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https://www.readbyqxmd.com/read/29235178/the-gp130-cytokine-il-11-regulates-engraftment-of-vav1-hematopoietic-stem-and-progenitor-cells-in-lethally-irradiated-recipients
#1
Serena De Vita, Yanhua Li, Chad E Harris, Meaghan K McGuinness, Clement Ma, David A Williams
During bone marrow transplantation (BMT), hematopoietic stem and progenitor cells (HSPCs) respond to signals from the hematopoietic microenvironment (HM) by coordinately activating molecular pathways through Rho GTPases, including Rac. We have previously shown that deletion of Vav1, a hematopoietic-specific activator of Rac, compromises engraftment of transplanted adult HSPCs without affecting steady-state hematopoiesis in adult animals. Here, we show that Vav1-/- fetal HSPCs can appropriately seed hematopoietic tissues during ontogeny but cannot engraft into lethally irradiated recipients...
December 13, 2017: Stem Cells
https://www.readbyqxmd.com/read/29229683/mesenchymal-stem-cells-promote-endothelial-progenitor-cell-migration-vascularization-and-bone-repair-in-tissue-engineered-constructs-via-activating-cxcr2-src-pkl-vav2-rac1
#2
Zhilin Li, Aijun Yang, Xiaolong Yin, Shiwu Dong, Fei Luo, Ce Dou, Xu Lan, Zhao Xie, Tianyong Hou, Jianzhong Xu, Junchao Xing
Tissue-engineered constructs (TECs) hold great promise for treating large bone defects. Incorporated mesenchymal stem cells (MSCs) can facilitate the vascularization of TECs. Nevertheless, the underlying mechanism remains ambiguous. Here we analyzed the roles of C-X-C chemokine receptor 2 (CXCR2) and its downstream signal pathways in MSC-induced endothelial progenitor cell (EPC) migration. Transwell assays and immunofluorescence staining were performed for cell migration analysis in vitro and in vivo, respectively...
December 11, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/29194596/truncated-isoform-vav3-1-is-highly-expressed-in-ovarian-cancer-stem-cells-and-clinically-relevant-in-predicting-prognosis-and-platinum-response
#3
Daniel Reimer, Maximilian Boesch, Dominik Wolf, Christian Marth, Sieghart Sopper, Jiri Hatina, Peter Altevogt, Walther Parson, Hubert Hackl, Alain G Zeimet
Vav3 is a key modulator of GTP-hydrolases of the Rho/Rac family, which are crucially involved in cell proliferation. Vav3 is alternatively spliced in full-length Vav3-alpha and N-terminal truncated Vav3.1 lacking its self-regulatory domains. The aim of this study was to estimate the clinical impact of Vav3 and all other Vav family members in ovarian cancer. Purification of a stem-cell like side-population (SP) from ovarian cancer cell lines was performed by flow cytometry/FACS. Differences in gene expression between SP and NSP were assessed by Gene Array analysis and confirmed by RT-PCR and immunoblot...
December 1, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/29155934/controlled-flow-diversion-in-hybrid-venoarterial-venous-extracorporeal-membrane-oxygenation
#4
Mehmet Cakici, Fatih Gumus, Evren Ozcinar, Cagdas Baran, Onat Bermede, Mustafa Bahadir Inan, Mustafa Serkan Durdu, Mustafa Sirlak, Ahmet Ruchan Akar
OBJECTIVES: Patients on venoarterial or venovenous extracorporeal membrane oxygenation (ECMO) support may require venoarterial-venous (VAV-ECMO) configuration during follow-up. We report 12 cases of VAV-ECMO with significant outflow steal. METHODS: Between October 2014 and November 2016, a total of 97 patients (56.6 ± 12.0 years; 59 men/38 women; body surface area 1.84 ± 0.36 m 2 ) were supported with venoarterial ECMO ( n  = 85) or venovenous ECMO ( n  = 12)...
August 16, 2017: Interactive Cardiovascular and Thoracic Surgery
https://www.readbyqxmd.com/read/29125705/m-tuberculosis-mce3c-promotes-mycobacteria-entry-into-macrophages-through-activation-of-%C3%AE-2-integrin-mediated-signaling-pathway
#5
Yong Zhang, Jie Li, Bingxi Li, Jing Wang, Cui Hua Liu
Establishment of infection by facultative intracellular pathogen Mycobacterium tuberculosis (Mtb) requires adherence to and internalization by macrophages. However, the effector molecules exploited by Mtb for entry into macrophages remain to be fully understood. The mammalian cell entry (Mce) proteins play an essential role in facilitating the internalization of mycobacteria into mammalian cells. Here we characterized Mtb Mce3C as a new mycobacterial surface protein that could promote mycobacterial adhesion to and invasion of macrophages in an RGD motif-dependent manner...
