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https://www.readbyqxmd.com/read/28400195/egfr-in-tumor-associated-myeloid-cells-promotes-development-of-colorectal-cancer-in-mice-and-associates-with-outcomes-of-patients
#1
Sriram Srivatsa, Mariel C Paul, Claudia Cardone, Martin Holcmann, Nicole Amberg, Paulina Pathria, Michaela A Diamanti, Markus Linder, Gerald Timelthaler, Hans P Dienes, Lukas Kenner, Fritz Wrba, Gerald W Prager, Stefan Rose-John, Robert Eferl, Giuseppina Liguori, Gerardo Botti, Erika Martinelli, Florian R Greten, Fortunato Ciardiello, Maria Sibilia
BACKGROUND & AIMS: Inhibitors of the epidermal growth factor receptor (EGFR) are the first-line therapy for patients with metastatic colorectal tumors without RAS mutations. However, EGFR inhibitors are ineffective in these patients, and tumor level of EGFR does not associate with response to therapy. We screened human colorectal tumors for EGFR-positive myeloid cells and investigated their association with patient outcome. We also performed studies in mice to evaluate how EGFR expression in tumor cells and myeloid cells contributes to development of colitis-associated cancer and ApcMin-dependent intestinal tumorigenesis...
April 8, 2017: Gastroenterology
https://www.readbyqxmd.com/read/28382965/p38%C3%AE-mapk-regulates-proliferation-and-differentiation-of-osteoclast-progenitors-and-bone-remodeling-in-an-aging-dependent-manner
#2
Qian Cong, Hao Jia, Ping Li, Shoutao Qiu, James Yeh, Yibin Wang, Zhen-Lin Zhang, Junping Ao, Baojie Li, Huijuan Liu
Bone mass is determined by the balance between bone formation, carried out by mesenchymal stem cell-derived osteoblasts, and bone resorption, carried out by monocyte-derived osteoclasts. Here we investigated the potential roles of p38 MAPKs, which are activated by growth factors and cytokines including RANKL and BMPs, in osteoclastogenesis and bone resorption by ablating p38α MAPK in LysM+monocytes. p38α deficiency promoted monocyte proliferation but regulated monocyte osteoclastic differentiation in a cell-density dependent manner, with proliferating p38α(-/-) cultures showing increased differentiation...
April 6, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28382721/the-two-component-system-vicrk-regulates-functions-associated-with-streptococcus-mutans-resistance-to-complement-immunity
#3
Lívia A Alves, Erika N Harth-Chu, Thaís H Palma, Rafael N Stipp, Flávia S Mariano, José F Höfling, Jacqueline Abranches, Renata O Mattos-Graner
Streptococcus mutans, a dental caries pathogen, can promote systemic infections upon reaching the bloodstream. The two-component system (TCS) VicRKSm of S. mutans regulates the synthesis of and interaction with sucrose-derived exopolysaccharides (EPS), processes associated with oral and systemic virulence. In this study, we investigated the mechanisms by which VicRKSm affects S. mutans susceptibility to blood-mediated immunity. Compared to parent strain UA159, the vicKSm isogenic mutant (UAvic) showed reduced susceptibility to deposition of C3b of complement, low binding to serum IgG, and low frequency of C3b/IgG-mediated opsonophagocytosis by PMN in a sucrose-independent way (p<0...
April 5, 2017: Molecular Oral Microbiology
https://www.readbyqxmd.com/read/28377485/ischemic-cerebroprotection-conferred-by-myeloid-lineage-restricted-or-global-cd39-transgene-expression
#4
Amy E Baek, Nadia R Sutton, Danica Petrovic-Djergovic, Hui Liao, Jessica Ray, Joan Park, Yogendra Kanthi, David J Pinsky
Background -Cerebral tissue damage after an ischemic event can be exacerbated by inflammation and thrombosis. Elevated extracellular ATP and ADP levels are associated with cellular injury, inflammation and thrombosis. Ectonucleoside triphosphate diphosphohydrolase-1 (CD39), an enzyme expressed on the plasmalemma of leukocytes and endothelial cells, suppresses platelet activation and leukocyte infiltration by phosphohydrolyzing ATP/ADP. To investigate the effects of increased CD39 in an in vivo cerebral ischemia model, we developed a transgenic (TG) mouse expressing human CD39 (hCD39)...
