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Type 6 secretion system

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https://www.readbyqxmd.com/read/28095608/esx-1-and-phthiocerol-dimycocerosates-of-mycobacterium-tuberculosis-act-in-concert-to-cause-phagosomal-rupture-and-host-cell-apoptosis
#1
Jacques Augenstreich, Ainhoa Arbues, Roxane Simeone, Evert Haanappel, Alice Wegener, Fadel Sayes, Fabien Le Chevalier, Christian Chalut, Wladimir Malaga, Christophe Guilhot, Roland Brosch, Catherine Astarie-Dequeker
Although phthiocerol dimycocerosates (DIM) are major virulence factors of Mycobacterium tuberculosis (Mtb), the causative agent of human tuberculosis, little is known about their mechanism of action. Localized in the outer membrane of mycobacterial pathogens, DIM are predicted to interact with host cell membranes. Interaction with eukaryotic membranes is a property shared with another virulence factor of Mtb, the early secretory antigenic target EsxA (also known as ESAT-6). This small protein, which is secreted by the type VII secretion system ESX-1 (T7SS/ESX-1), is involved in phagosomal rupture and cell death induced by virulent mycobacteria inside host phagocytes...
January 17, 2017: Cellular Microbiology
https://www.readbyqxmd.com/read/28066685/linoleic-acid-is-a-diabetes-relevant-stimulator-of-retinal-inflammation-in-human-retinal-muller-cells-and-microvascular-endothelial-cells
#2
Megan E Capozzi, Gary W McCollum, David B Cousins, John S Penn
OBJECTIVE: To determine the effect of oleic acid and linoleic acid on the production and secretion of specific diabetic retinopathy- (DR-) related cytokines: vascular endothelial growth factor (VEGF), interleukin-6 (IL-6), and interleukin-8 (IL-8) by human retinal glial cells, retinal endothelial cells, and retinal pigment epithelial cells. These expression profiles will be compared to those obtained by treatment of the same cell types with elevated D-glucose, a diabetes-relevant stimulus often used in retinal cell culture experiments...
December 2016: Journal of Diabetes & Metabolism
https://www.readbyqxmd.com/read/28057547/intracellular-signaling-modifications-involved-in-the-anti-inflammatory-effect-of-4-alkoxy-6-9-dichloro-1-2-4-triazolo-4-3-a-quinoxalines-on-macrophages
#3
Antonio J Ruiz-Alcaraz, María Tristán-Manzano, Antonio Guirado, Jesús Gálvez, María Martínez-Esparza, Pilar García-Peñarrubia
Inflammation is part of a complex biological response directed by the immune system to fight pathogens and maintain homeostasis. Dysregulation of the inflammatory process leads to development of chronic inflammatory or autoimmune diseases. Several cell types, such as macrophages, and cytokines such as interleukin 6 (IL-6) and tumor necrosis factor alpha (TNF-α) are involved in the regulation of inflammation. The important role played by these cytokines as mediators of the inflammatory process and the side effects of current therapies have promoted the search of new therapeutic alternatives...
January 3, 2017: European Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28032468/three-dimensional-culture-of-single-embryonic-stem-derived-neural-stem-progenitor-cells-in-fibrin-hydrogels-neuronal-network-formation-and-matrix-remodelling
#4
Ana R Bento, Pedro Quelhas, Maria J Oliveira, Ana P Pêgo, Isabel F Amaral
In an attempt to improve the efficacy of neural stem/progenitor cell (NSPC) based therapies, fibrin hydrogels are being explored to provide a favourable microenvironment for cell survival and differentiation following transplantation. In the present work, the ability of fibrin to support the survival, proliferation, and neuronal differentiation of NSPCs derived from embryonic stem (ES) cells under monolayer culture was explored. Single mouse ES-NSPCs were cultured within fibrin (fibrinogen concentration: 6 mg/ml) under neuronal differentiation conditions up to 14 days...
