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https://www.readbyqxmd.com/read/27916261/cis-bifenthrin-causes-immunotoxicity-in-murine-macrophages
#1
Xia Wang, Xingli Gao, Bingnan He, Yuanxiang Jin, Zhengwei Fu
Synthetic pyrethroids (SPs) are commonly used insecticides that have been detected in mammals, including humans, indicating a potential threat to human health. Bifenthrin (BF), as well as other pyrethroids, has been shown to possess neurotoxic, reproductive, hepatotoxic and nephrotoxic potential in mammals. However, studies regarding the immunotoxicity of BF and its mechanism are limited. In this study, we aim to exam the immunotoxicity of cis-BF on the murine macrophage cell line, RAW 264.7. MTT assay results demonstrated that cis-BF exposure induced apoptosis in RAW 264...
December 1, 2016: Chemosphere
https://www.readbyqxmd.com/read/27915128/cholesterol-reducing-agents-inhibit-assembly-of-type-i-parainfluenza-viruses
#2
Shringkhala Bajimaya, Tsuyoshi Hayashi, Tünde Frankl, Peter Bryk, Brian Ward, Toru Takimoto
Many enveloped RNA viruses utilize lipid rafts for the assembly of progeny virions, but the role of cholesterol, a major component of rafts, on paramyxovirus budding and virion formation is controversial. In this study, we analyzed the effects of FDA-approved cholesterol-reducing agents, gemfibrozil and lovastatin, on raft formation and assembly of human parainfluenza virus type 1 (hPIV1) and Sendai virus (SeV). Treatment of the human airway epithelial A549 cells with the agents, especially when combined, significantly decreased production of infectious hPIV1 and SeV...
December 1, 2016: Virology
https://www.readbyqxmd.com/read/27911363/generation-of-induced-pluripotent-stem-cells-from-human-melanoma-tumor-infiltrating-lymphocytes
#3
Hidehito Saito, Kumiko Iwabuchi, Noemi Fusaki, Fumito Ito
Adoptive transfer of ex vivo expanded autologous tumor-infiltrating lymphocytes (TILs) can mediate durable and complete responses in significant subsets of patients with metastatic melanoma. Major obstacles of this approach are the reduced viability of transferred T cells, caused by telomere shortening, and the limited number of TILs obtained from patients. Less-differentiated T cells with long telomeres would be an ideal T cell subset for adoptive T cell therapy;however, generating large numbers of these less-differentiated T cells is problematic...
November 11, 2016: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/27864696/generation-and-differentiation-of-induced-pluripotent-stem-cells-reveal-ankylosing-spondylitis-risk-gene-expression-in-bone-progenitors
#4
Gerlinde Layh-Schmitt, Shajia Lu, Fatemeh Navid, Stephen R Brooks, Emily Lazowick, Kathryn M Davis, Cristina Montagna, Massimo Gadina, Robert A Colbert
Axial spondyloarthritis (axSpA), which encompasses ankylosing spondylitis, is a complex genetic disease. Aberrant bone formation is a key feature of pathogenesis that can lead to ankylosis of the spine. Our objective is to determine, whether genes whose variants confer susceptibility to AS are expressed in bone progenitors like mesenchymal stem cells (MSCs). Since MSCs from bone marrow is difficult to obtain, we first examined, whether MSCs can be derived from induced pluripotent stem cells (iPSCs). Dermal fibroblasts of two axSpA patients and one healthy control were reprogrammed into iPSCs using a Sendai virus vector encoding pluripotency genes...
November 18, 2016: Clinical Rheumatology
https://www.readbyqxmd.com/read/27810048/patient-specific-and-genome-edited-induced-pluripotent-stem-cell-derived-cardiomyocytes-elucidate-single-cell-phenotype-of-brugada-syndrome
#5
Ping Liang, Karim Sallam, Haodi Wu, Yingxin Li, Ilanit Itzhaki, Priyanka Garg, Ying Zhang, Vittavat Vermglinchan, Feng Lan, Mingxia Gu, Tingyu Gong, Yan Zhuge, Chunjiang He, Antje D Ebert, Veronica Sanchez-Freire, Jared Churko, Shijun Hu, Arun Sharma, Chi Keung Lam, Melvin M Scheinman, Donald M Bers, Joseph C Wu
BACKGROUND: Brugada syndrome (BrS), a disorder associated with characteristic electrocardiogram precordial ST-segment elevation, predisposes afflicted patients to ventricular fibrillation and sudden cardiac death. Despite marked achievements in outlining the organ level pathophysiology of the disorder, the understanding of human cellular phenotype has lagged due to a lack of adequate human cellular models of the disorder. OBJECTIVES: The objective of this study was to examine single cell mechanism of Brugada syndrome using induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs)...
