keyword
MENU ▼
Read by QxMD icon Read
search

dt40

keyword
https://www.readbyqxmd.com/read/28926637/selective-cytotoxicity-of-the-anti-diabetic-drug-metformin-in-glucose-deprived-chicken-dt40-cells
#1
Kei Kadoda, Takahito Moriwaki, Masataka Tsuda, Hiroyuki Sasanuma, Masamichi Ishiai, Minoru Takata, Hiroshi Ide, Shin-Ichiro Masunaga, Shunichi Takeda, Keizo Tano
Metformin is a biguanide drug that is widely used in the treatment of diabetes. Epidemiological studies have indicated that metformin exhibits anti-cancer activity. However, the molecular mechanisms underlying this activity currently remain unclear. We hypothesized that metformin is cytotoxic in a tumor-specific environment such as glucose deprivation and/or low oxygen (O2) tension. We herein demonstrated that metformin was highly cytotoxic under glucose-depleted, but not hypoxic (2% O2) conditions. In order to elucidate the underlying mechanisms of this selective cytotoxicity, we treated exposed DNA repair-deficient chicken DT40 cells with metformin under glucose-depleted conditions and measured cellular sensitivity...
2017: PloS One
https://www.readbyqxmd.com/read/28867677/c-x-c-chemokine-receptor-type-4-cxcr4-is-a-key-receptor-for-chicken-primordial-germ-cell-migration
#2
Jeong Hyo Lee, Jeong-Woong Park, Si Won Kim, Joonghoon Park, Tae Sub Park
In mammals, germ cells originate outside of the developing gonads and follow a unique migration pattern through the embryonic tissue toward the genital ridges. Many studies have attempted to identify critical receptors and factors involved in germ cell migration. However, relatively few reports exist on germ cell receptors and chemokines that are involved in germ cell migration in avian species. In the present study, we investigated the specific migratory function of C-X-C chemokine receptor type 4 (CXCR4) in chicken primordial germ cells (PGCs)...
September 1, 2017: Journal of Reproduction and Development
https://www.readbyqxmd.com/read/28833843/a-novel-model-to-characterize-structure-and-function-of-brca1
#3
Dong Lin, Reza Izadpanah, Stephen E Braun, Eckhard Alt
BRCA1 plays a central role in DNA repair. Although N-terminal RING and C-terminal BRCT domains are studied, the functions of the central region of BRCA1 is poorly characterized. Here we report a structural and functional analysis of BRCA1 alleles and functional human BRCA1 in chicken B-lymphocyte cell line DT40. The combination of "Homologous Recombineering" and "RT-cassette" enables modifications of chicken BRCA1 gene in E.coli. Mutant BRCA1 knock-in DT40 cell lines were generated using BRCA1 mutation constructs by homologous recombination with a targeting efficiency of up to 100%...
August 18, 2017: Cell Biology International
https://www.readbyqxmd.com/read/28802254/tdp1-is-critical-for-the-repair-of-dna-breaks-induced-by-sapacitabine-a-nucleoside-also-targeting-atm-and-brca-deficient-tumors
#4
Muthana Al Abo, Hiroyuki Sasanuma, Xiaojun Liu, Vinodh N Rajapakse, Shar-Yin N Huang, Evgeny Kiselev, Shunichi Takeda, William Plunkett, Yves Pommier
2'-C-cyano-2'-deoxy-1-β-D-arabino-pentofuranosylcytosine (CNDAC) is the active metabolite of the anticancer drug, sapacitabine. CNDAC is incorporated into the genome during DNA replication and subsequently undergoes beta-elimination that generates single-strand breaks with abnormal 3'-ends. Because tyrosyl-DNA phosphodiesterase 1 (TDP1) selectively hydrolyzes non-phosphorylated 3'-blocking ends, we tested its role in the repair of CNDAC-induced DNA damage. We show that cells lacking TDP1 (avian TDP1-/- DT40 cells and human TDP1 KO TSCER2 and HCT116 cells) exhibit marked hypersensitivity to CNDAC...