April 4, 2017: Circulation
https://www.readbyqxmd.com/read/28369864/the-rice-lysm-receptor-like-kinase-oscerk1-is-required-for-the-perception-of-short-chain-chitin-oligomers-in-arbuscular-mycorrhizal-signaling
#5
Gennaro Carotenuto, Mireille Chabaud, Kana Miyata, Martina Capozzi, Naoya Takeda, Hanae Kaku, Naoto Shibuya, Tomomi Nakagawa, David G Barker, Andrea Genre
The rice lysin-motif (LysM) receptor-like kinase OsCERK1 is now known to have a dual role in both pathogenic and symbiotic interactions. Following the recent discovery that the Oscerk1 mutant is unable to host arbuscular mycorrhizal (AM) fungi, we have examined whether OsCERK1 is directly involved in the perception of the short-chain chitin oligomers (Myc-COs) identified in AM fungal exudates and shown to activate nuclear calcium (Ca(2+) ) spiking in the rice root epidermis. An Oscerk1 knockout mutant expressing the cameleon NLS-YC2...
March 29, 2017: New Phytologist
https://www.readbyqxmd.com/read/28336811/the-circadian-protein-bmal1-in-myeloid-cells-is-a-negative-regulator-of-allergic-asthma
#6
Zbigniew Zaslona, Sarah Case, James O Early, Stephen J Lalor, Rachel M McLoughlin, Anne M Curtis, Luke A O'Neill
Our body clock drives rhythms in the expression of genes that have a 24-hour periodicity. BMAL1 is a transcription factor, which is a crucial component in the molecular clock. A number of physiological processes, including immune function are modulated by the circadian clock. Asthma is of particular relevance to the area of circadian control of immunity, since it is a disease with very strong clinical evidence demonstrating regulation by circadian variation. Airway hypersensitivity and asthma attacks are more common at night in humans...
March 23, 2017: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/28298457/distinct-regulatory-effects-of-myeloid-cell-and-endothelial-cell-nox2-on-blood-pressure
#7
Can Martin Sag, Moritz Schnelle, Juqian Zhang, Colin E Murdoch, Sabine Kossmann, Andrea Protti, Celio X C Santos, Greta J Sawyer, Xiaohong Zhang, Heloise Mongue-Din, Daniel A Richards, Alison C Brewer, Oleksandra Prysyazhna, Lars S Maier, Philip Wenzel, Philip J Eaton, Ajay M Shah
Background -Hypertension due to increased renin angiotensin system (RAS) activation is associated with elevated reactive oxygen species (ROS) production. Previous studies implicate NADPH oxidase (Nox) proteins as important ROS sources during RAS activation, with different Nox isoforms being potentially involved. Among these, Nox2 is expressed in multiple cell types including endothelial cells, fibroblasts, immune cells and microglia. Blood pressure (BP) is regulated at central nervous system, renal and vascular levels but the cell-specific role of Nox2 in BP regulation is unknown...
March 15, 2017: Circulation
https://www.readbyqxmd.com/read/28287082/e3-ligase-fbxw7-is-critical-for-rig-i-stabilization-during-antiviral-responses
#8
Yinjing Song, Lihua Lai, Zhenlu Chong, Jia He, Yuanyuan Zhang, Yue Xue, Yiwei Xie, Songchang Chen, Ping Dong, Luoquan Chen, Zhimin Chen, Feng Dai, Xiaopeng Wan, Peng Xiao, Xuetao Cao, Yang Liu, Qingqing Wang
Viruses can escape from host recognition by degradation of RIG-I or interference with the RIG-I signalling to establish persistent infections. However, the mechanisms by which host cells stabilize RIG-I protein for avoiding its degradation are largely unknown. We report here that, upon virus infection, the E3 ubiquitin ligase FBXW7 translocates from the nucleus into the cytoplasm and stabilizes RIG-I. FBXW7 interacts with SHP2 and mediates the degradation and ubiquitination of SHP2, thus disrupting the SHP2/c-Cbl complex, which mediates RIG-I degradation...
