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Sample records for neutrophil membrane tether

  1. Molecular Structure of Membrane Tethers

    NARCIS (Netherlands)

    Baoukina, Svetlana; Marrink, Siewert J.; Tieleman, D. Peter

    2012-01-01

    Membrane tethers are nanotubes formed by a lipid bilayer. They play important functional roles in cell biology and provide an experimental window on lipid properties. Tethers have been studied extensively in experiments and described by theoretical models, but their molecular structure remains

  2. Membrane Tethering Complexes in the Endosomal System

    OpenAIRE

    Spang, Anne

    2016-01-01

    Vesicles that are generated by endocytic events at the plasma membrane are destined to early endosomes. A prerequisite for proper fusion is the tethering of two membrane entities. Tethering of vesicles to early endosomes is mediated by the class C core vacuole/endosome tethering (CORVET) complex, while fusion of late endosomes with lysosomes depends on the homotypic fusion and vacuole protein sorting (HOPS) complex. Recycling through the trans-Golgi network (TGN) and to the plasma membrane is...

  3. Membrane tethering complexes in the endosomal system

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    Anne eSpang

    2016-05-01

    Full Text Available Vesicles that are generated by endocytic events at the plasma membrane are destined to early endosomes. A prerequisite for proper fusion is the tethering of two membrane entities. Tethering of vesicles to early endosomes is mediated by the CORVET complex, while fusion of late endosomes with lysosomes depends on the HOPS complex. Recycling through the TGN and to the plasma membrane is facilitated by the GARP and EARP complexes, respectively. However, there are other tethering functions in the endosomal system as there are multiple pathways through which proteins can be delivered from endosomes to either the TGN or the plasma membrane. Furthermore, complexes that may be part of novel tethering complexes have been recently identified. Thus it is likely that more tethering factors exist. In this review, I will provide an overview of different tethering complexes of the endosomal system and discuss how they may provide specificity in membrane traffic.

  4. Models of dynamic extraction of lipid tethers from cell membranes

    International Nuclear Information System (INIS)

    Nowak, Sarah A; Chou, Tom

    2010-01-01

    When a ligand that is bound to an integral membrane receptor is pulled, the membrane and the underlying cytoskeleton can deform before either the membrane delaminates from the cytoskeleton or the ligand detaches from the receptor. If the membrane delaminates from the cytoskeleton, it may be further extruded and form a membrane tether. We develop a phenomenological model for this process by assuming that deformations obey Hooke's law up to a critical force at which the cell membrane locally detaches from the cytoskeleton and a membrane tether forms. We compute the probability of tether formation and show that tethers can be extruded only within an intermediate range of force loading rates and pulling velocities. The mean tether length that arises at the moment of ligand detachment is computed as are the force loading rates and pulling velocities that yield the longest tethers

  5. Self-assembled tethered bimolecular lipid membranes.

    Science.gov (United States)

    Sinner, Eva-Kathrin; Ritz, Sandra; Naumann, Renate; Schiller, Stefan; Knoll, Wolfgang

    2009-01-01

    This chapter describes some of the strategies developed in our group for designing, constructing and structurally and functionally characterizing tethered bimolecular lipid membranes (tBLM). We introduce this platform as a novel model membrane system that complements the existing ones, for example, Langmuir monolayers, vesicular liposomal dispersions and bimolecular ("black") lipid membranes. Moreover, it offers the additional advantage of allowing for studies of the influence of membrane structure and order on the function of integral proteins, for example, on how the composition and organization of lipids in a mixed membrane influence the ion translocation activity of integral channel proteins. The first strategy that we introduce concerns the preparation of tethered monolayers by the self-assembly of telechelics. Their molecular architecture with a headgroup, a spacer unit (the "tether") and the amphiphile that mimics the lipid molecule allows them to bind specifically to the solid support thus forming the proximal layer of the final architecture. After fusion of vesicles that could contain reconstituted proteins from a liposomal dispersion in contact to this monolayer the tethered bimolecular lipid membrane is obtained. This can then be characterized by a broad range of surface analytical techniques, including surface plasmon spectroscopies, the quartz crystal microbalance, fluorescence and IR spectroscopies, and electrochemical techniques, to mention a few. It is shown that this concept allows for the construction of tethered lipid bilayers with outstanding electrical properties including resistivities in excess of 10 MOmega cm2. A modified strategy uses the assembly of peptides as spacers that couple covalently via their engineered sulfhydryl or lipoic acid groups at the N-terminus to the employed gold substrate, while their C-terminus is being activated afterward for the coupling of, for example, dimyristoylphosphatidylethanol amine (DMPE) lipid molecules

