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https://www.readbyqxmd.com/read/28531165/a-japanese-encephalitis-virus-vaccine-inducing-antibodies-strongly-enhancing-in-vitro-infection-is-protective-in-pigs
#1
Obdulio García-Nicolás, Meret E Ricklin, Matthias Liniger, Nathalie J Vielle, Sylvie Python, Philippe Souque, Pierre Charneau, Artur Summerfield
The Japanese encephalitis virus (JEV) is responsible for zoonotic severe viral encephalitis transmitted by Culex mosquitoes. Although birds are reservoirs, pigs play a role as amplifying hosts, and are affected in particular through reproductive failure. Here, we show that a lentiviral JEV vector, expressing JEV prM and E proteins (TRIP/JEV.prME), but not JEV infection induces strong antibody-dependent enhancement (ADE) activities for infection of macrophages. Such antibodies strongly promoted infection via Fc receptors...
May 22, 2017: Viruses
https://www.readbyqxmd.com/read/28530235/hit-and-go-cas9-delivered-through-a-lentiviral-based-self-limiting-circuit
#2
Gianluca Petris, Antonio Casini, Claudia Montagna, Francesca Lorenzin, Davide Prandi, Alessandro Romanel, Jacopo Zasso, Luciano Conti, Francesca Demichelis, Anna Cereseto
In vivo application of the CRISPR-Cas9 technology is still limited by unwanted Cas9 genomic cleavages. Long-term expression of Cas9 increases the number of genomic loci non-specifically cleaved by the nuclease. Here we develop a Self-Limiting Cas9 circuit for Enhanced Safety and specificity (SLiCES) which consists of an expression unit for Streptococcus pyogenes Cas9 (SpCas9), a self-targeting sgRNA and a second sgRNA targeting a chosen genomic locus. The self-limiting circuit results in increased genome editing specificity by controlling Cas9 levels...
May 22, 2017: Nature Communications
https://www.readbyqxmd.com/read/28529599/snail-homolog-1-is-involved-in-epithelial-mesenchymal-transition-like-processes-in-human-glioblastoma-cells
#3
Caspar D Kühnöl, Carina Würfel, Martin S Staege, Christof Kramm
Despite advancements in neurosurgery, chemotherapy and radiation therapy, the outcome of patients with glioblastoma remains poor. The migration of tumor cells from the primary tumor site with subsequent invasion of these cells into the surrounding normal brain tissue is frequently responsible for relapse and treatment failure. The present study hypothesized that snail homolog 1 (SNAI1), a factor critically involved in the epithelial-mesenchymal transition (EMT) of human carcinoma cells, may also contribute to an invasive EMT-like phenotype of glioblastoma cells...
May 2017: Oncology Letters
https://www.readbyqxmd.com/read/28528701/expansion-and-purification-are-critical-for-the-therapeutic-application-of-pluripotent-stem-cell-derived-myogenic-progenitors
#4
Jaemin Kim, Alessandro Magli, Sunny S K Chan, Vanessa K P Oliveira, Jianbo Wu, Radbod Darabi, Michael Kyba, Rita C R Perlingeiro
Recent reports have documented the differentiation of human pluripotent stem cells toward the skeletal myogenic lineage using transgene- and cell purification-free approaches. Although these protocols generate myocytes, they have not demonstrated scalability, safety, and in vivo engraftment, which are key aspects for their future clinical application. Here we recapitulate one prominent protocol, and show that it gives rise to a heterogeneous cell population containing myocytes and other cell types. Upon transplantation, the majority of human donor cells could not contribute to myofiber formation...
May 18, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/28528695/protein-phosphatase-5-promotes-hepatocarcinogenesis-through-interaction-with-amp-activated-protein-kinase
#5
Yao-Li Chen, Man-Hsin Hung, Pei-Yi Chu, Tzu-I Chao, Ming-Hsien Tsai, Li-Ju Chen, Yung-Jen Hsiao, Chih-Ting Shih, Feng-Shu Hsieh, Kuen-Feng Chen
The serine-threonine protein phosphatase family members are known as critical regulators of various cellular functions, such as survival and transformation. Growing evidence suggests that pharmacological manipulation of phosphatase activity exhibits therapeutic benefits. Ser/Thr protein phosphatase 5 (PP5) is known to participate in glucocorticoid receptor (GR) and stress-induced signaling cascades that regulate cell growth and apoptosis, and has been shown to be overexpressed in various human malignant diseases...
