keyword
MENU ▼
Read by QxMD icon Read
search

Affinity maturation

keyword
https://www.readbyqxmd.com/read/28713775/salivary-tick-cystatin-omc2-targets-lysosomal-cathepsins-s-and-c-in-human-dendritic-cells
#1
Tina Zavašnik-Bergant, Robert Vidmar, Andreja Sekirnik, Marko Fonović, Jiří Salát, Lenka Grunclová, Petr Kopáček, Boris Turk
To ensure successful feeding tick saliva contains a number of inhibitory proteins that interfere with the host immune response and help to create a permissive environment for pathogen transmission. Among the potential targets of the salivary cystatins are two host cysteine proteases, cathepsin S, which is essential for antigen- and invariant chain-processing, and cathepsin C (dipeptidyl peptidase 1, DPP1), which plays a critical role in processing and activation of the granule serine proteases. Here, the effect of salivary cystatin OmC2 from Ornithodoros moubata was studied using differentiated MUTZ-3 cells as a model of immature dendritic cells of the host skin...
2017: Frontiers in Cellular and Infection Microbiology
https://www.readbyqxmd.com/read/28710641/a-ligand-binding-assay-to-measure-the-affinity-and-specificity-of-sterol-binding-proteins-in-vitro
#2
Rabih Darwiche, Roger Schneiter
Sterols are major constituents of the plasma membrane of eukaryotic cells and serve as a precursor for several classes of signaling molecules, including steroids and hydroxy sterols. They maintain the functionality and permeability barrier of the plasma membrane through lipid-lipid and lipid-protein interactions. The S. cerevisiae pathogen-related yeast proteins 1, 2, and 3 (Pry) belong to a large protein superfamily known as CAP/SCP/TAPS. Members of this superfamily have been implicated in a wide variety of processes, including immune defense in mammals and plants, pathogen virulence, sperm maturation and fertilization, venom toxicity, and prostate and brain cancer...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28701402/increased-durable-b-cell-and-adcc-responses-associated-with-t-helper-responses-to-hiv-1-envelope-in-macaques-vaccinated-with-gp140-occluded-at-the-cd4-receptor-binding-site
#3
Willy M J M Bogers, Susan W Barnett, Herman Oostermeijer, Ivonne G Nieuwenhuis, Niels Beenhakker, Daniella Mortier, Petra Mooij, Gerrit Koopman, Edmund Remarque, Gregoire Martin, Rachel Pei-Jen Lai, Antu K Dey, Yide Sun, Brian Burke, Guido Ferrari, David Montefiori, Loic Martin, David Davis, Indresh Srivastava, Jonathan L Heeney
Strategies are needed to improve the immunogenicity of HIV-1 envelope (Env) antigens for more long lived, efficacious HIV-1 vaccine induced B-cell responses. HIV-1 Env gp140 (native or un-cleaved molecules) or gp120 monomeric proteins elicit relatively poor B-cell responses which are short-lived. We hypothesized that Env engagement of the CD4 receptor on T-helper cells may result in anergic effects on T-cell recruitment and consequently a lack of strong robust and durable B-memory responses. To test this hypothesis we occluded the CD4 binding site (CD4bs) of gp140 by stable cross-linking with a 3kD CD4 miniprotein mimetic serving to block ligation of gp140 on CD4+T-cells while preserving CD4 inducible (CDi) neutralizing and epitopes targeted by antibody dependent cellular cytotoxic (ADCC) effector responses...
July 12, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28698213/gene-expression-profiles-of-brain-endothelial-cells-during-embryonic-development-at-bulk-and-single-cell-levels
#4
Mike Hupe, Minerva Xueting Li, Susanne Kneitz, Daria Davydova, Chika Yokota, Julianna Kele-Olovsson, Belma Hot, Jan M Stenman, Manfred Gessler
The blood-brain barrier is a dynamic interface that separates the brain from the circulatory system, and it is formed by highly specialized endothelial cells. To explore the molecular mechanisms defining the unique nature of vascular development and differentiation in the brain, we generated high-resolution gene expression profiles of mouse embryonic brain endothelial cells using translating ribosome affinity purification and single-cell RNA sequencing. We compared the brain vascular translatome with the vascular translatomes of other organs and analyzed the vascular translatomes of the brain at different time points during embryonic development...