  6. Fluid-membrane tethers: minimal surfaces and elastic boundary layers.

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    Powers, Thomas R; Huber, Greg; Goldstein, Raymond E

    2002-04-01

    Thin cylindrical tethers are common lipid bilayer membrane structures, arising in situations ranging from micromanipulation experiments on artificial vesicles to the dynamic structure of the Golgi apparatus. We study the shape and formation of a tether in terms of the classical soap-film problem, which is applied to the case of a membrane disk under tension subject to a point force. A tether forms from the elastic boundary layer near the point of application of the force, for sufficiently large displacement. Analytic results for various aspects of the membrane shape are given.

  7. Tethered and Polymer Supported Bilayer Lipid Membranes: Structure and Function

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    Jakob Andersson

    2016-05-01

    Full Text Available Solid supported bilayer lipid membranes are model systems to mimic natural cell membranes in order to understand structural and functional properties of such systems. The use of a model system allows for the use of a wide variety of analytical tools including atomic force microscopy, impedance spectroscopy, neutron reflectometry, and surface plasmon resonance spectroscopy. Among the large number of different types of model membranes polymer-supported and tethered lipid bilayers have been shown to be versatile and useful systems. Both systems consist of a lipid bilayer, which is de-coupled from an underlying support by a spacer cushion. Both systems will be reviewed, with an emphasis on the effect that the spacer moiety has on the bilayer properties.

  8. Emerging insights into the roles of membrane tethers from analysis of whole organisms: The tip of an iceberg?

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    Wei Hong eToh

    2016-02-01

    Full Text Available Membrane tethers have been identified throughout different compartments of the endomembrane system. It is now well established that a number of membrane tethers mediate docking of membrane carriers in anterograde and retrograde transport and in regulating the organization of membrane compartments. Much of our information on membrane tethers have been obtained from the analysis of individual membrane tethers in cultured cells. In the future it will be important to better appreciate the network of interactions mediated by tethers and the potential co-ordination of their collective functions in vivo. There are now a number of studies which have analyzed membrane tethers in tissues and organisms which are providing new insights into the role of this class of membrane protein at the physiological level. Here we review recent advances in the understanding of the function of membrane tethers from knock outs (or knock downs in whole organisms and from mutations in tethers associated with disease.

  9. A tethering complex drives the terminal stage of SNARE-dependent membrane fusion

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    D'Agostino, Massimo; Risselada, Herre Jelger; Lürick, Anna; Ungermann, Christian; Mayer, Andreas

    2017-11-01

    Membrane fusion in eukaryotic cells mediates the biogenesis of organelles, vesicular traffic between them, and exo- and endocytosis of important signalling molecules, such as hormones and neurotransmitters. Distinct tasks in intracellular membrane fusion have been assigned to conserved protein systems. Tethering proteins mediate the initial recognition and attachment of membranes, whereas SNARE (soluble N-ethylmaleimide-sensitive factor attachment protein receptor) protein complexes are considered as the core fusion engine. SNARE complexes provide mechanical energy to distort membranes and drive them through a hemifusion intermediate towards the formation of a fusion pore. This last step is highly energy-demanding. Here we combine the in vivo and in vitro fusion of yeast vacuoles with molecular simulations to show that tethering proteins are critical for overcoming the final energy barrier to fusion pore formation. SNAREs alone drive vacuoles only into the hemifused state. Tethering proteins greatly increase the volume of SNARE complexes and deform the site of hemifusion, which lowers the energy barrier for pore opening and provides the driving force. Thereby, tethering proteins assume a crucial mechanical role in the terminal stage of membrane fusion that is likely to be conserved at multiple steps of vesicular traffic. We therefore propose that SNAREs and tethering proteins should be considered as a single, non-dissociable device that drives fusion. The core fusion machinery may then be larger and more complex than previously thought.

