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V(d)J recombination

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https://www.readbyqxmd.com/read/29232168/high-throughput-screening-approach-for-identifying-compounds-that-inhibit-nonhomologous-end-joining
#1
Andrea L Bredemeyer, Bruce S Edwards, Mark K Haynes, Abigail J Morales, Yinan Wang, Oleg Ursu, Anna Waller, Larry A Sklar, Barry P Sleckman
DNA double-strand breaks (DSBs) are repaired primarily by homologous recombination (HR) or nonhomologous end joining (NHEJ). Compounds that modulate HR have shown promise as cancer therapeutics. The V(D)J recombination reaction, which assembles antigen receptor genes in lymphocytes, is initiated by the introduction of DNA DSBs at two recombining gene segments by the RAG endonuclease, followed by the NHEJ-mediated repair of these DSBs. Here, using HyperCyt automated flow cytometry, we develop a robust high-throughput screening (HTS) assay for NHEJ that utilizes engineered pre-B-cell lines where the V(D)J recombination reaction can be induced and monitored at a single-cell level...
December 1, 2017: SLAS Discovery
https://www.readbyqxmd.com/read/29204143/local-chromatin-features-including-pu-1-and-ikaros-binding-and-h3k4-methylation-shape-the-repertoire-of-immunoglobulin-kappa-genes-chosen-for-v-d-j-recombination
#2
Louise S Matheson, Daniel J Bolland, Peter Chovanec, Felix Krueger, Simon Andrews, Hashem Koohy, Anne E Corcoran
V(D)J recombination is essential for the generation of diverse antigen receptor (AgR) repertoires. In B cells, immunoglobulin kappa (Igκ) light chain recombination follows immunoglobulin heavy chain (Igh) recombination. We recently developed the DNA-based VDJ-seq assay for the unbiased quantitation of Igh VH and DH repertoires. Integration of VDJ-seq data with genome-wide datasets revealed that two chromatin states at the recombination signal sequence (RSS) of VH genes are highly predictive of recombination in mouse pro-B cells...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29176980/iragu-a-novel-inducible-and-reversible-mouse-model-for-ubiquitous-recombinase-activity
#3
Marie Bonnet, Leonor Morais Sarmento, Ana C Martins, Daniel Sobral, Joana Silva, Jocelyne Demengeot
Developing lymphocytes express the recombination activating genes (RAGs) 1 and 2 products that form a site specific recombinase complex (RAG), introducing double strand DNA breaks (DSBs) at recombination signal sequences (RSSs) flanking the V, D, and J gene segments in the antigen receptor loci. The subsequent steps in the reaction consist in the ligation of DSBs by ubiquitous enzymes of the non-homologous end joining DNA repair pathway. This mutagenesis process is responsible for the generation of the very large clonal diversity of T and B lymphocytes, itself allowing the recognition of a virtually open-ended antigenic universe...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29175053/the-evolutionary-conservation-of-the-bidirectional-activity-of-the-nwc-gene-promoter-in-jawed-vertebrates-and-the-domestication-of-the-rag-transposon
#4
Lukasz Sniezewski, Sylwia Janik, Agnieszka Laszkiewicz, Michal Majkowski, Pawel Kisielow, Malgorzata Cebrat
The RAG-1 and RAG-2 genes form a recombinase complex that is indispensable for V(D)J recombination, which generates the diversity of immunoglobulins and T-cell receptors. It is widely accepted that the presence of RAGs in the genomes of jawed vertebrates and other lineages is a result of the horizontal transfer of a mobile genetic element. While a substantial amount of evidence has been gathered that clarifies the nature of the RAG transposon, far less attention has been paid to the genomic site of its integration in various host organisms...
