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V(d)J recombination

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https://www.readbyqxmd.com/read/27924291/data-on-isoaspartylation-of-neuronal-elavl-proteins
#1
Mario A Pulido, Meleeneh Kazarian DerHartunian, Prerna Sehgal, Ite A Laird-Offringa
This article contains experimental data examining the propensity of neuronal ELAVL proteins to become isoaspartylated. The data are related to the article "Isoaspartylation appears to trigger small cell lung cancer-associated autoimmunity against neuronal protein ELAVL4" (M.A. Pulido, M.K. DerHartunian, Z. Qin, E.M. Chung, D.S. Kang, A.W. Woodham, J.A. Tsou, R. Klooster, O. Akbari, L. Wang, W.M. Kast, S.V. Liu, J.J.G.M. Verschuuren, D.W. Aswad, I.A. Laird-Offringa, 2016) [1], in which it was reported that the N-terminal region of recombinant human ELAVL4 protein, incubated under physiological conditions, acquires a type of highly immunogenic protein damage...
December 2016: Data in Brief
https://www.readbyqxmd.com/read/27913727/regulated-complex-assembly-safeguards-the-fidelity-of-sleeping-beauty-transposition
#2
Yongming Wang, Diana Pryputniewicz-Dobrinska, Enikö Éva Nagy, Christopher D Kaufman, Manvendra Singh, Steve Yant, Jichang Wang, Anna Dalda, Mark A Kay, Zoltán Ivics, Zsuzsanna Izsvák
The functional relevance of the inverted repeat structure (IR/DR) in a subgroup of the Tc1/mariner superfamily of transposons has been enigmatic. In contrast to mariner transposition, where a topological filter suppresses single-ended reactions, the IR/DR orchestrates a regulatory mechanism to enforce synapsis of the transposon ends before cleavage by the transposase occurs. This ordered assembly process shepherds primary transposase binding to the inner 12DRs (where cleavage does not occur), followed by capture of the 12DR of the other transposon end...
December 1, 2016: Nucleic Acids Research
https://www.readbyqxmd.com/read/27910350/optimization-and-application-of-cooled-avalanche-photodiodes-for-spectroscopic-fluctuation-measurements-with-ultra-fast-charge-exchange-recombination-spectroscopy
#3
D D Truong, R J Fonck, G R McKee
The Ultra-Fast Charge Exchange Recombination Spectroscopy (UF-CHERS) diagnostic is a highly specialized spectroscopic instrument with 2 spatial channels consisting of 8 spectral channels each and a resolution of ∼0.25 nm deployed at DIII-D to measure turbulent ion temperature fluctuations. Charge exchange emissions are obtained between 528 and 530 nm with 1 μs time resolution to study plasma instabilities. A primary challenge of extracting fluctuation measurements from raw UF-CHERS signals is photon and electronic noise...
November 2016: Review of Scientific Instruments
https://www.readbyqxmd.com/read/27898125/co2-reduction-over-nanbo3-and-natao3-perovskite-photocatalysts
#4
F Fresno, P Jana, P Reñones, J M Coronado, D P Serrano, V A de la Peña O'Shea
The activity of NaNbO3 and NaTaO3 perovskites for the photocatalytic reduction of CO2 is studied in this work. For this purpose, sodium niobate and tantalate have been prepared using solid-state reactions, extensively characterised by means of powder X-ray diffraction, UV-vis, photoluminescence and Raman spectroscopies and N2 adsorption isotherms, and tested in the gas-phase reduction of CO2 under UV light in a continuous flow photoreactor. NaNbO3 is constituted of an orthorhombically distorted perovskite structure, while a ca...
