineages. Mitochondrial DNA haplotypes are associated with a range of phenotypes and disease. To understand how mitochondrial DNA haplotypes induce these characteristics, we used four embryonic stem cell lines that have the same set of chromosomes but possess different mitochondrial DNA haplotypes...
2017: Cell Death Discovery
https://www.readbyqxmd.com/read/28891599/expression-in-escherichia-coli-of-fusion-protein-comprising-%C3%AE-conotoxin-txib-and-preservation-of-selectivity-to-nicotinic-acetylcholine-receptors-in-the-purified-product
#11
Jinpeng Yu, Xiaopeng Zhu, Yang Yang, Sulan Luo, Dongting Zhangsun
Nicotinic acetylcholine receptors (nAChRs) are ligand-gated ion channels, which are widely distributed in the central and peripheral nervous system. The α6β2* nAChR is an important subtype, which is closely associated with nicotine addiction and movement disorders etc. α-conotoxin TxIB with 16-amino acid residues specifically targets α6β2* nAChR with no obvious effect on other nAChR subtypes. However, chemical synthesis of TxIB is expensive, and the quantity of native TxIB extracted from cone snail is limited...
September 11, 2017: Chemical Biology & Drug Design
https://www.readbyqxmd.com/read/28891214/non-redundant-functions-of-the-dimeric-aba-receptor-bdpyl1-in-the-grass-brachypodium
#12
Oded Pri-Tal, Lidor Shaar-Moshe, Gil Wiseglass, Zvi Peleg, Assaf Mosquna
Abiotic stresses have severe detrimental effects on agricultural productivity worldwide. ABA levels rise in response to abiotic stresses, and play a role in coordinating physiological responses. ABA elicits its effects by binding a family of soluble receptors, increasing affinity of the receptors to type 2C phosphatases (PP2Cs) leading to phosphatase inhibition. In the current study, we conducted a comprehensive analysis of the ABA signaling pathway in the cereal model grass Brachypodium distachyon. The Brachypodium genome encodes a family of ten functionally conserved ABA receptors...
September 11, 2017: Plant Journal: for Cell and Molecular Biology
https://www.readbyqxmd.com/read/28890399/activated-brain-derived-neurotrophic-factor-trkb-signaling-in-rat-dorsal-and-ventral-hippocampi-following-10-day-electroconvulsive-seizure-treatment
#13
Shingo Enomoto, Kunio Shimizu, Masashi Nibuya, Eiji Suzuki, Kiyoshi Nagata, Takashi Kondo
Electroconvulsive therapy (ECT) is still the most effective strategy to treat severe and drug-resistant depressive disorders. Electroconvulsive seizure (ECS), which induces neuroplastic structural alterations and resilient behavioral changes in experimental animals, is the model of the ECT for human depression. ECT is typically administered three times per week for up to 4 weeks, while ECS treatments are administered daily for 10days. The increased expression of hippocampal brain-derived neurotrophic factor (BDNF) induced by antidepressive ECS treatment in experimental animals has been well documented...
September 7, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/28890257/effects-of-pdgf-bb-delivery-from-heparinized-collagen-sutures-on-the-healing-of-lacerated-chicken-flexor-tendon-in-vivo
#14
Mousa Younesi, Derrick M Knapik, Jameson Cumsky, Baris Ozgur Donmez, Ping He, Anowarul Islam, Greg Learn, Philip McClellan, Michael Bohl, Robert J Gillespie, Ozan Akkus
Flexor tendon lacerations are traditionally repaired by using non-absorbable monofilament sutures. Recent investigations have explored to improve the healing process by growth factor delivery from the sutures. However, it is difficult to conjugate growth factors to nylon or other synthetic sutures. This study explores the performance of a novel electrochemically aligned collagen suture in a flexor tendon repair model with and without platelet derived growth factor following complete tendon laceration in vivo...
September 7, 2017: Acta Biomaterialia
https://www.readbyqxmd.com/read/28882619/variable-domain-glycosylation-of-acpa-igg-a-missing-link-in-the-maturation-of-the-acpa-response
#15
Ayla C Kempers, Lise Hafkenscheid, Hans Ulrich Scherer, René E M Toes
Anti-citrullinated Protein Antibodies (ACPA) are excellent markers for Rheumatoid arthritis (RA) and are postulated to have a pathogenic role in the disease process. A multistep model for the evolution of the ACPA response in RA was proposed in which an initial break of tolerance causes, as "first hit", "silent" production of ACPA without any clinical symptoms. The model further proposes that the ACPA immune response matures upon a certain (unknown) trigger, a "second hit", which leads to epitope spreading, an increase in ACPA titres and extended isotype usage before clinical RA manifestations...
