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https://www.readbyqxmd.com/read/28086979/b-cell-repertoires-in-hla-sensitized-kidney-transplant-candidates-undergoing-desensitization-therapy
#1
John F Beausang, H Christina Fan, Rene Sit, Maria U Hutchins, Kshama Jirage, Rachael Curtis, Edward Hutchins, Stephen R Quake, Julie M Yabu
BACKGROUND: Kidney transplantation is the most effective treatment for end-stage renal disease. Sensitization refers to pre-existing antibodies against human leukocyte antigen (HLA) protein and remains a major barrier to successful transplantation. Despite implementation of desensitization strategies, many candidates fail to respond. Our objective was to determine whether measuring B cell repertoires could differentiate candidates that respond to desensitization therapy. METHODS: We developed an assay based on high-throughput DNA sequencing of the variable domain of the heavy chain of immunoglobulin genes to measure changes in B cell repertoires in 19 highly HLA-sensitized kidney transplant candidates undergoing desensitization and 7 controls with low to moderate HLA sensitization levels...
January 13, 2017: Journal of Translational Medicine
https://www.readbyqxmd.com/read/28081268/the-rice-dynamin-related-protein-osdrp1e-negatively-regulates-programmed-cell-death-by-controlling-the-release-of-cytochrome-c-from-mitochondria
#2
Zhiqiang Li, Bo Ding, Xueping Zhou, Guo-Liang Wang
Programmed cell death (PCD) mediated by mitochondrial processes has emerged as an important mechanism for plant development and responses to abiotic and biotic stress. However, the role of translocation of cytochrome c from the mitochondria to the cytosol during PCD remains unclear. Here, we demonstrate that the rice dynamin-related protein 1E (OsDRP1E) negatively regulates PCD by controlling mitochondrial structure and cytochrome c release. We used a map-based cloning strategy to isolate OsDRP1E from the lesion mimic mutant dj-lm and confirmed that the E409V mutation in OsDRP1E causes spontaneous cell death in rice...
January 12, 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28077674/population-structure-of-japanese-extraintestinal-pathogenic-escherichia-coli-and-its-relationship-with-antimicrobial-resistance
#3
Yasufumi Matsumura, Taro Noguchi, Michio Tanaka, Toru Kanahashi, Masaki Yamamoto, Miki Nagao, Shunji Takakura, Satoshi Ichiyama
OBJECTIVES: To define the population structure of extraintestinal pathogenic Escherichia coli (ExPEC) in Japan and its relationship with antimicrobial resistance and the major resistance mechanisms for fluoroquinolones and β-lactams, we designed a multicentre prospective study. METHODS: A total of 329 ExPEC isolates were collected at 10 Japanese acute-care hospitals during December 2014. We defined the clonal groups of ExPEC by fumC and fimH sequencing (CH typing)...
January 10, 2017: Journal of Antimicrobial Chemotherapy
https://www.readbyqxmd.com/read/28077637/role-of-litopenaeus-vannamei-yin-yang-1-in-the-regulation-of-the-white-spot-syndrome-virus-immediate-early-gene-ie1
#4
Ping-Han Huang, Ting-Yi Huang, Pei-Si Cai, Li-Kwan Chang
: Yin Yang 1 (YY1) is a multifunctional zinc-finger transcription factor that regulates many key cellular processes. In this study, we report the cloning of YY1 from shrimp, Litopenaeus vannamei, (LvYY1). The study shows that LvYY1 is ubiquitously expressed in shrimp tissues, and knockdown of LvYY1 expression by dsRNA injection in WSSV-infected shrimp reduced both mRNA levels of the WSSV immediate-early gene, ie1, as well as overall copy numbers of the WSSV genome. The cumulative mortality of infected shrimp also declined with LvYY1 dsRNA injection...
January 11, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28076841/clonal-evolution-in-therapy-related-neoplasms
#5
Emiliano Fabiani, Giulia Falconi, Luana Fianchi, Marianna Criscuolo, Tiziana Ottone, Laura Cicconi, Stefan Hohaus, Simona Sica, Massimiliano Postorino, Antonino Neri, Marta Lionetti, Giuseppe Leone, Francesco Lo-Coco, Maria Teresa Voso
Therapy-related myeloid neoplasms (t-MN) may occur as a late effect of cytotoxic therapy for a primary malignancy or autoimmune diseases in susceptible individuals. We studied the development of somatic mutations in t-MN, using a collection of follow-up samples from 14 patients with a primary hematologic malignancy, who developed a secondary leukemia (13 t-MN and 1 t-acute lymphoblastic leukemia), at a median latency of 73 months (range 18-108) from primary cancer diagnosis.Using Sanger and next generation sequencing (NGS) approaches we identified 8 mutations (IDH1 R132H, ASXL1 Y591*, ASXL1 S689*, ASXL1 R693*, SRSF2 P95H, SF3B1 K700E, SETBP1 G870R and TP53 Y220C) in seven of thirteen t-MN patients (54%), whereas the t-ALL patient had a t(4,11) translocation, resulting in the KMT2A/AFF1 fusion gene...
