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https://www.readbyqxmd.com/read/28867483/construction-of-a-versatile-expression-library-for-all-human-single-pass-transmembrane-proteins-for-receptor-pairings-by-high-throughput-screening
#1
Wei Yang, Søren Berg Padkjær, Jishu Wang, Zhe Sun, Bing Shan, Li Yang, Haibin Chen, Lishan Kang, Dennis Madsen, Xun Li, Chenxi Shen, Bingke Yu, Haisun Zhu, Tzu-Yuan Chao, Zhuoxiao Cao, Dapeng Li, Wei Liu, Yanping Du, Jinjing Xu, Dongxia Hao, Fengting Xu, Lujia Peng, Tengkun Li, Lin Wang, Lin Li, Haimei Xing, Di Liu, Zibing Liu, Zhishuang Guan, Wan Wang, Hong Cheng, Henrik Østergaard, Chihchuan Chang, Zhiru Yang, Esper Boel, Jing Su
Interactions between protein ligands and receptors play crucial roles in cell-cell signalling. Most of the human cell surface receptors have been identified in the post-Human Genome Project era but many of their corresponding ligands remain unknown. To facilitate the pairing of orphan receptors, 2762 sequences encoding all human single-pass transmembrane proteins were selected for inclusion into a mammalian-cell expression library. This expression library, consisting of all the individual extracellular domains (ECDs), was constructed as a Fab fusion for each protein...
September 1, 2017: Journal of Biotechnology
https://www.readbyqxmd.com/read/28863469/parasites-causing-cerebral-falciparum-malaria-bind-multiple-endothelial-receptors-and-express-epcr-and-icam-1-binding-pfemp1
#2
Nicaise Tuikue Ndam, Azizath Moussiliou, Thomas Lavstsen, Claire Kamaliddin, Anja T R Jensen, Atikatou Mama, Rachida Tahar, Christian W Wang, Jakob S Jespersen, Jules M Alao, Benoit Gamain, Thor G Theander, Philippe Deloron
Background: Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) mediates the binding and accumulation of infected erythrocytes (IE) to blood vessels and tissues. Specific interactions have been described between PfEMP1 and human endothelial proteins CD36, intercellular adhesion molecule-1 (ICAM-1), and endothelial protein C receptor (EPCR); however, cytoadhesion patterns typical for pediatric malaria syndromes and the associated PfEMP1 members are still undefined. Methods: In a cohort of 94 hospitalized children with malaria, we characterized the binding properties of IE collected on admission, and var gene transcription using quantitative polymerase chain reaction...
June 15, 2017: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/28834159/a-novel-protein-c-factor-vii-chimera-provides-new-insights-into-the-structural-requirements-for-cytoprotective-par1-signaling
#3
Eimear M Gleeson, Cormac J McDonnell, Erin E Soule, Orla Willis Fox, Hannah Rushe, Aisling Rehill, Owen P Smith, James S O'Donnell, Roger J S Preston
BACKGROUND: Activated protein C (APC) cell signaling is largely reliant upon its ability to mediate protease-activated receptor 1 (PAR1) proteolysis when bound to the endothelial cell protein C receptor (EPCR). Furthermore, EPCR-bound PC modulates PAR1 signaling by thrombin to induce APC-like endothelial cell (EC) cytoprotection. OBJECTIVE: The molecular determinants of EPCR-dependent cytoprotective PAR1 signaling remain poorly defined. To address this, a PC-factor VII (FVII) chimera (PC(FVII)(-82) ) possessing FVII N-terminal domains and conserved EPCR binding was characterized...
