153 research outputs found

    Cronica Troyana, en que se cõtiene la total y lamentable destruycion de la nombrada Troya

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    Copia digital. Valladolid : Junta de Castilla y León. Consejería de Cultura y Turismo, 2009-2010Autor tomado del prólogoTexto a dos col.Port. xil. a dos tinta

    Endothelial Cell Proteomic Response to Rickettsia conorii Infection Reveals Activation of the Janus Kinase (JAK)-Signal Transducer and Activator of Transcription (STAT)-Inferferon Stimulated Gene (ISG)15 Pathway and Reprogramming Plasma Membrane Integrin/Cadherin Signaling

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    Free PMC Article: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4762516/Rickettsia conorii is the etiologic agent of Mediterranean spotted fever, a re-emerging infectious disease with significant mortality. This Gram-negative, obligately intracellular pathogen is transmitted via tick bites, resulting in disseminated vascular endothelial cell infection with vascular leakage. In the infected human, Rickettsia conorii infects endothelial cells, stimulating expression of cytokines and pro-coagulant factors. However, the integrated proteomic response of human endothelial cells to R. conorii infection is not known. In this study, we performed quantitative proteomic profiling of primary human umbilical vein endothelial cells (HUVECs) with established R conorii infection versus those stimulated with endotoxin (LPS) alone. We observed differential expression of 55 proteins in HUVEC whole cell lysates. Of these, we observed induction of signal transducer and activator of transcription (STAT)1, MX dynamin-like GTPase (MX1), and ISG15 ubiquitin-like modifier, indicating activation of the JAK-STAT signaling pathway occurs in R. conorii-infected HUVECs. The down-regulated proteins included those involved in the pyrimidine and arginine biosynthetic pathways. A highly specific biotinylated cross-linking enrichment protocol was performed to identify dysregulation of 11 integral plasma membrane proteins that included up-regulated expression of a sodium/potassium transporter and down-regulation of α-actin 1. Analysis of Golgi and soluble Golgi fractions identified up-regulated proteins involved in platelet-endothelial adhesion, phospholipase activity, and IFN activity. Thirty four rickettsial proteins were identified with high confidence in the Golgi, plasma membrane, or secreted protein fractions. The host proteins associated with rickettsial infections indicate activation of interferon-STAT signaling pathways; the disruption of cellular adhesion and alteration of antigen presentation pathways in response to rickettsial infections are distinct from those produced by nonspecific LPS stimulation. These patterns of differentially expressed proteins suggest mechanisms of pathogenesis as well as methods for diagnosis and monitoring Rickettsia infections.This work was supported by NIAID Clinical Proteomics Center Grant HHSN272200800048C (to A.R.B.), University of Texas Medical Branch Clinical and Translational Science Award (CTSA) UL1TR000071 (to A.R.B.), and NIEHS Grant P30 ES006676 (to A.R.B.).info:eu-repo/semantics/publishedVersio

    Type IV secretion in Gram-negative and Gram-positive bacteria

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    Type IV secretion systems (T4SSs) are versatile multiprotein nanomachines spanning the entire cell envelope in Gram‐negative and Gram‐positive bacteria. They play important roles through the contact‐dependent secretion of effector molecules into eukaryotic hosts and conjugative transfer of mobile DNA elements as well as contact‐independent exchange of DNA with the extracellular milieu. In the last few years, many details on the molecular mechanisms of T4SSs have been elucidated. Exciting structures of T4SS complexes from Escherichia coli plasmids R388 and pKM101, Helicobacter pylori and Legionella pneumophila have been solved. The structure of the F‐pilus was also reported and surprisingly revealed a filament composed of pilin subunits in 1:1 stoichiometry with phospholipid molecules. Many new T4SSs have been identified and characterized, underscoring the structural and functional diversity of this secretion superfamily. Complex regulatory circuits also have been shown to control T4SS machine production in response to host cell physiological status or a quorum of bacterial recipient cells in the vicinity. Here, we summarize recent advances in our knowledge of ‘paradigmatic’ and emerging systems, and further explore how new basic insights are aiding in the design of strategies aimed at suppressing T4SS functions in bacterial infections and spread of antimicrobial resistances

    Defining the Processes Regulating Stress Erythropoiesis

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    The current thesis aimed at broadening our understanding of the processes governing stress erythropoiesis. Phenylhydrazine-induced haemolytic anaemia was utilised as a mouse model of acute stress erythropoiesis. An unbiased whole transcriptome analysis followed by a multi-parametric flow cytometry assessment of splenic stress erythroid precursors was performed. Here, it is identified for the first time, a subpopulation of erythroid precursors in the steady state spleen, which express a broad range of immune-related cell surface markers. These unique steady state splenic cells were termed ISEPs (Immune-marker- expressing Splenic Erythroid Precursors) and are hypothesised to represent potential stress erythroid progenitors. The concept of a possible ‘erythroid synapse’ between these ISEPs and erythroblastic island (EBI) macrophages was introduced. The existence of a specialised stress EBI that holds these ISEPs in a ‘dormant’ state during steady state conditions via the ‘erythroid synapse’ was postulated. It was shown that there is both a downregulation of immune marker mRNA and a significantly reduced frequency of ISEPs during stress erythropoiesis in mice. Downregulation of immune markers during stress erythropoiesis may result in a breakdown of the postulated stress EBIs, allowing unfettered accelerated proliferation and maturation of ISEPs during stress erythropoiesis. Mouse pregnancy was also shown to induce stress erythropoiesis. ISEPs were again depleted on examining the splenic niche erythroid precursor component in pregnant mice. In the non-pregnancy setting, there were hints of a greater erythroid stress response in female mice compared to male mice, and it was questioned whether this was an oestrogen-mediated effect. It is hoped that the insights gained from this thesis will be built on to further uncover the function and regulation of ISEPs, and thereby assist with treatment of human conditions displaying stress erythropoiesis

    Tels qu'ils nous voient : (Love come back : "Un pyjama pour deux")

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    Colonne Michel. Tels qu'ils nous voient : (Love come back : "Un pyjama pour deux") . In: Les Cahiers de la publicité, n°2, Les avenirs de la publicité. 1re partie : Les interrogations. pp. 124-125

    Civil society groups as actors in world politics - are they important? the international campaign to ban landmines and the coalition for the International Criminal Court.

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    Examine the role of civil society groups in the negotiation and conclusion of the Convention Banning Anti-Personnel Mines, and the Rome Statute of the International Criminal Court, so as to assess their importance as actors in world politics. Examine whether they can be seen as militating towards the creation of counter-hegemony or an alternative world order.Master of Science (International Relations

    Counterinsurgency campaigning and national security transformation : lessons from the Eelam war.

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    Examines insurgency and counterinsurgency (COIN) strategy vis-a-vis the ‘Eelam War’ in Sri Lanka and reveals the fact that overreaction by the state and its inability to adhere to principles of COIN could exacerbate the crisis in favour bf the insurgents.Master of Science (Strategic Studies
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