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Affinity maturation

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https://www.readbyqxmd.com/read/28544233/bcl6-overexpression-alters-gene-expression-profile-in-a-myeloma-cell-line-and-is-associated-with-decreased-dna-damage-response
#1
Kenichi Tahara, Makiko Takizawa, Arito Yamane, Yohei Osaki, Takuma Ishizaki, Takeki Mitsui, Akihiko Yokohama, Takayuki Saitoh, Norifumi Tsukamoto, Morio Matsumoto, Hirokazu Murakami, Yoshihisa Nojima, Hiroshi Handa
BCL6 attenuates DNA damage response (DDR) through gene repression and facilitates tolerance to genomic instability during immunoglobulin affinity maturation in germinal center (GC) B cells. Although BCL6 expression is repressed through normal differentiation of GC B cells into plasma cells, a recent study showed the ectopic expression of BCL6 in primary multiple myeloma (MM) cells. However, the functional roles of BCL6 in MM cells are largely unknown. Here, we report that overexpression of BCL6 in a MM cell line, KMS12PE, induced transcriptional repression of ataxia telangiectasia mutated (ATM), a DDR signaling kinase, which was associated with a reduction in γH2AX formation after DNA damage...
May 23, 2017: Cancer Science
https://www.readbyqxmd.com/read/28541550/integrity-of-immunoglobulin-variable-region-is-supported-by-ganp-during-aid-induced-somatic-hypermutation-in-germinal-center-b-cells
#2
Mohammed Mansour Abbas Eid, Mayuko Shimoda, Shailendra Kumar Singh, Sarah Ameen Almofty, Phuong Pham, Myron F Goodman, Kazuhiko Maeda, Nobuo Sakaguchi
Immunoglobulin (Ig) affinity maturation depends on somatic hypermutation (SHM) in variable (V) regions initiated by activation-induced cytidine deaminase (AID). AID induces transition mutations by C→U deamination on both strands, causing C:G→T:A. Error-prone repairs of U by base excision and mismatch repairs create transversion mutations at C/G and mutations at A/T sites. In Neuberger's model, it remained to clarify how transition/transversion repair is regulated. We investigate role of AID-interacting GANP (germinal-center associated nuclear protein) in IgV SHM profile...
May 24, 2017: International Immunology
https://www.readbyqxmd.com/read/28539442/extracellular-interactions-between-hepatitis-c-virus-and-secreted-apolipoprotein-e
#3
Zhihua Li, Yadong Li, Yanwei Bi, Hui Zhang, Yufeng Yao, Qihan Li, Wei Cun, Shaozhong Dong
Interactions between hepatitis C virus (HCV) and lipoproteins in humans play an important role in the efficient establishment of chronic infection. Apolipoprotein E (ApoE) on the HCV envelope mediates virus attachment to host cells as well as immune evasion. This interaction is thought to occur in hepatocytes, as ApoE plays dual functions in HCV assembly and maturation as well as cell attachment. In the present study, we found that secreted ApoE (sApoE) can also bind to viral particles via its C-terminal domain after HCV is released from the cell...
May 24, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28539189/the-individual-and-population-genetics-of-antibody-immunity
#4
REVIEW
Corey T Watson, Jacob Glanville, Wayne A Marasco
Antibodies (Abs) produced by immunoglobulin (IG) genes are the most diverse proteins expressed in humans. While part of this diversity is generated by recombination during B-cell development and mutations during affinity maturation, the germ-line IG loci are also diverse across human populations and ethnicities. Recently, proof-of-concept studies have demonstrated genotype-phenotype correlations between specific IG germ-line variants and the quality of Ab responses during vaccination and disease. However, the functional consequences of IG genetic variation in Ab function and immunological outcomes remain underexplored...
May 20, 2017: Trends in Immunology
https://www.readbyqxmd.com/read/28531287/bacterial-rna-polymerase-caps-rna-with-various-cofactors-and-cell-wall-precursors
#5
Christina Julius, Yulia Yuzenkova
Bacterial RNA polymerase is able to initiate transcription with adenosine-containing cofactor NAD+, which was proposed to result in a portion of cellular RNAs being 'capped' at the 5΄ end with NAD+, reminiscent of eukaryotic cap. Here we show that, apart from NAD+, another adenosine-containing cofactor FAD and highly abundant uridine-containing cell wall precursors, UDP-Glucose and UDP-N-acetylglucosamine are efficiently used to initiate transcription in vitro. We show that the affinity to NAD+ and UDP-containing factors during initiation is much lower than their cellular concentrations, and that initiation with them stimulates promoter escape...
