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https://www.readbyqxmd.com/read/28727807/digoxin-reveals-a-functional-connection-between-hiv-1-integration-preference-and-t-cell-activation
#1
Alexander Zhyvoloup, Anat Melamed, Ian Anderson, Delphine Planas, Chen-Hsuin Lee, Janos Kriston-Vizi, Robin Ketteler, Andy Merritt, Jean-Pierre Routy, Petronela Ancuta, Charles R M Bangham, Ariberto Fassati
HIV-1 integrates more frequently into transcribed genes, however the biological significance of HIV-1 integration targeting has remained elusive. Using a selective high-throughput chemical screen, we discovered that the cardiac glycoside digoxin inhibits wild-type HIV-1 infection more potently than HIV-1 bearing a single point mutation (N74D) in the capsid protein. We confirmed that digoxin repressed viral gene expression by targeting the cellular Na+/K+ ATPase, but this did not explain its selectivity. Parallel RNAseq and integration mapping in infected cells demonstrated that digoxin inhibited expression of genes involved in T-cell activation and cell metabolism...
July 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28711779/hyperactive-foxo1-results-in-lack-of-tip-stalk-identity-and-deficient-microvascular-regeneration-during-kidney-injury
#2
Lan T H Dang, Takahide Aburatani, Graham A Marsh, Bryce G Johnson, Stella Alimperti, Christine J Yoon, Angela Huang, Suzanne Szak, Naoki Nakagawa, Ivan Gomez, Shuyu Ren, Sarah K Read, Chris Sparages, Alfred C Aplin, Roberto F Nicosia, Chris Chen, Giovanni Ligresti, Jeremy S Duffield
Loss of the microvascular (MV) network results in tissue ischemia, loss of tissue function, and is a hallmark of chronic diseases. The incorporation of a functional vascular network with that of the host remains a challenge to utilizing engineered tissues in clinically relevant therapies. We showed that vascular-bed-specific endothelial cells (ECs) exhibit differing angiogenic capacities, with kidney microvascular endothelial cells (MVECs) being the most deficient, and sought to explore the underlying mechanism...
July 7, 2017: Biomaterials
https://www.readbyqxmd.com/read/28694034/insertion-and-deletion-derived-tumour-specific-neoantigens-and-the-immunogenic-phenotype-a-pan-cancer-analysis
#3
Samra Turajlic, Kevin Litchfield, Hang Xu, Rachel Rosenthal, Nicholas McGranahan, James L Reading, Yien Ning S Wong, Andrew Rowan, Nnennaya Kanu, Maise Al Bakir, Tim Chambers, Roberto Salgado, Peter Savas, Sherene Loi, Nicolai J Birkbak, Laurent Sansregret, Martin Gore, James Larkin, Sergio A Quezada, Charles Swanton
BACKGROUND: The focus of tumour-specific antigen analyses has been on single nucleotide variants (SNVs), with the contribution of small insertions and deletions (indels) less well characterised. We investigated whether the frameshift nature of indel mutations, which create novel open reading frames and a large quantity of mutagenic peptides highly distinct from self, might contribute to the immunogenic phenotype. METHODS: We analysed whole-exome sequencing data from 5777 solid tumours, spanning 19 cancer types from The Cancer Genome Atlas...
July 7, 2017: Lancet Oncology
https://www.readbyqxmd.com/read/28686611/yorkie-is-required-to-restrict-the-injury-responses-in-planarians
#4
Alexander Y T Lin, Bret J Pearson
Regeneration requires the precise integration of cues that initiate proliferation, direct differentiation, and ultimately re-pattern tissues to the proper size and scale. Yet how these processes are integrated with wounding responses remains relatively unknown. The freshwater planarian, Schmidtea mediterranea, is an ideal model to study the stereotyped proliferative and transcriptional responses to injury due to its high capacity for regeneration. Here, we characterize the effector of the Hippo signalling cascade, yorkie, during planarian regeneration and its role in restricting early injury responses...
July 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28671900/phenotyping-the-immune-response-to-trauma-a-multiparametric-systems-immunology-approach
#5
Anupamaa Seshadri, Gabriel A Brat, Brian K Yorkgitis, Joshua Keegan, James Dolan, Ali Salim, Reza Askari, James A Lederer
OBJECTIVE: Trauma induces a complex immune response that requires a systems biology research approach. Here, we used a novel technology, mass cytometry by time-of-flight, to comprehensively characterize the multicellular response to trauma. DESIGN: Peripheral blood mononuclear cells samples were stained with a 38-marker immunophenotyping cytometry by time-of-flight panel. Separately, matched peripheral blood mononuclear cells were stimulated in vitro with heat-killed Streptococcus pneumoniae or CD3/CD28 antibodies and stained with a 38-marker cytokine panel...