March 13, 2017: Nature Communications
https://www.readbyqxmd.com/read/28230048/differential-regulation-of-the-epr3-receptor-coordinates-membrane-restricted-rhizobial-colonization-of-root-nodule-primordia
#9
Yasuyuki Kawaharada, Mette W Nielsen, Simon Kelly, Euan K James, Kasper R Andersen, Sheena R Rasmussen, Winnie Füchtbauer, Lene H Madsen, Anne B Heckmann, Simona Radutoiu, Jens Stougaard
In Lotus japonicus, a LysM receptor kinase, EPR3, distinguishes compatible and incompatible rhizobial exopolysaccharides at the epidermis. However, the role of this recognition system in bacterial colonization of the root interior is unknown. Here we show that EPR3 advances the intracellular infection mechanism that mediates infection thread invasion of the root cortex and nodule primordia. At the cellular level, Epr3 expression delineates progression of infection threads into nodule primordia and cortical infection thread formation is impaired in epr3 mutants...
February 23, 2017: Nature Communications
https://www.readbyqxmd.com/read/28220415/analysis-for-protein-glycosylation-of-pattern-recognition-receptors-in-plants
#10
Takaakira Inokuchi, Yusuke Saijo
Recognition of molecules typical of microbes or aberrant cellular states, termed microbe- or danger-associated molecular patterns (MAMPs/DAMPs), respectively, provides an important step in plant and animal innate immunity. In plants, pattern recognition receptors (PRRs) identified to date are limited to membrane-associated proteins, of which the majority has an extracellular leucine-rich repeat (LRR) or lysine-motif (LysM) domain. These PRRs undergo quality control (QC) in the Endoplasmic Reticulum (ER) that is dependent on Asn (N)-linked glycosylation (Glc3Man9GlcNAc2 conjugation) of their extracellular domain...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28220411/peptidoglycan-isolation-and-binding-studies-with-lysm-type-pattern-recognition-receptors
#11
Ute Bertsche, Andrea A Gust
In the last decade, more and more plant receptors for complex carbohydrate structures have been described. However, studies on receptor binding to glycan ligands are often hampered due to the technical challenge to obtain pure preparations of homogeneous carbohydrate ligands such as bacterial peptidoglycan (PGN) in amounts suitable for studying protein-glycan interactions. Also, most approaches rely on the availability of defined soluble ligands, which in the case of glycans can rarely be synthesized but have to be purified from the respective microorganism...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28219823/proteomic-analysis-of-a-carbapenem-resistant-klebsiella-pneumoniae-strain-in-response-to-meropenem-stress
#12
Arbab Khan, Divakar Sharma, Mohammad Faheem, Deepa Bisht, Asad U Khan
OBJECTIVES: Antibiotic resistance has become a major problem in treating bacterial infections. The aim of this study was to elucidate the effects of meropenem on a blaKPC-2-harbouring multidrug-resistant clinical strain of Klebsiella pneumoniae through a proteomics approach in order to attain a deeper understanding of bacterial resistance strategies. METHODS: Analysis was performed by two-dimensional gel electrophoresis of whole-cell extracts of bacteria exposed to a sublethal concentration of meropenem compared with the untreated control...