May 22, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28516165/host-and-pathogen-derived-adjuvant-coatings-on-protein-nanoparticle-vaccines
#6
Timothy Z Chang, Ishatou Diambou, Jong Rok Kim, Baozhong Wang, Julie A Champion
Nanoparticulate and molecular adjuvants have shown great efficacy in enhancing immune responses, and the immunogenic vaccines of the future will most likely contain both. To investigate the immunostimulatory effects of molecular adjuvants on nanoparticle vaccines, we have designed ovalbumin (OVA) protein nanoparticles coated with two different adjuvants-flagellin (FliC) and immunoglobulin M (IgM). These proteins, derived from Salmonella and mice, respectively, are representatives of pathogen- and host-derived molecules that can enhance immune responses...
March 2017: Bioengineering & Translational Medicine
https://www.readbyqxmd.com/read/28516119/affinity-pulldown-of-biotinylated-rna-for-detection-of-protein-rna-complexes
#7
Amaresh C Panda, Jennifer L Martindale, Myriam Gorospe
RNA-binding proteins (RBPs) have recently emerged as crucial players in the regulation of gene expression. The interactions of RBPs with target mRNAs control the levels of gene products by altering different regulatory steps, including pre-mRNA splicing and maturation, nuclear mRNA export, and mRNA stability and translation (Glisovic et al., 2008). There are several methodologies available today to identify RNAs bound to specific RBPs; some detect only recombinant molecules in vitro, others detect recombinant and endogenous molecules, while others detect only endogenous molecules...
December 20, 2016: Bio-protocol
https://www.readbyqxmd.com/read/28507097/gene-duplication-and-neo-functionalization-in-the-evolutionary-and-functional-divergence-of-metazoan-copper-transporters-ctr1-and-ctr2
#8
Brandon L Logeman, L Kent Wood, Jaekwon Lee, Dennis J Thiele
Copper is an essential element for proper organismal development and is involved in a range of processes including oxidative phosphorylation, neuropeptide maturation, and connective tissue maturation. The copper transporter (Ctr) family of integral membrane proteins is ubiquitously found in eukaryotes and mediates the high-affinity transport of Cu+ across both the plasma membrane and endomembranes. While mammalian Ctr1 functions as a Cu+ transporter for Cu acquisition and is essential for embryonic development, a homologous protein, Ctr2, has been proposed to function as a low-affinity Cu transporter, a lysosomal Cu exporter, or a regulator of Ctr1 activity, but its functional and evolutionary relationship to Ctr1 is unclear...
May 15, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28505348/implication-of-the-box-c-d-snornp-assembly-factor-rsa1p-in-u3-snornp-assembly
#9
Benjamin Rothé, Xavier Manival, Nicolas Rolland, Christophe Charron, Véronique Senty-Ségault, Christiane Branlant, Bruno Charpentier
The U3 box C/D snoRNA is one key element of 90S pre-ribosome. It contains a 5΄ domain pairing with pre-rRNA and the U3B/C and U3C΄/D motifs for U3 packaging into a unique small nucleolar ribonucleoprotein particle (snoRNP). The RNA-binding protein Snu13/SNU13 nucleates on U3B/C the assembly of box C/D proteins Nop1p/FBL and Nop56p/NOP56, and the U3-specific protein Rrp9p/U3-55K. Snu13p/SNU13 has a much lower affinity for U3C΄/D but nevertheless forms on this motif an RNP with box C/D proteins Nop1p/FBL and Nop58p/NOP58...
May 13, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28503709/morphological-and-molecular-characterization-of-sarcocystis-arctica-like-sarcocysts-from-the-arctic-fox-vulpes-lagopus-from-alaska-usa
#10
Camila K Cerqueira-Cézar, Peter C Thompson, Shiv Kumar Verma, Joseph Mowery, Rafael Calero-Bernal, Fernando H Antunes Murata, David R Sinnett, Caroline Van Hemert, Benjamin M Rosenthal, Jitender P Dubey
The muscles of herbivores commonly harbor sarcocysts of parasites belonging to species in the genus Sarcocystis, but such muscle parasites are rare in carnivores. Here, we report Sarcocystis arctica-like sarcocysts in muscles of Arctic foxes (Vulpes lagopus) from Alaska, USA, for the first time. The tongues of 56 foxes were examined for Sarcocystis infection using several methods. Sarcocystis bradyzoites were detected in pepsin digests of 13 (23.2%), and sarcocysts were found in histological sections stained with hematoxylin and eosin (HE) of 9 (16...