  10. ER-to-plasma membrane tethering proteins regulate cell signaling and ER morphology.

    Science.gov (United States)

    Manford, Andrew G; Stefan, Christopher J; Yuan, Helen L; Macgurn, Jason A; Emr, Scott D

    2012-12-11

    Endoplasmic reticulum-plasma membrane (ER-PM) junctions are conserved structures defined as regions of the ER that tightly associate with the plasma membrane. However, little is known about the mechanisms that tether these organelles together and why such connections are maintained. Using a quantitative proteomic approach, we identified three families of ER-PM tethering proteins in yeast: Ist2 (related to mammalian TMEM16 ion channels), the tricalbins (Tcb1/2/3, orthologs of the extended synaptotagmins), and Scs2 and Scs22 (vesicle-associated membrane protein-associated proteins). Loss of all six tethering proteins results in the separation of the ER from the PM and the accumulation of cytoplasmic ER. Importantly, we find that phosphoinositide signaling is misregulated at the PM, and the unfolded protein response is constitutively activated in the ER in cells lacking ER-PM tether proteins. These results reveal critical roles for ER-PM contacts in cell signaling, organelle morphology, and ER function. Copyright © 2012 Elsevier Inc. All rights reserved.

  11. Neutrophil glycoprotein Mo1 is an integral membrane protein of plasma membranes and specific granules

    International Nuclear Information System (INIS)

    Stevenson, K.B.; Nauseef, W.M.; Clark, R.A.

    1987-01-01

    The glucoprotein Mo1 has previously been demonstrated to be on the cell surface and in the specific granule fraction of neutrophils and to be translocated to the cell surface during degranulation. It is not known, however, whether Mo1 is an integral membrane protein or a soluble, intragranular constituent loosely associated with the specific granule membrane. Purified neutrophils were disrupted by nitrogen cavitation and separated on Percoll density gradients into four fractions enriched for azurophilic granules, specific granules, plasma membrane, and cytosol, respectively. The glycoproteins in these fractions were labeled with 3 H-borohydride reduction, extracted with Triton X-114, and immunoprecipitated with 60.3, an anti-Mo1 monoclonal antibody. Mo1 was detected only in the specific granule and plasma membrane fractions and partitioned exclusively into the detergent-rich fraction consistent with Mo1 being an integral membrane protein. In addition, treatment of specific granule membranes with a high salt, high urea buffer to remove adsorbed or peripheral proteins failed to dissociate Mo1. These data support the hypothesis that Mo1 is an integral membrane protein of plasma and specific granule membranes in human neutrophils

  12. Inhibition of neutrophil migration by aggregated immunoglobulin attached to micropore membranes.

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    Kemp, A S; Brown, S

    1980-01-01

    The effect of substrate-bound immunoglobulin on neutrophil migration was examined. Immunoglobulin aggregates bound to micropore membranes inhibited the neutrophil response to a chemotactic stimulus. This inhibition was reversed by the presence of aggregates in suspension suggesting competition between substrate-bound and free aggregates for neutrophil surface binding sites. The immobilization of neutrophils by substrate-bound aggregated immunoglobulin suggests a mechanism for the accumulation of neutrophils at sites of immune complex deposition and tissue-bound antibodies in vivo. PMID:7380477

  13. Proteome profiling of human neutrophil granule subsets, secretory vesicles, and cell membrane

    DEFF Research Database (Denmark)

    Rørvig, Sara; Østergaard, Ole; Heegaard, Niels Henrik Helweg

    2013-01-01

    granules, SVs, and plasma membrane has been performed before. Here, we performed subcellular fractionation on freshly isolated human neutrophils by nitrogen cavitation and density centrifugation on a four-layer Percoll gradient. Granule subsets were pooled and subjected to SDS-PAGE, and gel pieces were in...... subcellular proteome profiles presented here may be used as a database in combination with the mRNA array database to predict and test the presence and localization of proteins in neutrophil granules and membranes....