February 20, 2017: Journal of Global Antimicrobial Resistance
https://www.readbyqxmd.com/read/28190384/lactic-acid-bacteria-with-concomitant-il-17-il-23-and-tnf%C3%AE-binding-ability-for-the-treatment-of-inflammatory-bowel-disease
#13
Staša Kosler, Borut Štrukelj, Aleš Berlec
BACKGROUND: Neutralization of proinflammatory cytokines is an established strategy in the treatment of inflammatory bowel disease (IBD). Systemic anti-TNFα antibodies have been used in the clinics for several years, while anti-IL-17/IL-23 antibodies have been less successful so far. We report the development of safe lactic acid bacterium Lb. salivarius with the ability to simultaneously bind IL-17A, IL-23 and TNFα that could be administered orally for the treatment of IBD. METHODS: Three different cytokine-binding non-Ig scaffolds (anti-IL-17A fynomer, anti-IL-23-binding adnectin and anti-TNFα-binding affibody) were cloned and expressed in L...
February 10, 2017: Current Pharmaceutical Biotechnology
https://www.readbyqxmd.com/read/28165624/myeloid-myd88-contributes-to-ethanol-induced-liver-injury-in-mice-linking-hepatocellular-death-to-inflammation
#14
Hao Zhou, Minja Yu, Sanjoy Roychowdhury, Carlos Sanz-Garcia, Katherine A Pollard, Megan R McMullen, Xiuli Liu, Xiaoxia Li, Laura E Nagy
BACKGROUND: Toll-like receptor 4 (TLR4) is critical for ethanol (EtOH)-induced liver injury. TLR4 signaling is mediated by 2 proximal adaptor molecules: myeloid differentiation primary response protein (MyD88) and TLR-domain-containing adaptor-inducing interferon-β (TRIF). Studies utilizing global knockouts of MyD88 and TRIF identified a predominant role for TRIF signaling in the progression of EtOH-induced liver injury. In contrast, IL-1 receptor, which signals solely via the MyD88 pathway, is also known to mediate EtOH-induced liver injury...
April 2017: Alcoholism, Clinical and Experimental Research
https://www.readbyqxmd.com/read/28120642/a-novel-mouse-model-of-conditional-irak-m-deficiency-in-myeloid-cells-application-in-lung-pseudomonas-aeruginosa-infection
#15
Di Jiang, Jennifer Matsuda, Reena Berman, Niccolette Schaefer, Connor Stevenson, James Gross, Bicheng Zhang, Amelia Sanchez, Liwu Li, Hong Wei Chu
Myeloid cells such as macrophages are critical to innate defense against infection. IL-1 receptor-associated kinase M (IRAK-M) is a negative regulator of TLR signaling during bacterial infection, but the role of myeloid cell IRAK-M in bacterial infection is unclear. Our goal was to generate a novel conditional knockout mouse model to define the role of myeloid cell IRAK-M during bacterial infection. Myeloid cell-specific IRAK-M knockout mice were generated by crossing IRAK-M floxed mice with LysM-Cre knock-in mice...
February 2017: Innate Immunity
https://www.readbyqxmd.com/read/28120013/secretory-expression-and-surface-display-of-a-new-and-biologically-active-single-chain-insulin-sci-59-analog-by-lactic-acid-bacteria
#16
Ruifeng Mao, Dongli Wu, Shimeng Hu, Kangping Zhou, Man Wang, Yefu Wang
Insulin plays an important role in drug therapies for diabetes mellitus and as the main route of insulin delivery, subcutaneous injection may cause local discomfort, hypoglycemia, hyperinsulinemia, and patient non-compliance. Therefore, oral delivery of insulin is more preferred. However, there is a low bioavailability due to insulin degradation by proteolytic enzymes and severe pH conditions along the gastrointestinal tract. In order to use the food-grade bacteria lactic acid bacteria (LAB) as oral delivery vehicles, a new and bioactive single-chain insulin (SCI-59) analog, containing the insulin B- and A-chains connected by an eight-residue linker (RSRGLPFR), was secretory expressed in Lactococcus lactis NZ3900 without using an antibiotic resistance gene and displayed onto the surface of various non-viable bacteria (NVBs) without genetic modification...
