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https://www.readbyqxmd.com/read/28214347/involvement-of-the-guanine-nucleotide-exchange-factor-vav3-in-central-nervous-system-development-and-plasticity
#1
Annika Ulc, Christine Gottschling, Ina Schäfer, David Wegrzyn, Simon van Leeuwen, Veronika Luft, Jacqueline Reinhard, Andreas Faissner
Small GTP-hydrolysing enzymes (GTPases) of the RhoA family play manifold roles in cell biology and are regulated by upstream guanine nucleotide exchange factors (GEFs). Herein, we focus on the GEFs of the Vav subfamily. Vav1 was originally described as a protooncogene of the hematopoietic lineage. The GEFs Vav2 and Vav3 are more broadly expressed in various tissues. In particular, the GEF Vav3 may play important roles in the developing nervous system during the differentiation of neural stem cells into the major lineages, namely neurons, oligodendrocytes and astrocytes...
February 18, 2017: Biological Chemistry
https://www.readbyqxmd.com/read/28157227/association-of-vav2-and-vav3-polymorphisms-with-cardiovascular-risk-factors
#2
Nuria Perretta-Tejedor, Javier Fernández-Mateos, Luis García-Ortiz, Manuel A Gómez-Marcos, José I Recio-Rodríguez, Cristina Agudo-Conde, Emiliano Rodriguez-Sánchez, Ana I Morales, Francisco J López-Hernández, José M López-Novoa, Rogelio González-Sarmiento, Carlos Martínez-Salgado
Hypertension, diabetes and obesity are cardiovascular risk factors closely associated to the development of renal and cardiovascular target organ damage. VAV2 and VAV3, members of the VAV family proto-oncogenes, are guanosine nucleotide exchange factors for the Rho and Rac GTPase family, which is related with cardiovascular homeostasis. We have analyzed the relationship between the presence of VAV2 rs602990 and VAV3 rs7528153 polymorphisms with cardiovascular risk factors and target organ damage (heart, vessels and kidney) in 411 subjects...
February 3, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28149575/veno-venous-extracorporeal-membrane-oxygenation-cannulation-techniques
#3
REVIEW
Carlo Banfi, Matteo Pozzi, Nils Siegenthaler, Marie-Eve Brunner, Didier Tassaux, Jean-Francois Obadia, Karim Bendjelid, Raphaël Giraud
The development of extracorporeal membrane oxygenation (ECMO) technology allows a new approach for the intensive care management of acute cardiac and/or respiratory failure in adult patients who are not responsive to conventional treatment. Current ECMO therapies provide a variety of options for the multidisciplinary teams who are involved in the management of these critically ill patients. In this regard, veno-venous ECMO (VV-ECMO) can provide quite complete respiratory support, even if this highly complex technique presents substantial risks, such as bleeding, thromboembolic events and infection...
December 2016: Journal of Thoracic Disease
https://www.readbyqxmd.com/read/28043871/bcl-2-inhibitors-reduce-steroid-insensitive-airway-inflammation
#4
Bao-Ping Tian, Li-Xia Xia, Zheng-Qiang Bao, Hao Zhang, Zhi-Wei Xu, Yuan-Yuan Mao, Chao Cao, Luan-Qing Che, Jin-Kai Liu, Wen Li, Zhi-Hua Chen, Songmin Ying, Hua-Hao Shen
BACKGROUND: Asthmatic inflammation is dominated by accumulation of either eosinophils, neutrophils, or both in the airways. Disposal of these inflammatory cells is the key to disease control. Eosinophilic airway inflammation is responsive to corticosteroid treatment, whereas neutrophilic inflammation is resistant and increases the burden of global health care. Corticosteroid-resistant neutrophilic asthma remains mechanistically poorly understood and requires novel effective therapeutic strategies...
December 31, 2016: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/27926862/vav-proteins-are-key-regulators-of-card9-signaling-for-innate-antifungal-immunity
#5
Susanne Roth, Hanna Bergmann, Martin Jaeger, Assa Yeroslaviz, Konstantin Neumann, Paul-Albert Koenig, Clarissa Prazeres da Costa, Lesley Vanes, Vinod Kumar, Melissa Johnson, Mauricio Menacho-Márquez, Bianca Habermann, Victor L Tybulewicz, Mihai Netea, Xosé R Bustelo, Jürgen Ruland
Fungal infections are major causes of morbidity and mortality, especially in immunocompromised individuals. The innate immune system senses fungal pathogens through Syk-coupled C-type lectin receptors (CLRs), which signal through the conserved immune adaptor Card9. Although Card9 is essential for antifungal defense, the mechanisms that couple CLR-proximal events to Card9 control are not well defined. Here, we identify Vav proteins as key activators of the Card9 pathway. Vav1, Vav2, and Vav3 cooperate downstream of Dectin-1, Dectin-2, and Mincle to engage Card9 for NF-κB control and proinflammatory gene transcription...
