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V(d)J recombination

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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
#1
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
#2
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
#3
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
#4
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
#5
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
#6
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
#7
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...
September 21, 2017: 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
#8
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...
September 6, 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
#9
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
#10
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
https://www.readbyqxmd.com/read/28857066/hypoparathyroidism
#11
REVIEW
Michael Mannstadt, John P Bilezikian, Rajesh V Thakker, Fadil M Hannan, Bart L Clarke, Lars Rejnmark, Deborah M Mitchell, Tamara J Vokes, Karen K Winer, Dolores M Shoback
Hypoparathyroidism is a disease characterized by inadequately low circulating concentrations of parathyroid hormone (PTH) resulting in low calcium levels and increased phosphate levels in the blood. Symptoms of the disease result from increased neuromuscular irritability caused by hypocalcaemia and include tingling, muscle cramps and seizures. The most common cause of the disease is inadvertent removal of, or injury to, the parathyroid glands during neck surgery, followed by genetic, idiopathic and autoimmune aetiologies...
August 31, 2017: Nature Reviews. Disease Primers
https://www.readbyqxmd.com/read/28852710/vapour-deposited-cesium-lead-iodide-perovskites-microsecond-charge-carrier-lifetimes-and-enhanced-photovoltaic-performance
#12
Eline M Hutter, Rebecca J Sutton, Sanjana Chandrashekar, Mojtaba Abdi-Jalebi, Samuel D Stranks, Henry J Snaith, Tom J Savenije
Metal halide perovskites such as methylammonium lead iodide (MAPbI3) are highly promising materials for photovoltaics. However, the relationship between the organic nature of the cation and the optoelectronic quality remains debated. In this work, we investigate the optoelectronic properties of fully inorganic vapour-deposited and spin-coated black-phase CsPbI3 thin films. Using the time-resolved microwave conductivity technique, we measure charge carrier mobilities up to 25 cm(2)/(V s) and impressively long charge carrier lifetimes exceeding 10 μs for vapour-deposited CsPbI3, while the carrier lifetime reaches less than 0...
August 11, 2017: ACS Energy Letters
https://www.readbyqxmd.com/read/28846869/xlf-cernunnos-an-important-but-puzzling-participant-in-the-nonhomologous-end-joining-dna-repair-pathway
#13
REVIEW
Vijay Menon, Lawrence F Povirk
DNA double strand breaks (DSBs) are one of the most deleterious DNA lesions that promote cell death, genomic instability and carcinogenesis. The two major cellular mechanisms that repair DSBs are Nonhomologous End-Joining (NHEJ) and Homologous Recombination Repair (HRR). NHEJ is the predominant pathway, in which XLF (also called Cernunnos) is a key player. Patients with XLF mutation exhibit microcephaly, lymphopenia, and growth retardation, and are immunodeficient and radiosensitive. During NHEJ, XLF interacts with XRCC4-Ligase IV, stimulates its ligase activity, and forms DNA-binding filaments of alternating XLF and XRCC4 dimers that may serve to align broken DNA and promote ligation of noncomplementary ends...
October 2017: DNA Repair
https://www.readbyqxmd.com/read/28834265/association-of-varroa-destructor-females-in-multiply-infested-cells-of-the-honey-bee-apis-mellifera
#14
Alexis L Beaurepaire, James D Ellis, Klemens J Krieger, Robin F A Moritz
The genetic diversity of Varroa destructor (Anderson and Trueman) is limited outside its natural range due to population bottlenecks and its propensity to inbreed. In light of the arms race between V. destructor and its honey bee (Apis mellifera L.) host, any mechanism enhancing population admixture of the mite may be favored. One way that admixture can occur is when two genetically dissimilar mites co-invade a brood cell, with the progeny of the foundresses admixing. We determined the relatedness of 393 pairs of V...
August 22, 2017: Insect Science
https://www.readbyqxmd.com/read/28833808/pharmacokinetics-safety-and-efficacy-of-a-recombinant-factor-ix-product-trenonacog-alfa-in-previously-treated-haemophilia-b-patients
#15
P W Collins, D V K Quon, M Makris, P Chowdary, C L Kempton, S J Apte, M V Ramanan, C R M Hay, B Drobic, Y Hua, T J Babinchak, E D Gomperts
INTRODUCTION: Trenonacog alfa (IB1001) is a recombinant factor IX (rFIX) manufactured in Chinese hamster ovary (CHO) cells. IB1001 was evaluated in a multicentre clinical trial with haemophilia B patients. AIM: The aim was to establish IB1001 pharmacokinetic non-inferiority to comparator rFIX, safety and efficacy in previously treated patients (PTPs) with haemophilia B. METHODS: Subjects were severe or moderately severe haemophilia B adult and adolescent PTPs with no history of FIX inhibitors...
