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https://www.readbyqxmd.com/read/28932816/a-quorum-sensing-system-that-regulates-streptococcus-pneumoniae-biofilm-formation-and-surface-polysaccharide-production
#1
Roger Junges, Gabriela Salvadori, Sudhanshu Shekhar, Heidi A Åmdal, Jimstan N Periselneris, Tsute Chen, Jeremy S Brown, Fernanda C Petersen
Despite vaccines, Streptococcus pneumoniae kills more than a million people yearly. Thus, understanding how pneumococci transition from commensals to pathogens is particularly relevant. Quorum sensing regulates collective behaviors and thus represents a potential driver of commensal-to-pathogen transitions. Rgg/small hydrophobic peptide (SHP) quorum-sensing systems are widespread in streptococci, yet they remain largely uncharacterized in S. pneumoniae. Using directional transcriptome sequencing, we show that the S...
September 2017: MSphere
https://www.readbyqxmd.com/read/28929190/mining-the-complex-family-of-protein-tyrosine-phosphatases-for-checkpoint-regulators-in-immunity
#2
Claudia Penafuerte, Luis Alberto Perez-Quintero, Valerie Vinette, Teri Hatzihristidis, Michel L Tremblay
The family of protein tyrosine phosphatases (PTPs) includes 107 genes in humans that are diverse in their structures and expression profiles. The majority are present in immune cells and play various roles in either inhibiting or promoting the duration and amplitude of signaling cascades. Several PTPs, including TC-PTP (PTPN2) and SHP-1 (PTPN6), have been recognized as being crucial for maintaining proper immune response and self-tolerance, and have gained recognition as true immune system checkpoint modulators...
September 20, 2017: Current Topics in Microbiology and Immunology
https://www.readbyqxmd.com/read/28928726/phosphoprotein-gene-contributes-to-the-enhanced-apoptosis-induced-by-wild-type-rabies-virus-gd-sh-01-in-vitro
#3
Qin Tian, Yifei Wang, Qiong Zhang, Jun Luo, He Jiang, Boyue Zhang, Mingzhu Mei, Fan Wu, Yuting Wu, Jiaojiao Peng, Teng Long, Yongwen Luo, Xiaofeng Guo
Previous research demonstrated that the matrix protein (M) and glycoprotein (G) of attenuated rabies virus (RABV) strains are involved in the induction of host cell apoptosis. In this work, we show that wild-type (wt) RABV GD-SH-01 induces significantly greater apoptosis than the attenuated strain HEP-Flury. In order to identify the gene(s) accounting for this phenotype, five recombinant RABVs (rRABVs) were constructed by replacing each single gene of HEP-Flury with the corresponding gene of GD-SH-01. By using these rRABVs, we found that not only M and G, but also the phosphoprotein (P) plays an important role in inducing apoptosis...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/28925102/continued-alcohol-misuse-in-human-cirrhosis-is-associated-with-an-impaired-gut-liver-axis
#4
Jasmohan S Bajaj, Genta Kakiyama, Derrick Zhao, Hajime Takei, Andrew Fagan, Phillip Hylemon, Huiping Zhou, William M Pandak, Hiroshi Nittono, Oliver Fiehn, Nita Salzman, Mary Holtz, Pippa Simpson, Edith A Gavis, Douglas M Heuman, Runping Liu, Dae Joong Kang, Masoumeh Sikaroodi, Patrick M Gillevet
BACKGROUND: Cirrhosis and alcohol can independently affect the gut-liver axis with systemic inflammation. However their concurrent impact in humans is unclear. AIM: Determine the effect of continued alcohol misuse on the gut-liver axis in cirrhotic patients. METHODS: Age and MELD-balanced cirrhotic patients who were currently drinking (Alc) or abstinent (NAlc), and healthy controls underwent serum and stool collection. A subset underwent upper endoscopy and colonoscopy for biopsies and duodenal fluid collection...
