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https://www.readbyqxmd.com/read/29036202/toxoplasma-gondii-induces-fak-src-stat3-signaling-during-infection-of-host-cells-that-prevents-parasite-targeting-by-autophagy
#1
Jose-Andres C Portillo, Luis Muniz-Feliciano, Yalitza Lopez Corcino, So Jung Lee, Jennifer Van Grol, Sarah J Parsons, William P Schiemman, Carlos S Subauste
Targeting of Toxoplasma gondii by autophagy is an effective mechanism by which host cells kill the protozoan. Thus, the parasite must avoid autophagic targeting to survive. Here we show that the mammalian cytoplasmic molecule Focal Adhesion Kinase (FAK) becomes activated during invasion of host cells. Activated FAK appears to accompany the formation of the moving junction (as assessed by expression the parasite protein RON4). FAK activation was inhibited by approaches that impaired β1 and β3 integrin signaling...
October 16, 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/29034237/proteomics-of-eosinophil-activation
#2
REVIEW
Deane F Mosher, Emily M Wilkerson, Keren B Turton, Alexander S Hebert, Joshua J Coon
We recently identified and quantified >7,000 proteins in non-activated human peripheral blood eosinophils using liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS) and described phosphoproteomic changes that accompany acute activation of eosinophils by interleukin-5 (IL5) (1). These data comprise a treasure trove of information about eosinophils. We illustrate the power of label-free LC-MS/MS quantification by considering four examples: complexity of eosinophil STATs, contribution of immunoproteasome subunits to eosinophil proteasomes, complement of integrin subunits, and contribution of platelet proteins originating from platelet-eosinophil complexes to the overall proteome...
2017: Frontiers in Medicine
https://www.readbyqxmd.com/read/29033288/the-therapeutic-antibody-lm609-selectively-inhibits-ligand-binding-to-human-%C3%AE-v%C3%AE-3-integrin-via-steric-hindrance
#3
Andrew J Borst, Zachary M James, William N Zagotta, Mark Ginsberg, Felix A Rey, Frank DiMaio, Marija Backovic, David Veesler
The LM609 antibody specifically recognizes αVβ3 integrin and inhibits angiogenesis, bone resorption, and viral infections in an arginine-glycine-aspartate-independent manner. LM609 entered phase II clinical trials for the treatment of several cancers and was also used for αVβ3-targeted radioimmunotherapy. To elucidate the mechanisms of recognition and inhibition of αVβ3 integrin, we solved the structure of the LM609 antigen-binding fragment by X-ray crystallography and determined its binding affinity for αVβ3...
October 7, 2017: Structure
https://www.readbyqxmd.com/read/29032524/patterns-and-levels-of-platelet-glycosylation-in-patients-with-coronary-heart-disease-and-type-2-diabetes-mellitus
#4
Liping Li, Chenxue Qu, Xuelian Wu, Juhua Dai, Yao Lu, Yan Gong, Ran You, Yaqi Liu
Coronary heart disease (CHD) and diabetes mellitus (DM) have high reactivity of platelets and an increased risk of thrombosis. Platelet glycosylation is closely related to platelet function and survival. However, the alteration of platelet glycosylation in CHD and T2DM still remains unknown. Platelet samples were obtained from 55 healthy controls and 102 patients, including 33 CHD, 30 T2DM and 39 CHD complicated with T2DM (CHD + T2DM). Platelet glycosylation was detected using eight-lectin based assay by flow cytometry...
October 14, 2017: Journal of Thrombosis and Thrombolysis
https://www.readbyqxmd.com/read/29031858/involvement-of-integrin-%C3%AE-1-fak-signaling-in-the-analgesic-effects-induced-by-glial-cell-line-derived-neurotrophic-factor-in-neuropathic-pain
#5
Hong-Jun Wang, Ge Song, Jian Liang, Yuan-Yuan Gao, Cun-Jin Wang
Treatment of neuropathic pain (NP) continues to be a clinical challenge and the underlying mechanisms of NP remain elusive. More evidence suggests that glial cell line-derived neurotrophic factor (GDNF) has potent anti-nociceptive effects on NP, but the underlying mechanisms are still largely unknown. Recent data have shown that integrin β1 plays an important part in NP induction, and that the activity of integrin β1 signaling is associated with the phosphorylation of the conserved threonines in the cytoplasmic domain and recruitment of focal adhesion kinase (FAK) to the integrin β1 tail and phosphorylation...
