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V(d)J recombination

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https://www.readbyqxmd.com/read/28089565/fgf21-is-an-exocrine-pancreas-secretagogue
#1
Katie C Coate, Genaro Hernandez, Curtis A Thorne, Shengyi Sun, Thao D V Le, Kevin Vale, Steven A Kliewer, David J Mangelsdorf
The metabolic stress hormone FGF21 is highly expressed in exocrine pancreas, where its levels are increased by refeeding and chemically induced pancreatitis. However, its function in the exocrine pancreas remains unknown. Here, we show that FGF21 stimulates digestive enzyme secretion from pancreatic acinar cells through an autocrine/paracrine mechanism that requires signaling through a tyrosine kinase receptor complex composed of an FGF receptor and β-Klotho. Mice lacking FGF21 accumulate zymogen granules and are susceptible to pancreatic ER stress, an effect that is reversed by administration of recombinant FGF21...
December 27, 2016: Cell Metabolism
https://www.readbyqxmd.com/read/28077438/fibroblast-drug-scavenging-increases-intratumoural-gemcitabine-accumulation-in-murine-pancreas-cancer
#2
E Hessmann, M S Patzak, L Klein, N Chen, V Kari, I Ramu, T E Bapiro, K K Frese, A Gopinathan, F M Richards, D I Jodrell, C Verbeke, X Li, R Heuchel, J M Löhr, S A Johnsen, T M Gress, V Ellenrieder, A Neesse
OBJECTIVE: Desmoplasia and hypovascularity are thought to impede drug delivery in pancreatic ductal adenocarcinoma (PDAC). However, stromal depletion approaches have failed to show clinical responses in patients. Here, we aimed to revisit the role of the tumour microenvironment as a physical barrier for gemcitabine delivery. DESIGN: Gemcitabine metabolites were analysed in LSL-Kras(G12D/+); LSL-Trp53(R172H/+); Pdx-1-Cre (KPC) murine tumours and matched liver metastases, primary tumour cell lines, cancer-associated fibroblasts (CAFs) and pancreatic stellate cells (PSCs) by liquid chromatography-mass spectrometry/mass spectrometry...
January 10, 2017: Gut
https://www.readbyqxmd.com/read/28067930/esr-study-of-atomic-hydrogen-and-tritium-in-solid-t2-and-t2-h2-matrices-below-1-k
#3
S Sheludiakov, J Ahokas, J Järvinen, L Lehtonen, O Vainio, S Vasiliev, D M Lee, V V Khmelenko
We report on the first ESR study of atomic hydrogen and tritium stabilized in solid T2 and T2:H2 matrices down to 70 mK. The concentrations of T atoms in pure T2 approached 2 × 10(20) cm(-3) (0.60%) and record-high concentrations of H atoms ∼1 × 10(20) cm(-3) (0.33%) were reached in T2:H2 solid mixtures where a fraction of T atoms became converted into H due to the isotopic exchange reaction T + H2 → TH + H. The maximum concentrations of unpaired T and H atoms were limited by their recombination which becomes enhanced by efficient atomic diffusion due to the presence of a large number of vacancies and phonons generated in the matrices by β-particles...
January 9, 2017: Physical Chemistry Chemical Physics: PCCP
https://www.readbyqxmd.com/read/28066506/reduced-voltage-losses-yield-10-efficient-fullerene-free-organic-solar-cells-with-1-v-open-circuit-voltages
#4
D Baran, T Kirchartz, S Wheeler, S Dimitrov, M Abdelsamie, J Gorman, R S Ashraf, S Holliday, A Wadsworth, N Gasparini, P Kaienburg, H Yan, A Amassian, C J Brabec, J R Durrant, I McCulloch
Optimization of the energy levels at the donor-acceptor interface of organic solar cells has driven their efficiencies to above 10%. However, further improvements towards efficiencies comparable with inorganic solar cells remain challenging because of high recombination losses, which empirically limit the open-circuit voltage (Voc) to typically less than 1 V. Here we show that this empirical limit can be overcome using non-fullerene acceptors blended with the low band gap polymer PffBT4T-2DT leading to efficiencies approaching 10% (9...
December 1, 2016: Energy & Environmental Science
https://www.readbyqxmd.com/read/28049106/linking-uterine-serous-carcinoma-to-brca1-2-associated-cancer-syndrome-a-meta-analysis-and-case-report
#5
REVIEW
M M de Jonge, A L Mooyaart, M P G Vreeswijk, C D de Kroon, T van Wezel, C J van Asperen, V T H B M Smit, O M Dekkers, T Bosse
BACKGROUND: Uterine serous carcinoma (USC) shows greater morphological, clinical and molecular similarities to high-grade ovarian tubal serous carcinoma than to other types of endometrial cancer. As high-grade ovarian tubal serous carcinoma is known to be associated with BRCA1/2 pathogenic germline mutations (PMs), we aimed to explore whether USC is also a constituent of hereditary breast and ovarian cancer syndrome. METHODS: Pubmed, EMBASE and Web of Science were searched in July 2016 for articles assessing the association between USC and germline BRCA1/2-PMs...