August 17, 2017: Haemophilia: the Official Journal of the World Federation of Hemophilia
https://www.readbyqxmd.com/read/28821745/metabolomics-and-genomics-combine-to-unravel-the-pathway-for-the-presence-of-fragrance-in-rice
#16
Venea Dara Daygon, Mariafe Calingacion, Louise C Forster, James J De Voss, Brett D Schwartz, Ben Ovenden, David E Alonso, Susan R McCouch, Mary J Garson, Melissa A Fitzgerald
Since it was first characterised in 1983, 2-acetyl-1-pyrroline (2AP) has been considered to be the most important aroma compound in rice. In this study, we show four other amine heterocycles: 6-methyl, 5-oxo-2,3,4,5-tetrahydropyridine (6M5OTP), 2-acetylpyrrole, pyrrole and 1-pyrroline, that correlate strongly with the production of 2AP, and are present in consistent proportions in a set of elite aromatic rice varieties from South East Asia and Australia as well as in a collection of recombinant inbred lines (RILs) derived from indica Jasmine-type varieties, Australian long grain varieties (temperate japonica) and Basmati-type rice (Grp V)...
August 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28794174/maternal-western-diet-age-specifically-alters-female-offspring-voluntary-physical-activity-and-dopamine-and-leptin-related-gene-expression
#17
Gregory N Ruegsegger, Kolter B Grigsby, Taylor J Kelty, Terese M Zidon, Thomas E Childs, Victoria J Vieira-Potter, David L Klinkebiel, Michael Matheny, Phillip J Scarpace, Frank W Booth
Prenatal overnutrition affects development into adulthood and influences risk of obesity. We assessed the transgenerational effect of maternal Western diet (WD) consumption on offspring physical activity. Voluntary wheel running was increased in juvenile (4-7 wk of age), but decreased in adult (16-19 wk of age), F1 female WD offspring In contrast, no wheel-running differences in F1 male offspring were observed. Increased wheel running in juvenile female WD offspring was associated with up-regulated dopamine receptor (DRD)-1 and -2 in the nucleus accumbens (NAc) and with down-regulated Lepr in the ventral tegmental area (VTA)...
August 9, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28783691/characterization-of-t-and-b-cell-repertoire-diversity-in-patients-with-rag-deficiency
#18
Yu Nee Lee, Francesco Frugoni, Kerry Dobbs, Irit Tirosh, Likun Du, Francesca A Ververs, Heng Ru, Lisa Ott de Bruin, Mehdi Adeli, Jacob H Bleesing, David Buchbinder, Manish J Butte, Caterina Cancrini, Karin Chen, Sharon Choo, Reem A Elfeky, Andrea Finocchi, Ramsay L Fuleihan, Andrew R Gennery, Dalia H El-Ghoneimy, Lauren A Henderson, Waleed Al-Herz, Elham Hossny, Robert P Nelson, Sung-Yun Pai, Niraj C Patel, Shereen M Reda, Pere Soler-Palacin, Raz Somech, Paolo Palma, Hao Wu, Silvia Giliani, Jolan E Walter, Luigi D Notarangelo
Recombination-activating genes 1 and 2 (RAG1 and RAG2) play a critical role in T and B cell development by initiating the recombination process that controls the expression of T cell receptor (TCR) and immunoglobulin genes. Mutations in the RAG1 and RAG2 genes in humans cause a broad spectrum of phenotypes, including severe combined immunodeficiency (SCID) with lack of T and B cells, Omenn syndrome, leaky SCID, and combined immunodeficiency with granulomas or autoimmunity (CID-G/AI). Using next-generation sequencing, we analyzed the TCR and B cell receptor (BCR) repertoire in 12 patients with RAG mutations presenting with Omenn syndrome (n = 5), leaky SCID (n = 3), or CID-G/AI (n = 4)...
December 16, 2016: Science Immunology
https://www.readbyqxmd.com/read/28776894/persept-1-a-phase-3-trial-of-activated-eptacog-beta-for-on-demand-treatment-of-haemophilia-inhibitor-related-bleeding
#19
M Wang, J B Lawrence, D V Quon, J Ducore, M L Simpson, L N Boggio, I S Mitchell, G Yuan, W A Alexander, J-F Schved
INTRODUCTION: Haemophilia A or B patients with inhibitors have been treated with FVIIa-containing bypassing agents for over 20 years. However, due to uncertainty regarding dose response and thrombotic risk, the use of a gradual, titrated, minimal dosing strategy remains prevalent, potentially hampering early haemostasis. AIM: Evaluate the dose-dependent efficacy, safety and immunogenicity of activated eptacog beta (rhFVIIa), a new recombinant inhibitor bypassing agent for the treatment of bleeding episodes (BEs)...
August 3, 2017: Haemophilia: the Official Journal of the World Federation of Hemophilia
https://www.readbyqxmd.com/read/28750002/dna-pkcs-controls-calcineurin-mediated-il-2-production-in-t-lymphocytes
#20
Ara Kim Wiese, Marie Schluterman Burdine, Richard H Turnage, Alan J Tackett, Lyle J Burdine
Loss of DNA-dependent protein kinase catalytic subunit (DNA-PKcs) activity in mammals results in severe combined immuno-deficiency (SCID). This SCID phenotype has been postulated to be due solely to the function of DNA-PKcs in V(D)J recombination, a process critical for lymphocyte maturation. However; we show that DNA-PKcs is required for IL-2 production via regulation of the calcineurin signaling pathway. Reducing DNA-PKcs activity in activated T cells either by shRNA or an inhibitor significantly reduced IL-2 production by blocking calcineurin activity and the translocation of NFAT into the nucleus...
2017: PloS One
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