August 11, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28795467/cenp-r-acts-bilaterally-as-a-tumor-suppressor-and-an-oncogene-in-the-two-stage-skin-carcinogenesis-model
#5
Kazuhiro Okumura, Naoko Kagawa, Megumi Saito, Yasuhiro Yoshizawa, Haruka Munakata, Eriko Isogai, Tatsuo Fukagawa, Yuichi Wakabayashi
CENP-R is a component of the CENP-O complex, including CENP-O, CENP-P, CENP-Q, CENP-R, and CENP-U and is constitutively localized to kinetochores throughout the cell cycle in vertebrates. CENP-R deficient chicken DT40 cells are viable and show very minor effect on mitosis. To investigate the functional roles of CENP-R in vivo, we generated CENP-R deficient mice (Cenp-r(-/-) ). Mice heterozygous or homozygous for Cenp-r null mutation are viable and healthy, with no apparent defect in growth and morphology, indicating Cenp-r is not essential for normal development...
August 9, 2017: Cancer Science
https://www.readbyqxmd.com/read/28760774/unperturbed-immune-function-despite-mutation-of-c-terminal-tyrosines-in-syk-previously-implicated-in-signaling-and-activity-regulation
#6
Vanessa Weis, Sebastian Königsberger, Susanne Amler, Jürgen Wienands, Friedemann Kiefer
The non-receptor tyrosine kinase Syk, a central regulator of immune cell differentiation and activation, is a promising drug target for treatment of leukemia, allergic and inflammatory diseases. The clinical failure of Syk inhibitors underscores the importance to understand the regulation of Syk function and activity.A series of previous studies emphasized the importance of three C-terminal tyrosines in Syk for kinase activity regulation, as docking sites for downstream effector molecules and for Ca(2+) mobilization...
July 31, 2017: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/28743004/association-of-m18bp1-knl2-with-cenp-a-nucleosome-is-essential-for-centromere-formation-in-non-mammalian-vertebrates
#7
Tetsuya Hori, Wei-Hao Shang, Masatoshi Hara, Mariko Ariyoshi, Yasuhiro Arimura, Risa Fujita, Hitoshi Kurumizaka, Tatsuo Fukagawa
Centromeres are specified and maintained by sequence-independent epigenetic mechanisms through the incorporation of CENP-A into centromeres. Given that CENP-A incorporation requires the Mis18 complex to be in the centromere region, it is necessary to precisely understand how the Mis18 complex localizes to the centromere region. Here, we showed that centromere localization of the Mis18 complex depends on CENP-A, but not CENP-C or CENP-T, in chicken DT40 cells. Furthermore, we demonstrated that M18BP1/KNL2, a member of the Mis18 complex, contained the CENP-C-like motif in chicken and other vertebrates, which is essential for centromere localization and M18BP1/KNL2 function in DT40 cells...
July 24, 2017: Developmental Cell
https://www.readbyqxmd.com/read/28695215/characterisation-of-a-stably-integrated-expression-system-for-exogenous-protein-expression-in-dt40
#8
Meliti Skouteri, Helfrid Hochegger, Antony M Carr
The use of constitutive promoters to drive exogenous protein expression is an important tool for the study of diverse biological processes. To create and characterise a stably integrated expression system for DT40 cells, we constructed integration cassettes for three commonly used promoter elements; CMV, CBA or CAG, and used these to stably integrate a TOPBP1 transgene at the OVA locus, a transcriptionally silent locus commonly used in DT40. We next performed a comparative analysis of protein expression levels and identified CAG as the most efficient of the promoter elements we have tested in DT40 cells...