  14. Synthesis and characterization of tethered lipid assemblies for membrane protein reconstitution (Review).

    Science.gov (United States)

    Veneziano, Rémi; Rossi, Claire; Chenal, Alexandre; Brenner, Catherine; Ladant, Daniel; Chopineau, Joël

    2017-09-28

    Biological membranes and their related molecular mechanisms are essential for all living organisms. Membranes host numerous proteins and are responsible for the exchange of molecules and ions, cell signaling, and cell compartmentation. Indeed, the plasma membrane delimits the intracellular compartment from the extracellular environment and intracellular membranes. Biological membranes also play a major role in metabolism regulation and cellular physiology (e.g., mitochondrial membranes). The elaboration of membrane based biomimetic systems allows us to reconstitute and investigate, in controlled conditions, biological events occurring at the membrane interface. A whole variety of model membrane systems have been developed in the last few decades. Among these models, supported membranes were developed on various hydrophilic supports. The use of solid supports enables the direct use of surface sensitive techniques (e.g., surface plasmon resonance, quartz crystal microbalance, and atomic force microscopy) to monitor and quantify events occurring at the membrane surface. Tethered bilayer membranes (tBLMs) could be considered as an achievement of the first solid supported membranes described by the McConnell group. Tethered bilayers on solid supports were designed to delimit an inside compartment from an outside one. They were used for measuring interactions with ligands or incorporating large membrane proteins or complexes without interference with the support. In this context, the authors developed an easy concept of versatile tBLMs assembled on amino coated substrates that are formed upon the vesicle fusion rupture process applicable to protein-free vesicles as well as proteoliposomes. The phospholipid bilayer (natural or synthetic lipids) incorporated 5% of 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-poly ethylene glycol-N-hydroxy succinimide to ensure the anchorage of the bilayer to the amino coated surface. The conditions for the formation of tBLMs on amino

  15. Subunit Organisation of In Vitro Reconstituted HOPS and CORVET Multisubunit Membrane Tethering Complexes

    Science.gov (United States)

    Guo, Zhong; Johnston, Wayne; Kovtun, Oleksiy; Mureev, Sergey; Bröcker, Cornelia; Ungermann, Christian; Alexandrov, Kirill

    2013-01-01

    Biochemical and structural analysis of macromolecular protein assemblies remains challenging due to technical difficulties in recombinant expression, engineering and reconstitution of multisubunit complexes. Here we use a recently developed cell-free protein expression system based on the protozoan Leishmania tarentolae to produce in vitro all six subunits of the 600 kDa HOPS and CORVET membrane tethering complexes. We demonstrate that both subcomplexes and the entire HOPS complex can be reconstituted in vitro resulting in a comprehensive subunit interaction map. To our knowledge this is the largest eukaryotic protein complex in vitro reconstituted to date. Using the truncation and interaction analysis, we demonstrate that the complex is assembled through short hydrophobic sequences located in the C-terminus of the individual Vps subunits. Based on this data we propose a model of the HOPS and CORVET complex assembly that reconciles the available biochemical and structural data. PMID:24312556

  16. Fast and facile fabrication of antifouling and hemocompatible PVDF membrane tethered with amino-acid modified PEG film

    Science.gov (United States)