December 29, 2016: Journal of Tissue Engineering and Regenerative Medicine
https://www.readbyqxmd.com/read/28018320/single-molecule-sequencing-pacbio-of-the-staphylococcus-capitis-nrcs-a-clone-reveals-the-basis-of-multidrug-resistance-and-adaptation-to-the-neonatal-intensive-care-unit-environment
#5
Patrícia Martins Simões, Hajar Lemriss, Yann Dumont, Sanâa Lemriss, Jean-Philippe Rasigade, Sophie Assant-Trouillet, Azeddine Ibrahimi, Saâd El Kabbaj, Marine Butin, Frédéric Laurent
The multi-resistant Staphylococcus capitis clone NRCS-A has recently been described as a major pathogen causing nosocomial, late-onset sepsis (LOS) in preterm neonates worldwide. NRCS-A representatives exhibit an atypical antibiotic resistance profile. Here, the complete closed genome (chromosomal and plasmid sequences) of NRCS-A prototype strain CR01 and the draft genomes of three other clinical NRCS-A strains from Australia, Belgium and the United Kingdom are annotated and compared to available non-NRCS-A S...
2016: Frontiers in Microbiology
https://www.readbyqxmd.com/read/28018292/obesity-an-immunometabolic-perspective
#6
REVIEW
Indrani Ray, Sushil K Mahata, Rajat K De
Obesity, characterized by chronic activation of inflammatory pathways, is a critical factor contributing to insulin resistance (IR) and type 2 diabetes (T2D). Free fatty acids (FFAs) are increased in obesity and are implicated as proximate causes of IR and induction of inflammatory signaling in adipose, liver, muscle, and pancreas. Cells of the innate immune system produce cytokines, and other factors that affect insulin signaling and result in the development of IR. In the lean state, adipose tissue is populated by adipose tissue macrophage of the anti-inflammatory M2 type (ATM2) and natural killer (NK) cells; this maintains the insulin-sensitive phenotype because ATM2 cells secrete IL10...
2016: Frontiers in Endocrinology
https://www.readbyqxmd.com/read/28013294/mutation-in-vps33a-affects-metabolism-of-glycosaminoglycans-a-new-type-of-mucopolysaccharidosis-with-severe-systemic-symptoms
#7
Hidehito Kondo, Nadezda Maksimova, Takanobu Otomo, Hisakazu Kato, Atsuko Imai, Yoshihiro Asano, Kaori Kobayashi, Satoshi Nojima, Akihiro Nakaya, Yusuke Hamada, Kaori Irahara, Elizaveta Gurinova, Aitalina Sukhomyasova, Anna Nogovicina, Mira Savvina, Tamotsu Yoshimori, Keiichi Ozono, Norio Sakai
Mucopolysaccharidoses (MPS) are a group of genetic deficiencies of lysosomal enzymes that catabolize glycosaminoglycans (GAG). Here we describe a novel MPS-like disease caused by a specific mutation in the VPS33A gene. We identified several Yakut patients showing typical manifestations of MPS: coarse facial features, skeletal abnormalities, hepatosplenomegaly, respiratory problems, mental retardation, and excess secretion of urinary GAG. However, these patients could not be diagnosed enzymatically as MPS. They showed extremely high levels of plasma heparan sulphate (HS, one of GAG); 60 times the normal reference range and 6 times that of MPS patients...
December 23, 2016: Human Molecular Genetics
https://www.readbyqxmd.com/read/27998463/-effects-of-anti-pd-l1-monoclonal-antibody-and-egfr-tki-on-the-expression-of-pd-l1-and-function-of-t-lymphocytes-in-egfr-mutated-lung-cancer-cells
#8
Y She, X Pan, Y F Xing, T Zhou, Z L Zhang, M H Shi, Y J Chen
Objective: To investigate the effects of anti-PD-L1 monoclonal antibody and EGFR-TKI on expression of soluble PD-L1 and function of T lymphocytes in EGFR-mutated lung cancer cells. Methods: Flow cytometry was used to analyze the expression of membrane PD-LI. ELISA was performed to detect the level of sPD-L1 in the supernatant of cultured EGFR-mutated and wild type lung cancer cells before and after erlotinib treatment.After treated with anti-PD-L1 monoclonal antibody alone and in combination with erlotinib, the proliferation of T lymphocytes in co-culture system was measured using Cell Counting Kit-8 (CCK-8) assay...