2017: Wellcome Open Research
https://www.readbyqxmd.com/read/28586432/locus-specific-chip-combined-with-ngs-analysis-reveals-genomic-regulatory-regions-that-physically-interact-with-the-pax5-promoter-in-a-chicken-b-cell-line
#9
Toshitsugu Fujita, Fusako Kitaura, Miyuki Yuno, Yutaka Suzuki, Sumio Sugano, Hodaka Fujii
Chromosomal interactions regulate genome functions, such as transcription, via dynamic chromosomal organization in the nucleus. In this study, we attempted to identify genomic regions that physically bind to the promoter region of the Pax5 gene, which encodes a master regulator for B cell lineage commitment, in a chicken B cell line, DT40, with the goal of obtaining mechanistic insight into transcriptional regulation through chromosomal interaction. We found that the Pax5 promoter bound to multiple genomic regions using locus-specific chromatin immunoprecipitation (locus-specific ChIP), a method for locus-specific isolation of target genomic regions, in combination with next-generation sequencing (NGS)...
June 6, 2017: DNA Research: An International Journal for Rapid Publication of Reports on Genes and Genomes
https://www.readbyqxmd.com/read/28552883/sel1l-dependent-substrates-require-derlin2-3-and-herp1-2-for-endoplasmic-reticulum-associated-degradation
#10
Takehiro Sugimoto, Satoshi Ninagawa, Shimpei Yamano, Tokiro Ishikawa, Tetsuya Okada, Shunichi Takeda, Kazutoshi Mori
Accumulation of unfolded/misfolded proteins in the endoplasmic reticulum (ER) activates the unfolded protein response (UPR). The ATF6 pathway is one of the three major pathways in vertebrates. Although ATF6, a transmembrane-type glycoprotein in the ER, functions as a UPR sensor/transducer, it is an unstable protein with a half-life of approximately 2 h and is constitutively subjected to the ER-associated degradation system with the location of the misfolded part in the ER lumen (ERAD-L). ERAD-L substrates are delivered to the cytosol through the retrotranslocon, which likely contains HRD1 (E3), gp78 (E3), SEL1L (a partner of HRD1), Derlin1/2/3 and Herp1/2...
July 4, 2017: Cell Structure and Function
https://www.readbyqxmd.com/read/28458162/a-genetic-study-based-on-pcna-ubiquitin-fusions-reveals-no-requirement-for-pcna-polyubiquitylation-in-dna-damage-tolerance
#11
Judit Z Gervai, Judit Gálicza, Zoltán Szeltner, Judit Zámborszky, Dávid Szüts
Post-translational modifications of Proliferating Cell Nuclear Antigen (PCNA) play a key role in regulating the bypass of DNA lesions during DNA replication. PCNA can be monoubiquitylated at lysine 164 by the RAD6-RAD18 ubiquitin ligase complex. Through this modification, PCNA can interact with low fidelity Y family DNA polymerases to promote translesion synthesis. Monoubiquitylated PCNA can be polyubiquitylated on lysine 63 of ubiquitin by a further ubiquitin-conjugating complex. This modification promotes a template switching bypass process in yeast, while its role in higher eukaryotes is less clear...
June 2017: DNA Repair
https://www.readbyqxmd.com/read/28431926/multiple-repair-pathways-mediate-cellular-tolerance-to-resveratrol-induced-dna-damage
#12
Ying Liu, Xiaohua Wu, Xiaoqing Hu, Ziyuan Chen, Hao Liu, Shunichi Takeda, Yong Qing
Resveratrol (RSV) has been reported to exert health benefits for the prevention and treatment of many diseases, including cancer. The anticancer mechanisms of RSV seem to be complex and may be associated with genotoxic potential. To better understand the genotoxic mechanisms, we used wild-type (WT) and a panel of isogenic DNA-repair deficient DT40 cell lines to identify the DNA damage effects and molecular mechanisms of cellular tolerance to RSV. Our results showed that RSV induced significant formation of γ-H2AX foci and chromosome aberrations (CAs) in WT cells, suggesting direct DNA damage effects...