July 11, 2017: Science Signaling
https://www.readbyqxmd.com/read/28696509/an-l-rna-aptamer-with-expanded-chemical-functionality-that-inhibits-microrna-biogenesis
#5
Adam Michael Kabza, Jonathan Thomas Sczepanski
In order to facilitate isolation of L-aptamers with novel RNA-binding properties, we have employed a cationic nucleotide, 5-aminoallyl-uridine, during the mirror image in vitro selection process. In this effort, we identified a modified L-RNA aptamer (MLRA) capable of binding oncogenic pre-miR-19a with exceptional affinity, and we show that the cationic modification is absolutely critical for binding. Furthermore, formation of the MLRA-pre-miR-19a complex inhibits Dicer-mediated cleavage of the pre-miR, thus blocking formation of the mature functional microRNA...
July 11, 2017: Chembiochem: a European Journal of Chemical Biology
https://www.readbyqxmd.com/read/28696260/biophysical-analysis-of-arabidopsis-protein-only-rnase-p-alone-and-in-complex-with-trna-provides-a-refined-model-of-trna-binding
#6
Franziska Pinker, Cédric Schelcher, Pablo Fernández-Millán, Anthony Gobert, Catherine Birck, Aurélien Thureau, Pierre Roblin, Philippe Giegé, Claude Sauter
RNase P is a universal enzyme that removes 5' leader sequences from tRNA precursors. The enzyme is therefore essential for maturation of functional tRNAs and mRNA translation. RNase P represents a unique example of an enzyme that can occur either as ribonucleoprotein or as protein alone. The latter form of the enzyme called PRORP (PRotein-Only RNase P) is widespread in eukaryotes, in which it can provide organellar or nuclear RNase P activities. Here, we have focused on Arabidopsis nuclear PRORP2 and its interaction with tRNA substrates...
July 10, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28683596/reslizumab-in-the-treatment-of-inadequately-controlled-asthma-in-adults-and-adolescents-with-elevated-blood-eosinophils-clinical-trial-evidence-and-future-prospects
#7
Jorge Máspero
Eosinophils have long been implicated as playing a central role in the pathophysiology of asthma in many patients, and eosinophilic asthma is now recognized as an important asthma endotype. Eosinophil differentiation, maturation, migration, and survival are primarily under the control of interleukin-5 (IL-5). Reslizumab is a humanized monoclonal (immunoglobulin G4/κ) antibody that binds with high affinity to circulating human IL-5 and downregulates the IL-5 signaling pathway, potentially disrupting the maturation and survival of eosinophils...
July 1, 2017: Therapeutic Advances in Respiratory Disease
https://www.readbyqxmd.com/read/28671952/differences-in-serum-iga-responses-to-hiv-1-gp41-in-elite-controllers-compared-to-viral-suppressors-on-highly-active-antiretroviral-therapy
#8
Rafiq Nabi, Zina Moldoveanu, Qing Wei, Elizabeth T Golub, Helen G Durkin, Ruth M Greenblatt, Betsy C Herold, Marek J Nowicki, Seble Kassaye, Michael W Cho, Abraham Pinter, Alan L Landay, Jiri Mestecky, Pamela A Kozlowski
Mechanisms responsible for natural control of human immunodeficiency type 1 (HIV) replication in elite controllers (EC) remain incompletely defined. To determine if EC generate high quality HIV-specific IgA responses, we used Western blotting to compare the specificities and frequencies of IgA to HIV antigens in serum of gender-, age- and race-matched EC and aviremic controllers (HC) and viremic noncontrollers (HN) on highly active antiretroviral therapy (HAART). Concentrations and avidity of IgA to HIV antigens were measured using ELISA or multiplex assays...
2017: PloS One
https://www.readbyqxmd.com/read/28661426/rational-design-of-recombinant-papain-like-cysteine-protease-optimal-domain-structure-and-expression-conditions-for-wheat-derived-enzyme-triticain-%C3%AE
#9
Neonila V Gorokhovets, Vladimir A Makarov, Anastasiia I Petushkova, Olga S Prokopets, Mikhail A Rubtsov, Lyudmila V Savvateeva, Evgeni Yu Zernii, Andrey A Zamyatnin
Triticain-α is a papain-like cysteine protease from wheat (Triticumaestivum L.) that possesses activity towards toxic gluten-derived peptides, and was thus proposed as a novel therapeutic tool for celiac disease. We report an original approach employing rational design of domain architecture of Triticain-α and selection of the appropriate expression system for development of cheap and efficient protocol yielding active recombinant enzyme. The segregated catalytic domain of Triticain-α did not adopt native structure in bacteria, neither being expressed as a single protein nor upon conjugation or co-expression with extrinsic chaperones...