September 19, 2017: Alcoholism, Clinical and Experimental Research
https://www.readbyqxmd.com/read/28919415/biophysical-characterization-of-the-interaction-between-heme-and-proteins-responsible-for-heme-transfer-in-streptococcus-pyogenes
#5
Masato Hoshino, Makoto Nakakido, Satoru Nagatoishi, Chihiro Aikawa, Ichiro Nakagawa, Kouhei Tsumoto
Streptococcus pyogenes, an important pathogen that causes a wide range of diseases, possesses the sia gene cluster, which encodes proteins involved in the heme acquisition system. Although this system was previously described, the molecular mechanism of effective heme transfer remains to be elucidated. Here, we have characterized the interactions between heme and each domain of Streptococcal hemoprotein receptor (Shr) and Streptococcal heme-binding protein (Shp). Our kinetic and thermodynamic analyses suggested that effective heme transfer within this system is achieved not only by affinity-based transfer but also by the difference of the binding driving force...
September 14, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28919113/hepatic-tmem30a-deficiency-causes-intrahepatic-cholestasis-by-impairing-expression-and-localization-of-bile-salt-transporters
#6
Leiming Liu, Lingling Zhang, Lin Zhang, Fan Yang, Xudong Zhu, Zhongjie Lu, Yeming Yang, Haiqi Lu, Lifeng Feng, Zhuo Wang, Hui Chen, Sheng Yan, Lin Wang, Zhenyu Ju, Hongchuan Jin, Xianjun Zhu
Mutations in ATP8B1 or ATP11C (members of P4-type ATPases) cause progressive familial intrahepatic cholestasis type 1 (PFIC1) in human or intrahepatic cholestasis in mice. Transmembrane protein 30A (TMEM30A), as a β-subunit, is essential for the function of P4-type ATPases including ATP8B1 and ATP11C, however, its role in the etiology of cholestasis remains poorly understood. To investigate the function of TMEM30A in bile salt homeostasis, we developed Tmem30a liver-specific knockout (LKO) mice. Tmem30a LKO mice suffered from hyperbilirubinaemia, hypercholanaemia, inflammatory infiltration, ductular proliferation and liver fibrosis...
September 14, 2017: American Journal of Pathology
https://www.readbyqxmd.com/read/28910973/lycorine-inhibits-the-growth-and-metastasis-of-breast-cancer-through-the-blockage-of-stat3-signaling-pathway
#7
Jian Wang, Jie Xu, Guoqiang Xing
Signal transducer and activator of transcription 3 (STAT3) is involved in the growth and metastasis of breast cancer, and represents a potential target for developing new anti-tumor drugs. The purpose of this study is to investigate whether Lycorine, a pyrrolo[de]phenanthridine ring-type alkaloid extracted from Amaryllidaceae genera, could inhibit breast cancer by targeting STAT3 signaling pathway. The human breast cancer cell lines were incubated with various concentrations of Lycorine, and cell proliferation, colony formation, cell cycle distribution, apoptosis, migration and invasion were assayed by several in vitro approaches...
September 1, 2017: Acta Biochimica et Biophysica Sinica
https://www.readbyqxmd.com/read/28901387/triptolide-blocks-the-stat3-signaling-pathway-through-induction-of-protein-tyrosine-phosphatase-shp-1-in-multiple-myeloma-cells
#8
Ji-Hun Kim, Byoungduck Park
Triptolide, an active component extracted from the medicinal plant Tripterygium wilfordii Hook F., has been used to treat various diseases, including lupus, cancer, rheumatoid arthritis and nephritic syndrome. The present study investigated the effects of triptolide on multiple myeloma using western blotting and an electrophoretic mobility shift assay. Triptolide was found to suppress the inducible and constitutive activation of signal transducer and activator of transcription 3 (STAT3), which is closely associated with inflammation and tumorigenesis...
