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https://www.readbyqxmd.com/read/28547769/evaluation-of-piggybac-mediated-cho-pools-to-enable-material-generation-to-support-glp-toxicology-studies
#1
Yashas Rajendra, Sowmya Balasubramanian, Neil A McCracken, Dawn L Norris, Zhirui Lian, Matthew G Schmitt, Christopher C Frye, Gavin C Barnard
Generating purified protein for GLP toxicology studies (GLP-Tox) represents an important and often rate limiting step in the biopharmaceutical drug development process. Toxicity testing requires large amounts of therapeutic protein (>100g), typically produced in a single 500L - 2,500L bioreactor, using the final CHO clonally-derived cell line (CDCL). One approach currently used to save time is to manufacture GLP-Tox material using pools of high-producing CHO CDCLs instead of waiting for the final CDCL. Recently, we reported CHO pools producing mAb titers >7 g/L using piggyBac-mediated gene integration (PB CHO pools)...
May 25, 2017: Biotechnology Progress
https://www.readbyqxmd.com/read/28489605/genetic-rearrangements-result-in-altered-gene-expression-and-novel-fusion-transcripts-in-s%C3%A3-zary-syndrome
#2
Katarzyna Iżykowska, Grzegorz K Przybylski, Claudia Gand, Floriane C Braun, Piotr Grabarczyk, Andreas W Kuss, Karolina Olek-Hrab, Armando N Bastidas Torres, Maarten H Vermeer, Willem H Zoutman, Cornelis P Tensen, Christian A Schmidt
Sézary syndrome (SS) is an aggressive, leukemic cutaneous T-cell lymphoma variant. Molecular pathogenesis of SS is still unclear despite many studies on genetic alterations, gene expression and epigenetic regulations. Through whole genome and transcriptome next generation sequencing nine Sézary syndrome patients were analyzed in terms of copy number variations and rearrangements affecting gene expression. Recurrent copy number variations were detected within 8q (MYC, TOX), 17p (TP53, NCOR1), 10q (PTEN, FAS), 2p (DNMT3A), 11q (USP28), 9p (CAAP1), but no recurrent rearrangements were identified...
June 13, 2017: Oncotarget
https://www.readbyqxmd.com/read/28480263/diagnosis-in-france-of-a-non-toxigenic-tox-gene-bearing-strain-of-corynebacterium-diphtheriae-in-a-young-male-back-from-senegal
#3
Typhaine Billard-Pomares, Cécile Rouyer, Violaine Walewski, Edgar Badell-Ocando, Marc Dumas, Coralie Zumelzu, Françoise Jaureguy, Sylvain Brisse, Frédéric Caux, Olivier Bouchaud, Etienne Carbonnelle
Cutaneous diphtheria is uncommon in Europe. In this study, we report a case of imported cutaneous infection due to a non-toxigenic but tox gene-bearing (NTTB) strain of Corynebacterium diphtheriae. The NTTB strains are recognized as emerging pathogens across Europe, and physicians and bacteriologists should be aware of the circulation of these strains.
2017: Open Forum Infectious Diseases
https://www.readbyqxmd.com/read/28464377/bile-salts-and-alkaline-ph-reciprocally-modulate-the-interaction-between-the-periplasmic-domains-of-vibrio-cholerae-toxr-and-toxs
#4
Charles R Midgett, Salvador Almagro-Moreno, Maria Pellegrini, Ronald K Taylor, Karen Skorupski, F Jon Kull
ToxR is a transmembrane transcription factor that is essential for virulence gene expression and human colonization by Vibrio cholerae. ToxR requires its operon partner ToxS, a periplasmic integral membrane protein, for full activity. These two proteins are thought to interact through their respective periplasmic domains, ToxRp and ToxSp. In addition, ToxR is thought to be responsive to various environmental cues, such as bile salts and alkaline pH, but how these factors influence ToxR is not yet understood...
May 2, 2017: Molecular Microbiology
https://www.readbyqxmd.com/read/28441483/discovery-of-a-novel-class-of-survival-motor-neuron-2-splicing-modifiers-for-the-treatment-of-spinal-muscular-atrophy
#5
Emmanuel Pinard, Luke Green, Michael Reutlinger, Marla Weetall, Nikolai A Naryshkin, John Baird, Karen S Chen, Sergey V Paushkin, Friedrich Metzger, Hasane Ratni
Spinal muscular atrophy (SMA) is caused by mutation or deletion of the survival motor neuron 1 (SMN1) gene, resulting in low levels of functional SMN protein. We have reported recently the identification of small molecules (coumarins, iso-coumarins and pyrido-pyrimidinones) that modify the alternative splicing of SMN2, a paralogous gene to SMN1, restoring the survival motor neuron (SMN) protein level in mouse models of SMA. Herein, we report our efforts to identify a novel chemotype as one strategy to potentially circumvent safety concerns from earlier derivatives such as in vitro phototoxicity and in vitro mutagenicity associated with compounds 1 and 2 or the in vivo retinal findings observed in a long-term chronic tox study with 3 at high exposures only...
