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Affinity maturation

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https://www.readbyqxmd.com/read/28444616/genome-wide-identification-of-grain-filling-genes-regulated-by-the-ossmf1-transcription-factor-in-rice
#1
Joung Sug Kim, Songhwa Chae, Kyong Mi Jun, Yoon-Mok Pahk, Tae-Ho Lee, Pil Joong Chung, Yeon-Ki Kim, Baek Hie Nahm
BACKGROUND: Spatial- and temporal-specific expression patterns are primarily regulated at the transcriptional level by gene promoters. Therefore, it is important to identify the binding motifs of transcription factors to better understand the networks associated with embryogenesis. RESULTS: Here, we used a protein-binding microarray (PBM) to identify the binding motifs of OsSMF1, which is a basic leucine zipper transcription factor involved in the regulation of rice seed maturation...
December 2017: Rice
https://www.readbyqxmd.com/read/28437464/inhibition-of-%C3%AE-v%C3%AE-3-integrin-induces-loss-of-cell-directionality-of-oral-squamous-carcinoma-cells-oscc
#2
Cyntia F Montenegro, Bruna C Casali, Rafael L B Lino, Bianca C Pachane, Patty K Santos, Alan R Horwitz, Heloisa S Selistre-de-Araujo, Marcelo L Lamers
The connective tissue formed by extracellular matrix (ECM) rich in fibronectin and collagen consists a barrier that cancer cells have to overpass to reach blood vessels and then a metastatic site. Cell adhesion to fibronectin is mediated by αvβ3 and α5β1 integrins through an RGD motif present in this ECM protein, thus making these receptors key targets for cell migration studies. Here we investigated the effect of an RGD disintegrin, DisBa-01, on the migration of human fibroblasts (BJ) and oral squamous cancer cells (OSCC, SCC25) on a fibronectin-rich environment...
2017: PloS One
https://www.readbyqxmd.com/read/28437065/a-macrocyclic-peptide-ligand-binds-the-oncogenic-microrna-21-precursor-and-suppresses-dicer-processing
#3
Matthew D Shortridge, Matthew J Walker, Tom Pavelitz, Yu Chen, Gabriele Varani
MicroRNAs (miRNAs) help orchestrate cellular growth and survival through post-transcriptional mechanisms. The dysregulation of miRNA biogenesis can lead to cellular growth defects, chemotherapeutic resistance and plays a direct role in the development of many chronic diseases. Among these RNAs, miR-21 is consistently overexpressed in most human cancers leading to the down regulation of key tumor suppressing and pro-apoptotic factors; suggesting that inhibition of miR-21 biogenesis could reverse these negative effects...
April 24, 2017: ACS Chemical Biology
https://www.readbyqxmd.com/read/28427157/the-anti-tumor-efficacy-of-3c23k-a-glyco-engineered-humanized-anti-misrii-antibody-in-an-ovarian-cancer-model-is-mainly-mediated-by-engagement-of-immune-effector-cells
#4
Pauline Estupina, Alexandre Fontayne, Jean-Marc Barret, Nathalie Kersual, Olivier Dubreuil, Marion Le Blay, Alexandre Pichard, Marta Jarlier, Martine Pugnière, Maëva Chauvin, Thierry Chardès, Jean-Pierre Pouget, Emmanuel Deshayes, Alexis Rossignol, Toufik Abache, Christophe de Romeuf, Aurélie Terrier, Lucie Verhaeghe, Christine Gaucher, Jean-François Prost, André Pèlegrin, Isabelle Navarro-Teulon
Ovarian cancer is the leading cause of death in women with gynecological cancers and despite recent advances, new and more efficient therapies are crucially needed. Müllerian Inhibiting Substance type II Receptor (MISRII, also named AMHRII) is expressed in most ovarian cancer subtypes and is a novel potential target for ovarian cancer immunotherapy. We previously developed and tested 12G4, the first murine monoclonal antibody (MAb) against human MISRII. Here, we report the humanization, affinity maturation and glyco-engineering steps of 12G4 to generate the Fc-optimized 3C23K MAb, and the evaluation of its in vivo anti-tumor activity...
February 24, 2017: Oncotarget
https://www.readbyqxmd.com/read/28423185/functional-identification-of-activity-regulated-high-affinity-glutamine-transport-in-hippocampal-neurons-inhibited-by-riluzole
#5
Jeffrey D Erickson
Glutamine (Gln) is considered the preferred precursor for the neurotransmitter pool of glutamate (Glu), the major excitatory transmitter in the mammalian CNS. Here, an activity-regulated, high-affinity Gln transport system is described in developing and mature neuron-enriched hippocampal cultures that is potently inhibited by riluzole (IC50 1.3 +/- 0.5μM), an anti-glutamatergic drug, and is blocked by low concentrations of 2-(methylamino)isobutyrate (MeAIB), a system A transport inhibitor. K(+) -stimulated MeAIB transport displays an affinity (Km ) for MeAIB of 37 +/- 1...