December 6, 2016: Cell Reports
https://www.readbyqxmd.com/read/27924718/co-activation-of-cultured-human-natural-killer-cells-enhanced-function-and-decreased-inhibition
#6
Doris Urlaub, Rauf Bhat, Birgitta Messmer, Carsten Watzl
Natural killer (NK) cells are important immune effector cells that protect the organism against viral infections and cancer. The cytotoxic activity of NK cells is induced by the engagement of a number of different activating surface receptors and controlled by inhibitory receptors to ensure self-tolerance. Resting NK cells need to be co-activated by involvement of at least two distinct activating receptors in order to induce their functional activity. However, in cultured NK cells, which have been expanded in cytokines such as interleukin (IL)-2, the engagement of a single activating receptor may be sufficient to induce their function...
2016: Journal of Toxicology and Environmental Health. Part A
https://www.readbyqxmd.com/read/27905395/outside-in-integrin-signalling-regulates-haematopoietic-stem-cell-function-via-periostin-itgav-axis
#7
Satish Khurana, Sarah Schouteden, Javed K Manesia, Albert Santamaria-Martínez, Joerg Huelsken, Adam Lacy-Hulbert, Catherine M Verfaillie
Integrins play an important role in haematopoietic stem cell (HSC) maintenance in the bone marrow niche. Here, we demonstrate that Periostin (Postn) via interaction with Integrin-αv (Itgav) regulates HSC proliferation. Systemic deletion of Postn results in peripheral blood (PB) anaemia, myelomonocytosis and lymphopenia, while the number of phenotypic HSCs increases in the bone marrow. Postn(-/-) mice recover faster from radiation injury with concomitant loss of primitive HSCs. HSCs from Postn(-/-) mice show accumulation of DNA damage generally associated with aged HSCs...
December 1, 2016: Nature Communications
https://www.readbyqxmd.com/read/27798963/the-iqgap1-n-terminus-forms-dimers-and-the-dimer-interface-is-required-for-binding-f-actin-and-calcium-bound-calmodulin
#8
Jing Liu, Vinodh B Kurella, Louis LeCour, Tomas Vanagunas, David K Worthylake
IQGAP1 is a multidomain scaffold protein involved in many cellular processes. We have determined the crystal structure of an N-terminal fragment spanning residues 1-191 (CHDF hereafter) that contains the entire calponin homology domain. The structure of the CHDF is very similar to those of other type 3 calponin homology domains like those from calponin, Vav, and the yeast IQGAP1 ortholog Rng2. However, in the crystal, two CHDF molecules form a "head-to-head" or parallel dimer through mostly hydrophobic interactions...
November 22, 2016: Biochemistry
https://www.readbyqxmd.com/read/27681838/ilex-kaushue-and-its-bioactive-component-3-5-dicaffeoylquinic-acid-protected-mice-from-lipopolysaccharide-induced-acute-lung-injury
#9
Yu-Li Chen, Tsong-Long Hwang, Huang-Ping Yu, Jia-You Fang, Kowit Yu Chong, Yao-Wen Chang, Chun-Yu Chen, Hsuan-Wu Yang, Wen-Yi Chang, Pei-Wen Hsieh
Acute lung injury (ALI) is a severe respiratory disease with high mortality rates worldwide. Recent reports suggest that human neutrophil elastase (HNE) plays a key role in the inflammatory response that is characteristic of ALI, which indicates that the development of HNE inhibitors could be an efficient treatment strategy. In the current study, an enzyme-based screening assay was used to identify effective HNE inhibitors from a number of traditional Chinese medicines (TCMs). Among them, a water extract of Ilex kaushue (IKWE) effectively inhibited HNE activity (IC50, 11...
September 29, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27662902/rhog-dock1-rac1-signaling-axis-is-perturbed-in-dhea-induced-polycystic-ovary-in-rat-model
#10
Vaibhave Ubba, Upendra Kumar Soni, Sangappa Chadchan, Vineet Kumar Maurya, Vijay Kumar, Ruchika Maurya, Himanshu Chaturvedi, Rajender Singh, Anila Dwivedi, Rajesh Kumar Jha
The function of RHOG, a RAC1 activator, was explored in the ovary during ovarian follicular development and pathological conditions. With the help of immunoblotting and immunolocalization, we determined the expression and localization of RHOG in normal (estrous cycle) and polycystic ovaries using Sprague Dawley (SD) rat model. Employing polymerase chain reaction and flow cytometry, we analyzed the transcript and expression levels of downstream molecules of RHOG, DOCK1, and RAC1 in the polycystic ovarian syndrome (PCOS) ovary along with normal antral follicular theca and granulosa cells after dehydroepiandrosterone (DHEA) supplementation...