September 6, 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/28898718/interleukin-17-regulates-shp-2-and-il-17ra-stat-3-dependent-cyr61-il-23-and-gm-csf-expression-and-rankl-mediated-osteoclastogenesis-by-fibroblast-like-synoviocytes-in-rheumatoid-arthritis
#9
Ramamoorthi Ganesan, Mahaboobkhan Rasool
Interleukin (IL)-17 predominately produced by the Th17 cells, plays a crucial role in the fibroblast-like synoviocytes (FLS) mediated disease process of rheumatoid arthritis (RA). IL-17 exerts its pathogenic effects in RA-FLS by IL-17/IL-17RA/STAT-3 signaling. Recent studies have shown that RA-FLS produces SHP-2, Cyr61, IL-23, GM-CSF and RANKL which results in worsening of the disease. However, whether IL-17/IL-17RA/STAT-3 signaling regulates SHP-2, Cyr61, IL-23, GM-CSF and RANKL expressions in RA-FLS remains unknown...
September 9, 2017: Molecular Immunology
https://www.readbyqxmd.com/read/28875936/high-mtor-activity-is-a-hallmark-of-reactive-natural-killer-cells-and-amplifies-early-signaling-through-activating-receptors
#10
Antoine Marçais, Marie Marotel, Sophie Degouve, Alice Koenig, Sébastien Fauteux-Daniel, Annabelle Drouillard, Heinrich Schlums, Sébastien Viel, Laurie Besson, Omran Allatif, Mathieu Bléry, Eric Vivier, Yenan Bryceson, Olivier Thaunat, Thierry Walzer
NK cell education is the process through which chronic engagement of inhibitory NK cell receptors by self MHC-I molecules preserves cellular responsiveness. The molecular mechanisms responsible for NK cell education remain unclear. Here, we show that mouse NK cell education is associated with a higher basal activity of the mTOR/Akt pathway, commensurate to the number of educating receptors. This higher activity was dependent on the SHP-1 phosphatase and essential for the improved responsiveness of reactive NK cells...
August 30, 2017: ELife
https://www.readbyqxmd.com/read/28833338/reptin-regulates-insulin-stimulated-akt-phosphorylation-in-hepatocellular-carcinoma-via-the-regulation-of-shp-1-ptpn6
#11
Anne-Aurélie Raymond, Joaquim Javary, Osman Breig, Véronique Neaud, Jean Rosenbaum
Hepatocellular carcinoma (HCC) is the main primary cancer of the liver. Many studies have shown that insulin resistance is a risk factor for HCC. We previously discovered the overexpression and oncogenic role of the Reptin/RUVBL2 ATPase in HCC. Here, we found that Reptin silencing enhanced insulin sensitivity in 2 HCC cell lines, as shown by a large potentiation of insulin-induced AKT phosphorylation on Ser473 and Thr308, and of downstream signalling. Reptin silencing did not affect the tyrosine phosphorylation of the insulin receptor nor of IRS1, but it enhanced the tyrosine phosphorylation of the p85 subunit of PI3K...
August 22, 2017: Cell Biochemistry and Function
https://www.readbyqxmd.com/read/28830075/streptococcal-heme-binding-protein-shp-promotes-virulence-and-contributes-to-the-pathogenesis-of-group-a-streptococcus-infection
#12
Xiaolan Zhang, Chunmei Lu, Fengmin Zhang, Yingli Song, Minghui Cai, Hui Zhu
Streptococcal heme binding protein (Shp) is involved in the process of heme acquisition in group A Streptococcus (GAS). However, no research thus far has examined the contribution of Shp to the virulence of GAS. To this end, we generated an isogenic strain lacking the shp gene (Δshp) and its complemented strain (Δshp-c) using the parent strain MGAS5005 (WT). Deletion of shp increased survival rates and neutrophil recruitment and reduced skin lesion sizes and GAS loads in the blood and the liver, lung, kidney and spleen in subcutaneous infections of mice...