April 19, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/28422790/particle-based-delivery-of-the-hiv-envelope-protein
#6
Benedikt Asbach, Ralf Wagner
PURPOSE OF REVIEW: A major focus in HIV vaccine research is the development of suitable antigens that elicit broadly neutralizing antibody responses targeting HIV's envelope protein (Env). Delivery of Env in a repetitive manner on particle-based carriers allows higher avidity interactions and is therefore expected to efficiently engage B cells, thus leading to affinity maturation that results in superior antibody responses characterized by improved breadth, potency, and durability. This review summarizes current work that is evaluating diverse types of such particulate carriers for Env delivery...
May 2017: Current Opinion in HIV and AIDS
https://www.readbyqxmd.com/read/28422751/twelve-year-survival-and-immune-correlates-in-dendritic-cell-vaccinated-melanoma-patients
#7
Stefanie Gross, Michael Erdmann, Ina Haendle, Steve Voland, Thomas Berger, Erwin Schultz, Erwin Strasser, Peter Dankerl, Rolf Janka, Stefan Schliep, Lucie Heinzerling, Karl Sotlar, Pierre Coulie, Gerold Schuler, Beatrice Schuler-Thurner
BACKGROUND: Reports on long-term (≥10 years) effects of cancer vaccines are missing. Therefore, in 2002, we initiated a phase I/II trial in cutaneous melanoma patients to further explore the immunogenicity of our DC vaccine and to establish its long-term toxicity and clinical benefit after a planned 10-year followup. METHODS: Monocyte-derived DCs matured by TNFα, IL-1β, IL-6, and PGE2 and then loaded with 4 HLA class I and 6 class II-restricted tumor peptides were injected intradermally in high doses over 2 years...
April 20, 2017: JCI Insight
https://www.readbyqxmd.com/read/28418769/persistency-of-neutralizing-anti-interferon-%C3%AE-antibodies-in-patients-with-multiple-sclerosis-treated-with-subcutaneous-interferon-%C3%AE-depends-on-antibody-titers-igg-subclasses-and-affinity-maturation
#8
Irena Dujmovic, Harald Hegen, Pedro Paz, Ed Croze, Florian Deisenhammer
Neutralizing antibodies may affect interferon (IFN)-β treatment efficacy, but mechanisms of neutralizing anti-drug antibody (ADA) evolution are not fully elucidated. We investigated the relationship between ADA titers, IgG subclass profile, and binding affinity with the development and persistency of neutralizing ADA in relapsing-remitting multiple sclerosis (MS) patients treated with subcutaneous IFN-β. A total of 94 patients, who had blood sampling at months 6, 12, 24, and 36 during IFN-β therapy, were included into this retrospective study and stratified to the following: non-neutralizing, transient, and persistent neutralizing ADA status...
April 18, 2017: Journal of Interferon & Cytokine Research
https://www.readbyqxmd.com/read/28414173/affinity-interactions-drive-post-implantation-drug-filling-even-in-the-presence-of-bacterial-biofilm
#9
Erika L Cyphert, Sean T Zuckerman, Horst A von Recum, Julius N Korley
Current post-operative standard of care for surgical procedures, including device implantations, dictates prophylactic antimicrobial therapy, but a percentage of patients still develop infections. Systemic antimicrobial therapy needed to treat such infections can lead to downstream tissue toxicities and generate drug-resistant bacteria. To overcome issues associated with systemic drug administration, a polymer incorporating specific drug affinity has been developed with the potential to be filled or refilled with antimicrobials, post-implantation, even in the presence of bacterial biofilm...
April 13, 2017: Acta Biomaterialia
https://www.readbyqxmd.com/read/28410371/determining-the-role-of-missense-mutations-in-the-pou-domain-of-hnf1a-that-reduce-the-dna-binding-affinity-a-computational-approach
#10
Sneha P, Thirumal Kumar D, George Priya Doss C, Siva R, Hatem Zayed
Maturity-onset diabetes of the young type 3 (MODY3) is a non-ketotic form of diabetes associated with poor insulin secretion. Over the past years, several studies have reported the association of missense mutations in the Hepatocyte Nuclear Factor 1 Alpha (HNF1A) with MODY3. Missense mutations in the POU homeodomain (POUH) of HNF1A hinder binding to the DNA, thereby leading to a dysfunctional protein. Missense mutations of the HNF1A were retrieved from public databases and subjected to a three-step computational mutational analysis to identify the underlying mechanism...