September 4, 2017: Clinical Immunology: the Official Journal of the Clinical Immunology Society
https://www.readbyqxmd.com/read/28882567/anaerobic-sulfatase-maturase-aslb-from-escherichia-coli-activates-human-recombinant-iduronate-2-sulfate-sulfatase-ids-and-n-acetylgalactosamine-6-sulfate-sulfatase-galns
#16
Carlos Javier Alméciga-Díaz, Andrés Dario Tolosa-Díaz, Luisa Natalia Pimentel, Yahir Andres Bonilla, Alexander Rodríguez-López, Angela J Espejo-Mojica, Juan D Patiño, Oscar F Sánchez, Janneth Gonzalez-Santos
Maturation of type I sulfatases requires the conversion of the cysteine (Cys) or serine (Ser) present in the active site to formylglycine (FGly). This activation represents a limiting step during the production of recombinant sulfatases in bacteria and eukaryotic hosts. AslB, YdeM and YidF have been proposed to participate in the activation of sulfatases in Escherichia coli. In this study, we combined in-silico and experimental approaches to study the interaction between Escherichia coli BL21(DE3) AslB and human sulfatases, more specifically iduronate-2-sulfate sulfatase (IDS) and N-acetylgalactosamine-6-sulfate sulfatase (GALNS)...
November 15, 2017: Gene
https://www.readbyqxmd.com/read/28882412/a-flavonoid-agonist-of-the-trkb-receptor-for-bdnf-improves-hippocampal-neurogenesis-and-hippocampus-dependent-memory-in-the-ts65dn-mouse-model-of-ds
#17
Fiorenza Stagni, Andrea Giacomini, Sandra Guidi, Marco Emili, Beatrice Uguagliati, Maria Elisa Salvalai, Valeria Bortolotto, Mariagrazia Grilli, Roberto Rimondini, Renata Bartesaghi
Intellectual disability is the unavoidable hallmark of Down syndrome (DS), with a heavy impact on public health. Reduced neurogenesis and impaired neuron maturation are considered major determinants of altered brain function in DS. Since the DS brain starts at a disadvantage, attempts to rescue neurogenesis and neuron maturation should take place as soon as possible. The brain-derived neurotrophic factor (BDNF) is a neurotrophin that plays a key role in brain development by specifically binding to tropomyosin-related kinase receptor B (TrkB)...
September 4, 2017: Experimental Neurology
https://www.readbyqxmd.com/read/28878619/mirna-enriched-in-human-neuroblast-nuclei-bind-the-maz-transcription-factor-and-their-precursors-contain-the-maz-consensus-motif
#18
Belinda J Goldie, Chantel Fitzsimmons, Judith Weidenhofer, Joshua R Atkins, Dan O Wang, Murray J Cairns
While the cytoplasmic function of microRNA (miRNA) as post-transcriptional regulators of mRNA has been the subject of significant research effort, their activity in the nucleus is less well characterized. Here we use a human neuronal cell model to show that some mature miRNA are preferentially enriched in the nucleus. These molecules were predominantly primate-specific and contained a sequence motif with homology to the consensus MAZ transcription factor binding element. Precursor miRNA containing this motif were shown to have affinity for MAZ protein in nuclear extract...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28878127/autoantibody-producing-plasmablasts-after-b-cell-depletion-identified-in-muscle-specific-kinase-myasthenia-gravis
#19
Panos Stathopoulos, Aditya Kumar, Richard J Nowak, Kevin C O'Connor
Myasthenia gravis (MG) is a B cell-mediated autoimmune disorder of neuromuscular transmission. Pathogenic autoantibodies to muscle-specific tyrosine kinase (MuSK) can be found in patients with MG who do not have detectable antibodies to the acetylcholine receptor (AChR). MuSK MG includes immunological and clinical features that are generally distinct from AChR MG, particularly regarding responsiveness to therapy. B cell depletion has been shown to affect a decline in serum autoantibodies and to induce sustained clinical improvement in the majority of MuSK MG patients...
September 7, 2017: JCI Insight
https://www.readbyqxmd.com/read/28874538/retraction-for-wang-et-al-somatic-hypermutation-maintains-antibody-thermodynamic-stability-during-affinity-maturation
#20
(no author information available yet)
No abstract text is available yet for this article.
September 5, 2017: Proceedings of the National Academy of Sciences of the United States of America
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