August 20, 2017: Journal of Thrombosis and Haemostasis: JTH
https://www.readbyqxmd.com/read/28804104/%C3%AE-cyperone-inhibits-pma-induced-epcr-shedding-through-pkc-pathway
#4
Yu Ma, Yi Zhao, Ran Zhang, Xiaoxia Liang, Zhongqiong Yin, Yi Geng, Gang Shu, Xu Song, Yuanfeng Zou, Lixia Li, Lizi Yin, Guizhou Yue, Yinglun Li, Gang Ye, Changliang He
α-Cyperone, a sesquiterpene compound represents 25.23% of the total oil and is the most abundant compound in C. rotundus oil. Endothelial cell protein C receptor (EPCR) is a main member in Protein C (PC) anti-coagulation system. EPCR could be shed from cell surface, and is mediated by Tumor necrosis factor-α converting enzyme (TACE). Nothing that EPCR is a marker of vascular barrier integrity in vascular inflammatory disease and takes part in systemic inflammatory disease. In this study, we investigated whether α-cyperone could inhibit EPCR shedding...
August 11, 2017: Biological & Pharmaceutical Bulletin
https://www.readbyqxmd.com/read/28770100/endothelial-protein-c-receptor-is-overexpressed-in-colorectal-cancer-as-a-result-of-amplification-and-hypomethylation-of-chromosome-20q
#5
Neeraj Lal, Carrie R Willcox, Andrew Beggs, Philippe Taniere, Aarti Shikotra, Peter Bradding, Richard Adams, David Fisher, Gary Middleton, Chris Tselepis, Benjamin E Willcox
Endothelial Protein C Receptor (EPCR) is a Major Histocompatibility Complex homologue, with established roles downregulating coagulation and in endothelial protection. Expressed predominantly on endothelium, EPCR affects inflammatory, apoptotic and cell proliferation pathways by binding to activated protein C (APC). However, EPCR can also be expressed on cancer cells, although the underlying reasons are unclear. Moreover, although EPCR has been linked with chemosensitivity in lung cancer, its clinical significance in many tumours is unknown...
July 2017: Journal of Pathology. Clinical Research
https://www.readbyqxmd.com/read/28732053/dysregulation-of-pulmonary-endothelial-protein-c-receptor-and-thrombomodulin-in-severe-falciparum-malaria-associated-ards-relevant-to-hemozoin
#6
Sitang Maknitikul, Natthanej Luplertlop, Georges E R Grau, Sumate Ampawong
To investigate the role of the protein C system, endothelial protein C receptor (EPCR) and thrombomodulin (TM) in the pathogenesis of malaria-associated acute respiratory distress syndrome (ARDS) in relation to hemozoin and proinflammatory cytokines-induced type II pneumocyte injury and -aggravated pulmonary resolution. A total of 29 left-over lung specimens that were obtained from patients who died from severe falciparum malaria were examined. Histopathological, immunohistochemical and electron microscopic analyses revealed that ARDS coexisted with pulmonary edema and systemic bleeding; the severity was dependent on the level of hemozoin deposition in the lung and internal alveolar hemorrhaging...
2017: PloS One
https://www.readbyqxmd.com/read/28667750/flt3-ligand-egfp-reporter-expression-characterizes-functionally-distinct-subpopulations-of-cd150-long-term-repopulating-murine-hematopoietic-stem-cells
#7
Julia Tornack, Yohei Kawano, Natalio Garbi, Günter J Hämmerling, Fritz Melchers, Motokazu Tsuneto
The pool of hematopoietic stem cells (HSCs) in the bone marrow is a mixture of resting, proliferating, and differentiating cells. Long-term repopulating HSCs (LT-HSC) are routinely enriched as Lin(-) Sca1(+) c-Kit(+) CD34(-) Flt3(-) CD150(+) CD48(-) cells. The Flt3 ligand (Flt3L) and its receptor Flt3 are important regulators of HSC maintenance, expansion and differentiation. Using Flt3L-eGFP reporter mice, we show that endogenous Flt3L-eGFP-reporter RNA expression correlates with eGFP-protein expression. This Flt3L-eGFP-reporter expression distinguishes two LT-HSC populations with differences in gene expressions and reconstituting potential...