2017: PloS One
https://www.readbyqxmd.com/read/28407558/cd11b-regulates-antibody-class-switching-via-induction-of-aid
#11
Seohyun Park, Hyunsub Sim, Hye-In Kim, Daecheol Jeong, Guang Wu, Soo Young Cho, Young Seek Lee, Hyung-Joo Kwon, Keunwook Lee
The integrin CD11b, which is encoded by the integrin subunit alpha M (ITGAM), is primarily expressed on the surface of innate immune cells. Genetic variations in ITGAM are among the strongest risk factors for systemic lupus erythematosus, an autoimmune disease characterized by the presence of autoantibodies. However, the regulatory function of CD11b in the antibody responses remains unclear. Here, we report the induction of CD11b in activated B2 B cells and define its unexpected role in immunoglobulin heavy chain class switch recombination (CSR)...
April 10, 2017: Molecular Immunology
https://www.readbyqxmd.com/read/28402444/stepwise-assembly-of-the-earliest-precursors-of-large-ribosomal-subunits-in-yeast
#12
Wu Chen, Zhensheng Xie, Fuquan Yang, Keqiong Ye
Small ribosomal subunits are co-transcriptionally assembled on the nascent precursor rRNA in Saccharomyces cerevisiae. It is unknown how the highly intertwined structure of 60S large ribosomal subunits is initially formed. Here, we affinity purified and analyzed a series of pre-60S particles assembled in vivo on plasmid-encoded pre-rRNA fragments of increasing lengths, revealing a spatiotemporal assembly map for 34 trans-acting assembly factors (AFs), 30 ribosomal proteins and 5S rRNA. The gradual association of AFs and ribosomal proteins with the pre-rRNA fragments strongly supports that the pre-60S is co-transcriptionally, rather than post-transcriptionally, assembled...
April 11, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28401063/scm-the-m-protein-of-streptococcus-canis-binds-immunoglobulin-g
#13
Simone Bergmann, Inga Eichhorn, Thomas P Kohler, Sven Hammerschmidt, Oliver Goldmann, Manfred Rohde, Marcus Fulde
The M protein of Streptococcus canis (SCM) is a virulence factor and serves as a surface-associated receptor with a particular affinity for mini-plasminogen, a cleavage product of the broad-spectrum serine protease plasmin. Here, we report that SCM has an additional high-affinity immunoglobulin G (IgG) binding activity. The ability of a particular S. canis isolate to bind to IgG significantly correlates with a scm-positive phenotype, suggesting a dominant role of SCM as an IgG receptor. Subsequent heterologous expression of SCM in non-IgG binding S...
2017: Frontiers in Cellular and Infection Microbiology
https://www.readbyqxmd.com/read/28398245/molecular-targets-for-pet-imaging-of-activated-microglia-the-current-situation-and-future-expectations
#14
REVIEW
Claire Tronel, Bérenger Largeau, Maria Joao Santiago Ribeiro, Denis Guilloteau, Anne-Claire Dupont, Nicolas Arlicot
Microglia, as cellular mediators of neuroinflammation, are implicated in the pathogenesis of a wide range of neurodegenerative diseases. Positron emission tomography (PET) imaging of microglia has matured over the last 20 years, through the development of radiopharmaceuticals targeting several molecular biomarkers of microglial activation and, among these, mainly the translocator protein-18 kDa (TSPO). Nevertheless, current limitations of TSPO as a PET microglial biomarker exist, such as low brain density, even in a neurodegenerative setting, expression by other cells than the microglia (astrocytes, peripheral macrophages in the case of blood brain barrier breakdown), genetic polymorphism, inducing a variation for most of TSPO PET radiopharmaceuticals' binding affinity, or similar expression in activated microglia regardless of its polarization (pro- or anti-inflammatory state), and these limitations narrow its potential interest...
April 11, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28396444/the-cryo-em-structure-of-yjeq-bound-to-the-30s-subunit-suggests-a-fidelity-checkpoint-function-for-this-protein-in-ribosome-assembly
#15
Aida Razi, Alba Guarné, Joaquin Ortega
Recent work suggests that bacterial YjeQ (RsgA) participates in the late stages of assembly of the 30S subunit and aids the assembly of the decoding center but also binds the mature 30S subunit with high affinity. To determine the function and mechanisms of YjeQ in the context of the mature subunit, we determined the cryo-EM structure of the fully assembled 30S subunit in complex with YjeQ at 5.8-Å resolution. We found that binding of YjeQ stabilizes helix 44 into a conformation similar to that adopted by the subunit during proofreading...