November 10, 2017: Cellular Microbiology
https://www.readbyqxmd.com/read/29124783/a-key-role-for-rac-and-pak-signaling-in-neutrophil-extracellular-traps-nets-formation-defines-a-new-potential-therapeutic-target
#6
M Gavillet, K Martinod, R Renella, D D Wagner, D A Williams
NET formation in mice (NETosis) is supported by reactive oxygen species (ROS) production by NADPH oxidase and histone hypercitrullination by peptidylarginine deiminase 4 (PAD4). Rac1 and Rac2, expressed in polymorphonuclear neutrophils (PMNs), regulate the cytoskeleton, cell shape, adhesion and migration and are also essential components of the NADPH oxidase complex. We aimed to explore the role of the Rac signaling pathway including the upstream guanosine exchange factor (GEF) activator, Vav, and a downstream effector, the p21-activated kinase, Pak, on NETosis in PMNs using a previously described flow-cytometry-based assay...
November 10, 2017: American Journal of Hematology
https://www.readbyqxmd.com/read/29070986/automated-semi-quantitative-analysis-of-breast-mri-potential-imaging-biomarker-for-the-prediction-of-tissue-response-to-neoadjuvant-chemotherapy
#7
Matthias Dietzel, Clemens Kaiser, Katja Pinker, Evelyn Wenkel, Matthias Hammon, Michael Uder, Barbara Bennani Baiti, Paola Clauser, Rüdiger Schulz-Wendtland, Pascal Baltzer
BACKGROUND: We aimed to investigate an automated semi-quantitative software as an imaging biomarker for the prediction of tissue response (TR) after completion of neoadjuvant chemotherapy (NAC). METHODS: Breast magnetic resonance imaging (MRI) (1.5T, protocol according to international recommendations) of 67 patients with biopsy-proven invasive breast cancer were examined before and after NAC. After completion of NAC, histopathologic assessments of TR were classified according to the Chevallier grading system (CG1/4: full/non-responder; CG2/C3: partial responder)...
September 2017: Breast Care
https://www.readbyqxmd.com/read/28974232/the-stem-cell-factor-sall4-is-an-essential-transcriptional-regulator-in-mixed-lineage-leukemia-rearranged-leukemogenesis
#8
Lina Yang, Li Liu, Hong Gao, Jaya Pratap Pinnamaneni, Deepthi Sanagasetti, Vivek P Singh, Kai Wang, Megumi Mathison, Qianzi Zhang, Fengju Chen, Qianxing Mo, Todd Rosengart, Jianchang Yang
BACKGROUND: The stem cell factor spalt-like transcription factor 4 (SALL4) plays important roles in normal hematopoiesis and also in leukemogenesis. We previously reported that SALL4 exerts its effect by recruiting important epigenetic factors such as DNA methyltransferases DNMT1 and lysine-specific demethylase 1 (LSD1/KDM1A). Both of these proteins are critically involved in mixed lineage leukemia (MLL)-rearranged (MLL-r) leukemia, which has a very poor clinical prognosis. Recently, SALL4 has been further linked to the functions of MLL and its target gene homeobox A9 (HOXA9)...
October 3, 2017: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/28967906/ezh2-promotes-neoplastic-transformation-through-vav-interaction-dependent-extranuclear-mechanisms
#9
N Venkatesan, J F Wong, K P Tan, H H Chung, Y H Yau, E Cukuroglu, A Allahverdi, L Nordenskiöld, J Göke, S Geifman-Shochat, V C L Lin, M S Madhusudhan, I-H Su
Recently, we reported that the histone methyltransferase, EZH2, controls leukocyte migration through interaction with the cytoskeleton remodeling effector, VAV, and direct methylation of the cytoskeletal regulatory protein, Talin. However, it is unclear whether this extranuclear, epigenetic-independent function of EZH2 has a profound impact on the initiation of cellular transformation and metastasis. Here, we show that EZH2 increases Talin1 methylation and cleavage, thereby enhancing adhesion turnover and promoting accelerated tumorigenesis...
October 2, 2017: Oncogene
https://www.readbyqxmd.com/read/28937614/a-novel-vav3-homolog-identified-in-lamprey-lampetra-japonica-with-roles-in-lipopolysaccharide-mediated-immune-response
#10
Yanqi Shen, Yishan Zhang, Yinglun Han, Peng Su, Meng Gou, Yue Pang, Qingwei Li, Xin Liu
Vav guanine nucleotide exchange factor 3 (Vav3), a Rho family GTPase, regulates multiple cell signaling pathways including those of T- and B-cell receptors in vertebrates through mediating the activities of the Rho family members. Whether the lamprey possesses Vav3 homolog and what role it plays in immune response remain unknown. Gene cloning, recombinant expression, antibody production and expression pattern analyses were performed to characterize the lamprey Vav3 in the current study. The lamprey Vav3 is closer to jawed vertebrates' Vav3 molecules (about 53% identities in general) than to Vav2 molecules of jawless and jawed vertebrates (about 51% identities in general) in sequence similarity...