September 22, 2016: Reproductive Sciences
https://www.readbyqxmd.com/read/27581360/perturbed-hematopoiesis-in-mice-lacking-atmin
#11
Fernando Anjos-Afonso, Joanna I Loizou, Amy Bradburn, Nnennaya Kanu, Sukhveer Purewal, Clive Da Costa, Dominique Bonnet, Axel Behrens
The ataxia telangiectasia mutated (ATM)-interacting protein ATMIN mediates noncanonical ATM signaling in response to oxidative and replicative stress conditions. Like ATM, ATMIN can function as a tumor suppressor in the hematopoietic system: deletion of Atmin under the control of CD19-Cre results in B-cell lymphomas in aging mice. ATM signaling is essential for lymphopoiesis and hematopoietic stem cell (HSC) function; however, little is known about the role of ATMIN in hematopoiesis. We thus sought to investigate whether the absence of ATMIN would affect primitive hematopoietic cells in an ATM-dependent or -independent manner...
October 20, 2016: Blood
https://www.readbyqxmd.com/read/27558332/tyrosine-kinase-signaling-pathways-in-neutrophils
#12
REVIEW
Krisztina Futosi, Attila Mócsai
Neutrophils play a critical role in antimicrobial host defense, but their improper activation also contributes to inflammation-induced tissue damage. Therefore, understanding neutrophil biology is important for the understanding, diagnosis, and therapy of both infectious and inflammatory diseases. Neutrophils express a large number of cell-surface receptors that sense extracellular cues and trigger various functional responses through complex intracellular signaling pathways. During the last several years, we and others have shown that tyrosine kinases play a critical role in those processes...
September 2016: Immunological Reviews
https://www.readbyqxmd.com/read/27519601/pediatric-cardiorespiratory-failure-successfully-managed-with-venoarterial-venous-extracorporeal-membrane-oxygenation-a-case-report
#13
Michihito Kyo, Shinichiro Ohshimo, Yoshiko Kida, Tatsutoshi Shimatani, Yusuke Torikoshi, Kei Suzuki, Satoshi Yamaga, Nobuyuki Hirohashi, Nobuaki Shime
BACKGROUND: Venoarterial-venous extracorporeal membrane oxygenation (VAV ECMO) configuration is a combined procedure of extracorporeal membrane oxygenation (ECMO). The proportion of cardiac and respiratory support can be controlled by adjusting arterial and venous return. Therefore, VAV ECMO can be applicable as a bridging therapy in the transition from venoarterial (VA) to venovenous (VV) ECMO. CASE PRESENTATION: We present an 11-year-old girl with chemotherapy-induced myocarditis requiring extracorporeal cardiorespiratory support...
2016: BMC Pulmonary Medicine
https://www.readbyqxmd.com/read/27298444/g9a-regulates-group-2-innate-lymphoid-cell-development-by-repressing-the-group-3-innate-lymphoid-cell-program
#14
Frann Antignano, Mitchell Braam, Michael R Hughes, Alistair L Chenery, Kyle Burrows, Matthew J Gold, Menno J Oudhoff, David Rattray, Timotheus Y Halim, Alissa Cait, Fumio Takei, Fabio M Rossi, Kelly M McNagny, Colby Zaph
Innate lymphoid cells (ILCs) are emerging as important regulators of homeostatic and disease-associated immune processes. Despite recent advances in defining the molecular pathways that control development and function of ILCs, the epigenetic mechanisms that regulate ILC biology are unknown. Here, we identify a role for the lysine methyltransferase G9a in regulating ILC2 development and function. Mice with a hematopoietic cell-specific deletion of G9a (Vav.G9a(-/-) mice) have a severe reduction in ILC2s in peripheral sites, associated with impaired development of immature ILC2s in the bone marrow...
June 27, 2016: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/27185381/hematopoietic-stem-cell-specific-gfp-expressing-transgenic-mice-generated-by-genetic-excision-of-a-pan-hematopoietic-reporter-gene
#15
Jessica Perez-Cunningham, Scott W Boyer, Mark Landon, E Camilla Forsberg
Selective labeling of specific cell types by expression of green fluorescent protein (GFP) within the hematopoietic system would have great utility in identifying, localizing, and tracking different cell populations in flow cytometry, microscopy, lineage tracing, and transplantation assays. In this report, we describe the generation and characterization of a new transgenic mouse line with specific GFP labeling of all nucleated hematopoietic cells and platelets. This new "Vav-GFP" mouse line labels the vast majority of hematopoietic cells with GFP during both embryonic development and adulthood, with particularly high expression in hematopoietic stem and progenitor cells (HSPCs)...
