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https://www.readbyqxmd.com/read/28430604/signal-transducing-adaptor-protein-2-promotes-generation-of-functional-long-term-memory-cd8-t-cells-by-preventing-terminal-effector-differentiation
#1
Daisuke Muraoka, Naohiro Seo, Tae Hayashi, Chisaki Hyuga-Amaike, Kana Okamori, Isao Tawara, Naozumi Harada, Hiroshi Shiku
Long-surviving memory CD8+ T cells generated by stimulation with appropriate tumor-associated antigens are the most aggressive and persistent tumoricidal effectors. In this event of memory CD8+ T cell development, the signal transducer and activator of transcription (STAT) proteins function as the crucial intracellular signaling molecules, but the regulatory mechanism of STATs in CD8+ T cells is not fully understood. In this study, we report for the first time, by using murine vaccination models, that signal-transducing adaptor protein-2 (STAP2) maintains the cytotoxicity of long-lived memory CD8+ T cells by controlling a STAT3/suppressor of cytokine signaling 3 (SOCS3) cascade...
February 16, 2017: Oncotarget
https://www.readbyqxmd.com/read/28427901/the-20kda-and-22kda-forms-of-human-growth-hormone-hgh-exhibit-different-intracellular-signalling-profiles-and-properties
#2
Liu Yao-Xia, Chen Jing-Yan, Tang Xia-Lian, Chen Ping, Zhang Min
Human Growth Hormone (hGH) includes two main variants. The first is 22 kilodalton GH (22K-GH), which is predominant in the blood circulation. The second most abundant variant is 20K-GH, which makes up 5-10% of the blood circulation. Both bind and activate the same receptor, called the human growth hormone receptor (GHR). However, the reason why 22K-GH and 20K-GH exhibit similar, but not identical physiological activities remains poorly understood. In this article, the intracellular signalling profiles between these two hormones were examined...
April 17, 2017: General and Comparative Endocrinology
https://www.readbyqxmd.com/read/28427458/whole-exome-sequencing-identifies-novel-candidate-predisposition-genes-for-familial-polycythemia-vera
#3
Elina A M Hirvonen, Esa Pitkänen, Kari Hemminki, Lauri A Aaltonen, Outi Kilpivaara
BACKGROUND: Polycythemia vera (PV), characterized by massive production of erythrocytes, is one of the myeloproliferative neoplasms. Most patients carry a somatic gain-of-function mutation in JAK2, c.1849G > T (p.Val617Phe), leading to constitutive activation of JAK-STAT signaling pathway. Familial clustering is also observed occasionally, but high-penetrance predisposition genes to PV have remained unidentified. RESULTS: We studied the predisposition to PV by exome sequencing (three cases) in a Finnish PV family with four patients...
April 20, 2017: Human Genomics
https://www.readbyqxmd.com/read/28427244/whole-genome-expression-analyses-of-type-2-diabetes-in-human-skin-reveal-altered-immune-function-and-burden-of-infection
#4
Chun Wu, Xiaopan Chen, Jing Shu, Chun-Ting Lee
Skin disorders are among most common complications associated with type 2 diabetes mellitus (T2DM). Although T2DM patients are known to have increased risk of infections and other T2DM-related skin disorders, their molecular mechanisms are largely unknown. This study aims to identify dysregulated genes and gene networks that are associated with T2DM in human skin. We compared the expression profiles of 56,318 transcribed genes on 74 T2DM cases and 148 gender- age-, and race-matched non-diabetes controls from the Genotype-Tissue Expression (GTEx) database...
March 11, 2017: Oncotarget
https://www.readbyqxmd.com/read/28426026/generation-of-multipotent-induced-cardiac-progenitor-cells-from-mouse-fibroblasts-and-potency-testing-in-ex-vivo-mouse-embryos
#5
Pratik A Lalit, Adriana M Rodriguez, Karen M Downs, Timothy J Kamp
Here we describe a protocol to generate expandable and multipotent induced cardiac progenitor cells (iCPCs) from mouse adult fibroblasts using forced expression of Mesp1, Tbx5, Gata4, Nkx2.5 and Baf60c (MTGNB) along with activation of Wnt and JAK/STAT signaling. This method does not use iPS cell factors and thus differs from cell activation and signaling-directed (CASD) reprogramming to cardiac progenitors. Our method is specific to direct CPC reprogramming, whereas CASD reprogramming can generate various cell types depending on culture conditions and raises the possibility of transitioning through a pluripotent cell state...