September 29, 2017: Pathogens and Disease
https://www.readbyqxmd.com/read/28827769/dose-related-liver-injury-of-geniposide-associated-with-the-alteration-in-bile-acid-synthesis-and-transportation
#13
Jingzhuo Tian, Jingjing Zhu, Yan Yi, Chunying Li, Yushi Zhang, Yong Zhao, Chen Pan, Shixie Xiang, Xiaolong Li, Guiqin Li, John W Newman, Xiaoyi Feng, Jing Liu, Jiayin Han, Lianmei Wang, Yue Gao, Michael R La Frano, Aihua Liang
Fructus Gardenia (FG), containing the major active constituent Geniposide, is widely used in China for medicinal purposes. Currently, clinical reports of FG toxicity have not been published, however, animal studies have shown FG or Geniposide can cause hepatotoxicity in rats. We investigated Geniposide-induced hepatic injury in male Sprague-Dawley rats after 3-day intragastric administration of 100 mg/kg or 300 mg/kg Geniposide. Changes in hepatic histomorphology, serum liver enzyme, serum and hepatic bile acid profiles, and hepatic bile acid synthesis and transportation gene expression were measured...
August 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28821631/6-methoxyethylamino-numonafide-inhibits-hepatocellular-carcinoma-xenograft-growth-as-a-single-agent-and-in-combination-with-sorafenib
#14
Yanning Liu, Guohua Lou, John T Norton, Chen Wang, Irawati Kandela, Shuai Tang, Nathaniel I Shank, Pankaj Gupta, Min Huang, Michael J Avram, Richard Green, Andrew Mazar, Daniel Appella, Zhi Chen, Sui Huang
Hepatocellular carcinoma (HCC) is the third leading form of cancer worldwide, and its incidence is increasing rapidly in the United States, tripling over the past 3 decades. The current chemotherapeutic strategies against localized and metastatic HCC are ineffective. Here we report that 6-methoxyethylamino-numonafide (MEAN) is a potent growth inhibitor of murine xenografts of 2 human HCC cell lines. At the same dose and with the same treatment strategies, MEAN was more efficacious in inhibiting tumor growth in mice than sorafenib, the only approved drug for HCC...
August 17, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28821113/fabrication-of-thermo-responsive-cotton-fabrics-using-poly-vinyl-caprolactam-co-hydroxyethyl-acrylamide-copolymer
#15
Min Xiao, Edurne González, Alexis Martell Monterroza, Margaret Frey
A thermo-responsive polymer with hydrophilic to hydrophobic transition behavior, poly(vinyl caprolactam-co-hydroxyethyl acrylamide) P(VCL-co-HEAA), was prepared by copolymerization of vinyl caprolactam and N-hydroxyethyl acrylamide via free radical solution polymerization. The resulting copolymer was characterized by Fourier transform infrared spectroscopy (FTIR), (1)H nuclear magnetic resonance (NMR), gel permeation chromatography (GPC), differential scanning calorimetry (DSC), and thermogravimetric analysis (TGA)...
October 15, 2017: Carbohydrate Polymers
https://www.readbyqxmd.com/read/28815370/effects-of-small-hydropower-plants-on-mercury-concentrations-in-fish
#16
Elaine C Cebalho, Sergi Díez, Manoel Dos Santos Filho, Claumir Cesar Muniz, Wilkinson Lázaro, Olaf Malm, Aurea R A Ignácio
Although the impacts of large dams on freshwater biota are relatively well known, the effects of small hydropower plants (SHP) are not well investigated. In this work, we studied if mercury (Hg) concentrations in fish rise in two tropical SHP reservoirs, and whether similar effects take place during impoundment. Total Hg concentrations in several fish species were determined at two SHP in the Upper Guaporé River basin floodplain, Brazil. In total, 185 specimens were analysed for Hg content in dorsal muscle and none of them reported levels above the safety limit (500 μg kg(-1)) for fish consumption recommended by the World Health Organisation (WHO)...