December 23, 2016: Zhonghua Zhong Liu za Zhi [Chinese Journal of Oncology]
https://www.readbyqxmd.com/read/27995367/paracoccidioides-brasiliensis-induces-cytokine-secretion-in-epithelial-cells-in-a-protease-activated-receptor-dependent-par-manner
#9
Priscila de Oliveira, Maria Aparecida Juliano, Aparecida Sadae Tanaka, Adriana Karaoglanovic Carmona, Saara Maria Batista Dos Santos, Bianca Carla Silva Campitelli de Barros, Paloma Korehisa Maza, Rosana Puccia, Erika Suzuki
Paracoccidioides brasiliensis is one of the etiological agents of the human systemic mycosis paracoccidioidomycosis. Protease-activated receptors (PARs) are expressed in many cell types and comprise a family of G protein-coupled receptors (PAR-1, PAR-2, and PAR-4), which may be activated by proteases secreted by several pathogens. In the present study, we showed that the pathogenic fungus P. brasiliensis secretes components that promote interleukin (IL)-6 and IL-8 secretion by the lung epithelial cell line A549...
December 19, 2016: Medical Microbiology and Immunology
https://www.readbyqxmd.com/read/27995095/roles-of-the-putative-type-iv-like-secretion-system-key-component-vird4-and-prsa-in-pathogenesis-of-streptococcus-suis-type-2
#10
Xiaowu Jiang, Yunkai Yang, Jingjing Zhou, Lexin Zhu, Yuanxing Gu, Xiaoyan Zhang, Xiaoliang Li, Weihuan Fang
Streptococcus suis type 2 (SS2) is a zoonotic pathogen causing septic infection, meningitis and pneumonia in pigs and humans. SS2 may cause streptococcal toxic shock syndrome (STSS) probably due to excessive release of inflammatory cytokines. A previous study indicated that the virD4 gene in the putative type IV-like secretion system (T4SS) within the 89K pathogenicity island specific for recent epidemic strains contributed to the development of STSS. However, the functional basis of VirD4 in STSS remains unclear...
2016: Frontiers in Cellular and Infection Microbiology
https://www.readbyqxmd.com/read/27989047/results-of-contemporary-valve-surgery-in-patients-with-carcinoid-heart-disease
#11
Thomas Kuntze, Tamer Owais, Maria-Anna Secknus, Daniel Kaemmerer, Richard Baum, Evaldas Girdauskas
BACKGROUND: Carcinoid tumor is a slow-growing type of neuroendocrine tumor, originating from enterochromaffin cells and secreting mainly serotonin. The diagnosis is based on clinical symptoms, hormone blood levels, radiological and nuclear imaging, and histological confirmation. However, most patients have metastases at the time of diagnosis because the clinical signs often remain unnoticed or are attributed to other abdominal conditions. In up to 50% of patients the endocardium is affected due to a hormonally active tumor profile...
May 2016: Journal of Heart Valve Disease
https://www.readbyqxmd.com/read/27976703/the-genome-of-rhizobiales-bacteria-in-predatory-ants-reveals-urease-gene-functions-but-no-genes-for-nitrogen-fixation
#12
Minna-Maria Neuvonen, Daniel Tamarit, Kristina Näslund, Juergen Liebig, Heike Feldhaar, Nancy A Moran, Lionel Guy, Siv G E Andersson
Gut-associated microbiota of ants include Rhizobiales bacteria with affiliation to the genus Bartonella. These bacteria may enable the ants to fix atmospheric nitrogen, but no genomes have been sequenced yet to test the hypothesis. Sequence reads from a member of the Rhizobiales were identified in the data collected in a genome project of the ant Harpegnathos saltator. We present an analysis of the closed 1.86 Mb genome of the ant-associated bacterium, for which we suggest the species name Candidatus Tokpelaia hoelldoblerii...