January 5, 2017: Oncotarget
https://www.readbyqxmd.com/read/28071872/mutant-botrocetin-2-inhibits-von-willebrand-factor-induced-platelet-agglutination
#6
T Matsui, A Hori, J Hamako, F Matsushita, Y Ozeki, Y Sakurai, M Hayakawa, M Matsumoto, Y Fujimura
BACKGROUND: Botrocetin-2 (Bot2) is a botrocetin-like protein composed of α and β subunits that have been cloned from the snake Bothrops jararaca. Bot2 binds specifically to von Willebrand factor (VWF), and the complex induces glycoprotein (GP) Ib-dependent platelet agglutination. OBJECTIVES: We exploited Bot2's VWF-binding capacity to try and create a mutant Bot2 that binds to VWF but inhibits platelet agglutination. METHODS AND RESULTS: Several point mutations were introduced into Bot2 cDNA, and the recombinant protein (rBot2) was purified on an anti-botrocetin column...
January 10, 2017: Journal of Thrombosis and Haemostasis: JTH
https://www.readbyqxmd.com/read/28069647/ribosomal-mutations-conferring-macrolide-resistance-in-legionella-pneumophila
#7
Ghislaine Descours, Christophe Ginevra, Nathalie Jacotin, Françoise Forey, Joëlle Chastang, Elisabeth Kay, Jerome Etienne, Gérard Lina, Patricia Doublet, Sophie Jarraud
OBJECTIVES: Monitoring the emergence of antibiotic resistance is a recent issue in the treatment of Legionnaires' disease. Macrolides are recommended as first-line therapy but resistance mechanisms have not been studied in Legionella species. Our aim was to determine the molecular basis of macrolide resistance in L. pneumophila METHODS: Twelve independent lineages were propagated under erythromycin or azithromycin pressure towards a high-level macrolide resistance from a common susceptible L...
January 9, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28068559/the-ageing-genome-clonal-mosaicism-and-chronic-disease
#8
REVIEW
Mitchell J Machiela, Stephen J Chanock
Clonal mosaicism arises when a postzygotic mutational event is detectable in subpopulations of cells as an alternative genotype while not present in the germline genome. Although described in a subset of pediatric disorders, new genomic technologies have detected higher than anticipated frequencies of clonal mosaicism in adult population studies, stimulating investigation as to how clonal mosaicism could contribute to chronic human diseases, such as cancer, diabetes and neurodegenerative disorders. It has also been postulated to be an important mechanism for functional cellular diversity, including the brain...
January 6, 2017: Current Opinion in Genetics & Development
https://www.readbyqxmd.com/read/28064410/detecting-n-ras-q61r-mutated-thyroid-neoplasias-by-immunohistochemistry
#9
A Crescenzi, F Fulciniti, M Bongiovanni, L Giovanella, Pierpaolo Trimboli
Recently, the immunohistochemistry (IHC) for N-RAS Q61R has been developed and commercialized for clinical practice. Here, we investigated the reliability of IHC to identify N-RAS Q61R mutated thyroid neoplasia. A series of 24 consecutive thyroid lesions undergone surgery following indeterminate cytology were enrolled. Paraffin sections were stained for IHC using the rabbit monoclonal anti-human N-RAS Q61R, clone SP174. N-RAS mutations in codon 61 were also investigated by automated sequencing. At histology, 12 cases of follicular carcinoma, cytologically defined as follicular lesions, 1 papillary cancer, 7 follicular adenomas, and 4 hyperplastic nodules were found...
January 7, 2017: Endocrine Pathology
https://www.readbyqxmd.com/read/28061810/pyviko-an-automated-python-tool-to-design-gene-knockouts-in-complex-viruses-with-overlapping-genes
#10
Louis J Taylor, Klaus Strebel
BACKGROUND: Gene knockouts are a common tool used to study gene function in various organisms. However, designing gene knockouts is complicated in viruses, which frequently contain sequences that code for multiple overlapping genes. Designing mutants that can be traced by the creation of new or elimination of existing restriction sites further compounds the difficulty in experimental design of knockouts of overlapping genes. While software is available to rapidly identify restriction sites in a given nucleotide sequence, no existing software addresses experimental design of mutations involving multiple overlapping amino acid sequences in generating gene knockouts...