    Zhang, Shuyou; Cao, Jingjing; Ma, Na; You, Meng; Wang, Xushan; Meng, Jianqiang

    2018-01-01

    A fast and facile protocol is reported aiming at improving the antifouling property and hemocompatibility of poly(vinylidene fluoride) (PVDF) membranes by tethering PEG hydrogel and zwitterion immobilization. The coated PEG hydrogel was first prepared by interfacial polymerization and tethered on an alkali treated PVDF membrane (PVDFA) surface via a simultaneous thio-ene and thiol-epoxy reaction. Then, the thiol groups of cysteine reacted with the epoxy groups in PEG hydrogel to fabricate the PVDFA-g-Cys membrane. The membrane fabrication was complete within less than 20 min and was conducted in mild conditions. The successful preparation of PVDFA-g-Cys membrane was confirmed by ATR-FTIR and XPS. Raman spectroscopy showed that the hydrogels covalently bonded to the PVDF membrane surface. The membrane retained its mechanical strength after modification. The SEM measurements suggested that the membrane became denser after hydrogel coating, meanwhile, the EDX test verified that the functional species uniformly distributed in the membrane matrix. Water contact angle (WCA), protein adsorption and protein filtration tests showed significant improvements in hydrophilicity and antifouling properties for the modified membrane. The negativity of the membrane surface measured by the streaming potential method provides a basis for protein resistance and hemocompatibility. Moreover, the suppressed platelet adhesion and prolonged plasma coagulant time show that the PVDFA-g-Cys membrane has ultralow thrombotic potential and better hemocompatibility. The reported surface modification method combing thio-ene and thio-epoxy chemistry not only facilitates fabrication of hemocompatible PVDF membrane but also provide an universal chemical platform for multifunctionalization of porous membranes.

  17. Phase coupling of a circadian neuropeptide with rest/activity rhythms detected using a membrane-tethered spider toxin.

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    Ying Wu

    2008-11-01

    Full Text Available Drosophila clock neurons are self-sustaining cellular oscillators that rely on negative transcriptional feedback to keep circadian time. Proper regulation of organismal rhythms of physiology and behavior requires coordination of the oscillations of individual clock neurons within the circadian control network. Over the last decade, it has become clear that a key mechanism for intercellular communication in the circadian network is signaling between a subset of clock neurons that secrete the neuropeptide pigment dispersing factor (PDF and clock neurons that possess its G protein-coupled receptor (PDFR. Furthermore, the specific hypothesis has been proposed that PDF-secreting clock neurons entrain the phase of organismal rhythms, and the cellular oscillations of other clock neurons, via the temporal patterning of secreted PDF signals. In order to test this hypothesis, we have devised a novel technique for altering the phase relationship between circadian transcriptional feedback oscillation and PDF secretion by using an ion channel-directed spider toxin to modify voltage-gated Na(+ channel inactivation in vivo. This technique relies on the previously reported "tethered-toxin" technology for cell-autonomous modulation of ionic conductances via heterologous expression of subtype-specific peptide ion channel toxins as chimeric fusion proteins tethered to the plasma membrane with a glycosylphosphatidylinositol (GPI anchor. We demonstrate for the first time, to our knowledge, the utility of the tethered-toxin technology in a transgenic animal, validating four different tethered spider toxin ion channel modifiers for use in Drosophila. Focusing on one of these toxins, we show that GPI-tethered Australian funnel-web spider toxin delta-ACTX-Hv1a inhibits Drosophila para voltage-gated Na(+ channel inactivation when coexpressed in Xenopus oocytes. Transgenic expression of membrane-tethered delta-ACTX-Hv1a in vivo in the PDF-secreting subset of clock neurons

  18. Mitochondrial membrane potential in human neutrophils is maintained by complex III activity in the absence of supercomplex organisation

    NARCIS (Netherlands)

    van Raam, Bram J.; Sluiter, Wim; de Wit, Elly; Roos, Dirk; Verhoeven, Arthur J.; Kuijpers, Taco W.

    2008-01-01

    BACKGROUND: Neutrophils depend mainly on glycolysis for their energy provision. Their mitochondria maintain a membrane potential (Deltapsi(m)), which is usually generated by the respiratory chain complexes. We investigated the source of Deltapsi(m) in neutrophils, as compared to peripheral blood

  19. Kidney injury molecule-1 and neutrophil gelatinase-associated lipocalin as prognostic markers in idiopathic membranous nephropathy

    NARCIS (Netherlands)

    Maas, Rutger J. H.; van den Brand, Jan A. J. G.; Waanders, Femke; Meijer, Esther; van Goor, Harry; Peters, Hilde P.; Hofstra, Julia M.; Wetzels, Jack F. M.

    Background: Urinary excretion of alpha-1-microglobulin and beta-2-microglobulin reflects tubular damage and predicts outcome in patients with idiopathic membranous nephropathy with reasonable accuracy. Urinary kidney injury molecule-1 and neutrophil gelatinase-associated lipocalin are novel

  20. Electrostatics and N-glycan-mediated membrane tethering of SCUBE1 is critical for promoting bone morphogenetic protein signalling.