May 15, 2017: Parasitology Research
https://www.readbyqxmd.com/read/28498321/bdnf-binds-its-pro-peptide-with-high-affinity-and-the-common-val66met-polymorphism-attenuates-the-interaction
#11
Koichi Uegaki, Haruko Kumanogoh, Toshiyuki Mizui, Takatsugu Hirokawa, Yasuyuki Ishikawa, Masami Kojima
Most growth factors are initially synthesized as precursors then cleaved into bioactive mature domains and pro-domains, but the biological roles of pro-domains are poorly understood. In the present study, we investigated the pro-domain (or pro-peptide) of brain-derived neurotrophic factor (BDNF), which promotes neuronal survival, differentiation and synaptic plasticity. The BDNF pro-peptide is a post-processing product of the precursor BDNF. Using surface plasmon resonance and biochemical experiments, we first demonstrated that the BDNF pro-peptide binds to mature BDNF with high affinity, but not other neurotrophins...
May 12, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28497961/evaluating-the-development-of-biocatalytic-technology-for-the-targeted-removal-of-perchlorate-from-drinking-water
#12
Justin M Hutchison, Jeremy S Guest, Julie L Zilles
Removing micropollutants is challenging in part because of their toxicity at low concentrations. A biocatalytic approach could harness the high affinity of enzymes for their substrates to address this challenge. The potential of biocatalysis relative to mature (non-selective ion exchange, selective exchange, and whole-cell biological reduction) and emerging (catalysis) perchlorate-removal technologies was evaluated through a quantitative sustainable design framework, and research objectives were prioritized to advance economic and environmental sustainability...
May 12, 2017: Environmental Science & Technology
https://www.readbyqxmd.com/read/28495929/tissue-factor-prothrombotic-activity-is-regulated-by-integrin-arf6-trafficking
#13
Andrea S Rothmeier, Patrizia Marchese, Florian Langer, Yuichi Kamikubo, Florence Schaffner, Joseph Cantor, Mark H Ginsberg, Zaverio M Ruggeri, Wolfram Ruf
OBJECTIVE: Coagulation initiation by tissue factor (TF) is regulated by cellular inhibitors, cell surface availability of procoagulant phosphatidylserine, and thiol-disulfide exchange. How these mechanisms contribute to keeping TF in a noncoagulant state and to generating prothrombotic TF remain incompletely understood. APPROACH AND RESULTS: Here, we study the activation of TF in primary macrophages by a combination of pharmacological, genetic, and biochemical approaches...
May 11, 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/28489883/bmp-7-induces-apoptosis-in-human-germinal-center-b-cells-and-is-influenced-by-tgf-%C3%AE-receptor-type-i-alk5
#14
Lise K Bollum, Kanutte Huse, Morten P Oksvold, Baoyan Bai, Vera I Hilden, Lise Forfang, Sun Ok Yoon, Sébastien Wälchli, Erlend B Smeland, June H Myklebust
Selection and maturation of B cells into plasma cells producing high-affinity antibodies occur in germinal centers (GC). GCs form transiently in secondary lymphoid organs upon antigen challenge, and the GC reaction is a highly regulated process. TGF-β is a potent negative regulator, but the influence of other family members including bone morphogenetic proteins (BMPs) is less known. Studies of human peripheral blood B lymphocytes showed that BMP-6 suppressed plasmablast differentiation, whereas BMP-7 induced apoptosis...
2017: PloS One
https://www.readbyqxmd.com/read/28485250/localization-of-trefoil-factor-family-peptide-3-in-epithelial-tissues-originating-from-the-three-germ-layers-of-developing-mouse-embryo
#15
Nikola Bijelić, Tatjana Belovari, Maja Tolušić Levak, Mirela Baus Lončar
Trefoil factor family (TFF) peptides are involved in the maintenance of epithelial integrity and epithelial restitution. Mature epithelial tissues originate from different embryonic germ layers. The objective of this research was to explore the presence and localization of TFF3 peptide in mouse embryonic epithelium and to examine if the occurrence of TFF3 is germ layer-dependent. Mouse embryos (14-18 days old) were fixed in 4% paraformaldehyde and embedded in paraffin. Immunohistochemistry was performed with affinity purified rabbit anti-TFF3 antibody, goat anti-rabbit biotinylated secondary antibody and streptavidin-horseradish peroxidase, followed by 3,3'-diaminobenzidine...