October 12, 2017: Brain Research Bulletin
https://www.readbyqxmd.com/read/29031069/synthesis-and-biological-evaluation-of-a-platinum-ii-c-rgdyk-conjugate-for-integrin-targeted-photodynamic-therapy
#6
T Chatzisideri, S Thysiadis, S Katsamakas, P Dalezis, I Sigala, T Lazarides, E Nikolakaki, D Trafalis, O A Gederaas, M Lindgren, V Sarli
A cancer-targeting conjugate 4 of a cyclometalated [N,C,N-Pt(II)] complex bearing a NˆCˆN 1,3-di(2-pyridyl)-benzene with c(RGDyK) peptide as guiding molecule was designed and synthesized for real-time drug delivery monitoring in cancer cells and photodynamic therapy (PDT). This conjugate demonstrates a mild cytostatic effect to six cancer cell lines expressing integrins at different extent, while possessing promising features for PDT. Conjugate 4 demonstrated rapid cell uptake by receptor-mediated endocytosis and efficient generation of (1)O2 upon irradiation...
September 28, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29030430/direct-binding-to-integrins-and-loss-of-disulfide-linkage-in-il-1%C3%AE-are-involved-in-the-agonistic-action-of-il-1%C3%AE
#7
Yoko K Takada, Jessica Yu, Masaaki Fujita, Jun Saegusa, Chun-Yi Wu, Yoshikazu Takada
There is a strong link between integrins and IL-1β, but the specifics of the role of integrins in IL-1β signaling are unclear. We describe that IL-1β specifically bound to integrins αvβ3 and α5β1. The E128K mutation in the IL1R-binding site enhanced integrin binding. We studied if direct integrin binding is involved in IL-1β signaling. We compared sequences of IL-1β and IL-1 receptor antagonist (IL1RN), which is an IL-1β homologue but has no agonistic activity. Several surface-exposed Lys residues are present in IL-1β, but not in IL1RN...
October 13, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29030401/a-comparison-of-whole-genome-sequencing-to-multigene-panel-testing-in-hypertrophic-cardiomyopathy-patients
#8
Allison L Cirino, Neal K Lakdawala, Barbara McDonough, Lauren Conner, Dale Adler, Mark Weinfeld, Patrick O'Gara, Heidi L Rehm, Kalotina Machini, Matthew Lebo, Carrie Blout, Robert C Green, Calum A MacRae, Christine E Seidman, Carolyn Y Ho
BACKGROUND: As DNA sequencing costs decline, genetic testing options have expanded. Whole exome sequencing and whole genome sequencing (WGS) are entering clinical use, posing questions about their incremental value compared with disease-specific multigene panels that have been the cornerstone of genetic testing. METHODS AND RESULTS: Forty-one patients with hypertrophic cardiomyopathy who had undergone targeted hypertrophic cardiomyopathy genetic testing (either multigene panel or familial variant test) were recruited into the MedSeq Project, a clinical trial of WGS...
October 2017: Circulation. Cardiovascular Genetics
https://www.readbyqxmd.com/read/29030222/vascular-changes-in-tumors-resistant-to-a-vascular-disrupting-nanoparticle-treatment
#9
Shweta Sharma, Aman P Mann, Tarmo Mölder, Venkata Ramana Kotamraju, Robert Mattrey, Tambet Teesalu, Erkki Ruoslahti
Anti-angiogenic and vascular disrupting therapies rely on the dependence of tumors on new blood vessels to sustain tumor growth. We previously reported a potent vascular disrupting agent, a theranostic nanosystem consisting of a tumor vasculature-homing peptide (CGKRK) fused to a pro-apoptotic peptide [D(KLAKLAK)2] coated on iron oxide nanoparticles. This nanosystem showed promising therapeutic efficacy in glioblastoma (GBM) and breast cancer models. However, complete control of the tumors was not achieved, and some tumors became non-responsive to the treatment...
October 10, 2017: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/29029772/inhibition-of-mammalian-target-of-rapamycin-signaling-with-rapamycin-prevents-trauma-induced-heterotopic-ossification
#10
Ammar T Qureshi, Devaveena Dey, Erin M Sanders, Jonathan G Seavey, Allison M Tomasino, Kaitlyn Moss, Benjamin Wheatley, David Cholok, Shawn Loder, John Li, Benjamin Levi, Thomas A Davis
A pressing clinical need exists for 63% to 65% of combat-wounded service members and 11% to 20% of civilians who develop heterotopic ossification (HO) after blast-related extremity injury and traumatic injuries, respectively. The mammalian target of rapamycin pathway is a central cellular sensor of injury. We evaluated the prophylactic effects of rapamycin, a selective inhibitor of mammalian target of rapamycin signaling, on HO formation in a rat model of blast-related, polytraumatic extremity injury. Rapamycin was administered intraperitoneally daily for 14 days at 0...