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    Liao, Wei-Ju; Tsao, Ku-Chi; Yang, Ruey-Bing

    2016-03-01

    SCUBE1 (S1), a secreted and membrane-bound glycoprotein, has a modular protein structure composed of an N-terminal signal peptide sequence followed by nine epidermal growth factor (EGF)-like repeats, a spacer region and three cysteine-rich (CR) motifs with multiple potential N-linked glycosylation sites, and one CUB domain at the C-terminus. Soluble S1 is a biomarker of platelet activation but an active participant of thrombosis via its adhesive EGF-like repeats, whereas its membrane-associated form acts as a bone morphogenetic protein (BMP) co-receptor in promoting BMP signal activity. However, the mechanism responsible for the membrane tethering and the biological importance of N-glycosylation of S1 remain largely unknown. In the present study, molecular mapping analysis identified a polycationic segment (amino acids 501-550) in the spacer region required for its membrane tethering via electrostatic interactions possibly with the anionic heparan sulfate proteoglycans. Furthermore, deglycosylation by peptide N-glycosidase F treatment revealed that N-glycans within the CR motif are essential for membrane recruitment through lectin-mediated surface retention. Injection of mRNA encoding zebrafish wild-type but not N-glycan-deficient scube1 restores the expression of haematopoietic and erythroid markers (scl and gata1) in scube1-knockdown embryos. We describe novel mechanisms in targeting S1 to the plasma membrane and demonstrate that N-glycans are required for S1 functions during primitive haematopoiesis in zebrafish. © 2016 Authors; published by Portland Press Limited.

  1. Gene transfer and expression in human neutrophils. The phox homology domain of p47phox translocates to the plasma membrane but not to the membrane of mature phagosomes

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    Brzezinska Agnieszka A

    2006-12-01

    Full Text Available Abstract Background Neutrophils are non-dividing cells with poor survival after isolation. Consequently, exogenous gene expression in neutrophils is challenging. We report here the transfection of genes and expression of active proteins in human primary peripheral neutrophils using nucleofection. Results Exogenous gene expression in human neutrophils was achieved 2 h post-transfection. We show that neutrophils transfected by nucleofection are functional cells, able to respond to soluble and particulate stimuli. They conserved the ability to undergo physiological processes including phagocytosis. Using this technique, we were able to show that the phox homology (PX domain of p47phox localizes to the plasma membrane in human neutrophils. We also show that RhoB, but not the PX domain of p47phox, is translocated to the membrane of mature phagosomes. Conclusion We demonstrated that cDNA transfer and expression of exogenous protein in human neutrophils is compatible with cell viability and is no longer a limitation for the study of protein function in human neutrophils.

  2. Elongated membrane tethers, individually anchored by high affinity α4β1/VCAM-1 complexes, are the quantal units of monocyte arrests.

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    Calvin Chu

    Full Text Available The α4β1 integrin facilitates both monocyte rolling and adhesion to the vascular endothelium and is physiologically activated by monocyte chemoattractant protein (MCP-1. The current study investigated the initial events in the adhesion of THP-1 cells to immobilized Vascular Cell Adhesion Molecule 1 (VCAM-1. Using AFM force measurements, cell adhesion was shown to be mediated by two populations of α4β1/VCAM-1 complexes. A low affinity form of α4β1 was anchored to the elastic elements of the cytoskeleton, while a higher affinity conformer was coupled to the viscous elements of the cell membrane. Within 100 ms of contact, THP-1 cells, stimulated by co-immobilized MCP-1, exhibited a tremendous increase in adhesion to VCAM-1. Enhanced cell adhesion was accompanied by a local decoupling of the cell membrane from the cytoskeleton and the formation of long membrane tethers. The tethers were individually anchored by multiple α4β1/VCAM-1 complexes that prolonged the extension of the viscous tethers. In vivo, the formation of these membrane tethers may provide the quantal structural units for the arrest of rolling monocytes within the blood vessels.