November 22, 2017: Developmental and Comparative Immunology
https://www.readbyqxmd.com/read/29143737/validation-of-elisa-methods-for%C3%A2-quantification-of-the-major-birch-allergen-bet-v-1-bsp090
#5
S Kaul, J Zimmer, O Dehus, A Constanzo, A DaasConstanzo, K-H Buchheit, J Asturias, M C Arilla, D Barber, A Bertocchi, B Brunetto, J A Carnes, M Chapman, G Chaudemanche, J Dayan-Kenigsberg, S Döring, F Führer, M T Gallego, P Iacovacci, K M Hanschmann, T Holzhauser, M Hrabina, A Ledesma, P Moingeon, E Nony, C Pini, G Plunkett, M Raulf, G Reese, E Sandberg, I Sander, B Smith, D Strecker, C Valerio, R van Ree, B Weber, S Vieths
To date, the potency of allergen products in Europe is expressed in manufacturer-specific units relative to a product-specific in-house reference. Consequently, cross-product comparability of allergen products from different manufacturers with respect to strength and efficacy is impossible. The Biological Standardisation Programme (BSP) project BSP090 addresses this issue via the establishment of reference standards in conjunction with ELISA methods for the quantification of major allergens in allergen products...
2017: Pharmeuropa Bio & Scientific Notes
https://www.readbyqxmd.com/read/29138356/the-soluble-pro-renin-receptor-does-not-influence-lithium-induced-diabetes-insipidus-but-does-provoke-beiging-of-white-adipose-tissue-in-mice
#6
Kevin T Yang, Fei Wang, Xiaohan Lu, Kexin Peng, Tianxin Yang, J David Symons
Earlier we reported that the recombinant soluble (pro) renin receptor sPRR-His upregulates renal aquoporin-2 (AQP2) expression, and attenuates polyuria associated with nephrogenic diabetes insipidus (NDI) induced by vasopressin type 2 receptor (V2R) antagonism. Patients that receive lithium therapy develop polyuria associated NDI that might be secondary to downregulation of renal AQP2. We hypothesized that sPRR-His attenuates indices of NDI associated with lithium treatment. Eight-week-old male C57/BL6 mice consumed chow supplemented with LiCl (40 mmol/kg diets) for 14 days...
November 2017: Physiological Reports
https://www.readbyqxmd.com/read/29126456/virological-response-hiv-1-drug-resistance-mutations-and-genetic-diversity-among-patients-on-first-line-antiretroviral-therapy-in-n-djamena-chad-findings-from-a-cross-sectional-study
#7
Chatté Adawaye, Joseph Fokam, Erick Kamangu, Hamit Mahamat Alio, Aoudalkarim Moussa Chahad, Fabrice Susin, Ali Mahamat Moussa, Tchombou Hig-Zounet Bertin, Abdelsalam Tidjani, Dolores Vaira, Michel Moutschen
BACKGROUND: The national antiretroviral therapy in the Republic of Chad provides free of charge antiretroviral regimens and therapeutic monitoring for patients receiving antiretroviral therapy nationwide. For a successful programmatic uptake, these efforts merit to be supported by thorough assessments of antiretroviral therapy response and HIV-1 drug resistance surveillance, especially with risks of cross-resistance due to the gradual stavudine phasing out in such national settings. We therefore evaluated the virological response to antiretroviral therapy, HIV-1 drug resistance emergence and circulating HIV-1 clades in a Chad context...
November 10, 2017: BMC Research Notes
https://www.readbyqxmd.com/read/29120707/using-specific-recombinant-gonadotropins-to-induce-spermatogenesis-and-spermiation-in-the-european-eel-anguilla-anguilla
#8
D S Peñaranda, V Gallego, C Rozenfeld, J G Herranz-Jusdado, L Pérez, A Gómez, I Giménez, J F Asturiano
New specific European eel (Anguilla anguilla) recombinant gonadotropins (aarGths) produced in the ovarian cells of Chinese hamsters (CHO) were used to induce maturation in captive male eels. In the first experiment, five different hormonal treatments were assayed: one group was given a constant dose of recombinant European eel follicle-stimulating hormone (aarFsh; 4 μg/fish) for 9 weeks, and the second group received a constant dose of recombinant European eel luteinizing hormone (aarLh; 2 μg/fish) also for 9 weeks...