July 1, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/28642358/epcr-a-novel-marker-of-cultured-cord-blood-hscs
#8
Gaëlle H Martin, Christopher Y Park
No abstract text is available yet for this article.
June 22, 2017: Blood
https://www.readbyqxmd.com/read/28603500/epcr-gene-ser219gly-polymorphism-and-venous-thromboembolism-a-meta-analysis-of-9-494-subjects
#9
Yan-Yan Li, Jing-Jing Wu, Xin-Xing Yang, Hong-Yu Geng, Ge Gong, Hyun Jun Kim
Background: Although endothelial cell protein C receptor (EPCR) gene Ser219Gly polymorphism has been associated with venous thromboembolism (VTE) susceptibility, no clear consensus has yet been reached. Objective and methods: A meta-analysis of 9,494 subjects from 13 individual studies was conducted to better elucidate the potential relationship between the EPCR gene Ser219Gly polymorphism and VTE. Pooled odds ratios (ORs) and their corresponding 95% confidence intervals (CIs) were evaluated by using fixed or random effect models...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/28538400/carbon-monoxide-releasing-molecule-2-suppresses-thrombomodulin-and-endothelial-protein-c-receptor-expression-of-human-umbilical-vein-endothelial-cells-induced-by-lipopolysaccharide-in-vitro
#10
Xianglin Meng, Dongsheng Fei, Mingming Liu, Songlin Yang, Ning Song, Lei Jiang, Kai Kang, Chuanchuan Nan, Yunpeng Luo, Shangha Pan, Mingyan Zhao
OBJECTIVE: The aim of this study was to observe the counter-effect of carbon monoxide-releasing molecule-2 (CORM-2) on lipopolysaccharide (LPS)-suppressed thrombomodulin (TM) and endothelial protein C receptor (EPCR) expressions from human umbilical vein endothelial cell (HUVEC), and to reveal its mechanisms. METHODS: HUVECs were divided into 5 treatment groups, wherein reagents were added simultaneously. TM and EPCR proteins of the cells and the culture medium levels of soluble TM, soluble EPCR, and matrix metalloproteinase-2 (MMP-2) were detected after administration, whereas mRNA levels of TM and EPCR, as well as nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) activity among groups, were also evaluated...
May 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28524456/endothelial-microparticles-released-by-activated-protein-c-protect-beta-cells-through-epcr-par1-and-annexin-a1-fpr2-pathways-in-islets
#11
Guillaume Kreutter, Mohamad Kassem, Ali El Habhab, Philippe Baltzinger, Malak Abbas, Julie Boisrame-Helms, Lamia Amoura, Jean Peluso, Blandine Yver, Zobairi Fatiha, Geneviève Ubeaud-Sequier, Laurence Kessler, Florence Toti
Islet transplantation is associated with early ischaemia/reperfusion, localized coagulation and redox-sensitive endothelial dysfunction. In animal models, islet cytoprotection by activated protein C (aPC) restores islet vascularization and protects graft function, suggesting that aPC triggers various lineages. aPC also prompts the release of endothelial MP that bear EPCR, its specific receptor. Microparticles (MP) are plasma membrane procoagulant vesicles, surrogate markers of stress and cellular effectors...
May 19, 2017: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/28522939/identification-of-protein-targets-in-cerebral-endothelial-cells-for-brain-arteriovenous-malformation-avms-molecular-therapies
#12
Margaret Simonian, Rachel R Ogorzalek Loo, Nalaka Rannulu, Joseph A Loo, Mark P Molloy, Marcus A Stoodley
BACKGROUND: To develop a new molecular targeted treatment for brain (AVMs), identification of membrane proteins that are localised on the AVM endothelium is crucial. Current treatment methods are surgery and radiosurgery. However, complete occlusion post radiosurgery are achieved within 3 years, while patient remain at risk of haemorrhage. This study aims to identify potential protein targets in AVM endothelial cells that discriminate these vessels from normal vessels; these proteins targets will be investigated for the molecular therapy of brain AVMs to promote rapid thrombosis after radiosurgery...
