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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
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
Fernando Anjos-Afonso, Joanna I Loizou, Amy Bradburn, Nnennaya Kanu, Sukhveer Purewal, Clive Da Costa, Dominique Bonnet, Axel Behrens
The ATM-interacting protein ATMIN mediates non-canonical 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 if the absence of ATMIN would affect primitive hematopoietic cells in an ATM-dependent or -independent manner...
August 31, 2016: Blood
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
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
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
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
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
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
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
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...
2016: Cell Death & Disease
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
Eva Bauer, Michaela Schlederer, Ruth Scheicher, Jaqueline Horvath, Petra Aigner, Ana-Iris Schiefer, Renate Kain, Heinz Regele, Gregor Hoermann, Günter Steiner, Lukas Kenner, Veronika Sexl, Andreas Villunger, Richard Moriggl, Dagmar Stoiber
The t(12;21) translocation generating the ETV6/RUNX1 fusion gene represents the most frequent chromosomal rearrangement in childhood leukemia. Presence of ETV6/RUNX1 alone is usually not sufficient for leukemia onset, and additional genetic alterations have to occur in ETV6/RUNX1-positive cells to cause transformation. We have previously generated an ETV6/RUNX1 transgenic mouse model where the expression of the fusion gene is restricted to CD19-positive B cells. Since BCL2 family members have been proposed to play a role in leukemogenesis, we investigated combined effects of ETV6/RUNX1 with exogenous expression of the antiapoptotic protein BCL2 by crossing ETV6/RUNX1 transgenic animals with Vav-BCL2 transgenic mice...
March 15, 2016: Oncotarget
Amanda L Fry, Jocelyn T Laboy, Huiyan Huang, Anne C Hart, Kenneth R Norman
Sleep is evolutionarily conserved and required for organism homeostasis and survival. Despite this importance, the molecular and cellular mechanisms underlying sleep are not well understood. Caenorhabditis elegans exhibits sleep-like behavioral quiescence and thus provides a valuable, simple model system for the study of cellular and molecular regulators of this process. In C. elegans, epidermal growth factor receptor (EGFR) signaling is required in the neurosecretory neuron ALA to promote sleep-like behavioral quiescence after cellular stress...
March 2016: Genetics
Jenny Hagenblad, Hugo R Oliveira, Nils E G Forsberg, Matti W Leino
BACKGROUND: Rye, Secale cereale L., has historically been a crop of major importance and is still a key cereal in many parts of Europe. Single populations of cultivated rye have been shown to capture a large proportion of the genetic diversity present in the species, but the distribution of genetic diversity in subspecies and across geographical areas is largely unknown. Here we explore the structure of genetic diversity in landrace rye and relate it to that of wild and feral relatives...
2016: BMC Plant Biology
Wesam H Abdulaal, Catherine R Walker, Ryan Costello, Elena Redondo-Castro, Ilgiz A Mufazalov, Athina Papaemmanouil, Nancy J Rothwell, Stuart M Allan, Ari Waisman, Emmanuel Pinteaux, Werner Müller
IL-1 is a key cytokine known to drive chronic inflammation and to regulate many physiological, immunological, and neuroimmunological responses via actions on diverse cell types of the body. To determine the mechanisms of IL-1 actions as part of the inflammatory response in vivo, we generated a conditional IL-1 receptor 1 (IL-1R1) mouse mutant using the Cre/LoxP system (IL-1R1(fl/fl) ). In the mutant generated, exon 5, which encodes part of the extracellular-binding region of the receptor, is flanked by LoxP sites, thereby inactivating the two previously described functional IL-1R1 gene transcripts after Cre-mediated recombination...
April 2016: European Journal of Immunology
S Dutta, A Krause, S Vosberg, T Herold, B Ksienzyk, L Quintanilla-Martinez, B Tizazu, M Chopra, A Graf, S Krebs, H Blum, P A Greif, A Vetter, K Metzeler, M Rothenberg-Thurley, M R Schneider, M Dahlhoff, K Spiekermann, U Zimber-Strobl, E Wolf, S K Bohlander
The CALM/AF10 fusion gene is found in various hematological malignancies including acute myeloid leukemia (AML), T-cell acute lymphoblastic leukemia and malignant lymphoma. We have previously identified the leukemia stem cell (LSC) in a CALM/AF10-driven murine bone marrow transplant AML model as B220+ lymphoid cells with B-cell characteristics. To identify the target cell for leukemic transformation or 'cell of origin of leukemia' (COL) in non-disturbed steady-state hematopoiesis, we inserted the CALM/AF10 fusion gene preceded by a loxP-flanked transcriptional stop cassette into the Rosa26 locus...
May 2016: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
Natalia Zaldua, Francisco Llavero, Alain Artaso, Patricia Gálvez, Hadriano M Lacerda, Luis A Parada, José L Zugaza
Small GTPases of the Ras superfamily are capable of activating E2F-dependent transcription leading to cell proliferation, but the molecular mechanisms are poorly understood. In this study, using immortalized chicken DT40 B cell lines to investigate the role of the Vav/Rac signalling cascade on B cell proliferation, it is shown that the proliferative response triggered by B cell receptor activation is dramatically reduced in the absence of Vav3 expression. Analysis of this proliferative defect shows that in the absence of Vav3 expression, retinoblastoma protein (RB) phosphorylation and the subsequent E2F activation do not take place...
February 2016: FEBS Journal
Chun-Yu Chen, Yann-Lii Leu, Yu Fang, Chwan-Fwu Lin, Liang-Mou Kuo, Wei-Che Sung, Yung-Fong Tsai, Pei-Jen Chung, Ming-Chung Lee, Yu-Ting Kuo, Hsuan-Wu Yang, Tsong-Long Hwang
The leaves of Perilla frutescens (L.) Britt. have been traditionally used as an herbal medicine in East Asian countries to treat a variety diseases. In this present study, we investigated the inhibitory effects of P. frutescens extract (PFE) on N-formyl-Met-Leu-Phe (fMLF)-stimulated human neutrophils and the underlying mechanisms. PFE (1, 3, and 10 μg/ml) inhibited superoxide anion production, elastase release, reactive oxygen species formation, CD11b expression, and cell migration in fMLF-activated human neutrophils in dose-dependent manners...
2015: Scientific Reports
Martin J Baker, Dingxin Pan, Heidi C E Welch
PURPOSE OF REVIEW: The review describes the roles of Rho- and Rap-guanosine triphosphatases (GTPases) and of their activators, guanine-nucleotide exchange factors (GEFs), and inhibitors, GTPase activating proteins (GAPs), in neutrophil recruitment from the blood stream into inflamed tissues, with a focus on recently identified roles in neutrophils, endothelial cells, and platelets. RECENT FINDINGS: Recent studies have identified important roles of Rho- and Rap-GTPases, and of their GEFs and GAPs, in the neutrophil recruitment cascade...
January 2016: Current Opinion in Hematology
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