November 3, 2017: Theriogenology
https://www.readbyqxmd.com/read/29100269/activation-induced-cytidine-deaminase-prevents-pro-b-cell-acute-lymphoblastic-leukemia-by-functioning-as-a-negative-regulator-in-rag1-deficient-pro-b-cells
#9
Franziska Auer, Deborah Ingenhag, Stefan Pinkert, Sven Kracker, Salima Hacein-Bey-Abina, Marina Cavazzana, Michael Gombert, Alberto Martin-Lorenzo, Min-Hui Lin, Carolina Vicente-Dueñas, Isidro Sánchez-García, Arndt Borkhardt, Julia Hauer
Activation-induced cytidine deaminase (AID) is essential for somatic hypermutation and class switch recombination in mature B-cells, while AID was also shown to play a role in developing pre-BCR/BCR-positive B-cells of the bone marrow. To further elucidate a potential function of Aid in the bone marrow prior to V(D)J-recombination, we utilized an in vivo model which exerts a B-cell developmental arrest at the pro-B cell stage with low frequencies of pro-B cell acute lymphoblastic leukemia (pro-B ALL) development...
September 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/29061645/homologous-recombination-dna-repair-pathway-disruption-and-retinoblastoma-protein-loss-are-associated-with-exceptional-survival-in-high-grade-serous-ovarian-cancer
#10
Dale W Garsed, Kathryn Alsop, Sian Fereday, Catherine Emmanuel, Catherine J Kennedy, Dariush Etemadmoghadam, Bo Gao, Val Gebski, Valérie Garès, Elizabeth L Christie, Maartje C A Wouters, Katy Milne, Joshy George, Ann-Marie Patch, Jason Li, Gisela Mir Arnau, Timothy Semple, Sreeja R Gadipally, Yoke-Eng Chiew, Joy Hendley, Thomas Mikeska, Giada V Zapparoli, Kaushalya Amarasinghe, Sean M Grimmond, John V Pearson, Nicola Waddell, Jillian Hung, Colin J R Stewart, Raghwa Sharma, Prue E Allan, Peter F Rambau, Nadia Traficante, Orla McNally, Linda Mileshkin, Anne Hamilton, Sumitra Ananda, Marisa Grossi, Paul A Cohen, Yee C Leung, Robert M Rome, Philip Beale, Penny Blomfield, Michael Friedlander, Alison Brand, Alexander Dobrovic, Martin Köbel, Paul Harnett, Brad H Nelson, David D L Bowtell, Anna deFazio
Purpose: Women with epithelial ovarian cancer generally have a poor prognosis; however, a subset of patients has an unexpected dramatic and durable response to treatment. We sought to identify clinical, pathological, and molecular determinants of exceptional survival in women with high-grade serous cancer (HGSC), a disease associated with the majority of ovarian cancer deaths.Experimental Design: We evaluated the histories of 2,283 ovarian cancer patients and, after applying stringent clinical and pathological selection criteria, identified 96 with HGSC that represented significant outliers in terms of treatment response and overall survival...
October 23, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29045554/veliparib-with-temozolomide-or-carboplatin-paclitaxel-versus-placebo-with-carboplatin-paclitaxel-in-patients-with-brca1-2-locally-recurrent-metastatic-breast-cancer-randomized-phase-ii-study
#11
H S Han, V Diéras, M Robson, M Palácová, P K Marcom, A Jager, I Bondarenko, D Citrin, M Campone, M L Telli, S M Domchek, M Friedlander, B Kaufman, J E Garber, Y Shparyk, E Chmielowska, E H Jakobsen, V Kaklamani, W Gradishar, C K Ratajczak, C Nickner, Q Qin, J Qian, S P Shepherd, S J Isakoff, S Puhalla
Background: Homologous recombination defects in BRCA1/2-mutated tumors result in sensitivity to poly(ADP-ribose) polymerase (PARP) inhibitors, which interfere with DNA damage repair. Veliparib, a potent PARP inhibitor, enhanced the antitumor activity of platinum agents and temozolomide in early phase clinical trials. This phase II study examined the safety and efficacy of intermittent veliparib with carboplatin/paclitaxel (VCP) or temozolomide (VT) in patients with BRCA1/2-mutated breast cancer...