May 2017: Nature Protocols
https://www.readbyqxmd.com/read/28425748/a-field-analysis-trial-comparing-the-turnaround-times-of-routine-and-stat-red-blood-cell-immunohematology-testing
#6
Katie Sackett, Andrea Kjell, Abigail M Schneider, Claudia S Cohn
The turnaround time (TAT) for pre-transfusion testing is important for prompt clinical decision-making. TAT includes the time between the arrival of the sample and the initiation of testing, plus the processing time (PT) required to generate and report a result. The TAT in larger blood banks is mostly dependent upon the capability of the analyzer used. In smaller blood banks, where manual work is often performed, the TAT is dependent on availability and experience of staff, testing resources, and workload. Our site performed a comparative analysis of the ORTHO VISION® (Ortho Clinical Diagnostics, Raritan, NJ) and the Echo® (Immucor, Norcross, GA) blood bank analyzers, using the TAT and PT of standard blood bank tests as the outcome metrics...
January 2017: Immunohematology
https://www.readbyqxmd.com/read/28424262/magnesium-reduces-hepatic-lipid-accumulation-in-yellow-catfish-pelteobagrus-fulvidraco-and-modulates-lipogenesis-and-lipolysis-via-ppara-jak-stat-and-ampk-pathways-in-hepatocytes
#7
Chuan-Chuan Wei, Kun Wu, Yan Gao, Li-Han Zhang, Dan-Dan Li, Zhi Luo
Background: Magnesium influences hepatic lipid deposition in vertebrates, but the underlying mechanism is unknown.Objective: We used yellow catfish and their isolated hepatocytes to test the hypothesis that magnesium influences lipid deposition by modulating lipogenesis and lipolysis.Methods: Juvenile yellow catfish (mean ± SEM weight: 3.43 ± 0.02 g, 3 mo old, mixed sex) were fed a 0.14- (low), 0.87- (intermediate) or 2.11- (high) g Mg/kg diet for 56 d. Primary hepatocytes were incubated for 48 h in control or MgSO4-containing medium with or without 2-h pretreatment with an inhibitor (AG490, GW6471, or Compound C)...
April 19, 2017: Journal of Nutrition
https://www.readbyqxmd.com/read/28424246/enteropathy-associated-t-cell-lymphoma-subtypes-are-characterized-by-loss-of-function-of-setd2
#8
Andrea B Moffitt, Sarah L Ondrejka, Matthew McKinney, Rachel E Rempel, John R Goodlad, Chun Huat Teh, Sirpa Leppa, Susanna Mannisto, Panu E Kovanen, Eric Tse, Rex K H Au-Yeung, Yok-Lam Kwong, Gopesh Srivastava, Javeed Iqbal, Jiayu Yu, Kikkeri Naresh, Diego Villa, Randy D Gascoyne, Jonathan Said, Magdalena B Czader, Amy Chadburn, Kristy L Richards, Deepthi Rajagopalan, Nicholas S Davis, Eileen C Smith, Brooke C Palus, Tiffany J Tzeng, Jane A Healy, Patricia L Lugar, Jyotishka Datta, Cassandra Love, Shawn Levy, David B Dunson, Yuan Zhuang, Eric D Hsi, Sandeep S Dave
Enteropathy-associated T cell lymphoma (EATL) is a lethal, and the most common, neoplastic complication of celiac disease. Here, we defined the genetic landscape of EATL through whole-exome sequencing of 69 EATL tumors. SETD2 was the most frequently silenced gene in EATL (32% of cases). The JAK-STAT pathway was the most frequently mutated pathway, with frequent mutations in STAT5B as well as JAK1, JAK3, STAT3, and SOCS1 We also identified mutations in KRAS, TP53, and TERT Type I EATL and type II EATL (monomorphic epitheliotropic intestinal T cell lymphoma) had highly overlapping genetic alterations indicating shared mechanisms underlying their pathogenesis...