May 18, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/28526038/phosphorylation-of-tau-at-y18-but-not-tau-fyn-binding-is-required-for-tau-to-modulate-nmda-receptor-dependent-excitotoxicity-in-primary-neuronal-culture
#6
Takashi Miyamoto, Liana Stein, Reuben Thomas, Biljana Djukic, Praveen Taneja, Joseph Knox, Keith Vossel, Lennart Mucke
BACKGROUND: Hyperexcitability of neuronal networks can lead to excessive release of the excitatory neurotransmitter glutamate, which in turn can cause neuronal damage by overactivating NMDA-type glutamate receptors and related signaling pathways. This process (excitotoxicity) has been implicated in the pathogenesis of many neurological conditions, ranging from childhood epilepsies to stroke and neurodegenerative disorders such as Alzheimer's disease (AD). Reducing neuronal levels of the microtubule-associated protein tau counteracts network hyperexcitability of diverse causes, but whether this strategy can also diminish downstream excitotoxicity is less clear...
May 19, 2017: Molecular Neurodegeneration
https://www.readbyqxmd.com/read/28525970/the-immunoregulatory-role-of-alpha-enolase-in-dendritic-cell-function-during-chlamydia-infection
#7
Khamia Ryans, Yusuf Omosun, Danielle N McKeithen, Tankya Simoneaux, Camilla C Mills, Nathan Bowen, Francis O Eko, Carolyn M Black, Joseph U Igietseme, Qing He
BACKGROUND: We have previously reported that interleukin-10 (IL-10) deficient dendritic cells (DCs) are potent antigen presenting cells that induced elevated protective immunity against Chlamydia. To further investigate the molecular and biochemical mechanism underlying the superior immunostimulatory property of IL-10 deficient DCs we performed proteomic analysis on protein profiles from Chlamydia-pulsed wild-type (WT) and IL-10(-/-) DCs to identify differentially expressed proteins with immunomodulatory properties...
May 19, 2017: BMC Immunology
https://www.readbyqxmd.com/read/28525387/sestrin-2-suppresses-cells-proliferation-through-ampk-mtorc1-pathway-activation-in-colorectal-cancer
#8
Jin-Lai Wei, Min Fang, Zhong-Xue Fu, Shou-Ru Zhang, Jin-Bao Guo, Rong Wang, Zhen-Bing Lv, Yong-Fu Xiong
Sestrin 2 is a conserved antioxidant protein that reduces reactive oxygen species (ROS) and inhibits mammalian target of rapamycin complex 1 (mTORC1). We previously showed that sestrin 2 is abnormally decreased in colorectal cancer (CRC). To elucidate the molecular mechanism behind the potential contribution of sestrin 2 to CRC, we used a lentiviral expression vector system to determine the effects of sestrin 2 overexpression on human CRC cells. We found that sestrin 2 overexpression decreased ROS production, inhibited cell growth, and stimulated apoptosis in two CRC cell lines...
May 3, 2017: Oncotarget
https://www.readbyqxmd.com/read/28522262/transglutaminase-2-modulation-of-nf-%C3%AE%C2%BAb-signaling-in-astrocytes-is-independent-of-its-ability-to-mediate-astrocytic-viability-in-ischemic-injury
#9
Julianne Feola, Alan Barton, Abdullah Akbar, Jeffrey Keillor, Gail V W Johnson
Transglutaminase 2 (TG2) is a multifunctional protein that can contribute to cell death and cell survival processes in a variety of disease contexts. Within the brain, TG2 has been shown to promote cell death in ischemic injury when expressed in astrocytes (Colak and Johnson, 2012). However, the specific functions and characteristics of astrocytic TG2 that mediate this effect are largely unknown. Therefore, the goal of this study was to investigate the role of astrocytic TG2 in mediating cellular viability processes in the context of ischemic injury, with a specific focus on its contributions to intracellular signaling cascades...
May 15, 2017: Brain Research
https://www.readbyqxmd.com/read/28520795/birc6-mediates-imatinib-resistance-independently-of-mcl-1
#10
Denis O Okumu, Michael P East, Merlin Levine, Laura E Herring, Raymond Zhang, Thomas S K Gilbert, David W Litchfield, Yanping Zhang, Lee M Graves
Baculoviral IAP repeat containing 6 (BIRC6) is a member of the inhibitors of apoptosis proteins (IAPs), a family of functionally and structurally related proteins that inhibit apoptosis. BIRC6 has been implicated in drug resistance in several different human cancers, however mechanisms regulating BIRC6 have not been extensively explored. Our phosphoproteomic analysis of an imatinib-resistant chronic myelogenous leukemia (CML) cell line (MYL-R) identified increased amounts of a BIRC6 peptide phosphorylated at S480, S482, and S486 compared to imatinib-sensitive CML cells (MYL)...