November 8, 2016: Journal of the American College of Cardiology
https://www.readbyqxmd.com/read/27791088/hepatitis-c-virus-promotes-virion-secretion-through-cleavage-of-the-rab7-adaptor-protein-rilp
#6
Ann L Wozniak, Abby Long, Kellyann N Jones-Jamtgaard, Steven A Weinman
Hepatitis C virus (HCV) is an enveloped RNA virus that modifies intracellular trafficking processes. The mechanisms that HCV and other viruses use to modify these events are poorly understood. In this study, we observed that two different RNA viruses, HCV and Sendai, cause inhibition of ras-related protein Rab-7 (Rab7)-dependent endosome-lysosome fusion. In both cases, viral infection causes cleavage of the Rab7 adaptor protein RILP (Rab interacting lysosomal protein), which is responsible for linking Rab7 vesicles to dynein motor complexes...
November 1, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27789404/establishment-of-ehmt1-mutant-induced-pluripotent-stem-cell-ipsc-line-from-a-11-year-old-kleefstra-syndrome-ks-patient-with-autism-and-normal-intellectual-performance
#7
Eszter Varga, Csilla Nemes, Zsuzsanna Táncos, István Bock, Sára Berzsenyi, György Lévay, Viktor Román, Julianna Kobolák, András Dinnyés
Peripheral blood was collected from a clinically characterized female Kleefstra syndrome patient with a heterozygous, de novo, premature termination codon (PTC) mutation (NM_024757.4(EHMT1):c.3413G>A; p.Trp1138Ter). Peripheral blood mononuclear cells (PBMCs) were reprogrammed with the human OSKM transcription factors using the Sendai-virus (SeV) delivery system. The pluripotency of transgene-free iPSC line was verified by the expression of pluripotency-associated markers and by in vitro spontaneous differentiation towards the 3 germ layers...
October 2, 2016: Stem Cell Research
https://www.readbyqxmd.com/read/27789397/generation-of-human-ips-cell-line-ctl07-ii-from-human-fibroblasts-under-defined-and-xeno-free-conditions
#8
Malin Kele, Kelly Day, Harriet Rönnholm, Jens Schuster, Niklas Dahl, Anna Falk
CTL07-II is a healthy feeder-free and characterized human induced pluripotent stem (iPS) cell line. Cultured under xeno-free and defined conditions. The line is generated from healthy human fibroblasts with non-integrating Sendai virus vectors encoding the four Yamanaka factors, OCT4, SOX2, KLF4 and cMYC. The generated iPS cells are free from reprogramming vectors and their purity, karyotypic stability and pluripotent capacity is confirmed.
September 30, 2016: Stem Cell Research
https://www.readbyqxmd.com/read/27783035/the-microtubule-inhibitor-podofilox-inhibits-an-early-entry-step-of-human-cytomegalovirus
#9
Tobias Cohen, Toni M Schwarz, Frederic Vigant, Thomas J Gardner, Rosmel E Hernandez, Benhur Lee, Domenico Tortorella
Human cytomegalovirus is a ubiquitous β-herpesvirus that infects many different cell types through an initial binding to cell surface receptors followed by a fusion event at the cell membrane or endocytic vesicle. A recent high-throughput screen to identify compounds that block a step prior to viral gene expression identified podofilox as a potent and nontoxic inhibitor. Time-of-addition studies in combination with quantitative-PCR analysis demonstrated that podofilox limits an early step of virus entry at the cell surface...
October 24, 2016: Viruses
https://www.readbyqxmd.com/read/27774301/sendai-virus-intra-host-population-dynamics-and-host-immunocompetence-influence-viral-virulence-during-in%C3%A2-vivo-passage
#10
José Peña, Haiyin Chen-Harris, Jonathan E Allen, Mona Hwang, Maher Elsheikh, Shalini Mabery, Helle Bielefeldt-Ohmann, Adam T Zemla, Richard A Bowen, Monica K Borucki
In vivo serial passage of non-pathogenic viruses has been shown to lead to increased viral virulence, and although the precise mechanism(s) are not clear, it is known that both host and viral factors are associated with increased pathogenicity. Under- or overnutrition leads to a decreased or dysregulated immune response and can increase viral mutant spectrum diversity and virulence. The objective of this study was to identify the role of viral mutant spectra dynamics and host immunocompetence in the development of pathogenicity during in vivo passage...
January 2016: Virus Evolution
https://www.readbyqxmd.com/read/27764162/novel-strategy-to-control-transgene-expression-mediated-by-a-sendai-virus-based-vector-using-a-nonstructural-c-protein-and-endogenous-micrornas
#11
Masayuki Sano, Minoru Iijima, Manami Ohtaka, Mahito Nakanishi
Tissue-specific control of gene expression is an invaluable tool for studying various biological processes and medical applications. Efficient regulatory systems have been utilized to control transgene expression in various types of DNA viral or integrating viral vectors. However, existing regulatory systems are difficult to transfer into negative-strand RNA virus vector platforms because of significant differences in their transcriptional machineries. In this study, we developed a novel strategy for regulating transgene expression mediated by a cytoplasmic RNA vector based on a replication-defective and persistent Sendai virus (SeVdp)...