April 19, 2017: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/28424232/spatiotemporal-regulation-of-cell-fusion-by-jnk-and-jak-stat-signaling-during-drosophila-wound-healing
#9
Ji-Hyun Lee, Chan-Wool Lee, Si-Hyoung Park, Kwang-Min Choe
Cell-cell fusion is widely observed during development and disease and imposes a dramatic change on participating cells. Cell fusion should be tightly controlled, but the underlying mechanism is poorly understood. Here, we found that the JAK/STAT pathway suppressed cell fusion during wound healing and delimited the event to the vicinity of the wound in the Drosophila larval epidermis. In the absence of JAK/STAT signaling, a large syncytium containing 3-fold the number of nuclei observed in wild-type tissue formed in wounded epidermis...
April 19, 2017: Journal of Cell Science
https://www.readbyqxmd.com/read/28422733/the-transcriptional-stat3-is-a-potential-target-whereas-transcriptional-stat5a-5b-6-are-new-biomarkers-for-prognosis-in-human-breast-carcinoma
#10
Hua-Tao Wu, Jing Liu, Guan-Wu Li, Jia-Xin Shen, Yi-Teng Huang
Signal Transducer and Activators of Transcription (STAT) is a set of transcription factors, involved in diverse cellular functions. Evidences from cell lines, mouse models and human tissues implicate these transcription factors in the oncogenesis of breast cancer. However, the diverse expression patterns and prognostic values of 7 STATs remain to be elucidated. In the current study, we mined the transcriptional and survival data of STATs in patients with breast carcinoma (BC) through ONCOMINE, bc-GenExMiner, Kaplan-Meier Plotter and cBioPortal...
March 31, 2017: Oncotarget
https://www.readbyqxmd.com/read/28422713/sel120-34a-is-a-novel-cdk8-inhibitor-active-in-aml-cells-with-high-levels-of-serine-phosphorylation-of-stat1-and-stat5-transactivation-domains
#11
Tomasz Rzymski, Michał Mikula, Eliza Żyłkiewicz, Agnieszka Dreas, Katarzyna Wiklik, Aniela Gołas, Katarzyna Wójcik, Magdalena Masiejczyk, Anna Wróbel, Izabela Dolata, Agata Kitlińska, Małgorzata Statkiewicz, Urszula Kuklinska, Krzysztof Goryca, Łukasz Sapała, Aleksandra Grochowska, Aleksandra Cabaj, Małgorzata Szajewska-Skuta, Ewelina Gabor-Worwa, Katarzyna Kucwaj, Arkadiusz Białas, Adam Radzimierski, Michał Combik, Jakub Woyciechowski, Maciej Mikulski, Renata Windak, Jerzy Ostrowski, Krzysztof Brzózka
Inhibition of oncogenic transcriptional programs is a promising therapeutic strategy. A substituted tricyclic benzimidazole, SEL120-34A, is a novel inhibitor of Cyclin-dependent kinase 8 (CDK8), which regulates transcription by associating with the Mediator complex. X-ray crystallography has shown SEL120-34A to be a type I inhibitor forming halogen bonds with the protein's hinge region and hydrophobic complementarities within its front pocket. SEL120-34A inhibits phosphorylation of STAT1 S727 and STAT5 S726 in cancer cells in vitro...
April 4, 2017: Oncotarget
https://www.readbyqxmd.com/read/28420927/in-silico-analysis-of-fragile-histidine-triad-involved-in-regression-of-carcinoma
#12
Muhammad Asif Rasheed, Fatima Tariq, Sara Afzal, Shazia Mannanv
Hepatocellular carcinoma (HCCa) is a primary malignancy of the liver. Many different proteins are involved in HCCa including insulin growth factor (IGF) II , signal transducers and activators of transcription (STAT) 3, STAT4, mothers against decapentaplegic homolog 4 (SMAD 4), fragile histidine triad (FHIT) and selective internal radiation therapy (SIRT) etc. The present study is based on the bioinformatics analysis of FHIT protein in order to understand the proteomics aspect and improvement of the diagnosis of the disease based on the protein...