September 22, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28930674/a-protein-scaffold-coordinates-src-mediated-jnk-activation-in-response-to-metabolic-stress
#11
Shashi Kant, Claire L Standen, Caroline Morel, Dae Young Jung, Jason K Kim, Wojciech Swat, Richard A Flavell, Roger J Davis
Obesity is a major risk factor for the development of metabolic syndrome and type 2 diabetes. How obesity contributes to metabolic syndrome is unclear. Free fatty acid (FFA) activation of a non-receptor tyrosine kinase (SRC)-dependent cJun NH2-terminal kinase (JNK) signaling pathway is implicated in this process. However, the mechanism that mediates SRC-dependent JNK activation is unclear. Here, we identify a role for the scaffold protein JIP1 in SRC-dependent JNK activation. SRC phosphorylation of JIP1 creates phosphotyrosine interaction motifs that bind the SH2 domains of SRC and the guanine nucleotide exchange factor VAV...
September 19, 2017: Cell Reports
https://www.readbyqxmd.com/read/28927664/the-c1-domain-of-vav3-a-novel-potential-therapeutic-target
#12
Jessica S Kelsey, Tamás Géczy, Christopher J Kaler, Peter M Blumberg
Vav1/2/3 comprise a protein family with guanyl nucleotide exchange activity for Rho and Rac as well as with motifs conferring adapter activity. Biologically, Vav1 plays a critical role in hematologic cell signaling, whereas Vav2/3 have a wider tissue distribution, but all 3 Vav proteins are implicated in cancer development. A structural feature of Vav1/2/3 is the presence of an atypical C1 domain, which possesses close structural homology to the typical C1 domains of protein kinase C but which fails to bind the second messenger diacylglycerol or the potent analogs, the phorbol esters...
December 2017: Cellular Signalling
https://www.readbyqxmd.com/read/28801739/-the-new-treatment-procedures-of-the-dguv-from-the-perspective-of-an-injury-type-procedure-vav-clinic
#13
REVIEW
M Oberst
The new treatment procedures of the German Statutory Accident Insurance (DGUV) have ramifications for the injury type procedure clinics (VAV) from medical, economic and structural aspects. Whereas the latter can be assessed as positive, the medical and economical aspects are perceived as being negative. Problems arise from the partially unclear formulation of the injury type catalogue, which results in unpleasant negotiations with the occupational insurance associations with respect to financial remuneration for services rendered...
September 2017: Der Unfallchirurg
https://www.readbyqxmd.com/read/28795321/nkg2d-gene-polymorphisms-are-associated-with-disease-control-of-chronic-myeloid-leukemia-by-dasatinib
#14
Ryujiro Hara, Makoto Onizuka, Erika Matsusita, Eri Kikkawa, Yoshihiko Nakamura, Hiromichi Matsushita, Daisuke Ohgiya, Hiromichi Murayama, Shinichiro Machida, Ken Ohmachi, Yukari Shirasugi, Yoshiaki Ogawa, Hiroshi Kawada, Kiyoshi Ando
A recent study reported that treatment-free remission (TFR) of chronic myeloid leukemia (CML) after dasatinib (Das) treatment was significantly associated with natural killer (NK) cell proliferation in the peripheral blood. However, biomarkers to predict lymphocytosis or successful TFR are not well characterized. In order to clarify individual differences in NK cell responses among patients treated with Das, we retrospectively analyzed the association between polymorphisms in the natural killer group 2D receptor [NKG2D; also known as killer cell lectin like receptor K1 (KLRK1)] gene and clinical outcomes in 31 patients treated with Das as first-line treatment for CML...
November 2017: International Journal of Hematology
https://www.readbyqxmd.com/read/28716125/mercury-alters-endogenous-phosphorylation-profiles-of-syk-in-murine-b-cells
#15
Joseph A Caruso, Nicholas Carruthers, Namhee Shin, Randal Gill, Paul M Stemmer, Allen Rosenspire
BACKGROUND: Epidemiological evidence and animal models suggest that exposure to low and non-neurotoxic concentrations of mercury may contribute to idiosyncratic autoimmune disease. Since defects in function and signaling in B cells are often associated with autoimmunity, we investigated whether mercury exposure might alter B cell responsiveness to self-antigens by interfering with B cell receptor (BCR) signal transduction. In this study we determined the effects of mercury on the protein tyrosine kinase SYK, a critical protein involved in regulation of the BCR signaling pathway...