April 19, 2017: Toxicology in Vitro: An International Journal Published in Association with BIBRA
https://www.readbyqxmd.com/read/28380422/the-dominant-role-of-proofreading-exonuclease-activity-of-replicative-polymerase-%C3%AE%C2%B5-in-cellular-tolerance-to-cytarabine-ara-c
#13
Masataka Tsuda, Kazuhiro Terada, Masato Ooka, Koji Kobayashi, Hiroyuki Sasanuma, Ryo Fujisawa, Toshiki Tsurimoto, Junpei Yamamoto, Shigenori Iwai, Kei Kadoda, Remi Akagawa, Shar-Yin Naomi Huang, Yves Pommier, Julian E Sale, Shunichi Takeda, Kouji Hirota
Chemotherapeutic nucleoside analogs, such as Ara-C, 5-Fluorouracil (5-FU) and Trifluridine (FTD), are frequently incorporated into DNA by the replicative DNA polymerases. However, it remains unclear how this incorporation kills cycling cells. There are two possibilities: Nucleoside analog triphosphates inhibit the replicative DNA polymerases, and/or nucleotide analogs mis-incorporated into genomic DNA interfere with the next round of DNA synthesis as replicative DNA polymerases recognize them as template DNA lesions, arresting synthesis...
May 16, 2017: Oncotarget
https://www.readbyqxmd.com/read/28322935/early-pathogenesis-during-infectious-bursal-disease-in-susceptible-chickens-is-associated-with-changes-in-b-cell-genomic-methylation-and-loss-of-genome-integrity
#14
Nick A Ciccone, Lorraine P Smith, William Mwangi, Amy Boyd, Andrew J Broadbent, Adrian L Smith, Venugopal Nair
We propose a model by which an increase in the genomic modification, 5-hydroxymethylcytosine (5hmC), contributes to B cell death within the chicken bursa of Fabricus (BF) infected with infectious bursal disease virus (IBDV). Our findings indicate that, following an IBDV infection, Rhode Island Red (RIR) chickens have fewer surviving B cells and higher levels of 5hmC in the BF than the more resistant 15l line of birds. Elevated genomic 5hmC levels within the RIR BF are associated with markers of immune responses: infiltrating T cells and increased expression of CD40L, FasL and iNOS...
August 2017: Developmental and Comparative Immunology
https://www.readbyqxmd.com/read/28301039/bach2-regulates-aid-mediated-immunoglobulin-gene-conversion-and-somatic-hypermutation-in-dt40-b-cells
#15
Paulina M Budzyńska, Minna K Kyläniemi, Teemu Kallonen, Anni I Soikkeli, Kalle-Pekka Nera, Olli Lassila, Jukka Alinikula
The transcription factor Bach2 is required for germinal center formation, somatic hypermutation (SHM), and class-switch recombination (CSR) of immunoglobulins. SHM and CSR are initiated by activation-induced cytidine deaminase (AID) which has potential to induce human B cell lymphoma. To understand the role of Bach2 in AID-mediated immunoglobulin gene diversification processes, we established a BACH2-deficient DT40 B cell line. We show that in addition to allowing SHM, Bach2 drives immunoglobulin gene conversion (GCV), another AID-dependent antibody gene diversification process...
June 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/28296036/targeting-of-c-type-lectin-like-receptor%C3%A2-2-or-p2y12-for-the-prevention-of-platelet-activation-by-immunotherapeutic-cpg-oligodeoxynucleotides
#16
C Delierneux, N Donis, L Servais, O Wéra, C Lecut, M Vandereyken, L Musumeci, S Rahmouni, J Schneider, J A Eble, P Lancellotti, C Oury
Essentials CpG oligodeoxynucleotide (ODN) immuotherapeutics cause undesired platelet activating effects. It is crucial to understand the mechanisms of these effects to identify protective strategies. CpG ODN-induced platelet activation depends on C-type lectin-like receptor 2 (CLEC-2) and P2Y12. Targeting CLEC-2 or P2Y12 fully prevents CpG ODN-induced platelet activation and thrombosis. SUMMARY: Background Synthetic phosphorothioate-modified CpG oligodeoxynucleotides (ODNs) show potent immunostimulatory properties that are widely exploited in clinical trials of anticancer treatment...