December 15, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27932059/classical-transient-receptor-potential-6-trpc6-channels-support-myofibroblast-differentiation-and-development-of-experimental-pulmonary-fibrosis
#13
Katharina Hofmann, Susanne Fiedler, Sarah Vierkotten, Jonas Weber, Stephan Klee, Jie Jia, Wolfgang Zwickenpflug, Veit Flockerzi, Ursula Storch, Ali Önder Yildirim, Thomas Gudermann, Melanie Königshoff, Alexander Dietrich
Pulmonary fibrosis (PF) is a chronic progressive lung disease without effective medical treatment options leading to respiratory failure and death within 3-5years of diagnosis. The pathological process of PF is driven by aberrant wound-healing involving fibroblasts and myofibroblasts differentiated by secreted profibrotic transforming growth factor β (TGF-β1). Classical transient receptor potential 6 (TRPC6), a Na(+)- and Ca(2+)-permeable cation channel, is able to promote myofibroblast conversion of primary rat cardiac and human dermal fibroblasts and TRPC6-deficiency impaired wound healing after injury...
February 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/27931183/evolution-of-mitosome-metabolism-and-invasion-related-proteins-in-cryptosporidium
#14
Shiyou Liu, Dawn M Roellig, Yaqiong Guo, Na Li, Michael A Frace, Kevin Tang, Longxian Zhang, Yaoyu Feng, Lihua Xiao
BACKGROUND: The switch from photosynthetic or predatory to parasitic life strategies by apicomplexans is accompanied with a reductive evolution of genomes and losses of metabolic capabilities. Cryptosporidium is an extreme example of reductive evolution among apicomplexans, with losses of both the mitosome genome and many metabolic pathways. Previous observations on reductive evolution were largely based on comparative studies of various groups of apicomplexans. In this study, we sequenced two divergent Cryptosporidium species and conducted a comparative genomic analysis to infer the reductive evolution of metabolic pathways and differential evolution of invasion-related proteins within the Cryptosporidium lineage...
December 8, 2016: BMC Genomics
https://www.readbyqxmd.com/read/27925697/prevalence-of-sj%C3%A3-gren-s-syndrome-in-brazilian-patients-infected-with-human-t-cell-lymphotropic-virus
#15
Daniela Assis do Vale, Jorge Casseb, Augusto César Penalva de Oliveira, Ivo Bussoloti Filho, Suzana Cantanhede Orsini Machado de Sousa, Karem López Ortega
BACKGROUND: Human T-lymphotropic virus type I (HTLV-I) is known to be associated with neoplastic and neurodegenerative changes, and it is believed to be associated with various systemic inflammatory diseases, including Sjögren's syndrome (SS). Although HTLV-I infection is endemic in Brazil, there is no information regarding the association between HTLV-I infection and SS in the Brazilian population. The objective of this study was to determine the prevalence of SS in HTLV-I-infected individuals and the prevalence of HTLV-I infection in individuals diagnosed with SS...
December 7, 2016: Journal of Oral Pathology & Medicine
https://www.readbyqxmd.com/read/27924821/critical-role-of-tslp-responsive-mucosal-dendritic-cells-in-the-induction-of-nasal-antigen-specific-iga-response
#16
S Joo, Y Fukuyama, E J Park, Y Yuki, Y Kurashima, R Ouchida, S F Ziegler, H Kiyono
Thymic stromal lymphopoietin (TSLP) is an interleukin-7 (IL-7)-like cytokine involved in T helper 2 type immune responses. The primary target of TSLP is myeloid dendritic cells (DCs), however, little is known about the mechanism by which TSLP elicits respiratory IgA immune responses upon mucosal immunization. Here, we found that the levels of TSLP and TSLPR were upregulated in the mucosal DCs of mice nasally immunized with pneumococcal surface protein A (PspA) plus cholera toxin (CT) compared with those immunized with PspA alone...