April 2017: JPMA. the Journal of the Pakistan Medical Association
https://www.readbyqxmd.com/read/28420489/mast-cells-emerge-as-mediators-of-atherosclerosis-special-emphasis-on-il-37-inhibition
#13
REVIEW
Pio Conti, Gianfranco Lessiani, Spyridon K Kritas, Gianpaolo Ronconi, Aessandro Caraffa, Theoharis C Theoharides
In atherosclerosis lipoproteins stimulate the innate immune response, leading to the release of inflammatory cytokines and chemokines. Hypercholesterolemia may activate the synthesis and release of inflammatory cytokines such as IL-1, which induces TNF release in mast cells (MCs). IL-1 and IL-1 family members orchestrate a broadening list of inflammatory diseases, including atherosclerosis. MCs are implicated in the pathophysiology of several diseases including allergy and inflammation. Activated MCs, located perivascularly, contribute to inflammation in atherosclerosis by producing inflammatory cytokines...
April 12, 2017: Tissue & Cell
https://www.readbyqxmd.com/read/28420002/associations-between-stat-gene-polymorphisms-and-psoriasis-in-northeastern-china
#14
Jing Zhou, Yuzhen Li, Donglin Sun
BACKGROUND: Psoriasis is an autoimmune disease with genetic and environmental factors. Based on the roles of STATs (signaling transducers and activators of transcription) in autoimmune diseases, it is assumed STAT gene polymorphisms are associated with psoriasis. OBJECTIVES: To study the association between STAT gene polymorphisms and psoriasis in the northeastern Chinese population. METHODS: Eight single-nucleotide polymorphisms were genotyped: rs2293152, rs3816769, rs4796793, and rs744166 in STAT3, rs7574865 and rs3024866 in STAT4, and rs324011 and rs3024974 in STAT6, using SNaPshot methods...
April 19, 2017: Dermatology: International Journal for Clinical and Investigative Dermatology
https://www.readbyqxmd.com/read/28419653/hcv-viremia-associates-with-nk-cell-activation-and-dysfunction-in-anti-retroviral-hiv-hcv-co-infected-subjects
#15
E Papasavvas, L Azzoni, X Yin, Q Liu, J Joseph, A Mackiewicz, B Ross, K M Lynn, J M Jacobson, K Mounzer, J R Kostman, L J Montaner
The impact of Hepatitis C virus (HCV) RNA levels on immune status in chronically HCV mono-infected when compared to HIV/HCV co-infected on antiretroviral therapy (ART) remains poorly understood. A total of 78 African American subjects HCV viremic/naïve to HCV treatment (33 HCV genotype 1 mono-infected, 45 HCV genotype 1/HIV co-infected on ART) were studied. Clinical and liver enzymes measurements were performed. Whole blood was analyzed for immune subset changes by flow-cytometry. Peripheral blood mononuclear cells (PBMC) were used for same-day constitutive and in vitro Interferon (IFN)-α-induced Signal Transducer and Activator of Transcription (STAT) phosphorylation, K562 target cell lysis and K562 target cell recognition-mediated IFN-γ production...
April 17, 2017: Journal of Viral Hepatitis
https://www.readbyqxmd.com/read/28419468/activation-of-the-akt-creb-signaling-axis-by-a-proline-rich-heptapeptide-confers-resistance-to-stress-induced-cell-death-and-inflammation
#16
Johannes Herkel, Jörg Schrader, Neta Erez, Ansgar W Lohse, Irun R Cohen
Cell stress of various kinds can lead to the induction of cell death and a damaging inflammatory response. Hence, a goal of therapeutic cell-stress management is to develop agents that might effectively regulate undesirable cell death and inflammation. To that end, we developed a synthetic peptide of 7 amino acids based on structural mimicry to a functional domain of p53, a key factor in the responses of cells to stressful stimuli. This heptapeptide, which we term Stressin-1, was found to inhibit both cell death and the secretion of inflammatory mediators by various cell types in response to different stressful agents in vitro...