2016: PloS One
https://www.readbyqxmd.com/read/27743889/the-tar-rna-binding-protein-is-required-for-immunoresponces-triggered-by-cardiovirus-infection
#12
Akihiko Komuro, Yuya Homma, Takaharu Negoro, Glen N Barber, Curt M Horvath
LGP2 and MDA5 cooperate to detect viral RNA in the cytoplasm of Picornavirus-infected cells and activate innate immune responses. To further define regulatory components of RNA recognition by LGP2/MDA5, a yeast two-hybrid screen was used to identify LGP2-interacting proteins. The screening has identified the TAR-RNA binding protein (TRBP), which is known to be an essential factor for RNA interference (RNAi). Immuno-precipitation experiments demonstrated that TRBP interacted specifically with LGP2 but not with related RIG-I-like receptors, RIG-I or MDA5...
October 12, 2016: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27736772/tax1bp1-restrains-virus-induced-apoptosis-by-facilitating-itch-mediated-degradation-of-the-mitochondrial-adaptor-mavs
#13
Young Bong Choi, Noula Shembade, Kislay Parvatiyar, Siddharth Balachandran, Edward William Harhaj
The host response to RNA virus infection consists of an intrinsic innate immune response and the induction of apoptosis as mechanisms to restrict viral replication. The mitochondrial adaptor molecule MAVS plays critical roles in coordinating both virus-induced type I interferon production and apoptosis; however, the regulation of MAVS-mediated apoptosis is poorly understood. Here, we show that the adaptor protein TAX1BP1 functions as a negative regulator of virus-induced apoptosis. TAX1BP1-deficient cells are highly sensitive to apoptosis in response to infection with the RNA viruses vesicular stomatitis virus and Sendai virus and transfection with poly(I:C)...
October 10, 2016: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/27696911/alpha-a-crystallin-protects-lens-epithelial-cell-derived-ipsc-like-cells-against-apoptosis-induced-by-oxidative-stress
#14
Yixin Yu, Haibo Jiang, Haibo Li, Weitao Song, Xiaobo Xia
Cataract, the leading cause of blindness worldwide, is caused by the apoptosis of lens epithelial cells (LECs). αA-crystallin is a major structural protein of the lens. However, the antiapoptotic function of αA-crystallin in lens stem cells remains unclear. In this study, primary LECs were isolated from postnatal 3-5 days of SD rats and transfected by Sendai virus loaded with four factors, OCT3/4, Sox2, c-Myc, and Klf4, to induced pluripotent stem cells (iPSCs). LEC-iPSC-like cells were identified by immunofluorescent staining...
October 2016: Cellular Reprogramming
https://www.readbyqxmd.com/read/27666791/development-refractoriness-of-mll-rearranged-human-b-cell-acute-leukemias-to-reprogramming-into-pluripotency
#15
Alvaro Muñoz-López, Damià Romero-Moya, Cristina Prieto, Verónica Ramos-Mejía, Antonio Agraz-Doblas, Ignacio Varela, Marcus Buschbeck, Anna Palau, Xonia Carvajal-Vergara, Alessandra Giorgetti, Anthony Ford, Majlinda Lako, Isabel Granada, Neus Ruiz-Xivillé, Sandra Rodríguez-Perales, Raul Torres-Ruíz, Ronald W Stam, Jose Luis Fuster, Mario F Fraga, Mahito Nakanishi, Gianni Cazzaniga, Michela Bardini, Isabel Cobo, Gustavo F Bayon, Agustin F Fernandez, Clara Bueno, Pablo Menendez
Induced pluripotent stem cells (iPSCs) are a powerful tool for disease modeling. They are routinely generated from healthy donors and patients from multiple cell types at different developmental stages. However, reprogramming leukemias is an extremely inefficient process. Few studies generated iPSCs from primary chronic myeloid leukemias, but iPSC generation from acute myeloid or lymphoid leukemias (ALL) has not been achieved. We attempted to generate iPSCs from different subtypes of B-ALL to address the developmental impact of leukemic fusion genes...