  3. Anaplasma phagocytophilum inhibits human neutrophil apoptosis via upregulation of bfl-1, maintenance of mitochondrial membrane potential and prevention of caspase 3 activation.

    Science.gov (United States)

    Ge, Yan; Yoshiie, Kiyotaka; Kuribayashi, Futoshi; Lin, Mingqun; Rikihisa, Yasuko

    2005-01-01

    The inhibition of neutrophil apoptosis plays a central role in human granulocytic anaplasmosis. Intracellular signalling pathways through which the obligatory intracellular bacterium Anaplasma phagocytophilum inhibits the spontaneous apoptosis of human peripheral blood neutrophils were investigated. bfl-1 mRNA levels in uninfected neutrophils after 12 h in culture were reduced to approximately 5-25% of 0 h levels, but remained high in infected neutrophils. The eukaryotic RNA synthesis inhibitor, actinomycin D, prevented the maintenance of bfl-1 mRNA levels by A. phagocytophilum. Differences in mcl-1, bax, bcl-w, bad or bak mRNA levels in infected versus uninfected neutrophils were not remarkable. By using mitochondrial fluorescent dyes, Mitotracker Red and JC-1, it was found that most uninfected neutrophils lost mitochondrial membrane potential after 10-12 h incubation, whereas A. phagocytophilum-infected neutrophils maintained high membrane potential. Caspase 3 activity and the degree of apoptosis were lower in dose-dependent manner in A. phagocytophilum-infected neutrophils at 16 h post infection, as compared to uninfected neutrophils. Anti-active caspase 3 antibody labelling showed less positively stained population in infected neutrophils compared to those in uninfected neutrophils after 12 h incubation. These results suggest that A. phagocytophilum inhibits human neutrophil apoptosis via transcriptional upregulation of bfl-1 and inhibition of mitochondria-mediated activation of caspase 3.

  4. Tethering of hyperbranched polyols using PEI as a building block to synthesize antifouling PVDF membranes

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    Wang, Xushan; Wang, Zihong; Wang, Zhe; Cao, Yu; Meng, Jianqiang

    2017-10-01

    Antifouling PVDF membranes were prepared by grafting hyperbranched polyols on the membrane surface via a three-step modification method. The membrane was first prepared by alkaline treatment to introduce alkenyl groups, then chemically immobilizing hyperbranched poly(ethyleneimine) (HPEI) on membrane surface through Michael reaction followed by ring opening reaction of the glycidol with amine groups. Chemical compositions, surface morphology and physicochemical properties of the original and modified membranes were characterized via attenuated total refection-Fourier transform infrared spectroscopy (ATR-FTIR), X-ray photoelectron spectroscopy (XPS), scanning electron microscopy (SEM), water contact angle (WCA) and zeta potential measurements. The antifouling property of the modified membrane was assessed by the static bovine serum albumin (BSA) and lysozyme (LZM) adsorption as well as cross-flow filtration of BSA aqueous solution. The results explicate that surface modification using hyperbranched polymers can alter membrane chemistry and morphology significantly. In contrast to the original PVDF membrane, the modified membrane shows superhydrophilic property and relatively high capability to resist nonspecific protein adsorption. Three HPEIs were used for modification and the obtained PVDFA-g-PG60,000 membrane has a static BSA protein adsorption of 45 μg/cm2 and shows the highest protein resistance. However, the PVDF-g-PG membrane is positively charged due to the unreacted amine groups. As a result, the PVDF-g-PG membranes also show high flux decline during the filtration of BSA aqueous solution due to the electrostatic interaction. In spite of that, the PVDF-g-PG membranes still maintain high flux recovery ratio and good washing properties.