2017: PloS One
https://www.readbyqxmd.com/read/28516844/clues-for-two-step-virion-infectivity-factor-regulation-by-core-binding-factor-beta
#11
Youwei Ai, Jianzhang Ma, Xiaojun Wang
Lentiviruses threaten human and animal health. Virion infectivity factor (Vif) is essential for the infectivity of most lentiviruses, except for the equine infectious anaemia virus (EIAV). Vif promotes viral infectivity by recruiting a Cullin-based E3 ligase to induce the degradation of a class of host restriction factors, named APOBEC3. Core binding factor beta (CBF-β) is necessary for several primate lentiviral Vif functions, including HIV-1 Vif. Although much progress has been made in understanding the contribution of CBF-β to Vif function, the precise mechanism has not yet been fully elucidated...
May 18, 2017: Journal of General Virology
https://www.readbyqxmd.com/read/28515942/a-tandem-cd19-cd20-car-lentiviral-vector-drives-on-target-and-off-target-antigen-modulation-in-leukemia-cell-lines
#12
Dina Schneider, Ying Xiong, Darong Wu, Volker Nӧlle, Sarah Schmitz, Waleed Haso, Andrew Kaiser, Boro Dropulic, Rimas J Orentas
BACKGROUND: Clinical success with chimeric antigen receptor (CAR)- based immunotherapy for leukemia has been accompanied by the associated finding that antigen-escape variants of the disease are responsible for relapse. To target hematologic malignancies with a chimeric antigen receptor (CAR) that targets two antigens with a single vector, and thus potentially lessen the chance of leukemic escape mutations, a tandem-CAR approach was investigated. METHODS: Antigen binding domains from the FMC63 (anti-CD19) and Leu16 (anti-CD20) antibodies were linked in differing configurations to transmembrane and T cell signaling domains to create tandem-CARs...
2017: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/28512685/modeling-brain-lentiviral-infections-during-antiretroviral-therapy-in-aids
#13
Weston C Roda, Michael Y Li, Michael S Akinwumi, Eugene L Asahchop, Benjamin B Gelman, Kenneth W Witwer, Christopher Power
Understanding HIV-1 replication and latency in different reservoirs is an ongoing challenge in the care of patients with HIV/AIDS. A mathematical model was created to describe and predict the viral dynamics of HIV-1 and SIV infection within the brain during effective combination antiretroviral therapy (cART). The mathematical model was formulated based on the biology of lentiviral infection of brain macrophages and used to describe the dynamics of transmission and progression of lentiviral infection in brain...
May 16, 2017: Journal of Neurovirology
https://www.readbyqxmd.com/read/28510612/suppression-of-id1-expression-in-colon-cancer-cells-increases-sensitivity-to-5-fluorouracil
#14
Tomasz Przybyła, Monika Sakowicz-Burkiewicz, Izabela Maciejewska, Hanna Bielarczyk, Tadeusz Pawełczyk
Adjuvant chemotherapy with 5-fluorouracil remains the basic treatment for patients with advanced colorectal carcinoma. The major obstacle in successful treatment is the ability of CRC cells to acquire chemoresistance. Here we examined the impact of ID1 silencing on the sensitivity of CRC cells to 5-FU. To suppress ID1 expression in HT-29 and HCT-116 cells the cells were transduced with a lentiviral vector carrying the ID1 silencing sequence. Cells with silenced ID1 showed altered expression of epithelial and mesenchymal markers and exhibited increased proliferation rate compared to the parental cells...
May 17, 2017: Acta Biochimica Polonica
https://www.readbyqxmd.com/read/28510330/rhesus-macaque-ipsc-generation-and-maintenance
#15
Ravi Chandra Yada, So Gun Hong, Yongshun Lin, Thomas Winkler, Cynthia E Dunbar
The rhesus macaque (Macaca mulatta) is physiologically and phylogenetically similar to humans, and therefore represents an invaluable model for the pre-clinical assessment of the safety and feasibility of iPSC-derived cell therapies. The use of an excisable polycistronic lentiviral STEMCCA vector to reprogram rhesus fibroblasts or bone marrow stromal cells (BMSCs) into RhiPSCs is described. After reprogramming, the pluripotency transgenes can be removed by transient expression of Cre, leaving a residual genetic tag that may be useful for identification of RhiPSC-derived tissues in vivo...