October 11, 2016: Stem Cell Reports
https://www.readbyqxmd.com/read/27628546/-cancer-immunotherapy-using-human-induced-pluripotent-stem-cell-derived-dendritic-cells-ipsdcs-expressing-carcinoembryonic-antigen
#16
Junya Kitadani, Toshiyasu Ojima, Hiromitsu Iwamoto, Hiroaki Tabata, Mikihito Nakamori, Masaki Nakamura, Masahiro Katsuda, Motoki Miyazawa, Keiji Hayata, Hiroki Yamaue
The difficulty in obtaining a sufficient number of functional dendritic cells(DCs)is a well-known serious problem in DCbased immunotherapy. Therefore, we used induced pluripotent stem cell-derived DCs(iPSDCs). We have reported that mouse iPSDCs are equivalent to BMDCs, in terms of maturation and antigen presentation. In this study, the antitumor immune response of human iPSDCs expressing the carcinoembryonic antigen was examined, to determine its clinical application in gastrointestinal cancer. Human iPS cells were established from healthy human fibroblasts using a Sendai virus vector, and human iPSDCs were differentiated under a feeder-free culture...
September 2016: Gan to Kagaku Ryoho. Cancer & Chemotherapy
https://www.readbyqxmd.com/read/27621475/loss-of-rig-i-leads-to-a-functional-replacement-with-mda5-in-the-chinese-tree-shrew
#17
Ling Xu, Dandan Yu, Yu Fan, Li Peng, Yong Wu, Yong-Gang Yao
The function of the RIG-I-like receptors (RLRs; including RIG-I, MDA5, and LGP2) as key cytoplasmic sensors of viral pathogen-associated molecular patterns (PAMPs) has been subjected to numerous pathogenic challenges and has undergone a dynamic evolution. We found evolutionary evidence that RIG-I was lost in the Chinese tree shrew lineage. Along with the loss of RIG-I, both MDA5 (tMDA5) and LGP2 (tLGP2) have undergone strong positive selection in the tree shrew. tMDA5 or tMDA5/tLGP2 could sense Sendai virus (an RNA virus posed as a RIG-I agonist) for inducing type I IFN, although conventional RIG-I and MDA5 were thought to recognize distinct RNA structures and viruses...
September 27, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27617014/neutrophil-extracellular-traps-enhance-early-inflammatory-response-in-sendai-virus-induced-asthma-phenotype
#18
Antonina Akk, Luke E Springer, Christine T N Pham
Paramyxoviral infection in childhood has been linked to a significant increased rate of asthma development. In mice, paramyxoviral infection with the mouse parainfluenza virus type I, Sendai virus (Sev), causes a limited bronchiolitis followed by persistent asthma traits. We have previously shown that the absence of cysteine protease dipeptidyl peptidase I (DPPI) dampened the acute lung inflammatory response and the subsequent asthma phenotype induced by Sev. Adoptive transfer of wild-type neutrophils into DPPI-deficient mice restored leukocyte influx, the acute cytokine response, and the subsequent mucous cell metaplasia that accompanied Sev-induced asthma phenotype...
2016: Frontiers in Immunology
https://www.readbyqxmd.com/read/27606350/sendai-virus-an-rna-virus-with-no-risk-of-genomic-integration-delivers-crispr-cas9-for-efficient-gene-editing
#19
Arnold Park, Patrick Hong, Sohui T Won, Patricia A Thibault, Frederic Vigant, Kasopefoluwa Y Oguntuyo, Justin D Taft, Benhur Lee
The advent of RNA-guided endonuclease (RGEN)-mediated gene editing, specifically via CRISPR/Cas9, has spurred intensive efforts to improve the efficiency of both RGEN delivery and targeted mutagenesis. The major viral vectors in use for delivery of Cas9 and its associated guide RNA, lentiviral and adeno-associated viral systems, have the potential for undesired random integration into the host genome. Here, we repurpose Sendai virus, an RNA virus with no viral DNA phase and that replicates solely in the cytoplasm, as a delivery system for efficient Cas9-mediated gene editing...
2016: Molecular Therapy. Methods & Clinical Development
https://www.readbyqxmd.com/read/27600544/simultaneous-mutation-of-g275a-and-p276a-in-the-matrix-protein-of-newcastle-disease-virus-decreases-virus-replication-and-budding
#20
Haixu Xu, Zhiqiang Duan, Yu Chen, Jiajia Liu, Xin Cheng, Jingjing Liu, Jie Zhu, Xiaoquan Wang, Xiaowen Liu, Shunlin Hu, Xiufan Liu
The matrix (M) protein of Newcastle disease virus (NDV) is a highly conserved hydrophobic viral protein. In some paramyxoviruses (measles virus and Sendai virus), the paired glycine (G) near the C terminus of the M protein may form a turn that mediates the specific interaction with the cell membrane. Similar amino acids (glycine-proline [GP], at position 275-276) exist in the M protein of NDV. However, the role of these residues in the replication and pathogenicity of NDV is unknown. In this study, recombinant NDV with the sequence GP/AA or LGP/GGL in the M protein was generated to investigate the role of this conserved sequence...
December 2016: Archives of Virology
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