August 16, 2017: Environmental Science and Pollution Research International
https://www.readbyqxmd.com/read/28811476/lyn-and-fyn-function-as-molecular-switches-that-control-immunoreceptors-to-direct-homeostasis-or-inflammation
#17
Sanae Ben Mkaddem, Amaya Murua, Héloise Flament, Dimitri Titeca-Beauport, Carine Bounaix, Luca Danelli, Pierre Launay, Marc Benhamou, Ulrich Blank, Eric Daugas, Nicolas Charles, Renato C Monteiro
Immunoreceptors can transduce either inhibitory or activatory signals depending on ligand avidity and phosphorylation status, which is modulated by the protein kinases Lyn and Fyn. Here we show that Lyn and Fyn control immune receptor signaling status. SHP-1 tyrosine 536 phosphorylation by Lyn activates the phosphatase promoting inhibitory signaling through the immunoreceptor. By contrast, Fyn-dependent phosphorylation of SHP-1 serine 591 inactivates the phosphatase, enabling activatory immunoreceptor signaling...
August 15, 2017: Nature Communications
https://www.readbyqxmd.com/read/28808239/compound-a-influences-gene-regulation-of-the-dexamethasone-activated-glucocorticoid-receptor-by-alternative-cofactor-recruitment
#18
S J Desmet, N Bougarne, L Van Moortel, L De Cauwer, J Thommis, M Vuylsteke, D Ratman, R Houtman, J Tavernier, K De Bosscher
The glucocorticoid receptor (GR) is a transcription factor of which the underlying gene regulatory mechanisms are complex and incompletely understood. The non-steroidal anti-inflammatory Compound A (CpdA), a selective GR modulating compound in various cell models, has been shown to favour GR-mediated gene repression but not GR-mediated gene activation. Shifting balances towards only a particular subset of GR gene regulatory events may be of benefit in the treatment of inflammatory diseases. We present evidence to support that the combination of CpdA with Dexamethasone (DEX), a classic steroidal GR ligand, can shape GR function towards a unique gene regulatory profile in a cell type-dependent manner...
August 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28805978/obeticholic-acid-a-selective-farnesoid-x-receptor-agonist-regulates-bile-acid-homeostasis-in-sandwich-cultured-human-hepatocytes
#19
Yuanyuan Zhang, Jonathan P Jackson, Robert L St Claire, Kimberly Freeman, Kenneth R Brouwer, Jeffrey E Edwards
Farnesoid X receptor (FXR) is a master regulator of bile acid homeostasis through transcriptional regulation of genes involved in bile acid synthesis and cellular membrane transport. Impairment of bile acid efflux due to cholangiopathies results in chronic cholestasis leading to abnormal elevation of intrahepatic and systemic bile acid levels. Obeticholic acid (OCA) is a potent and selective FXR agonist that is 100-fold more potent than the endogenous ligand chenodeoxycholic acid (CDCA). The effects of OCA on genes involved in bile acid homeostasis were investigated using sandwich-cultured human hepatocytes...
August 2017: Pharmacology Research & Perspectives
https://www.readbyqxmd.com/read/28798401/the-tyrosine-kinase-inhibitor-nintedanib-activates-shp-1-and-induces-apoptosis-in-triple-negative-breast-cancer-cells
#20
Chun-Yu Liu, Tzu-Ting Huang, Pei-Yi Chu, Chun-Teng Huang, Chia-Han Lee, Wan-Lun Wang, Ka-Yi Lau, Wen-Chun Tsai, Tzu-I Chao, Jung-Chen Su, Ming-Huang Chen, Chung-Wai Shiau, Ling-Ming Tseng, Kuen-Feng Chen
Triple-negative breast cancer (TNBC) remains difficult to treat and urgently needs new therapeutic options. Nintedanib, a multikinase inhibitor, has exhibited efficacy in early clinical trials for HER2-negative breast cancer. In this study, we examined a new molecular mechanism of nintedanib in TNBC. The results demonstrated that nintedanib enhanced TNBC cell apoptosis, which was accompanied by a reduction of p-STAT3 and its downstream proteins. STAT3 overexpression suppressed nintedanib-mediated apoptosis and further increased the activity of purified SHP-1 protein...
August 11, 2017: Experimental & Molecular Medicine
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