September 5, 2016: Photochemical & Photobiological Sciences
https://www.readbyqxmd.com/read/27886492/role-of-excited-states-in-high-order-harmonic-generation
#5
S Beaulieu, S Camp, D Descamps, A Comby, V Wanie, S Petit, F Légaré, K J Schafer, M B Gaarde, F Catoire, Y Mairesse
We investigate the role of excited states in high-order harmonic generation by studying the spectral, spatial, and temporal characteristics of the radiation produced near the ionization threshold of argon by few-cycle laser pulses. We show that the population of excited states can lead either to direct extreme ultraviolet emission through free induction decay or to the generation of high-order harmonics through ionization from these states and recombination to the ground state. By using the attosecond lighthouse technique, we demonstrate that the high-harmonic emission from excited states is temporally delayed by a few femtoseconds compared to the usual harmonics, leading to a strong nonadiabatic spectral redshift...
November 11, 2016: Physical Review Letters
https://www.readbyqxmd.com/read/27883081/v-d-j-recombination-process-and-the-pre-b-to-immature-b-cells-transition-are-altered-in-fanca-mice
#6
Thuy Vy Nguyen, Patrycja Pawlikowska, Virginie Firlej, Filippo Rosselli, Saïd Aoufouchi
B-lymphocytes in the bone marrow (BM) must generate a functional B-cell receptor and overcome the negative selection induced by reactivity with autoantigens. Two rounds of DNA recombination are required for the production of functional immunoglobulin heavy (Ig-HCs) and light (LCs) chains necessary for the continuation of B-lymphocyte development in the BM. Both rounds depend on the joint action of recombination activating gene-1 (RAG-1) and RAG-2 endonucleases with the DNA non-homologous end-joining pathway...
November 24, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27882538/gene-therapy-with-mesenchymal-stem-cells-expressing-ifn%C3%A3-ameliorates-neuroinflammation-in-experimental-models-of-multiple-sclerosis
#7
C Marin-Bañasco, K Benabdellah, C Melero-Jerez, B Oliver, M J Pinto-Medel, I Hurtado-Guerrero, F de Castro, D Clemente, O Fernández, F Martin, L Leyva, M Suardíaz
BACKGROUND AND PURPOSE: Recombinant IFNß is one of the first line treatments in multiple sclerosis (MS), despite its lack of efficiency in some patients. In this context, mesenchymal stem cells (MSCs) represent a promising therapeutic alternative due to their immunomodulatory properties and multipotency. Moreover, taking advantage of their pathotropism ability, these cells can be genetically modified to be used as carriers for delivering or secreting therapeutic drugs into injured tissues...
November 24, 2016: British Journal of Pharmacology
https://www.readbyqxmd.com/read/27876017/increased-wnt5a-in-squamous-cell-lung-carcinoma-inhibits-endothelial-cell-motility
#8
J Rapp, E Kiss, M Meggyes, E Szabo-Meleg, D Feller, G Smuk, T Laszlo, V Sarosi, T F Molnar, K Kvell, J E Pongracz
BACKGROUND: Angiogenesis is important both in normal tissue function and disease and represents a key target in lung cancer (LC) therapy. Unfortunately, the two main subtypes of non-small-cell lung cancers (NSCLC) namely, adenocarcinoma (AC) and squamous cell carcinoma (SCC) respond differently to anti-angiogenic e.g. anti-vascular endothelial growth factor (VEGF)-A treatment with life-threatening side effects, often pulmonary hemorrhage in SCC. The mechanisms behind such adverse reactions are still largely unknown, although peroxisome proliferator activator receptor (PPAR) gamma as well as Wnt-s have been named as molecular regulators of the process...
November 23, 2016: BMC Cancer
https://www.readbyqxmd.com/read/27863852/the-rag-recombinase-beyond-breaking
#9
Chloé Lescale, Ludovic Deriano
DNA double-strand breaks (DSBs) are commonly seen as lesions that threaten genome integrity and contribute to cancer and aging processes. However, in the context of antigen receptor gene assembly, known as V(D)J recombination, DSBs are obligatory intermediates that allow the establishment of genetic diversity and adaptive immunity. V(D)J recombination is initiated when the lymphoid-restricted recombination-activating genes RAG1 and RAG2 are expressed and form a site-specific endonuclease (the RAG nuclease or RAG recombinase)...