June 30, 2017: Critical Care Medicine
https://www.readbyqxmd.com/read/28593993/myc-activation-cooperates-with-vhl-and-ink4a-arf-loss-to-induce-clear-cell-renal-cell-carcinoma
#6
Sean T Bailey, Aleisha M Smith, Jordan Kardos, Sara E Wobker, Harper L Wilson, Bhavani Krishnan, Ryoichi Saito, Hyo Jin Lee, Jing Zhang, Samuel C Eaton, Lindsay A Williams, Ujjawal Manocha, Dorien J Peters, Xinchao Pan, Thomas J Carroll, Dean W Felsher, Vonn Walter, Qing Zhang, Joel S Parker, Jen Jen Yeh, Richard A Moffitt, Janet Y Leung, William Y Kim
Renal carcinoma is a common and aggressive malignancy whose histopathogenesis is incompletely understood and that is largely resistant to cytotoxic chemotherapy. We present two mouse models of kidney cancer that recapitulate the genomic alterations found in human papillary (pRCC) and clear cell RCC (ccRCC), the most common RCC subtypes. MYC activation results in highly penetrant pRCC tumours (MYC), while MYC activation, when combined with Vhl and Cdkn2a (Ink4a/Arf) deletion (VIM), produce kidney tumours that approximate human ccRCC...
June 8, 2017: Nature Communications
https://www.readbyqxmd.com/read/28520934/the-smap1-2-proteins-of-the-crenarchaeon-sulfolobus-solfataricus-interact-with-the-exosome-and-stimulate-a-rich-tailing-of-transcripts
#7
Birgit Märtens, Linlin Hou, Fabian Amman, Michael T Wolfinger, Elena Evguenieva-Hackenberg, Udo Bläsi
The conserved Sm and Sm-like proteins are involved in different aspects of RNA metabolism. Here, we explored the interactome of SmAP1 and SmAP2 of the crenarchaeon Sulfolobus solfataricus (Sso) to shed light on their physiological function(s). Both, SmAP1 and SmAP2 co-purified with several proteins involved in RNA-processing/modification, translation and protein turnover as well as with components of the exosome involved in 3΄ to 5΄ degradation of RNA. In follow-up studies a direct interaction with the poly(A) binding and accessory exosomal subunit DnaG was demonstrated...
May 18, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28414090/rituximab-treatment-circumvents-the-prognostic-impact-of-tumor-infiltrating-t-cells-in-follicular-lymphoma-patients
#8
Luc Xerri, Sarah Huet, Jeffrey M Venstrom, Edith Szafer-Glusman, Bettina Fabiani, Danielle Canioni, Catherine Chassagne-Clément, Peggy Dartigues-Cuilléres, Fréderic Charlotte, Camille Laurent, Benedicte Gelas-Dore, Christopher R Bolen, Elizabeth Punnoose, Reda Bouabdallah, Pauline Brice, Franck Morschhauser, Guillaume Cartron, Daniel Olive, Gilles Salles
Previous immunohistochemical (IHC) studies showed controversial data about the prognostic value of tumor infiltrating lymphocytes (TIL) in follicular lymphoma (FL). In order to clarify this issue, a large series of FL samples from rituximab-treated patients enrolled in the randomized PRIMA trial were examined. IHC was quantified using automated image analysis in 417, 287, 418, 406, 379, and 369 patients for CD3, CD4, CD8, PD1, ICOS, and FOXP3; respectively. RNAseq analysis was used to quantify TIL-related mRNA transcripts from 148 patients...
April 13, 2017: Human Pathology
https://www.readbyqxmd.com/read/28409421/the-impact-of-microenvironment-on-the-synovial-sarcoma-transcriptome
#9
Huifeng Jin, Jared J Barrott, Matthew G Cable, Michael J Monument, Daniel M Lerman, Kyllie Smith-Fry, Dakota Nollner, Kevin B Jones
Synovial sarcoma (SS) is initiated by a t(X;18) chromosomal translocation and resultant SS18-SSX fusion oncogene. Only a few SS cell lines exist. None has been compared to its source tumor. In order to compare matched tumor and cell line pairs, we performed RNAseq on 3 tumor/cell line pairs from a genetically engineered mouse model of SS, as well as 2 pairs from human SS tumors. Transcriptomes of mouse tumors and derivative cell lines deviated significantly. Differentially expressed genes highlighted inflammatory infiltrates and metabolism...