January 7, 2017: BMC Microbiology
https://www.readbyqxmd.com/read/28060828/enhancement-of-microbial-biodesulfurization-via-genetic-engineering-and-adaptive-evolution
#11
Jia Wang, Robert R Butler, Fan Wu, Jean-François Pombert, John J Kilbane, Benjamin C Stark
In previous work from our laboratories a synthetic gene encoding a peptide ("Sulpeptide 1" or "S1") with a high proportion of methionine and cysteine residues had been designed to act as a sulfur sink and was inserted into the dsz (desulfurization) operon of Rhodococcus erythropolis IGTS8. In the work described here this construct (dszAS1BC) and the intact dsz operon (dszABC) cloned into vector pRESX under control of the (Rhodococcus) kstD promoter were transformed into the desulfurization-negative strain CW25 of Rhodococcus qingshengii...
2017: PloS One
https://www.readbyqxmd.com/read/28054745/the-discovery-of-alzheimer-causing-mutations-in-the-app-gene-and-the-formulation-of-the-amyloid-cascade-hypothesis
#12
REVIEW
John Hardy
The cloning of APP and genetic analysis of families with Alzheimer's disease were both reported in 1987 and much present work on the disease is based upon the foundations laid at that time. Progress was not smooth however, and many errors were made. In this memoir, I lay out both the progress and the errors. This article is protected by copyright. All rights reserved.
January 5, 2017: FEBS Journal
https://www.readbyqxmd.com/read/28054163/genetic-variation-and-population-structure-of-cucumber-green-mottle-mosaic-virus
#13
Li-Xia Rao, Yushuang Guo, Li-Li Zhang, Xue-Ping Zhou, Jian Hong, Jian-Xiang Wu
Cucumber green mottle mosaic virus (CGMMV) is a single-stranded, positive sense RNA virus infecting cucurbitaceous plants. In recent years, CGMMV has become an important pathogen of cucurbitaceous crops including watermelon, pumpkin, cucumber and bottle gourd in China, causing serious losses to their production. In this study, we surveyed CGMMV infection in various cucurbitaceous crops grown in Zhejiang Province and in several seed lots purchased from local stores with the dot enzyme-linked immunosorbent assay (dot-ELISA), using a CGMMV specific monoclonal antibody...
January 4, 2017: Archives of Virology
https://www.readbyqxmd.com/read/28049516/genetic-clustering-and-polymorphism-of-the-merozoite-surface-protein-3-of-plasmodium-knowlesi-clinical-isolates-from-peninsular-malaysia
#14
Jeremy Ryan De Silva, Yee Ling Lau, Mun Yik Fong
BACKGROUND: The simian malaria parasite Plasmodium knowlesi has been reported to cause significant numbers of human infection in South East Asia. Its merozoite surface protein-3 (MSP3) is a protein that belongs to a multi-gene family of proteins first found in Plasmodium falciparum. Several studies have evaluated the potential of P. falciparum MSP3 as a potential vaccine candidate. However, to date no detailed studies have been carried out on P. knowlesi MSP3 gene (pkmsp3). The present study investigates the genetic diversity, and haplotypes groups of pkmsp3 in P...
January 3, 2017: Parasites & Vectors
https://www.readbyqxmd.com/read/28045487/probing-the-allosteric-role-of-the-%C3%AE-5-subunit-of-%C3%AE-3%C3%AE-4%C3%AE-5-nicotinic-acetylcholine-receptors-by-functionally-selective-modulators-and-ligands
#15
Caroline Ray, Erik J Soderblom, Yushi Bai, F Ivy Carroll, Marc G Caron, Larry S Barak
Nicotinic acetylcholine receptors regulate the nicotine dependence encountered with cigarette smoking, and this has stimulated a search for drugs binding the responsible receptor subtypes. Studies link a gene cluster encoding for α3β4α5-D398N nicotinic acetylcholine receptors to lung cancer risk as well as link a second mutation in this cluster to an increased risk for nicotine dependence. However, there are currently no recognized drugs for discriminating α3β4α5 signaling. In this study we describe the development of homogenous HEK-293 cell clones of α3β4 and α3β4α5 receptors appropriate for drug screening and characterizing biochemical and pharmacological properties of incorporated α5 subunits...