September 29, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/29038163/bcl11a-is-a-critical-component-of-a-transcriptional-network-that-activates-rag-expression-and-vdj-recombination
#12
Baeck-Seung Lee, Bum-Kyu Lee, Vishwanath R Iyer, Barry P Sleckman, Arthur L Shaffer, Gregory C Ippolito, Haley O Tucker, Joseph D Dekker
Recombination activating gene 1 (RAG1) and RAG2 are critical enzymes for initiating variable-diversity-joining (VDJ) segment recombination, an essential process for antigen receptor expression and lymphocyte development. The BCL11A transcription factor is required for B cell and Plasmacytoid dendritic cell (pDC) development, but its molecular function(s) in early B cell fate specification and commitment are unknown. We show here that the major B cell isoform, BCL11A-XL, binds directly to the RAG1 promoter as well as directly to regulatory regions of transcription factors previously implicated in both B cell and pDC development to activate RAG1 and RAG2 transcription in pro- and pre-B cells...
October 16, 2017: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/29030471/retraction-for-lee-et-al-the-bcl11a-transcription-factor-directly-activates-rag-gene-expression-and-v-d-j-recombination
#13
Baeck-Seung Lee, Joseph D Dekker, Bum-Kyu Lee, Vishwanath R Iyer, Barry P Sleckman, Arthur L Shaffer, Gregory C Ippolito, Philip W Tucker
No abstract text is available yet for this article.
November 1, 2017: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/28991925/next-generation-elisa-diagnostic-assay-for-chagas-disease-based-on-the-combination-of-short-peptidic-epitopes
#14
Juan Mucci, Santiago J Carmona, Romina Volcovich, Jaime Altcheh, Estefanía Bracamonte, Jorge D Marco, Morten Nielsen, Carlos A Buscaglia, Fernán Agüero
Chagas Disease, caused by the protozoan Trypanosoma cruzi, is a major health and economic problem in Latin America for which no vaccine or appropriate drugs for large-scale public health interventions are yet available. Accurate diagnosis is essential for the early identification and follow up of vector-borne cases and to prevent transmission of the disease by way of blood transfusions and organ transplantation. Diagnosis is routinely performed using serological methods, some of which require the production of parasite lysates, parasite antigenic fractions or purified recombinant antigens...
October 2017: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/28959243/rnase-h-as-gene-modifier-driver-of-evolution-and-antiviral-defense
#15
REVIEW
Karin Moelling, Felix Broecker, Giancarlo Russo, Shinichi Sunagawa
Retroviral infections are 'mini-symbiotic' events supplying recipient cells with sequences for viral replication, including the reverse transcriptase (RT) and ribonuclease H (RNase H). These proteins and other viral or cellular sequences can provide novel cellular functions including immune defense mechanisms. Their high error rate renders RT-RNases H drivers of evolutionary innovation. Integrated retroviruses and the related transposable elements (TEs) have existed for at least 150 million years, constitute up to 80% of eukaryotic genomes and are also present in prokaryotes...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/28952637/ultraviolet-phototoxicity-of-upconversion-nanoparticles-illuminated-with-near-infrared-light
#16
K E Mironova, D A Khochenkov, A N Generalova, V V Rocheva, N V Sholina, A V Nechaev, V A Semchishen, S M Deyev, A V Zvyagin, E V Khaydukov
Recently introduced upconversion nanoparticles (UCNPs) have pushed the depth of photodynamic therapy (PDT) treatment to the centimetre range by converting deeply-penetrating near-infrared (NIR) radiation to visible radiation for photoexcitation of PDT drugs. Here we demonstrate that the direct exposure of the cancer tissue to phototoxic ultraviolet radiation generated by NIR-photoexcited UCNPs enabled successful PDT. To this aim, core/shell UCNPs of the formula NaYF4:Yb(3+)Tm(3+)/NaYF4 featuring an enhanced band in the ultraviolet UV-A and UV-B spectral bands were rationally designed and synthesised...