April 13, 2017: Cancer Microenvironment: Official Journal of the International Cancer Microenvironment Society
https://www.readbyqxmd.com/read/28405501/pdl1-expression-is-a-poor-prognosis-factor-in-soft-tissue-sarcomas
#10
François Bertucci, Pascal Finetti, Delphine Perrot, Agnès Leroux, Françoise Collin, Axel Le Cesne, Jean-Michel Coindre, Jean-Yves Blay, Daniel Birnbaum, Emilie Mamessier
Soft-tissue sarcomas (STS) are a group of rare, heterogeneous, and aggressive tumors, with high metastatic risk and relatively few efficient systemic therapies. In the quest for new treatments, the immune system represents an attractive therapeutic target. Recently, PD1/PDL1 inhibitors showed very promising results in patients with solid tumors. PDL1 expression has been rarely studied in STS, in small series only, by using immunohistochemistry (IHC), and with non-concordant prognostic implications. Here, we have analyzed PDL1 mRNA expression in 758 clinical STS samples retrospectively profiled using DNA microarrays and RNAseq, and searched for correlations with clinicopathological variables including metastasis-free survival (MFS) after surgery...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28400082/immune-dysregulation-in-immunodeficiency-disorders-the-role-of-t-cell-receptor-sequencing
#11
REVIEW
Gabriel K Wong, James M Heather, Sara Barmettler, Mark Cobbold
Immune dysregulation is a prominent feature of primary immunodeficiency disorders, which commonly manifested as autoimmunity, cytopenias and inflammatory bowel disease. In partial T-cell immunodeficiency disorders, it has been proposed that the imbalance between effector and regulatory T-cells drives the breakdown of peripheral tolerance. While there is no robust test for immune dysregulation, the T-cell receptor repertoire is used as a surrogate marker, and has been shown to be perturbed in a number of immunodeficiency disorders featuring immune dysregulation including Omenn's Syndrome, Wiskott-Aldrich Syndrome, and common variable immunodeficiency...
April 8, 2017: Journal of Autoimmunity
https://www.readbyqxmd.com/read/28383283/global-analysis-of-gene-expression-reveals-mrna-superinduction-is-required-for-the-inducible-immune-response-to-a-bacterial-pathogen
#12
Kevin C Barry, Nicholas T Ingolia, Russell E Vance
The inducible innate immune response to infection requires a concerted process of gene expression that is regulated at multiple levels. Most global analyses of the innate immune response have focused on transcription induced by defined immunostimulatory ligands, such as lipopolysaccharide. However, the response to pathogens involves additional complexity, as pathogens interfere with virtually every step of gene expression. How cells respond to pathogen-mediated disruption of gene expression to nevertheless initiate protective responses remains unclear...
April 6, 2017: ELife
https://www.readbyqxmd.com/read/28286708/transcriptomic-analysis-reveals-metabolic-switches-and-surface-remodeling-as-key-processes-for-stage-transition-in-trypanosoma-cruzi
#13
Luisa Berná, Maria Laura Chiribao, Gonzalo Greif, Matias Rodriguez, Fernando Alvarez-Valin, Carlos Robello
American trypanosomiasis is a chronic and endemic disease which affects millions of people. Trypanosoma cruzi, its causative agent, has a life cycle that involves complex morphological and functional transitions, as well as a variety of environmental conditions. This requires a tight regulation of gene expression, which is achieved mainly by post-transcriptional regulation. In this work we conducted an RNAseq analysis of the three major life cycle stages of T. cruzi: amastigotes, epimastigotes and trypomastigotes...
2017: PeerJ
https://www.readbyqxmd.com/read/28192147/systemic-innate-immune-activation-in-food-protein-induced-enterocolitis-syndrome
#14
Ritobrata Goswami, Ana Belen Blazquez, Roman Kosoy, Adeeb Rahman, Anna Nowak-Węgrzyn, M Cecilia Berin
BACKGROUND: Food protein-induced enterocolitis syndrome (FPIES) is a non-IgE-mediated food allergy of infancy whose pathophysiology is poorly understood. OBJECTIVES: We set out to identify and phenotype allergen-responsive cells in peripheral blood of a cohort of subjects undergoing supervised food challenge for FPIES. METHODS: We profiled antigen-responsive cells in PBMCs by flow cytometry, and examined cells in whole blood obtained before and after challenge by CyTOF mass cytometry and RNAseq...
June 2017: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/28138401/t-cadherin-in-prostate-cancer-relationship-with-cancer-progression-differentiation-and-drug-resistance
#15
Boris Dasen, Tatjana Vlajnic, Chantal Mengus, Christian Ruiz, Lukas Bubendorf, Giulio Spagnoli, Stephen Wyler, Paul Erne, Thérèse J Resink, Maria Philippova
Prostate cancer represents the second leading cause of cancer-related death in men. T-cadherin (CDH13) is an atypical GPI-anchored member of the cadherin family of adhesion molecules. Its gene was reported to be downregulated in a small series of prostate tumours. T-cadherin protein expression/localisation in prostate tissue has never been investigated. The purpose of our study was to analyse CDH13 gene and protein levels in large sets of healthy and cancer prostate tissue specimens and evaluate CDH13 effects on the sensitivity of prostate cancer cells to chemotherapy...