April 10, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28386257/the-other-function-class-ii-restricted-antigen-presentation-by-b-cells
#16
REVIEW
Lital N Adler, Wei Jiang, Kartik Bhamidipati, Matthew Millican, Claudia Macaubas, Shu-Chen Hung, Elizabeth D Mellins
Mature B lymphocytes (B cells) recognize antigens using their B cell receptor (BCR) and are activated to become antibody-producing cells. In addition, and integral to the development of a high-affinity antibodies, B cells utilize the specialized major histocompatibility complex class II (MHCII) antigen presentation pathway to process BCR-bound and internalized protein antigens and present selected peptides in complex with MHCII to CD4+ T cells. This interaction influences the fate of both types of lymphocytes and shapes immune outcomes...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28385906/probe-dependent-negative-allosteric-modulators-of-the-long-chain-free-fatty-acid-receptor-ffa4
#17
Kenneth R Watterson, Steffen V F Hansen, Brian Hudson, Elisa Alvarez-Curto, Sheikh Z Raihan, Carlos M G Azevedo, Gabriel Martin, Julia Dunlop, Stephen J Yarwood, Trond Ulven, Graeme Milligan
High affinity and selective antagonists that are able to block the actions of both endogenous and synthetic agonists of G protein-coupled receptors are integral to analysis of receptor function and to support suggestions of therapeutic potential. Although there is great interest in the potential of free fatty acid receptor 4 (FFA4) as a novel therapeutic target for the treatment of type II diabetes, the broad distribution pattern of this receptor suggests it may play a range of roles beyond glucose homeostasis in different cells and tissues...
April 6, 2017: Molecular Pharmacology
https://www.readbyqxmd.com/read/28382822/a-chemically-inducible-helper-module-for-detecting-protein-protein-interactions-with-tunable-sensitivity-based-on-kippis
#18
Daiki Kashima, Raiji Kawade, Teruyuki Nagamune, Masahiro Kawahara
As protein-protein interactions (PPIs) play essential roles in regulating their functional consequences in cells, methods to detect PPIs in living cells are desired for correct understanding of intracellular PPIs and pharmaceutical development therefrom. Here we demonstrate a c-kit-based PPI screening (KIPPIS) system in combination with a chemically inducible helper module for detecting PPIs in living mammalian cells. In this system, a mutant of FK506-binding protein 12 (FKBPF36V) is fused with a protein of interest and the intracellular domain of a receptor tyrosine kinase c-kit...
April 6, 2017: Analytical Chemistry
https://www.readbyqxmd.com/read/28377239/role-of-the-c-terminal-and-chitin-insertion-domains-on-enzymatic-activity-of-endochitinase-chia74-of-bacillus-thuringiensis
#19
Estefania O Juárez-Hernández, Luz E Casados-Vázquez, Dennis K Bideshi, R Salcedo-Hernández, José E Barboza-Corona
ChiA74 has modular structure that includes a secretion signal peptide (sp) sequence, and catalytic (CD), chitin insertion (CID), fibronectin type-III (FnIII) and chitin binding (CBD) domains. We described for the first time the existence of a putative CID in ChiA74. Mature ChiA74 lacking its sp sequence (rChiA74Δsp, ∼70kDa) and two truncated versions, rChiA74Δsp-60, rChiA74Δsp-50 lacking, respectively, CBD and CDB-FnIII were produced. rChiA74Δsp and rChiA74Δsp-60 are unstable and were processed to generate stable proteins of ∼50kDa...
April 2, 2017: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/28376268/ahr-mediates-an-anti-inflammatory-feed-back-mechanism-in-human-langerhans-cells-involving-fc%C3%AE%C2%B5ri-and-ido
#20
Susanne Koch, Tim J Stroisch, Julia Vorac, Nadine Herrmann, Nicole Leib, Sylvia Schnautz, Helene Kirins, Irmgard Förster, Heike Weighardt, Thomas Bieber
BACKGROUND: Aryl hydrocarbon receptor (AhR), an important regulator of immune responses, is activated by UVB irradiation in the skin. Langerhans cells (LC) in the epidermis of atopic dermatitis (AD) patients carry the high affinity receptor for IgE, FcεRI, and are crucially involved in the pathogenesis of AD by inducing inflammatory responses and regulating tolerogenic processes. OBJECTIVES: We investigated AhR and AhR repressor (AhRR) expression and functional consequences of AhR activation in human ex vivo skin cells and in in vitro generated LC...
April 4, 2017: Allergy
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