2017: Clinical Proteomics
https://www.readbyqxmd.com/read/28480559/the-endothelial-protein-c-receptor-is-a-potential-stem-cell-marker-for-epidermal-keratinocytes
#13
Meilang Xue, Suat Dervish, Benjamin Chan, Christopher J Jackson
Endothelial protein C receptor (EPCR) is a specific receptor for anticoagulant protein C and expressed by human epidermis and cultured keratinocytes. Here we investigated whether: (a) the level of EPCR in keratinocytes is associated with their growth potential; and (b) EPCR is a potential marker for human epidermal stem cells. Human keratinocytes isolated from foreskins or adult skin tissues were transfected with EPCR siRNA or EPCR overexpressing plasmids. Cell proliferation, long term proliferation potential, colony forming efficiency (CFE), and in vitro epidermal regeneration ability of EPCR(high) and EPCR(l) °(w) cells were assessed...
May 7, 2017: Stem Cells
https://www.readbyqxmd.com/read/28448740/sequencing-on-the-solid-5500xl-system-in-depth-characterization-of-the-gc-bias
#14
Simone Roeh, Peter Weber, Monika Rex-Haffner, Jan M Deussing, Elisabeth B Binder, Mira Jakovcevski
Different types of sequencing biases have been described and subsequently improved for a variety of sequencing systems, mostly focusing on the widely used Illumina systems. Similar studies are missing for the SOLiD 5500xl system, a sequencer which produced many data sets available to researchers today. Describing and understanding the bias is important to accurately interpret and integrate these published data in various ongoing research projects. We report a particularly strong GC bias for this sequencing system when analyzing a defined gDNA mix of 5 microbes with a wide range of different GC contents (20-72%) when comparing to the expected distribution and Illumina MiSeq data from the same DNA pool...
July 4, 2017: Nucleus
https://www.readbyqxmd.com/read/28435976/-role-of-igg-plasma-cells-in-the-change-of-protein-c-system-in-ulcerative-colitis
#15
Xu-Hong Lin, Jun-Ling Guo, Yu-Qing Wen, Yu-Xia Li, Dan-Dan Wei, Rui-Lin Yang, Xiao-Yun Mu, Hui-Chao Wang
The present study is designed to explore the role of plasma cells in the change of protein C system (PCS) in ulcerative colitis (UC). Dextran sulfate sodium (DSS, 4% in concentration) was used to induce mouse UC model. The plasma cells and the type of immune complex in colon were observed by immunofluorescence. The amount and type of plasma cells separated from colonic mucosal lamina propria were detected by flow cytometry using anti-CD54(+)CD38(+) and IgA/M/G antibodies, respectively. After stimulation of macrophages by IgG type immune complex, TNF-α and IL-6 levels were evaluated by ELISA...
April 25, 2017: Sheng Li Xue Bao: [Acta Physiologica Sinica]
https://www.readbyqxmd.com/read/28415941/endothelial-protein-c-receptor-polymorphisms-and-risk-of-sepsis-in-a-chinese-population
#16
Yanbing Liang, Xia Huang, Yujie Jiang, Yueqiu Qin, Dingwei Peng, Yuqing Huang, Jin Li, Suren R Sooranna, Liao Pinhu
Objective To examine the potential relationship of EPCR polymorphisms and the risk of sepsis in a Chinese population. Methods Snapshot SNP genotyping assays and DNA sequencing methods were used to detect polymorphisms of the EPCR gene, rs2069948C/T (2532C/T) and rs867186A/G (6936A/G), in 64 patients with sepsis and in 113 controls. Soluble EPCR (sEPCR) was measured by ELISA. Results There were significant differences in the allele and genotype frequencies of EPCR gene rs2069948C/T and allele frequencies of rs867186A/G between male and female patients and controls...