May 2017: Journal of Thrombosis and Haemostasis: JTH
https://www.readbyqxmd.com/read/28235482/srsf1-3-contributes-to-diversification-of-the-immunoglobulin-variable-region-gene-by-promoting-accumulation-of-aid-in-the-nucleus
#17
Yuka Kawaguchi, Hiroaki Nariki, Naoko Kawamoto, Yuichi Kanehiro, Satoshi Miyazaki, Mari Suzuki, Masaki Magari, Hiroshi Tokumitsu, Naoki Kanayama
Activation-induced cytidine deaminase (AID) is essential for diversification of the Ig variable region (IgV). AID is excluded from the nucleus, where it normally functions. However, the molecular mechanisms responsible for regulating AID localization remain to be elucidated. The SR-protein splicing factor SRSF1 is a nucleocytoplasmic shuttling protein, a splicing isoform of which called SRSF1-3, has previously been shown to contribute to IgV diversification in chicken DT40 cells. In this study, we examined whether SRSF1-3 functions in IgV diversification by promoting nuclear localization of AID...
April 1, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28208594/immunomodulatory-and-anti-ibdv-activities-of-the-polysaccharide-aex-from-coccomyxa-gloeobotrydiformis
#18
Qiang Guo, Qiang Shao, Wenping Xu, Lei Rui, Ryo Sumi, Fumio Eguchi, Zandong Li
A number of polysaccharides have been reported to show immunomodulatory and antiviral activities against various animal viruses. AEX is a polysaccharide extracted from the green algae, Coccomyxa gloeobotrydiformis. The aim of this study was to examine the function of AEX in regulating the immune response in chickens and its capacity to inhibit the infectious bursal disease virus (IBDV), to gain an understanding of its immunomodulatory and antiviral ability. Here, preliminary immunological tests in vitro showed that the polysaccharide AEX can activate the chicken peripheral blood molecular cells' (PBMCs) response by inducing the production of cytokines and NO, promote extracellular antigen presentation but negatively regulate intracellular antigen presentation in chicken splenic lymphocytes, and promote the proliferation of splenic lymphocytes and DT40 cells...
February 10, 2017: Marine Drugs
https://www.readbyqxmd.com/read/28130783/the-trpm7-channel-kinase-regulates-store-operated-calcium-entry
#19
Malika Faouzi, Tatiana Kilch, F David Horgen, Andrea Fleig, Reinhold Penner
KEY POINTS: Pharmacological and molecular inhibition of transient receptor potential melastatin 7 (TRPM7) reduces store-operated calcium entry (SOCE). Overexpression of TRPM7 in TRPM7(-/-) cells restores SOCE. TRPM7 is not a store-operated calcium channel. TRPM7 kinase rather than channel modulates SOCE. TRPM7 channel activity contributes to the maintenance of store Ca(2+) levels at rest. ABSTRACT: The transient receptor potential melastatin 7 (TRPM7) is a protein that combines an ion channel with an intrinsic kinase domain, enabling it to modulate cellular functions either by conducting ions through the pore or by phosphorylating downstream proteins via its kinase domain...
May 15, 2017: Journal of Physiology
https://www.readbyqxmd.com/read/28086922/transcriptional-profiles-in-bursal-b-lymphoid-dt40-cells-infected-with-very-virulent-infectious-bursal-disease-virus
#20
Rong Quan, Shanshan Zhu, Li Wei, Jing Wang, Xu Yan, Zixuan Li, Jue Liu
BACKGROUND: Infectious bursal disease virus (IBDV) causes a highly contagious, immunosuppressive disease in chickens. The virus mainly infects immature B lymphocytes in the bursa of Fabricius (BF). Chicken B cell line DT40, an avian leukosis virus-induced B cell line, supports very virulent IBDV (vvIBDV) infection in vitro and thereby serves as a good model for investigating the infection and pathogenesis of this virus. However, a transcriptome-wide understanding of the interaction between vvIBDV and B cells has not yet been achieved...
January 13, 2017: Virology Journal
keyword
keyword
2327
1
2
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read
×

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"