May 25, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28327672/tox-and-adipoq-gene-polymorphisms-are-associated-with-antipsychotic-induced-weight-gain-in-han-chinese
#6
Shen Li, Chengai Xu, Yuan Tian, Xueshi Wang, Rui Jiang, Miaomiao Zhang, Lili Wang, Guifu Yang, Ying Gao, Chenyu Song, Yukun He, Ying Zhang, Jie Li, Wei-Dong Li
To find the genetic markers related to the antipsychotic-induced weight gain (AIWG), we analyzed associations among candidate gene single-nucleotide polymorphisms (SNPs) and quantitative traits of weight changes and lipid profiles in a Chinese Han population. A total of 339 schizophrenic patients, including 86 first-episode patients (FEPs), meeting the entry criteria were collected. All patients received atypical antipsychotic drug monotherapy and hospitalization and were followed for 12 weeks. Forty-three SNPs in 23 candidate genes were calculated for quantitative genetic association with AIWG, performed by PLINK...
March 22, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28295044/novel-transcriptome-assembly-and-comparative-toxicity-pathway-analysis-in-mahi-mahi-coryphaena-hippurus-embryos-and-larvae-exposed-to-deepwater-horizon-oil
#7
Elvis Genbo Xu, Edward M Mager, Martin Grosell, E Starr Hazard, Gary Hardiman, Daniel Schlenk
The impacts of Deepwater Horizon (DWH) oil on morphology and function during embryonic development have been documented for a number of fish species, including the economically and ecologically important pelagic species, mahi-mahi (Coryphaena hippurus). However, further investigations on molecular events and pathways responsible for developmental toxicity have been largely restricted due to the limited molecular data available for this species. We sought to establish the de novo transcriptomic database from the embryos and larvae of mahi-mahi exposed to water accommodated fractions (HEWAFs) of two DWH oil types (weathered and source oil), in an effort to advance our understanding of the molecular aspects involved during specific toxicity responses...
March 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/27902437/development-validation-and-implementation-of-a-quadruplex-real-time-pcr-assay-for-identification-of-potentially-toxigenic-corynebacteria
#8
Aruni De Zoysa, Androulla Efstratiou, Ginder Mann, Timothy G Harrison, Norman K Fry
Toxigenic corynebacteria are uncommon in the UK; however, laboratory confirmation by the national reference laboratory can inform public health action according to national guidelines. Standard phenotypic tests for identification and toxin expression of isolates can take from ≥24 to ≥48 h from receipt. To decrease the time to result, a real-time PCR (qPCR) assay was developed for confirmation of both identification of Corynebacterium diphtheriae and Corynebacterium ulcerans/Corynebacterium pseudotuberculosis and detection of the diphtheria toxin gene...
December 2016: Journal of Medical Microbiology
https://www.readbyqxmd.com/read/27888230/toxreporter-viewing-the-genome-through-the-eyes-of-a-toxicologist
#9
Mark Gosink
One of the many roles of a toxicologist is to determine if an observed adverse event (AE) is related to a previously unrecognized function of a given gene/protein. Towards that end, he or she will search a variety of public and propriety databases for information linking that protein to the observed AE. However, these databases tend to present all available information about a protein, which can be overwhelming, limiting the ability to find information about the specific toxicity being investigated. ToxReporter compiles information from a broad selection of resources and limits display of the information to user-selected areas of interest...
2016: Database: the Journal of Biological Databases and Curation
https://www.readbyqxmd.com/read/27862604/whole-genome-sequencing-of-cytogenetically-balanced-chromosome-translocations-identifies-potentially-pathological-gene-disruptions-and-highlights-the-importance-of-microhomology-in-the-mechanism-of-formation
#10
Daniel Nilsson, Maria Pettersson, Peter Gustavsson, Alisa Förster, Wolfgang Hofmeister, Josephine Wincent, Vasilios Zachariadis, Britt-Marie Anderlid, Ann Nordgren, Outi Mäkitie, Valtteri Wirta, Max Käller, Francesco Vezzi, James R Lupski, Magnus Nordenskjöld, Elisabeth Syk Lundberg, Claudia M B Carvalho, Anna Lindstrand
Most balanced translocations are thought to result mechanistically from nonhomologous end joining or, in rare cases of recurrent events, by nonallelic homologous recombination. Here, we use low-coverage mate pair whole-genome sequencing to fine map rearrangement breakpoint junctions in both phenotypically normal and affected translocation carriers. In total, 46 junctions from 22 carriers of balanced translocations were characterized. Genes were disrupted in 48% of the breakpoints; recessive genes in four normal carriers and known dominant intellectual disability genes in three affected carriers...