December 31, 2016: European Journal of Cancer
https://www.readbyqxmd.com/read/27995306/t-cell-receptor-gene-recombinations-in-human-tumor-specimen-exome-files-detection-of-t-cell-receptor-%C3%AE-vdj-recombinations-associates-with-a-favorable-oncologic-outcome-for-bladder-cancer
#6
Mohammad D Samy, Wei Lue Tong, John M Yavorski, Wade J Sexton, George Blanck
Understanding tumor-resident T cells is important for cancer prognosis and treatment options. Conventional, solid tumor specimen exome files can be searched directly for recombined T cell receptor (TcR)-α segments; RNASeq files can include TcR-β VDJ recombinations. To learn whether there are medically relevant uses of exome-based detection of TcR V(D)J recombinations in the tumor microenvironment, we searched cancer genome atlas and Moffitt Cancer Center, tumor specimen exome files for TcR-β, TcR-γ, and TcR-δ recombinations, for bladder and stomach cancer...
December 19, 2016: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/27979968/rag-recombinase-as-a-selective-pressure-for-genome-evolution
#7
D Passagem-Santos, M Bonnet, D Sobral, I Trancoso, J G Silva, V M Barreto, A Athanasiadis, J Demengeot, J B Pereira-Leal
The RAG recombinase is a domesticated transposable element co-opted in jawed vertebrates to drive the process of the so-called V(D)J recombination, which is the hallmark of the adaptive immune system to produce antigen receptors. RAG targets, namely, the Recombination Signal Sequences (RSS), are rather long and degenerated sequences, which highlights the ability of the recombinase to interact with a wide range of target sequences, including outside of antigen receptor loci. The recognition of such cryptic targets by the recombinase threatens genome integrity by promoting aberrant DNA recombination, as observed in lymphoid malignancies...
December 14, 2016: Genome Biology and Evolution
https://www.readbyqxmd.com/read/27973733/new-insights-into-the-evolutionary-origins-of-the-rag-proteins-and-v-d-j-recombination
#8
REVIEW
Lina Marcela Carmona, David G Schatz
The adaptive immune system of jawed vertebrates relies on V(D)J recombination as one of the main processes to generate the diverse array of receptors necessary for the recognition of a wide range of pathogens. The DNA cleavage reaction necessary for the assembly of the antigen receptor genes from an array of potential gene segments is mediated by the Recombination Activating Gene proteins RAG1 and RAG2. The RAG proteins have been proposed to originate from a transposable element (TE) as they share mechanistic and structural similarities with several families of transposases and are themselves capable of mediating transposition...
December 14, 2016: FEBS Journal
https://www.readbyqxmd.com/read/27965356/structure-of-nanodisc-reconstituted-vacuolar-atpase-proton-channel-definition-of-the-interaction-of-rotor-and-stator-and-implications-for-enzyme-regulation-by-reversible-dissociation
#9
Nicholas J Stam, Stephan Wilkens
Eukaryotic vacuolar H+-ATPase (V-ATPase) is a multi-subunit enzyme complex that acidifies subcellular organelles and the extracellular space. V-ATPase consists of soluble V1-ATPase and membrane-integral Vo proton-channel sectors. To investigate the mechanism of V-ATPase regulation by reversible disassembly, we recently determined a cryo electron microscopy (EM) reconstruction of yeast Vo. The structure indicated that when V1 is released from Vo, the N-terminal cytoplasmic domain of subunit a (aNT) changes conformation to bind rotor subunit d...
December 13, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27940462/molecular-variability-and-genetic-relationship-among-brazilian-strains-of-the-sugarcane-smut-fungus
#10
Juliana Benevenuto, Daniel P Longatto, Gislaine V Reis, Natalia Mielnichuk, Alessandra C Palhares, Giselle Carvalho, Suzane Saito, Maria C Quecine, Alvaro Sanguino, Maria Lucia C Vieira, Luis Eduardo A Camargo, Silvana Creste, Claudia B Monteiro-Vitorello
Sporisorium scitamineum is the fungus that causes sugarcane smut disease. Despite of the importance of sugarcane for Brazilian agribusiness and the persistence of the pathogen in most cropping areas, genetic variation studies are still missing for Brazilian isolates. In this study, sets of isolates were analyzed using two molecular markers (AFLP and telRFLP) and ITS sequencing. Twenty-two whips were collected from symptomatic plants in cultivated sugarcane fields of Brazil. A total of 41 haploid strains of compatible mating types were selected from individual teliospores and used for molecular genetic analyses...
December 2016: FEMS Microbiology Letters
https://www.readbyqxmd.com/read/27924291/data-on-isoaspartylation-of-neuronal-elavl-proteins
#11
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
#12
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
#13
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
#14
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
#15
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
#16
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
#17
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
#18
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
#19
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
#20
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
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