November 15, 2016: Mechanisms of Ageing and Development
https://www.readbyqxmd.com/read/27843625/safety-and-immunogenicity-of-the-prame-cancer-immunotherapeutic-in-metastatic-melanoma-results-of-a-phase-i-dose-escalation-study
#10
R Gutzmer, L Rivoltini, E Levchenko, A Testori, J Utikal, P A Ascierto, L Demidov, J J Grob, R Ridolfi, D Schadendorf, P Queirolo, A Santoro, C Loquai, B Dreno, A Hauschild, E Schultz, T P Lesimple, N Vanhoutte, B Salaun, M Gillet, S Jarnjak, P M De Sousa Alves, J Louahed, V G Brichard, F F Lehmann
PURPOSE: The PRAME tumour antigen is expressed in several tumour types but in few normal adult tissues. A dose-escalation phase I/II study (NCT01149343) assessed the safety, immunogenicity and clinical activity of the PRAME immunotherapeutic (recombinant PRAME protein (recPRAME) with the AS15 immunostimulant) in patients with advanced melanoma. Here, we report the phase I dose-escalation study segment. PATIENTS AND METHODS: Patients with stage IV PRAME-positive melanoma were enrolled to 3 consecutive cohorts to receive up to 24 intramuscular injections of the PRAME immunotherapeutic...
2016: ESMO Open
https://www.readbyqxmd.com/read/27835690/vidjil-a-web-platform-for-analysis-of-high-throughput-repertoire-sequencing
#11
Marc Duez, Mathieu Giraud, Ryan Herbert, Tatiana Rocher, Mikaël Salson, Florian Thonier
BACKGROUND: The B and T lymphocytes are white blood cells playing a key role in the adaptive immunity. A part of their DNA, called the V(D)J recombinations, is specific to each lymphocyte, and enables recognition of specific antigenes. Today, with new sequencing techniques, one can get billions of DNA sequences from these regions. With dedicated Repertoire Sequencing (RepSeq) methods, it is now possible to picture population of lymphocytes, and to monitor more accurately the immune response as well as pathologies such as leukemia...
2016: PloS One
https://www.readbyqxmd.com/read/27830975/deficiency-of-xlf-and-paxx-prevents-dna-double-strand-break-repair-by-non-homologous-end-joining-in-lymphocytes
#12
Putzer J Hung, Bo-Ruei Chen, Rosmy George, Caleb Liberman, Abigail J Morales, Pedro Colon-Ortiz, Jessica K Tyler, Barry P Sleckman, Andrea L Bredemeyer
Non-homologous end joining (NHEJ) is a major DNA double-strand break (DSB) repair pathway that functions in all phases of the cell cycle. NHEJ repairs genotoxic and physiological DSBs, such as those generated by ionizing radiation and during V(D)J recombination at antigen receptor loci, respectively. DNA end joining by NHEJ relies on the core factors Ku70, Ku80, XRCC4, and DNA Ligase IV. Additional proteins also play important roles in NHEJ. The XRCC4-like factor (XLF) participates in NHEJ through its interaction with XRCC4, and XLF deficiency in humans leads to immunodeficiency and increased sensitivity to ionizing radiation...
November 10, 2016: Cell Cycle
https://www.readbyqxmd.com/read/27825771/riches-in-rags-revealing-the-v-d-j-recombinase-through-high-resolution-structures
#13
REVIEW
Karla K Rodgers
Development of the adaptive immune system is dependent on V(D)J recombination, which forms functional antigen receptor genes through rearrangement of component gene segments. The V(D)J recombinase, comprising recombination-activating proteins RAG1 and RAG2, guides the initial DNA cleavage events to the recombination signal sequence (RSS), which flanks each gene segment. Although the enzymatic steps for RAG-mediated endonucleolytic activity were established over two decades ago, only recently have high-resolution structural studies of the catalytically active core regions of the RAG proteins shed light on conformational requirements for the reaction...