December 7, 2016: Mucosal Immunology
https://www.readbyqxmd.com/read/27917866/umbilical-cord-derived-mesenchymal-stem-cells-instruct-monocytes-towards-an-il10-producing-phenotype-by-secreting-il6-and-hgf
#17
Yinan Deng, Yingcai Zhang, Linsen Ye, Tong Zhang, Jintao Cheng, Guihua Chen, Qi Zhang, Yang Yang
Human UC-MSCs are regarded as an attractive alternative to BM-MSCs for clinical applications due to their easy preparation, higher proliferation and lower immunogenicity. However, the mechanisms underlying immune suppression by UC-MSCs are still unclear. We studied the mechanism of inhibition by UC-MSCs during the differentiation of monocytes into DCs and focused on the specific source and the role of the involved cytokines. We found that UC-MSCs suppressed monocyte differentiation into DCs and instructed monocytes towards other cell types, with clear decreases in the expression of co-stimulatory molecules, in the secretion of inflammatory factors and in allostimulatory capacity...
December 5, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27880834/overexpressed-proteins-in-hypervirulent-clade-8-and-clade-6-strains-of-escherichia-coli-o157-h7-compared-to-e-coli-o157-h7-edl933-clade-3-strain
#18
Natalia Amigo, Qi Zhang, Ariel Amadio, Qunjie Zhang, Wanderson M Silva, Baiyuan Cui, Zhongjian Chen, Mariano Larzabal, Jinlong Bei, Angel Cataldi
Escherichia coli O157:H7 is responsible for severe diarrhea and hemolytic uremic syndrome (HUS), and predominantly affects children under 5 years. The major virulence traits are Shiga toxins, necessary to develop HUS and the Type III Secretion System (T3SS) through which bacteria translocate effector proteins directly into the host cell. By SNPs typing, E. coli O157:H7 was separated into nine different clades. Clade 8 and clade 6 strains were more frequently associated with severe disease and HUS. In this study, we aimed to identify differentially expressed proteins in two strains of E...
2016: PloS One
https://www.readbyqxmd.com/read/27872241/the-type-iii-effector-nled-from-enteropathogenic-e-coli-differentiates-between-host-substrates-p38-and-jnk
#19
Kristina Creuzburg, Cristina Giogha, Tania Wong Fok Lung, Nichollas E Scott, Sabrina Mühlen, Elizabeth L Hartland, Jaclyn S Pearson
Enteropathogenic Escherichia coli (EPEC) is a gastrointestinal pathogen that utilises a type III secretion system (T3SS) to inject an array of virulence effector proteins into host enterocytes to subvert numerous cellular processes for successful colonisation and dissemination. The T3SS effector NleD is a 28 kDa zinc metalloprotease that is translocated into host enterocytes where it directly cleaves and inactivates the MAP kinase signaling proteins, JNK and p38. Here a library of 91 random transposon based, in-frame, linker insertion mutants of NleD were tested for their ability to cleave JNK and p38 during transient transfection of cultured epithelial cells...
November 21, 2016: Infection and Immunity
https://www.readbyqxmd.com/read/27870481/glycemic-effect-and-safety-of-a-systemic-partial-glucokinase-activator-pf-04937319-in-patients-with-type-2-diabetes-mellitus-inadequately-controlled-on-metformin-a-randomized-crossover-active-controlled-study
#20
William S Denney, Douglas S Denham, Michael R Riggs, Neeta B Amin
Glucokinase enhances glucose conversion to glucose-6-phosphate, causing glucose-stimulated insulin secretion from pancreatic β cells and increased hepatic glucose uptake. PF-04937319 is a partial glucokinase activator designed to maintain efficacy with reduced hypoglycemia risk. In this randomized, double-blind, double-dummy, 3-period crossover phase 1b study, patients aged 18-70 years with type 2 diabetes mellitus and on metformin received once-daily PF-04937319 (300 mg), split-dose PF-04937319 (150+100 mg; breakfast+lunch), or sitagliptin (100 mg once daily)...
November 2016: Clinical Pharmacology in Drug Development
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