June 29, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28659353/alterations-in-the-thymic-selection-threshold-skew-the-self-reactivity-of-the-tcr-repertoire-in-neonates
#10
Mengqi Dong, Patricio Artusa, Stephanie A Kelly, Marilaine Fournier, Troy A Baldwin, Judith N Mandl, Heather J Melichar
Neonatal and adult T cells differ in their effector functions. Although it is known that cell-intrinsic differences in mature T cells contribute to this phenomenon, the factors involved remain unclear. Given emerging evidence that the binding strength of a TCR for self-peptide presented by MHC (self-pMHC) impacts T cell function, we sought to determine whether altered thymic selection influences the self-reactivity of the TCR repertoire during ontogeny. We found that conventional and regulatory T cell subsets in the thymus of neonates and young mice expressed higher levels of cell surface CD5, a surrogate marker for TCR avidity for self-pMHC, as compared with their adult counterparts, and this difference in self-reactivity was independent of the germline bias of the neonatal TCR repertoire...
June 28, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28656266/peroxisome-proliferator-activated-receptor-%C3%AE-agonist-suppresses-mast-cell-maturation-and-induces-apoptosis
#11
Yu Zhang, Xinqian Li, Shengjian Fang, Zhenghua Zhu, Min Yao, Liyun Ying, Liwei Zhu, Zhaoxin Ma, Weihua Wang
Peroxisome proliferator-activated receptor gamma (PPAR γ), is important in the immunoregulation of the allergic response. Mast cells are the most important inflammatory cells in immediate hypersensitivity and allergic diseases. However, there is limited information regarding the effects of PPAR γ on mast cell maturation. In the present study, mouse bone marrow‑derived mast cells (BMMCs) were cultured in interleukin (IL)‑3 and stem cell factor (SCF), in the presence or absence of the PPAR γ agonist, pioglitazone (PIO)...
August 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28655759/rbm25-is-a-global-splicing-factor-promoting-inclusion-of-alternatively-spliced-exons-and-is-itself-regulated-by-lysine-mono-methylation
#12
Scott M Carlson, Cameron M Soulette, Ze Yang, Joshua E Elias, Angela N Brooks, Or Gozani
In eukaryotes, pre-mRNA splicing removes non-coding intron sequences to produce mature mRNA. This removal is controlled in part by RNA-binding proteins that regulate alternative splicing decisions through interactions with the splicing machinery. RNA binding motif protein 25 (RBM25) is a putative splicing factor strongly conserved across eukaryotic lineages. However, the role of RBM25 in global splicing regulation and its cellular functions are unknown. Here we show that RBM25 is required for viability of multiple human cell lines, suggesting that it could play a key role in pre-mRNA splicing...
June 27, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28654654/identification-and-characterization-of-acka-dependent-protein-acetylation-in-neisseria-gonorrhoeae
#13
Deborah M B Post, Birgit Schilling, Lorri M Reinders, Alexandria K D'Souza, Margaret R Ketterer, Steven J Kiel, Aroon T Chande, Michael A Apicella, Bradford W Gibson
Neisseria gonorrhoeae, the causative agent of gonorrhea, has a number of factors known to contribute to pathogenesis; however, a full understanding of these processes and their regulation has proven to be elusive. Post-translational modifications (PTMs) of bacterial proteins are now recognized as one mechanism of protein regulation. In the present study, Western blot analyses, with an anti-acetyl-lysine antibody, indicated that a large number of gonococcal proteins are post-translationally modified. Previous work has shown that Nε-lysine acetylation can occur non-enzymatically with acetyl-phosphate (AcP) as the acetyl donor...
2017: PloS One
https://www.readbyqxmd.com/read/28650481/germinal-center-development-of-memory-b-cells-driven-by-il-9-from-follicular-helper-t-cells
#14
Yifeng Wang, Jingwen Shi, Jiacong Yan, Zhengtao Xiao, Xiaoxiao Hou, Peiwen Lu, Shiyue Hou, Tianyang Mao, Wanli Liu, Yuanwu Ma, Lianfeng Zhang, Xuerui Yang, Hai Qi
Germinal centers (GCs) support high-affinity, long-lived humoral immunity. How memory B cells develop in GCs is not clear. Through the use of a cell-cycle-reporting system, we identified GC-derived memory precursor cells (GC-MP cells) that had quit cycling and reached G0 phase while in the GC, exhibited memory-associated phenotypes with signs of affinity maturation and localized toward the GC border. After being transferred into adoptive hosts, GC-MP cells reconstituted a secondary response like genuine memory B cells...