November 5, 2016: Trends in Biochemical Sciences
https://www.readbyqxmd.com/read/27820605/molecular-level-analysis-of-the-serum-antibody-repertoire-in-young-adults-before-and-after-seasonal-influenza-vaccination
#14
Jiwon Lee, Daniel R Boutz, Veronika Chromikova, M Gordon Joyce, Christopher Vollmers, Kwanyee Leung, Andrew P Horton, Brandon J DeKosky, Chang-Han Lee, Jason J Lavinder, Ellen M Murrin, Constantine Chrysostomou, Kam Hon Hoi, Yaroslav Tsybovsky, Paul V Thomas, Aliaksandr Druz, Baoshan Zhang, Yi Zhang, Lingshu Wang, Wing-Pui Kong, Daechan Park, Lyubov I Popova, Cornelia L Dekker, Mark M Davis, Chalise E Carter, Ted M Ross, Andrew D Ellington, Patrick C Wilson, Edward M Marcotte, John R Mascola, Gregory C Ippolito, Florian Krammer, Stephen R Quake, Peter D Kwong, George Georgiou
Molecular understanding of serological immunity to influenza has been confounded by the complexity of the polyclonal antibody response in humans. Here we used high-resolution proteomics analysis of immunoglobulin (referred to as Ig-seq) coupled with high-throughput sequencing of transcripts encoding B cell receptors (BCR-seq) to quantitatively determine the antibody repertoire at the individual clonotype level in the sera of young adults before and after vaccination with trivalent seasonal influenza vaccine...
December 2016: Nature Medicine
https://www.readbyqxmd.com/read/27813533/transgenic-mouse-model-of-igm-lymphoproliferative-disease-mimicking-waldenstr%C3%A3-m-macroglobulinemia
#15
V S Tompkins, R Sompallae, T R Rosean, S Walsh, M Acevedo, A L Kovalchuk, S-S Han, X Jing, C Holman, J E Rehg, S Herms, J S Sunderland, H C Morse, S Janz
Waldenström macroglobulinemia (WM) is a low-grade incurable immunoglobulin M(+) (IgM(+)) lymphoplasmacytic lymphoma for which a genetically engineered mouse model of de novo tumor development is lacking. On the basis of evidence that the pro-inflammatory cytokine, interleukin 6 (IL6), and the survival-enhancing oncoprotein, B cell leukemia 2 (BCL2), have critical roles in the natural history of WM, we hypothesized that the enforced expression of IL6 and BCL2 in mice unable to perform immunoglobulin class switch recombination may result in a lymphoproliferative disease that mimics WM...
November 4, 2016: Blood Cancer Journal
https://www.readbyqxmd.com/read/27766961/vdjml-a-file-format-with-tools-for-capturing-the-results-of-inferring-immune-receptor-rearrangements
#16
Inimary T Toby, Mikhail K Levin, Edward A Salinas, Scott Christley, Sanchita Bhattacharya, Felix Breden, Adam Buntzman, Brian Corrie, John Fonner, Namita T Gupta, Uri Hershberg, Nishanth Marthandan, Aaron Rosenfeld, William Rounds, Florian Rubelt, Walter Scarborough, Jamie K Scott, Mohamed Uduman, Jason A Vander Heiden, Richard H Scheuermann, Nancy Monson, Steven H Kleinstein, Lindsay G Cowell
BACKGROUND: The genes that produce antibodies and the immune receptors expressed on lymphocytes are not germline encoded; rather, they are somatically generated in each developing lymphocyte by a process called V(D)J recombination, which assembles specific, independent gene segments into mature composite genes. The full set of composite genes in an individual at a single point in time is referred to as the immune repertoire. V(D)J recombination is the distinguishing feature of adaptive immunity and enables effective immune responses against an essentially infinite array of antigens...
October 6, 2016: BMC Bioinformatics
https://www.readbyqxmd.com/read/27752662/tunneling-chemical-exchange-reaction-d-hd-%C3%A2-d2-h-in-solid-hd-and-d2-at-temperatures-below-1-k
#17
S Sheludiakov, J Ahokas, J Järvinen, D Zvezdov, L Lehtonen, O Vainio, S Vasiliev, D M Lee, V V Khmelenko
We report on a study of the exchange tunneling reaction D + HD → D2 + H in a pure solid HD matrix and in a D2 matrix with a 0.23% HD admixture at temperatures between 130 mK and 1.5 K. We found that the exchange reaction rates, kexHD ∼ 3 × 10(-27) cm(3) s(-1) in the pure HD matrix, and kexD2 = 9(4) × 10(-28) cm(3) s(-1) in the D2 matrix, are nearly independent of temperature within this range. This confirms the quantum tunnelling nature of these reactions, and their ability to proceed at temperatures down to absolute zero...