January 2017: Journal of Pathology. Clinical Research
https://www.readbyqxmd.com/read/28068412/a-comparison-of-gene-expression-profiles-between-glucocorticoid-responder-and-non-responder-bovine-trabecular-meshwork-cells-using-rna-sequencing
#16
Jaclyn Y Bermudez, Hannah C Webber, Bartley Brown, Terry A Braun, Abbot F Clark, Weiming Mao
The most common ocular side effect of glucocorticoid (GC) therapy is GC-induced ocular hypertension (OHT) and GC-induced glaucoma (GIG). GC-induced OHT occurs in about 40% of the general population, while the other 60% are resistant. This study aims to determine the genes and pathways involved in differential GC responsiveness in the trabecular meshwork (TM). Using paired bovine eyes, one eye was perfusion-cultured with 100nM dexamethasone (DEX), while the fellow eye was used to establish a bovine TM (BTM) cell strain...
2017: PloS One
https://www.readbyqxmd.com/read/28003262/defining-the-clonality-of-peripheral-t-cell-lymphomas-using-rna-seq
#17
Scott D Brown, Greg Hapgood, Christian Steidl, Andrew P Weng, Kerry J Savage, Robert A Holt
Motivation: In T-cell lymphoma, malignant T cells arising from a founding clone share an identical T cell receptor (TCR) and can be identified by the over-representation of this TCR relative to TCRs from the patient's repertoire of normal T cells. Here, we demonstrate that TCR information extracted from RNA-seq data can provide a higher resolution view of peripheral T cell lymphomas (PTCLs) than that provided by conventional methods. Results: For 60 subjects with PTCL, flow cytometry/FACS was used to identify and sort aberrant T cell populations from diagnostic lymph node cell suspensions...
April 15, 2017: Bioinformatics
https://www.readbyqxmd.com/read/27999734/molecular-and-clinical-characterization-of-pd-l1-expression-at-transcriptional-level-via-976-samples-of-brain-glioma
#18
Zheng Wang, Chuanbao Zhang, Xing Liu, Zhiliang Wang, Lihua Sun, Guanzhang Li, Jingshan Liang, Huimin Hu, Yanwei Liu, Wei Zhang, Tao Jiang
Background: PD-L1 has been widely reported as immune check points in a range of malignancies as well as some immune-originated diseases. In glioma, the role of PD-L1 remains unclear. We aimed at investigating its role at transcriptome level and relationship with clinical practice. Method and patients: In total, 976 glioma samples with transcriptome data, including 301 microarray data from Chinese Glioma Genome Atlas (CGGA project) and 675 RNAseq data from TCGA project, were enrolled into our study. Clinical and IDH mutation data were also available...
2016: Oncoimmunology
https://www.readbyqxmd.com/read/27995306/t-cell-receptor-gene-recombinations-in-human-tumor-specimen-exome-files-detection-of-t-cell-receptor-%C3%AE-vdj-recombinations-associates-with-a-favorable-oncologic-outcome-for-bladder-cancer
#19
Mohammad D Samy, Wei Lue Tong, John M Yavorski, Wade J Sexton, George Blanck
Understanding tumor-resident T cells is important for cancer prognosis and treatment options. Conventional, solid tumor specimen exome files can be searched directly for recombined T cell receptor (TcR)-α segments; RNASeq files can include TcR-β VDJ recombinations. To learn whether there are medically relevant uses of exome-based detection of TcR V(D)J recombinations in the tumor microenvironment, we searched cancer genome atlas and Moffitt Cancer Center, tumor specimen exome files for TcR-β, TcR-γ, and TcR-δ recombinations, for bladder and stomach cancer...
March 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/27994070/characterization-of-meningeal-type-2-innate-lymphocytes-and-their-response-to-cns-injury
#20
Sachin P Gadani, Igor Smirnov, Ashtyn T Smith, Christopher C Overall, Jonathan Kipnis
The meningeal space is occupied by a diverse repertoire of immune cells. Central nervous system (CNS) injury elicits a rapid immune response that affects neuronal survival and recovery, but the role of meningeal inflammation remains poorly understood. Here, we describe type 2 innate lymphocytes (ILC2s) as a novel cell type resident in the healthy meninges that are activated after CNS injury. ILC2s are present throughout the naive mouse meninges, though are concentrated around the dural sinuses, and have a unique transcriptional profile...
February 2017: Journal of Experimental Medicine
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