May 16, 2017: Current Protocols in Stem Cell Biology
https://www.readbyqxmd.com/read/28506831/cryab-promotes-the-invasion-and-metastasis-of-colorectal-cancer-via-epithelial-mesenchymal-transition
#16
Chuanbing Shi, Xiaojun Yang, Xiaodong Bu, Ning Hou, Pingsheng Chen
Alpha B-crystallin (CRYAB, HSPB5) is a protein that was first discovered in the lens of the eye. It is a member of the small heat-shock protein family (sHsps). CRYAB functions primarily as a molecular chaperone to prevent the aggregation and degradation of damaged unfolded proteins due to cellular damage resulting from heat shock, radiation, oxidative stress, and other insults, thereby promoting cell survival and preventing apoptosis. In recent years, the role of CRYAB in tumorigenesis, tumor invasion, and metastasis has received increasing attention...
May 12, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28506571/tumor-necrosis-factor-receptor-associated-factor-traf-6-inhibition-mitigates-the-pro-inflammatory-roles-and-proliferation-of-rheumatoid-arthritis-fibroblast-like-synoviocytes
#17
Lang-Jing Zhu, Tie-Cheng Yang, Qiang Wu, Li-Ping Yuan, Zhen-Wei Chen, Min-Hong Luo, Hai-Ou Zeng, Dong-Ling He, Cai-Ju Mo
BACKGROUND: Rheumatoid arthritis (RA) fibroblast-like synoviocytes (FLSs) play a crucial role in RA through producing inflammatory cytokines and proteases which could cause cartilage destruction. We showed previously that elevated expression of tumor necrosis factor receptor-associated factor 6 (TRAF6) in RA synovium correlated significantly with the severity of synovitis and the number of infiltrated inflammatory cells. The aims of this study are to detect the roles of TRAF6 in RA-FLSs...
May 12, 2017: Cytokine
https://www.readbyqxmd.com/read/28506310/unexpected-evolutionarily-conserved-rapid-effects-of-viral-infection-on-oxytocin-receptor-and-tgf-%C3%AE-psmad3
#18
Yutong Liu, Irina Conboy
BACKGROUND: shRNA lentiviral vectors are extensively used for gene knockdowns in mammalian cells, and non-target shRNAs typically are considered the proper experimental control for general changes caused by RNAi. However, the effects of non-target lentivirus controls on the modulation of cell signaling pathways remain largely unknown. In this study, we evaluated the effect of control lentiviral transduction on oxytocin receptor (OXTR) expression through the ERK/MAPK pathway in mouse and human skeletal muscle cells, on myogenic activity, and in vivo on mouse muscle regeneration...
May 15, 2017: Skeletal Muscle
https://www.readbyqxmd.com/read/28505239/foxo1-promotes-mitophagy-in-the-podocytes-of-diabetic-male-mice-via-the-pink1-parkin-pathway
#19
Wen Li, Mengmeng Du, Qingzhu Wang, Xiaojun Ma, Lina Wu, Feng Guo, Hongfei Ji, Fengjuan Huang, Guijun Qin
We recently showed that Forkhead-box class O1 (FoxO1) activation protects against high glucose-induced injury by preventing mitochondrial dysfunction in the rat kidney cortex. In addition, FoxO1 has been reported to mediate PINK1 transcription and promote autophagy in response to mitochondrial oxidative stress in murine cardiomyocytes. In this study, we ascertained whether over-expressing FoxO1 in the kidney cortex reverses pre-established diabetic nephropathy in animal models. The effect of FoxO1 on mitophagy signaling pathways was evaluated in mouse podocytes...
May 12, 2017: Endocrinology
https://www.readbyqxmd.com/read/28504970/osteoclast-proton-pump-regulator-atp6v1c1-enhances-breast-cancer-growth-by-activating-the-mtorc1-pathway-and-bone-metastasis-by-increasing-v-atpase-activity
#20
Matthew McConnell, Shengmei Feng, Wei Chen, Guochun Zhu, Dejun Shen, Selvarangan Ponnazhagan, Lianfu Deng, Yi-Ping Li
It is known that V-ATPases (vacuolar H+-ATPase) are involved in breast cancer growth and metastasis. Part of this action is similar to their role in osteoclasts, where they're involved in extracellular acidification and matrix destruction; however, the roles of their subunits in cancer cell proliferation, signaling, and other pro-tumor actions are not well established. Analysis of TCGA data shows that V-ATPase subunit Atp6v1c1 is overexpressed or amplified in 34% of human breast cancer cases, with a 2-fold decrease in survival at 12 years...
May 2, 2017: Oncotarget
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