October 18, 2016: Physical Chemistry Chemical Physics: PCCP
https://www.readbyqxmd.com/read/27749002/novel-factor-viii-variants-with-a-modified-furin-cleavage-site-improve-the-efficacy-of-gene-therapy-for-hemophilia-a
#18
G N Nguyen, L A George, J I Siner, R J Davidson, C B Zander, X L Zheng, V R Arruda, R M Camire, D E Sabatino
BACKGROUND: The major challenge for developing gene-based therapies for hemophilia A is that human factor VIII (hFVIII) has intrinsic properties that result in inefficient biosynthesis. During intracellular processing, hFVIII is predominantly cleaved at a Paired basic Amino acid Cleaving Enzyme (PACE) or furin cleavage site to yield a heterodimer that is the major form of secreted protein. Previous studies with B-domain deleted (BDD) canine FVIII and hFVIII-R1645H, both differing from hFVIII by a single amino acid at this site, suggested that these proteins are secreted mainly in a single polypeptide chain (SC) form and exhibit enhanced function...
October 17, 2016: Journal of Thrombosis and Haemostasis: JTH
https://www.readbyqxmd.com/read/27734097/genetic-analysis-of-net-form-net-blotch-resistance-in-barley-lines-ciho-5791-and-tifang-against-a-global-collection-of-p-teres-f-teres-isolates
#19
V M Koladia, J D Faris, J K Richards, R S Brueggeman, S Chao, T L Friesen
A CIho 5791 × Tifang recombinant inbred mapping population was developed and used to identify major dominant resistance genes on barley chromosomes 6H and 3H in CI5791 and on 3H in Tifang. The barley line CIho 5791 confers high levels of resistance to Pyrenophora teres f. teres, causal agent of net form net blotch (NFNB), with few documented isolates overcoming this resistance. Tifang barley also harbors resistance to P. teres f. teres which was previously shown to localize to barley chromosome 3H. A CIho 5791 × Tifang F6 recombinant inbred line (RIL) population was developed using single seed descent...
October 12, 2016: TAG. Theoretical and Applied Genetics. Theoretische und Angewandte Genetik
https://www.readbyqxmd.com/read/27717299/niraparib-maintenance-therapy-in-platinum-sensitive-recurrent-ovarian-cancer
#20
Mansoor R Mirza, Bradley J Monk, Jørn Herrstedt, Amit M Oza, Sven Mahner, Andrés Redondo, Michel Fabbro, Jonathan A Ledermann, Domenica Lorusso, Ignace Vergote, Noa E Ben-Baruch, Christian Marth, Radosław Mądry, René D Christensen, Jonathan S Berek, Anne Dørum, Anna V Tinker, Andreas du Bois, Antonio González-Martín, Philippe Follana, Benedict Benigno, Per Rosenberg, Lucy Gilbert, Bobbie J Rimel, Joseph Buscema, John P Balser, Shefali Agarwal, Ursula A Matulonis
Background Niraparib is an oral poly(adenosine diphosphate [ADP]-ribose) polymerase (PARP) 1/2 inhibitor that has shown clinical activity in patients with ovarian cancer. We sought to evaluate the efficacy of niraparib versus placebo as maintenance treatment for patients with platinum-sensitive, recurrent ovarian cancer. Methods In this randomized, double-blind, phase 3 trial, patients were categorized according to the presence or absence of a germline BRCA mutation (gBRCA cohort and non-gBRCA cohort) and the type of non-gBRCA mutation and were randomly assigned in a 2:1 ratio to receive niraparib (300 mg) or placebo once daily...
October 7, 2016: New England Journal of Medicine
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