October 5, 2017: American Journal of Pathology
https://www.readbyqxmd.com/read/29028109/research-on-the-correlation-of-urine-calcium-integrin-binding-protein-1-and-pro-bnp-with-ischemic-heart-failure
#11
L Zhang, F Tang, L-P Cai, H-L Wang, Z Wang
OBJECTIVE: To investigate the correlation between the levels of urine calcium integrin binding protein-1 (CIB1) and serum precursor N-terminal brain natriuretic peptide (pro-BNP) and ischemic heart failure. PATIENTS AND METHODS: 30 patients diagnosed as acute ischemic heart failure for the first time in our hospital from January to August 2016 were continuously selected as the observation group 1, 30 patients with chronic stable ischemic heart failure as the observation group 2, and 30 healthy volunteers as the control group...
September 2017: European Review for Medical and Pharmacological Sciences
https://www.readbyqxmd.com/read/29026524/beyond-adhesion-%C3%A2-emerging-roles-for-integrins-in-control-of-the-tumor-microenvironment
#12
REVIEW
Whitney Longmate, C Michael DiPersio
While integrins were originally discovered as cell adhesion receptors, recent studies have reinforced the concept that integrins have central roles in cancer that extend far beyond controlling cell adhesion and migration. Indeed, as transmembrane cell surface receptors that occupy a critical position at the interface of cellular and extracellular interactions and are capable of both "inside-out" and "outside-in" signaling, integrins are uniquely poised to regulate the cell's ability to promote, sense, and react to changes in the tumor microenvironment...
2017: F1000Research
https://www.readbyqxmd.com/read/29024645/helicobacter-pylori-employs-a-unique-basolateral-type-iv-secretion-mechanism-for-caga-delivery
#13
Nicole Tegtmeyer, Silja Wessler, Vittorio Necchi, Manfred Rohde, Aileen Harrer, Tilman T Rau, Carmen Isabell Asche, Manja Boehm, Holger Loessner, Ceu Figueiredo, Michael Naumann, Ralf Palmisano, Enrico Solcia, Vittorio Ricci, Steffen Backert
The Helicobacter pylori (Hp) type IV secretion system (T4SS) forms needle-like pili, whose binding to the integrin-β1 receptor results in injection of the CagA oncoprotein. However, the apical surface of epithelial cells is exposed to Hp, whereas integrins are basolateral receptors. Hence, the mechanism of CagA delivery into polarized gastric epithelial cells remains enigmatic. Here, we demonstrate that T4SS pilus formation during infection of polarized cells occurs predominantly at basolateral membranes, and not at apical sites...
October 11, 2017: Cell Host & Microbe
https://www.readbyqxmd.com/read/29024385/integrin-%C3%AE-3-is-required-for-the-attachment-retention-and-therapeutic-benefits-of-human-cardiospheres-in-myocardial-infarction
#14
Suyun Liu, Zhian Jiang, Li Qiao, Bingyan Guo, Wenliang Xiao, Xiaoguang Zhang, Liang Chang, Yongjun Li
Cardiovascular diseases remain the leading causes of death worldwide. Stem cell therapy offers a promising option to regenerate injured myocardium. Among the various types of stem cells, cardiosphere cells represent a mixture of intrinsic heart stem cells and supporting cells. The safety and efficacy of cardiosphere cells have been demonstrated in recent clinical trials. Cell-matrix interaction plays an important role in mediating the engraftment of injected stem cells. Here, we studied the role of integrin β-3 in cardiosphere-mediated cell therapy in a mouse model of myocardial infarction...
October 11, 2017: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/29023785/cns-synapses-are-stabilized-trans-synaptically-by-laminins-and-laminin-interacting-proteins
#15
Dale D Hunter, Mary K Manglapus, Galina Bachay, Thomas Claudepierre, Michael W Dolan, Kelly-Ann Gesuelli, William J Brunken
The retina expresses several laminins in the outer plexiform layer (OPL), where they may provide an extracellular scaffold for synapse stabilization. Mice with a targeted deletion of the laminin β2 gene (Lamb2) exhibit retinal disruptions: photoreceptor synapses in the OPL are disorganized and the retinal physiological response is attenuated. We hypothesize that laminins are required for proper trans-synaptic alignment. To test this, we compared the distribution, expression, association and modification of several pre- and post-synaptic elements in wild-type and Lamb2-null retinae...