January 3, 2017: ACS Chemical Biology
https://www.readbyqxmd.com/read/28044225/simple-mssm-a-simple-and-efficient-method-for-simultaneous-multi-site-saturation-mutagenesis
#16
Feng Cheng, Jian-Miao Xu, Chao Xiang, Zhi-Qiang Liu, Li-Qing Zhao, Yu-Guo Zheng
OBJECTIVE: To develop a practically simple and robust multi-site saturation mutagenesis (MSSM) method that enables simultaneously recombination of amino acid positions for focused mutant library generation. RESULTS: A general restriction enzyme-free and ligase-free MSSM method (Simple-MSSM) based on prolonged overlap extension PCR (POE-PCR) and Simple Cloning techniques. As a proof of principle of Simple-MSSM, the gene of eGFP (enhanced green fluorescent protein) was used as a template gene for simultaneous mutagenesis of five codons...
January 2, 2017: Biotechnology Letters
https://www.readbyqxmd.com/read/28043510/effects-of-sorbitol-and-glycerol-on-the-structure-dynamics-and-stability-of-mycobacterium-tuberculosis-pyrazinamidase
#17
Mehrnoosh Khajehzadeh, Faramarz Mehrnejad, Mohammad Pazhang, Farahnoosh Doustdar
OBJECTIVE/BACKGROUND: Mycobacterium tuberculosis pyrazinamidase (PZase) is known an enzyme that is involved in degradation of pyrazinamide to ammonia and pyrazinoic acid. Pyrazinamide is an important first-line drug used in the short-course treatment of tuberculosis. Previous investigations have indicated that the pyrazinamide (PZA)-resistant M. tuberculosis strains are caused by point mutations in the PZase enzyme which is the activator of the prodrug PZA. Although the general fold of PZase was determined, the structural and functional properties of the enzyme in solution were not understood very well...
December 2016: International Journal of Mycobacteriology
https://www.readbyqxmd.com/read/28042089/paf53-is-essential-in-mammalian-cells-crispr-cas9-fails-to-eliminate-paf53-expression
#18
Lawrence I Rothblum, Katrina Rothblum, Eugenie Chang
When mammalian cells are nutrient and/or growth factor deprived, exposed to inhibitors of protein synthesis, stressed by heat shock or grown to confluence, rDNA transcription is essentially shut off. Various mechanisms are available to accomplish this downshift in ribosome biogenesis. Muramatsu's laboratory (Hanada et al., 1996) first demonstrated that mammalian PAF53 was essential for specific rDNA transcription and that PAF53 levels were regulated in response to growth factors. While S. cerevisae A49, the homologue of vertebrate PAF53, is not essential for viability (Liljelund et al...
December 29, 2016: Gene
https://www.readbyqxmd.com/read/28041846/change-in-ighv-mutational-status-of-cll-suggests-origin-from-multiple-clones
#19
Afaf Osman, Christopher D Gocke, Douglas E Gladstone
BACKGROUND: Fluorescence in situ hybridization and immunoglobulin (Ig) heavy-chain variable-region (IgHV) mutational status are used to predict outcome in chronic lymphocytic leukemia (CLL). Although DNA aberrations change over time, IgHV sequences and mutational status are considered stable. PATIENTS AND METHODS: In a retrospective review, 409 CLL patients, between 2008 and 2015, had IgHV analysis: 56 patients had multiple analyses performed. Seven patients' IgHV results changed: 2 from unmutated to mutated and 5 from mutated to unmutated IgHV sequence...
November 21, 2016: Clinical Lymphoma, Myeloma & Leukemia
https://www.readbyqxmd.com/read/28038927/cellular-immune-response-to-%C3%AE-2-glycoprotein-i-valine-leucine-247-phenotypes-in-mexican-patients-with-primary-antiphospholipid-syndrome
#20
Carlos A Núñez-Álvarez, Diego F Hernández-Ramírez, Araceli Martinez-Castillo, Virginia Pascual Ramos, Javier Cabiedes, Alicia Ortega, Antonio R Cabral
: Homozygote genotype V(247) of the β2-glycoprotein-I (β2GP-I) gene has been associated with anti-β2GP-I and thrombosis in patients with primary anti-phospholipid syndrome APS (PAPS). However, the cellular immune response to β2GP-I(247) has been little studied. OBJECTIVE: To evaluate the immune cellular proliferation in response to native and non-native β2GP-I(247) valine/leucine phenotype from Mexican patients with PAPS. METHODS: We studied 10 patients with PAPS and 10 healthy control subjects (HC)...
December 27, 2016: Human Immunology
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