July 17, 2017: BMC Immunology
https://www.readbyqxmd.com/read/28666733/virtual-screening-synthesis-and-biological-evaluation-of-dna-intercalating-antiviral-agents
#16
Kyrylo Klimenko, Sergey Lyakhov, Marina Shibinskaya, Alexander Karpenko, Gilles Marcou, Dragos Horvath, Marina Zenkova, Elena Goncharova, Rinat Amirkhanov, Andrei Krysko, Sergei Andronati, Igor Levandovskiy, Pavel Polishchuk, Victor Kuz'min, Alexandre Varnek
This paper describes computer-aided design of new anti-viral agents against Vaccinia virus (VACV) potentially acting as nucleic acid intercalators. Earlier obtained experimental data for DNA intercalation affinities and activities against Vesicular stomatitis virus (VSV) have been used to build, respectively, pharmacophore and QSAR models. These models were used for virtual screening of a database of 245 molecules generated around typical scaffolds of known DNA intercalators. This resulted in 12 hits which then were synthesized and tested for antiviral activity against VaV together with 43 compounds earlier studied against VSV...
August 15, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28642279/role-of-myd88-signaling-in-the-imiquimod-induced-mouse-model-of-psoriasis-focus-on-innate-myeloid-cells
#17
Sara Costa, Olivia Marini, Dalila Bevilacqua, Anthony L DeFranco, Baidong Hou, Silvia Lonardi, William Vermi, Pamela Rodegher, Anna Panato, Franco Tagliaro, Clifford A Lowell, Marco A Cassatella, Giampiero Girolomoni, Patrizia Scapini
Psoriasis is a chronic skin disease associated with deregulated activation of immune cells and keratinocytes. In this study, we used the imiquimod (IMQ)-induced mouse model of psoriasis to dissect better the contribution of hematopoietic and skin-resident stromal cells to psoriasis development. The comparison of disease development in mice carrying the hematopoietic cell-specific deletion of MyD88 (Myd88(fl/fl)Vav-cre(+) mice) with mice carrying the total MyD88 deficiency (Myd88(-/-) mice), we show that the progression of skin and systemic inflammation, as well as of epidermal thickening, was completely dependent on MyD88 expression in hematopoietic cells...
September 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28641662/-effect-of-pdk1-on-neutrophil-differentiation
#18
Wei-Li Wang, Le Wang, Tian-Yuan Hu, Cong Li, Wei-Ping Yuan
OBJECTIVE: To knock out PDK1 by using Vav-Cre and observe the effects of PDK1 knock out on the ratio, number and differentiation of neutrophil. METHODS: The PDK1 expression level of Vav-Cre;PDK1(lox/lox) mouse in the bone marrow cells was analyzed by RT-PCR. The effect of PDK1 on hematopoietic progenitor was observed by CFU-C assay, and the effect of PDK1 on the ratio and number of neutrophil was detected by flow cytometric analysis. RESULTS: The RNA expression level of bone marrow cells of Vav-Cre;PDK1(lox/lox) mouse was dramatically lower than that of the control mouse...
June 2017: Zhongguo Shi Yan Xue Ye Xue za Zhi
https://www.readbyqxmd.com/read/28577909/sox7-expression-is-critically-required-in-flk1-expressing-cells-for-vasculogenesis-and-angiogenesis-during-mouse-embryonic-development
#19
Andrew J Lilly, Andrzej Mazan, Daryl A Scott, Georges Lacaud, Valerie Kouskoff
The transcriptional program that regulates the differentiation of endothelial precursor cells into a highly organized vascular network is still poorly understood. Here we explore the role of SOX7 during this process, performing a detailed analysis of the vascular defects resulting from either a complete deficiency in Sox7 expression or from the conditional deletion of Sox7 in FLK1-expressing cells. We analysed the consequence of Sox7 deficiency from E7.5 onward to determine from which stage of development the effect of Sox7 deficiency can be observed...
August 2017: Mechanisms of Development
https://www.readbyqxmd.com/read/28534985/microarray-analysis-of-differentially-expressed-genes-in-l929-mouse-fibroblast-cells-exposed-to-leptin-and-hypoxia
#20
Ping Ouyang, Sen Wang, He Zhang, Zhigang Huang, Pei Wei, Ye Zhang, Zhuguo Wu, Tao Li
Leptin and hypoxia are pro-fibrotic factors involved in fibrogenesis, however, the gene expression profiles remain to be fully elucidated. The aim of the present study was to investigate the regulatory roles of leptin and hypoxia on the L929 mouse fibroblast cell line. The cells were assigned to a normoxia, normoxia with leptin, hypoxia, and hypoxia with leptin group. The cDNA expression was detected using an Agilent mRNA array platform. The differentially expressed genes (DEGs) in response to leptin and hypoxia were identified using reverse transcription‑quantitative polymerase chain reaction analysis, followed by clustering analysis, Gene Ontology analysis and pathway analysis...
July 2017: Molecular Medicine Reports
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