April 2017: Journal of International Medical Research
https://www.readbyqxmd.com/read/28408624/activated-protein-c-inhibits-neutrophil-extracellular-trap-formation-in-vitro-and-activation-in-vivo
#17
Laura D Healy, Cristina Puy, José A Fernández, Annachiara Mitrugno, Ravi S Keshari, Nyiawung A Taku, Tiffany T Chu, Xiao Xu, András Gruber, Florea Lupu, John H Griffin, Owen J T McCarty
Activated protein C (APC) is a multifunctional serine protease with anticoagulant, cytoprotective, and anti-inflammatory activities. In addition to the cytoprotective effects of APC on endothelial cells, podocytes, and neurons, APC cleaves and detoxifies extracellular histones, a major component of neutrophil extracellular traps (NETs). NETs promote pathogen clearance but also can lead to thrombosis; the pathways that negatively regulate NETosis are largely unknown. Thus, we studied whether APC is capable of directly inhibiting NETosis via receptor-mediated cell signaling mechanisms...
May 26, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28408459/epcr-expression-marks-um171-expanded-cd34-cord-blood-stem-cells
#18
Iman Fares, Jalila Chagraoui, Bernhard Lehnertz, Tara MacRae, Nadine Mayotte, Elisa Tomellini, Léo Aubert, Philippe P Roux, Guy Sauvageau
A small subset of human cord blood CD34(+) cells express endothelial protein C receptor (EPCR/CD201/PROCR) when exposed to the hematopoietic stem cell (HSC) self-renewal agonist UM171. In this article, we show that EPCR-positive UM171-treated cells, as opposed to EPCR-negative cells, exhibit robust multilineage repopulation and serial reconstitution ability in immunocompromised mice. In contrast to other stem cell markers, such as CD38, EPCR expression is maintained when cells are introduced in culture, irrespective of UM171 treatment...
June 22, 2017: Blood
https://www.readbyqxmd.com/read/28367652/astragaloside-iv-inhibits-pma-induced-epcr-shedding-through-mapks-and-pkc-pathway
#19
Yu Ma, Yi Zhao, Ran Zhang, Xiaoxia Liang, Zhongqiong Yin, Yi Geng, Gang Shu, Xu Song, Yuanfeng Zou, Lixia Li, Lizi Yin, Guizhou Yue, Yinglun Li, Gang Ye, Changliang He
Astragaloside IV (AS-IV), a main active substance isolated from Astragalus membranaceus Bunge, has been shown to have multiple pharmacological effects. Endothelial cell protein C receptor (EPCR) is a marker of inflammation, and is also a major member of protein C (PC) anti-coagulation system. EPCR can be cut off from the cell surface by tumor necrosis factor-α converting enzyme (TACE), which is controlled through mitogen-activated protein kinase (MAPK) and protein kinase C (PKC) pathways. To develop novel therapeutic drug for EPCR shedding, the effect of AS-IV was studied in phorbol-12-myristate 13-acetate (PMA)-induced human umbilical vein endothelial cells (HUVECs) and the potential molecular mechanism of AS-IV action was investigated...
June 2017: Immunopharmacology and Immunotoxicology
https://www.readbyqxmd.com/read/28353616/associations-between-polymorphisms-in-coagulation-related-genes-and-venous-thromboembolism-a-meta-analysis-with-trial-sequential-analysis
#20
REVIEW
Jun Jiang, Kang Liu, Junjie Zou, Hao Ma, Hongyu Yang, Xiwei Zhang, Yuanyong Jiao
BACKGROUND: Recently, several studies showed that the polymorphisms in the coagulation-related genes might be associated with venous thromboembolism (VTE); however, the results were still controversial. We performed a meta-analysis with trial sequential analysis to investigate the associations between the endothelial cell-activated protein C receptor (EPCR) rs9574, F11 rs2289252, F11 rs2036914, FGG rs2066865, FGG rs1049636, CYP4V2 rs13146272, SERPINC1 rs2227589, and GP6 rs1613662 polymorphisms with the risk of VTE...
March 2017: Medicine (Baltimore)
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