February 2017: Human Mutation
https://www.readbyqxmd.com/read/27773722/prediction-of-pharmacokinetic-and-toxicological-parameters-of-a-4-phenylcoumarin-isolated-from-geopropolis-in-silico-and-in-vitro-approaches
#11
Marcos Guilherme da Cunha, Gilson César Nobre Franco, Marcelo Franchin, John A Beutler, Severino Matias de Alencar, Masaharu Ikegaki, Pedro Luiz Rosalen
In silico and in vitro methodologies have been used as important tools in the drug discovery process, including from natural sources. The aim of this study was to predict pharmacokinetic and toxicity (ADME/Tox) properties of a coumarin isolated from geopropolis using in silico and in vitro approaches. Cinnamoyloxy-mammeisin (CNM) isolated from Brazilian M. scutellaris geopropolis was evaluated for its pharmacokinetic parameters by in silico models (ACD/Percepta™ and MetaDrug™ software). Genotoxicity was assessed by in vitro DNA damage signaling PCR array...
November 30, 2016: Toxicology Letters
https://www.readbyqxmd.com/read/27766406/cd164-identifies-cd4-t-cells-highly-expressing-genes-associated-with-malignancy-in-s%C3%A3-zary-syndrome-the-s%C3%A3-zary-signature-genes-fcrl3-tox-and-mir-214
#12
Bernice M Benoit, Neha Jariwala, Geraldine O'Connor, Landon K Oetjen, Timothy M Whelan, Adrienne Werth, Andrea B Troxel, Hélène Sicard, Lisa Zhu, Christopher Miller, Junko Takeshita, Daniel W McVicar, Brian S Kim, Alain H Rook, Maria Wysocka
Sézary syndrome (SS), a leukemic variant of cutaneous T-cell lymphoma (CTCL), is associated with a significantly shorter life expectancy compared to skin-restricted mycosis fungoides. Early diagnosis of SS is, therefore, key to achieving enhanced therapeutic responses. However, the lack of a biomarker(s) highly specific for malignant CD4(+) T cells in SS patients has been a serious obstacle in making an early diagnosis. We recently demonstrated the high expression of CD164 on CD4(+) T cells from Sézary syndrome patients with a wide range of circulating tumor burdens...
January 2017: Archives of Dermatological Research
https://www.readbyqxmd.com/read/27630847/recent-outbreaks-of-diphtheria-in-dibrugarh-district-assam-india
#13
Partha Pratim Das, Saurav Jyoti Patgiri, Lahari Saikia, Debosmita Paul
Diphtheria is still a significant child health problem in countries with low immunization coverage. Reports of diphtheria in adult population are also increasing. Here we describe three recent outbreaks of diphtheria in Dibrugarh district, Assam in two consecutive years. The study was undertaken in Assam Medical College & Hospital, Dibrugarh after the diagnosis of two Diphtheria cases in the month of September and October 2015 and another in January 2016. Outbreak investigation was done after defining operational definition and throat swabs were collected from thirty three (33) individuals including three (3) index cases and thirty (30) close contacts...
July 2016: Journal of Clinical and Diagnostic Research: JCDR
https://www.readbyqxmd.com/read/27465145/characterisation-of-clostridium-difficile-strains-isolated-from-groote-schuur-hospital-cape-town-south-africa
#14
B Kullin, T Brock, N Rajabally, F Anwar, G Vedantam, S Reid, V Abratt
The C. difficile infection rate in South Africa is concerning. Many strains previously isolated from diarrhetic patients at Groote Schuur Hospital were ribotype 017. This study further characterised these strains with respect to their clonal relationships, antibiotic susceptibility, toxin production and various attributes impacting on pathogen colonisation. Multilocus variable-number tandem-repeat analysis (MLVA) was used to characterise all C. difficile isolates. Antibiotic susceptibility was determined by E-test and PCR-based analysis of the ermB, gyrA and gyrB genes...
October 2016: European Journal of Clinical Microbiology & Infectious Diseases
https://www.readbyqxmd.com/read/27291708/evolution-epidemiology-and-diversity-of-corynebacterium-diphtheriae-new-perspectives-on-an-old-foe
#15
REVIEW
Vartul Sangal, Paul A Hoskisson
Diphtheria is a debilitating disease caused by toxigenic Corynebacterium diphtheriae strains and has been effectively controlled by the toxoid vaccine, yet several recent outbreaks have been reported across the globe. Moreover, non-toxigenic C. diphtheriae strains are emerging as a major global health concern by causing severe pharyngitis and tonsillitis, endocarditis, septic arthritis and osteomyelitis. Molecular epidemiological investigations suggest the existence of outbreak-associated clones with multiple genotypes circulating around the world...