October 12, 2017: Nanoscale
https://www.readbyqxmd.com/read/28941616/elisa-for-detection-of-variant-rabbit-haemorrhagic-disease-virus-rhdv2-antigen-in-liver-extracts
#17
K P Dalton, A Podadera, V Granda, I Nicieza, D Del Llano, R González, J R de Los Toyos, M García Ocaña, F Vázquez, J M Martín Alonso, J M Prieto, F Parra, R Casais
The emergence and rapid spread of variant of the rabbit hemorrhagic disease virus (RHDV2) require new diagnostic tools to ensure that efficient control measures are adopted. In the present study, a specific sandwich enzyme-linked immunosorbent assay (ELISA) for detection of RHDV2 antigens in rabbit liver homogenates, based on the use of an RHDV2-specific monoclonal antibody (Mab) 2D9 for antigen capture and an anti-RHDV2 goat polyclonal antibody (Pab), was developed. This ELISA was able to successfully detect RHDV2 and RHDV2 recombinant virions with high sensitivity (100%) and specificity (97...
January 2018: Journal of Virological Methods
https://www.readbyqxmd.com/read/28888370/biophysical-and-biological-properties-of-small-linear-peptides-derived-from-crotamine-a-cationic-antimicrobial-antitumoral-toxin-with-cell-penetrating-and-cargo-delivery-abilities
#18
C Dal Mas, D A Pinheiro, J D Campeiro, B Mattei, V Oliveira, E B Oliveira, A Miranda, K R Perez, M A F Hayashi
Crotamine is a natural polypeptide from snake venom which delivers nucleic acid molecules into cells, besides having pronounced affinity for negatively charged membranes and antifungal activity. We previously demonstrated that crotamine derived short linear peptides were not very effective as antifungal, although the non-structured recombinant crotamine was overridingly more potent compared to the native structured crotamine. Aiming to identify the features necessary for the antifungal activity of crotamine, two linear short peptides, each comprising half of the total positively charged amino acid residues of the full-length crotamine were evaluated here to show that these linear peptides keep the ability to interact with lipid membrane model systems with different phospholipid compositions, even after forming complexes with DNA...
December 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28882611/generation-and-crispr-cas9-editing-of-transformed-progenitor-b-cells-as-a-pseudo-physiological-system-to-study-dna-repair-gene-function-in-v-d-j-recombination
#19
Hélène Lenden Hasse, Chloé Lescale, Joy J Bianchi, Wei Yu, Marie Bedora-Faure, Ludovic Deriano
Antigen receptor gene assembly is accomplished in developing lymphocytes by the V(D)J recombination reaction, which can be separated into two steps: DNA cleavage by the recombination-activating gene (RAG) nuclease and joining of DNA double strand breaks (DSBs) by components of the nonhomologous end joining (NHEJ) pathway. Deficiencies for NHEJ factors can result in immunodeficiency and a propensity to accumulate genomic instability, thus highlighting the importance of identifying all players in this process and deciphering their functions...
September 4, 2017: Journal of Immunological Methods
https://www.readbyqxmd.com/read/28867784/the-complex-interplay-between-dna-injury-and-repair-in-enzymatically-induced-mutagenesis-and-dna-damage-in-b-lymphocytes
#20
REVIEW
Mahnoush Bahjat, Jeroen E J Guikema
Lymphocytes are endowed with unique and specialized enzymatic mutagenic properties that allow them to diversify their antigen receptors, which are crucial sensors for pathogens and mediators of adaptive immunity. During lymphocyte development, the antigen receptors expressed by B and T lymphocytes are assembled in an antigen-independent fashion by ordered variable gene segment recombinations (V(D)J recombination), which is a highly ordered and regulated process that requires the recombination activating gene products 1 & 2 (RAG1, RAG2)...
August 30, 2017: International Journal of Molecular Sciences
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