October 12, 2017: Journal of Comparative Neurology
https://www.readbyqxmd.com/read/29021578/strong-binding-of-platelet-integrin-%C3%AE-iib%C3%AE-3-to-fibrin-clots-potential-target-to-destabilize-thrombi
#16
Peter Höök, Rustem I Litvinov, Oleg V Kim, Shixin Xu, Zhiliang Xu, Joel S Bennett, Mark S Alber, John W Weisel
The formation of platelet thrombi is determined by the integrin αIIbβ3-mediated interactions of platelets with fibrinogen and fibrin. Blood clotting in vivo is catalyzed by thrombin, which simultaneously induces fibrinogen binding to αIIbβ3 and converts fibrinogen to fibrin. Thus, after a short time, thrombus formation is governed by αIIbβ3 binding to fibrin fibers. Surprisingly, there is little understanding of αIIbβ3 interaction with fibrin polymers. Here we used an optical trap-based system to measure the binding of single αIIbβ3 molecules to polymeric fibrin and compare it to αIIbβ3 binding to monomeric fibrin and fibrinogen...
October 11, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29021395/hcmv-utilizes-a-non-traditional-stat1-activation-cascade-via-signaling-through-egfr-and-integrins-to-efficiently-promote-the-motility-differentiation-and-polarization-of-infected-monocytes
#17
Donna Collins-McMillen, Emily V Stevenson, Jung Heon Kim, Byeong-Jae Lee, Stephen J Cieply, Maciej T Nogalski, Gary C Chan, Robert W Frost, Caroline R Spohn, Andrew D Yurochko
Human cytomegalovirus infects peripheral blood monocytes and triggers biological changes that promote viral dissemination and persistence. We have shown that HCMV induces a pro-inflammatory state in infected monocytes, resulting in enhanced monocyte motility and transendothelial migration, prolonged monocyte survival, and differentiation toward a long-lived M1-like macrophage phenotype. Our data indicate that HCMV triggers these changes, in the absence of de novo viral gene expression and replication, through engagement and activation of EGFR and integrins on the surface of monocytes...
October 11, 2017: Journal of Virology
https://www.readbyqxmd.com/read/29021221/cancer-associated-fibroblasts-promote-directional-cancer-cell-migration-by-aligning-fibronectin
#18
Begum Erdogan, Mingfang Ao, Lauren M White, Anna L Means, Bryson M Brewer, Lijie Yang, M Kay Washington, Chanjuan Shi, Omar E Franco, Alissa M Weaver, Simon W Hayward, Deyu Li, Donna J Webb
Cancer-associated fibroblasts (CAFs) are major components of the carcinoma microenvironment that promote tumor progression. However, the mechanisms by which CAFs regulate cancer cell migration are poorly understood. In this study, we show that fibronectin (Fn) assembled by CAFs mediates CAF-cancer cell association and directional migration. Compared with normal fibroblasts, CAFs produce an Fn-rich extracellular matrix with anisotropic fiber orientation, which guides the cancer cells to migrate directionally...
October 11, 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/29021139/paxillin-binding-to-the-cytoplasmic-domain-of-cd103-promotes-cell-adhesion-and-effector-functions-for-cd8-resident-memory-t-cells-in-tumors
#19
Ludiane Gauthier, Stephanie Corgnac, Marie Boutet, Gwendoline Gros, Pierre Validire, Georges Bismuth, Fathia Mami-Chouaib
CD8+/CD103+ tissue resident memory T cells (TRM cells) accumulate in several human solid tumors where they have been associated with a favorable prognosis. However, the role of CD103 - the α subunit of the integrin αEβ7 (also known as CD103) - in the retention and functions of these TRM is undefined. In this report, we investigated the role of CD103 cytoplasmic domain and the focal adhesion-associated protein paxillin (Pxn) in downstream signaling and functional activities triggered through αE/CD103 chain...
October 11, 2017: Cancer Research
https://www.readbyqxmd.com/read/29021002/collagen-triple-helix-repeat-containing-1-cthrc1-activates-integrin-%C3%AE-3-fak-signaling-and-promotes-metastasis-in-ovarian-cancer
#20
Biying Guo, Huan Yan, Luying Li, Kemin Yin, Fang Ji, Shu Zhang
BACKGROUND: Metastasis is the major cause of morbidity and mortality in patients with epithelial ovarian cancer (EOC), however the mechanisms that underline this process are poorly understood. Collagen triple helix repeat containing-1 (CTHRC1) is a 28-kDa secreted protein reported to be involved in vascular remodeling, bone formation and morphogenesis. This study aimed to investigate the role of CTHRC1 in promoting the metastasis of EOC and to elucidate the underlying molecular mechanisms...
October 11, 2017: Journal of Ovarian Research
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