April 17, 2017: Immunology
https://www.readbyqxmd.com/read/28417332/assessment-of-the-prognostic-and-discriminating-value-of-the-novel-bioscore-system-for-breast-cancer-a-seer-database-analysis
#17
Omar Abdel-Rahman
BACKGROUND: An updated bioscore has been proposed within the context of the 8th edition American Joint Committee on Cancer (AJCC) staging system for breast cancer. This study seeks to validate the discriminating value of this bioscore among non-metastatic breast cancer patients registered within the surveillance, epidemiology, and end results (SEER) database. METHODS: Through SEER*Stat program, SEER database (2010-2013) was accessed and bioscore was formulated for each patient...
April 17, 2017: Breast Cancer Research and Treatment
https://www.readbyqxmd.com/read/28415697/down-regulation-of-interleukin-7-receptor-il-7r-contributes-to-central-nervous-system-demyelination
#18
Xudan Lei, Shijiao Cai, Yang Chen, Jianlin Cui, Yajie Wang, Zongjin Li, Yuhao Li
Interleukin 7 receptor (IL-7R) has been associated with the pathogenesis of multiple sclerosis (MS), though the mechanisms are not clear. Because myelin expression is highly conserved between zebrafish and mammals, zebrafish have become an ideal model for studying demyelination. We used a transgenic (Tg; mbp:nfsB-egfp) zebrafish line in which oligodendrocytes expressed green fluorescent protein (GFP) from the larval stage to adulthood. Exposing adult transgenic zebrafish to metronidazole induced demyelination that resembled the morphological changes associated with the early stages of MS...
March 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/28415601/regulatory-network-of-gata3-in-pediatric-acute-lymphoblastic-leukemia
#19
Qianqian Hou, Fei Liao, Shouyue Zhang, Duyu Zhang, Yan Zhang, Xueyan Zhou, Xuyang Xia, Yuanxin Ye, Hanshuo Yang, Zhaozhi Li, Leiming Wang, Xi Wang, Zhigui Ma, Yiping Zhu, Liang Ouyang, Yuelan Wang, Hui Zhang, Li Yang, Heng Xu, Yang Shu
GATA3 polymorphisms were reported to be significantly associated with susceptibility of pediatric B-lineage acute lymphoblastic leukemia (ALL), by impacting on GATA3 expression. We noticed that ALL-related GATA3 polymorphism located around in the tissue-specific enhancer, and significantly associated with GATA3 expression. Although the regulatory network of GATA3 has been well reported in T cells, the functional status of GATA3 is poorly understood in B-ALL. We thus conducted genome-wide gene expression association analyses to reveal expression associated genes and pathways in nine independent B-ALL patient cohorts...
March 21, 2017: Oncotarget
https://www.readbyqxmd.com/read/28415594/interaction-of-epstein-barr-virus-genes-with-human-gastric-carcinoma-transcriptome
#20
Ruiyuan Zhang, Michael J Strong, Melody Baddoo, Zhen Lin, Yu-Ping Wang, Erik K Flemington, Yao-Zhong Liu
Gastric carcinoma (GC) is a leading cause of mortality. 10% of GC cases are related with EBV (Epstein-Barr virus) infection. The detailed mechanistic roles EBV genes play and especially the interaction between the viral genes and human genes in GC remain unclear. In this study, raw fastq data from 285 GC samples were downloaded from TCGA (The Cancer Genome Atlas), including 25 EBV positive (EBV+) GC samples and 260 EBV negative (EBV-) GC samples. RNA-seq based expression data were generated for both human genes (among all the samples) and for the EBV genes (among the 25 EBV+ samples)...
March 21, 2017: Oncotarget
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