January 24, 2017: Applied Microbiology and Biotechnology
https://www.readbyqxmd.com/read/28099857/a-systems-approach-reveals-mavs-signaling-in-myeloid-cells-as-critical-for-resistance-to-ebola-virus-in-murine-models-of-infection
#17
Mukta Dutta, Shelly J Robertson, Atsushi Okumura, Dana P Scott, Jean Chang, Jeffrey M Weiss, Gail L Sturdevant, Friederike Feldmann, Elaine Haddock, Abhilash I Chiramel, Sanket S Ponia, Jonathan D Dougherty, Michael G Katze, Angela L Rasmussen, Sonja M Best
The unprecedented 2013-2016 outbreak of Ebola virus (EBOV) resulted in over 11,300 human deaths. Host resistance to RNA viruses requires RIG-I-like receptor (RLR) signaling through the adaptor protein, mitochondrial antiviral signaling protein (MAVS), but the role of RLR-MAVS in orchestrating anti-EBOV responses in vivo is not known. Here we apply a systems approach to MAVS(-/-) mice infected with either wild-type or mouse-adapted EBOV. MAVS controlled EBOV replication through the expression of IFNα, regulation of inflammatory responses in the spleen, and prevention of cell death in the liver, with macrophages implicated as a major cell type influencing host resistance...
January 17, 2017: Cell Reports
https://www.readbyqxmd.com/read/28062700/intravital-imaging-of-neutrophil-recruitment-reveals-the-efficacy-of-fpr1-blockade-in-hepatic-ischemia-reperfusion-injury
#18
Masaki Honda, Takayuki Takeichi, Shintaro Hashimoto, Daiki Yoshii, Kaori Isono, Shintaro Hayashida, Yuki Ohya, Hidekazu Yamamoto, Yasuhiko Sugawara, Yukihiro Inomata
Neutrophils are considered responsible for the pathophysiological changes resulting from hepatic ischemia-reperfusion (I/R) injury, which is a complication of trauma, shock, liver resection, and transplantation. Recently, evidence is accumulating that formyl-peptide receptor (FPR) signaling constitutes an important danger signal that guides neutrophils to sites of inflammation. This study aimed to investigate dynamic neutrophil recruitment using two-photon laser-scanning microscopy (TPLSM) in response to FPR1 blockade during hepatic I/R...
January 6, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28003382/mek1-2-inhibition-promotes-macrophage-reparative-properties
#19
Matthew E Long, William E Eddy, Ke-Qin Gong, Lara L Lovelace-Macon, Ryan S McMahan, Jean Charron, W Conrad Liles, Anne M Manicone
Macrophages have important functional roles in regulating the timely promotion and resolution of inflammation. Although many of the intracellular signaling pathways involved in the proinflammatory responses of macrophages are well characterized, the components that regulate macrophage reparative properties are less well understood. We identified the MEK1/2 pathway as a key regulator of macrophage reparative properties. Pharmacological inhibition of the MEK1/2 pathway by a MEK1/2 inhibitor (MEKi) significantly increased expression of IL-4/IL-13 (M2)-responsive genes in murine bone marrow-derived and alveolar macrophages...
January 15, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/27990146/comparative-transcriptomic-analysis-of-virulence-factors-in-leptosphaeria-maculans-during-compatible-and-incompatible-interactions-with-canola
#20
Humira Sonah, Xuehua Zhang, Rupesh K Deshmukh, M Hossein Borhan, W G Dilantha Fernando, Richard R Bélanger
Leptosphaeria maculans is a hemibiotrophic fungus that causes blackleg of canola (Brassica napus), one of the most devastating diseases of this crop. In the present study, transcriptome profiling of L. maculans was performed in an effort to understand and define the pathogenicity genes that govern both the biotrophic and the necrotrophic phase of the fungus, as well as those that separate a compatible from an incompatible interaction. For this purpose, comparative RNA-seq analyses were performed on L. maculans isolate D5 at four different time points following inoculation on susceptible cultivar Topas-DH16516 or resistant introgression line Topas-Rlm2...
2016: Frontiers in Plant Science
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