September 2016: Infection, Genetics and Evolution
https://www.readbyqxmd.com/read/27263417/the-frequency-of-genes-encoding-exotoxin-a-and-exoenzyme-s-in-pseudomonas-aeruginosa-strains-isolated-from-burn-patients
#16
Azar Dokht Khosravi, Fatemeh Shafie, Effat Abbasi Montazeri, Soodabeh Rostami
BACKGROUND: Pseudomonas aeruginosa infections have emerged as a major infectious disease threat in recent decades with infection particularly in immunocompromised hosts. P. aeruginosa possesses several virulence factors with involvement in pathogenesis. The aim of this study was to examine the prevalence of virulence genes of toxA and toxS and to analyze their relation to antimicrobial resistance of the isolates. METHODS: In total 185 clinical isolates of P. aeruginosa were collected from burn patients...
August 2016: Burns: Journal of the International Society for Burn Injuries
https://www.readbyqxmd.com/read/27229865/neurospora-crassa-tox-1-gene-encodes-a-ph-and-temperature-tolerant-mini-cellulase
#17
Yue Xiao, Qiongsi Zhang, Yiquan Luo, Ying Zhang, Xi Luo, Yuchuan Wang, Weiguo Cao, Vito De Pinto, Qiuyun Liu, Gang Li
Cellulases that endure extreme conditions are essential in various industrial sectors. This study reports a mini-cellulase gene tox-1 from Neurospora crassa. The gene tox-1 was cloned in Escherichia coli after chimerization with the YebF gene and substitutions of certain isoleucine and valine with leucine residues. The yeast transformants could grow on rice straw-agar medium. The 44-amino acid peptide and its two mutant variants displayed potent cellulase activities in Congo Red assay and enzymatic assays. Conservative replacements with leucine have substantially increased the stabilities and half-lives of the peptides at alkaline pH and low and high temperatures and also the tolerance to organic solvents and surfactants, on the basis of activities toward cellose...
June 15, 2016: Journal of Agricultural and Food Chemistry
https://www.readbyqxmd.com/read/27070241/burkholderia-glumae-toxa-is-a-dual-specificity-methyltransferase-that-catalyzes-the-last-two-steps-of-toxoflavin-biosynthesis
#18
Michael K Fenwick, Benjamin Philmus, Tadhg P Begley, Steven E Ealick
Toxoflavin is a major virulence factor of the rice pathogen Burkholderia glumae. The tox operon of B. glumae contains five putative toxoflavin biosynthetic genes toxABCDE. ToxA is a predicted S-adenosylmethionine-dependent methyltransferase, and toxA knockouts of B. glumae are less virulent in plant infection models. In this study, we show that ToxA performs two consecutive methylations to convert the putative azapteridine intermediate, 1,6-didemethyltoxoflavin, to toxoflavin. In addition, we report a series of crystal structures of ToxA complexes that reveals the molecular basis of the dual methyltransferase activity...
May 17, 2016: Biochemistry
https://www.readbyqxmd.com/read/26981424/identification-of-tox-chromatin-binding-properties-and-downstream-targets-by-damid-seq
#19
António Miguel de Jesus Domingues, Benedetta Artegiani, Andreas Dahl, Federico Calegari
In recent years, DNA adenine methyltransferase identification (DamID) has emerged as a powerful tool to profile protein-DNA interaction on a genome-wide scale. While DamID has been primarily combined with microarray analyses, which limits the spatial resolution and full potential of this technique, our group was the first to combine DamID with sequencing (DamID-Seq) for characterizing the binding loci and properties of a transcription factor (Tox) (sequencing data available at NCBI's Gene Expression Omnibus under the accession number GSE64240)...
March 2016: Genomics Data
https://www.readbyqxmd.com/read/26885442/tox-gene-a-novel-target-for-human-cancer-gene-therapy
#20
REVIEW
Xin Yu, Zheng Li
Thymocyte selection-associated high mobility group box factor (TOX) is a member of an evolutionarily conserved DNA-binding protein family and is expressed in several immune-relevant cell subsets. TOX encodes a nuclear protein of the high-mobility group box superfamily. It contains a DNA-binding domain, which allows it to regulate transcription by modifying local chromatin structure and modulating the formation of multi-protein complexes. Previous studies have shown that TOX play important roles in immune system...
2015: American Journal of Cancer Research
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