May 9, 2017: Bosnian Journal of Basic Medical Sciences
https://www.readbyqxmd.com/read/28483642/structural-insights-into-the-molecular-function-of-human-2fe-2s-bola1-grx5-and-2fe-2s-bola3-grx5-complexes
#16
Veronica Nasta, Andrea Giachetti, Simone Ciofi-Baffoni, Lucia Banci
Members of the monothiol glutaredoxin family and members of the BolA-like protein family have recently emerged as specific interacting partners involved in iron-sulfur protein maturation and redox regulation pathways. It is known that human mitochondrial BOLA1 and BOLA3 form [2Fe-2S] cluster-bridged dimeric heterocomplexes with the monothiol glutaredoxin GRX5. The structure and cluster coordination of the two [2Fe-2S] heterocomplexes as well as their molecular function are, however, not defined yet. Experimentally-driven structural models of the two [2Fe-2S] cluster-bridged dimeric heterocomplexes, the relative stability of the two complexes and the redox properties of the [2Fe-2S] cluster bound to these complexes are here presented on the basis of UV/vis, CD, EPR and NMR spectroscopy and computational protein-protein docking...
May 5, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28483194/co-localization-of-a-cd1d-binding-glycolipid-with-an-adenovirus-based-malaria-vaccine-for-a-potent-adjuvant-effect
#17
Xiangming Li, Jing Huang, Akira Kawamura, Ryota Funakoshi, Steven A Porcelli, Moriya Tsuji
A CD1d-binding, invariant (i) natural killer T (NKT)-cell stimulatory glycolipid, α-Galactosylceramide (αGalCer), has been shown to act as an adjuvant. We previously identified a fluorinated phenyl ring-modified αGalCer analog, 7DW8-5, displaying a higher binding affinity for CD1d molecule and more potent adjuvant activity than αGalCer. In the present study, 7DW8-5 co-administered intramuscularly (i.m.) with a recombinant adenovirus expressing a Plasmodium yoelii circumsporozoite protein (PyCSP), AdPyCS, has led to a co-localization of 7DW8-5 and a PyCSP in draining lymph nodes (dLNs), particularly in dendritic cells (DCs)...
May 31, 2017: Vaccine
https://www.readbyqxmd.com/read/28480618/beyond-chemoreception-diverse-tasks-of-soluble-olfactory-proteins-in-insects
#18
Paolo Pelosi, Immacolata Iovinella, Jiao Zhu, Guirong Wang, Francesca R Dani
Odorant-binding proteins (OBPs) and chemosensory proteins (CSPs) are regarded as carriers of pheromones and odorants in insect chemoreception. These proteins are typically located in antennae, mouth organs and other chemosensory structures; however, members of both classes of proteins have been detected recently in other parts of the body and various functions have been proposed. The best studied of these non-sensory tasks is performed in pheromone glands, where OBPs and CSPs solubilise hydrophobic semiochemicals and assist their controlled release into the environment...
May 7, 2017: Biological Reviews of the Cambridge Philosophical Society
https://www.readbyqxmd.com/read/28479713/assessment-of-reactive-gingival-lesions-of-oral-cavity-a-histopathological-study
#19
Santosh Hunasgi, Anila Koneru, M Vanishree, Vardendra Manvikar
BACKGROUND: In the literature, many studies were attempted to analyze the distribution of oral reactive lesions in terms of age, gender and location. However, very few studies have focused on the detailed histopathological features of these reactive lesions of oral cavity. Thus, the purpose of this paper is to document the occurrence, distribution and various histopathological features of reactive gingival lesions. MATERIALS AND METHODS: This study is a retrospective archival review of reactive gingival lesions of oral cavity such as irritational fibroma (IF), inflammatory gingival hyperplasia (IGF), pyogenic granuloma (PG), peripheral giant cell granuloma (PGCG) and peripheral ossifying fibroma involving gingival tissues...
January 2017: Journal of Oral and Maxillofacial Pathology: JOMFP
https://www.readbyqxmd.com/read/28472513/insights-from-engineering-the-affibody-fc-interaction-with-a-computational-experimental-method
#20
Masoumeh Nosrati, Sara Solbak, Olle Nordesjö, Mikael Nissbeck, Daniel F A R Dourado, Ken G Andersson, Mohammad Reza Housaindokht, John Löfblom, Anders Virtanen, U Helena Danielson, Samuel Coulbourn Flores
The interaction between the Staphylococcal Protein A (SpA) domain B (the basis of the Affibody) molecule and the Fc of IgG is key to the use of Affibodies in affinity chromatography and in potential therapies against certain inflammatory diseases. Despite its importance and four-decade history, to our knowledge this interaction has never been affinity matured. We elucidate reasons why single-substitutions in the SpA which improve affinity to Fc may be very rare, and also discover substitutions which potentially serve several engineering purposes...
May 3, 2017: Protein Engineering, Design & Selection: PEDS
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