August 2017: Nature Immunology
https://www.readbyqxmd.com/read/28645089/drug-resistance-mechanism-of-l10f-l10f-n88s-and-l90m-mutations-in-crf01_ae-hiv-1-protease-molecular-dynamics-simulations-and-binding-free-energy-calculations
#15
C S Vasavi, Ramasamy Tamizhselvi, Punnagai Munusami
HIV-1 protease plays a crucial role in viral replication and maturation, which makes it one of the most attractive targets for anti-retroviral therapy. The majority of HIV infections in developing countries are due to non-B subtype. Subtype AE is spreading rapidly and infecting huge population worldwide. The mutations in the active site of subtype AE directly impair the interactions with the inhibitor. The non-active site mutations influence the binding of the inhibitor indirectly and their resistance mechanism is not well understood...
June 8, 2017: Journal of Molecular Graphics & Modelling
https://www.readbyqxmd.com/read/28643870/type-iii-metacaspases-calcium-dependent-activity-proposes-new-function-for-the-p10-domain
#16
Marina Klemenčič, Christiane Funk
Metacaspases are a subgroup of caspase homologues represented in bacteria, algae and plants. Although type I and type II metacaspases are present in plants, recently discovered and uncharacterized type III metacaspases can only be found in algae which have undergone secondary endosymbiosis. We analysed the expression levels of all 13 caspase homologues in the cryptophyte Guillardia theta in vivo and biochemically characterized its only type III metacaspase, GtMC2, in vitro. Type III metacaspase GtMC2 was shown to be an endopeptidase with a preference for basic amino acids in the P1 position, which exhibited specific N-terminal proteolytic cleavage for full catalytic efficiency...
June 23, 2017: New Phytologist
https://www.readbyqxmd.com/read/28636966/the-torc-that-gets-the-gc-cycling
#17
Elissa K Deenick, Stuart G Tangye
The signaling pathways regulating positive selection in germinal centers (GCs) are incompletely understood. Ersching et al. (2017) identify a critical but temporal role for the action of the kinase mechanistic target of rapamycin complex (mTORC1), which promotes key changes in GC B cells and thereby facilitates affinity maturation.
June 20, 2017: Immunity
https://www.readbyqxmd.com/read/28636954/germinal-center-selection-and-affinity-maturation-require-dynamic-regulation-of-mtorc1-kinase
#18
Jonatan Ersching, Alejo Efeyan, Luka Mesin, Johanne T Jacobsen, Giulia Pasqual, Brian C Grabiner, David Dominguez-Sola, David M Sabatini, Gabriel D Victora
During antibody affinity maturation, germinal center (GC) B cells cycle between affinity-driven selection in the light zone (LZ) and proliferation and somatic hypermutation in the dark zone (DZ). Although selection of GC B cells is triggered by antigen-dependent signals delivered in the LZ, DZ proliferation occurs in the absence of such signals. We show that positive selection triggered by T cell help activates the mechanistic target of rapamycin complex 1 (mTORC1), which promotes the anabolic program that supports DZ proliferation...
June 20, 2017: Immunity
https://www.readbyqxmd.com/read/28630428/nuclear-accumulation-of-symplekin-promotes-cellular-proliferation-and-dedifferentiation-in-an-erk1-2-dependent-manner
#19
Chen Zhang, Hai-Lei Mao, Yi Cao
Symplekin is a multifunctional protein that localizes to both tight junctions and the nucleus in polarized epithelial cells, with confirmed roles in mRNA maturation, transcriptional modulation and tight-junction assembly. However, the mechanisms governing its subcellular distribution and related functions remain unclear. In this study, we found that symplekin primarily localizes to the nuclei of cultured dedifferentiated colorectal cancer cells, and nuclear symplekin showed higher phosphorylation and binding affinity with YBX3 than its membrane fraction...
June 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28630079/what-are-the-primary-limitations-in-b-cell-affinity-maturation-and-how-much-affinity-maturation-can-we-drive-with-vaccination-lessons-from-the-antibody-response-to-hiv-1
#20
Gabriel D Victora, Hugo Mouquet
Most broadly neutralizing antibodies to HIV-1 have in common an extreme degree of somatic hypermutation (SHM), which correlates with their ability to neutralize multiple viral strains. However, achieving such extreme SHM by immunization remains a challenge. Here, we discuss how antigenic variation during HIV-1 infection may work to exacerbate SHM by permitting multiple iterative cycles of affinity maturation in germinal centers, and speculate on how this could be recapitulated through vaccination.
June 19, 2017: Cold Spring Harbor Perspectives in Biology
keyword
keyword
42604
1
2
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read
×

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"