August 2016: Experimental Hematology
https://www.readbyqxmd.com/read/27153556/a-role-for-multiple-chimeric-antigen-receptor-expressing-leukocytes-in-antigen-specific-responses-to-cancer
#16
Carmen S M Yong, Liza B John, Christel Devaud, Miles H Prince, Ricky W Johnstone, Joseph A Trapani, Phillip K Darcy, Michael H Kershaw
While adoptive immunotherapy using chimeric antigen receptor (CAR)-modified T cells can induce remission of some tumors, the role of other CAR-modified leukocytes is not well characterized. In this study, we characterize the function of leukocytes including natural killer (NK) cells, macrophages and CAR T cells from transgenic mice expressing a CAR under the control of the pan-hematopoietic promoter, vav, and determine the ability of these mice to respond to ERB expressing tumors. We demonstrate the anti-tumor functions of leukocytes, including antigen specific cytotoxicity and cytokine secretion...
June 7, 2016: Oncotarget
https://www.readbyqxmd.com/read/27108937/validation-of-device-algorithm-to-differentiate-pacemaker-mediated-tachycardia-from-tachycardia-due-to-atrial-tracking
#17
James E Ip, Bruce B Lerman
BACKGROUND: Current cardiac devices cannot always differentiate between pacemaker-mediated tachycardia (PMT) and tracking of sinus or atrial tachycardia. We previously derived a novel algorithm for distinguishing the 2 mechanisms based on the specific termination response to postventricular atrial refractory period extension, atrial rates, and changes in atrial electrogram morphology. OBJECTIVE: The purpose of this study was to evaluate how this algorithm would have performed in a clinical setting based on previously recorded PMT events...
August 2016: Heart Rhythm: the Official Journal of the Heart Rhythm Society
https://www.readbyqxmd.com/read/27082941/increased-epo-levels-are-associated-with-bone-loss-in-mice-lacking-phd2-in-epo-producing-cells
#18
Martina Rauner, Kristin Franke, Marta Murray, Rashim Pal Singh, Sahar Hiram-Bab, Uwe Platzbecker, Max Gassmann, Merav Socolovsky, Drorit Neumann, Yankel Gabet, Triantafyllos Chavakis, Lorenz C Hofbauer, Ben Wielockx
The main oxygen sensor HIF prolyl hydroxylase 2 (PHD2) is a critical regulator of tissue homeostasis during erythropoiesis, hematopoietic stem cell maintenance and wound healing. Recent studies point towards a role for the PHD2-erythropoietin (EPO) axis in the modulation of bone remodeling, even though the studies produced conflicting results. Here, we used a number of mouse strains deficient of PHD2 in different cell types to address the role of PHD2 and its downstream targets HIF-1α and HIF-2α in bone remodeling...
April 15, 2016: Journal of Bone and Mineral Research: the Official Journal of the American Society for Bone and Mineral Research
https://www.readbyqxmd.com/read/27054336/eiger-induced-cell-death-relies-on-rac1-dependent-endocytosis
#19
W Ruan, A Srinivasan, S Lin, k-I Kara, P A Barker
Signaling via tumor necrosis factor receptor (TNFR) superfamily members regulates cellular life and death decisions. A subset of mammalian TNFR proteins, most notably the p75 neurotrophin receptor (p75NTR), induces cell death through a pathway that requires activation of c-Jun N-terminal kinases (JNKs). However the receptor-proximal signaling events that mediate this remain unclear. Drosophila express a single tumor necrosis factor (TNF) ligand termed Eiger (Egr) that activates JNK-dependent cell death. We have exploited this model to identify phylogenetically conserved signaling events that allow Egr to induce JNK activation and cell death in vivo...
April 7, 2016: Cell Death & Disease
https://www.readbyqxmd.com/read/26972179/kras-is-required-for-adult-hematopoiesis
#20
Alisa Damnernsawad, Guangyao Kong, Zhi Wen, Yangang Liu, Adhithi Rajagopalan, Xiaona You, Jinyong Wang, Yun Zhou, Erik A Ranheim, Hongbo R Luo, Qiang Chang, Jing Zhang
Previous studies indicate that Kras is dispensable for fetal liver hematopoiesis, but its role in adult hematopoiesis remains unclear. Here, we generated a Kras conditional knockout allele to address this question. Deletion of Kras in adult bone marrow (BM) is mediated by Vav-Cre or inducible Mx1-Cre. We find that loss of Kras leads to greatly reduced thrombopoietin (TPO) signaling in hematopoietic stem cells (HSCs) and multipotent progenitors (MPPs), while stem cell factor-evoked ERK1/2 activation is not affected...
July 2016: Stem Cells
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