  5. The neutrophil to lymphocyte ratio in patients supported with extracorporeal membrane oxygenation.

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    Yost, Gardner; Bhat, Geetha; Pappas, Patroklos; Tatooles, Antone

    2018-04-01

    The neutrophil to lymphocyte ratio (NLR) has proven to be a robust predictor of mortality in a wide range of cardiovascular diseases. This study investigated the predictive value of the NLR in patients supported by extracorporeal membrane oxygenation (ECMO) systems. This study included 107 patients who underwent ECMO implantation for cardiogenic shock. Median preoperative NLR was used to divide the cohort, with Group 1 NLR <14.2 and Group 2 with NLR ≥14.2. Survival, the primary outcome, was compared between groups. The study cohort was composed of 64 (60%) males with an average age 53.1 ± 14.9 years. Patients in Group 1 had an average NLR of 7.5 ± 3.5 compared to 27.1 ± 19.9 in Group 2. Additionally, those in Group 2 had significantly higher preoperative blood urea nitrogen (BUN) and age. Survival analysis indicated a thirty-day survival of 56.2%, with significantly worsened mortality in patients with NLR greater than 14.2, p=0.047. Our study shows the NLR has prognostic value in patients undergoing ECMO implantation. Leukocytes are known contributors to myocardial damage and neutrophil infiltration is associated with damage caused by myocardial ischemia.

  6. Kidney injury molecule-1 and neutrophil gelatinase-associated lipocalin as prognostic markers in idiopathic membranous nephropathy.

    Science.gov (United States)

    Maas, Rutger Jh; van den Brand, Jan Ajg; Waanders, Femke; Meijer, Esther; Goor van, Harry; Peters, Hilde P; Hofstra, Julia M; Wetzels, Jack Fm

    2016-01-01

    Urinary excretion of alpha-1-microglobulin and beta-2-microglobulin reflects tubular damage and predicts outcome in patients with idiopathic membranous nephropathy with reasonable accuracy. Urinary kidney injury molecule-1 and neutrophil gelatinase-associated lipocalin are novel biomarkers of tubular damage. We investigated if these markers could improve prediction of outcome in idiopathic membranous nephropathy. We measured kidney injury molecule-1 and neutrophil gelatinase-associated lipocalin in urine samples from patients with idiopathic membranous nephropathy, who had nephrotic proteinuria and normal renal function. Excretion of alpha-1-microglobulin and beta-2-microglobulin had been measured previously. Progression was defined as a serum creatinine rise >30%, a rise in serum creatinine to an absolute value of ≥135 µmol/L, or a clinical decision to start immunosuppressive therapy. Remission was defined as proteinuria 50% reduction from baseline. Sixty-nine patients were included. Median follow-up was 35 months (interquartile range 18-63 months). Progression occurred in 30 patients (44%), and spontaneous remission in 36 (52%). Kidney injury molecule-1 and neutrophil gelatinase-associated lipocalin excretion rates were significantly correlated with each other, and with alpha-1-microglobulin and beta-2-microglobulin. The areas under the receiver operating characteristic curves for progression were 0.75 (0.62-0.87) for kidney injury molecule-1 and 0.74 (0.62-0.87) for neutrophil gelatinase-associated lipocalin. In multivariate analysis with either alpha-1-microglobulin and beta-2-microglobulin, kidney injury molecule-1 and neutrophil gelatinase-associated lipocalin did not independently predict outcome. Kidney injury molecule-1 and neutrophil gelatinase-associated lipocalin excretion rates correlated with excretion rates of other tubular damage markers and predicted outcome in patients with idiopathic membranous nephropathy. They did not add prognostic value

  7. Ligand binding to G protein-coupled receptors in tethered cell membranes

    DEFF Research Database (Denmark)

    Martinez, Karen L.; Meyer, Bruno H.; Hovius, Ruud

    2003-01-01

    for the surface immobilization of membrane proteins was developed using the prototypic seven transmembrane neurokinin-1 receptor. The receptor was expressed as a biotinylated protein in mammalian cells. Membranes from cell homogenates were selectively immobilized on glass surfaces covered with streptavidin. TIRF...... measurements showed that a fluorescent agonist binds to the receptor on the sensor surface with similar affinity as to the receptor in live cells. This approach offers the possibility to investigate minute amounts of membrane protein in an active form and in its native environment without purification....

  8. GRASP: A multitasking tether

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    Catherine eRabouille

    2016-01-01

    Full Text Available Originally identified as Golgi stacking factors in vitro, the Golgi reassembly stacking protein (GRASP family has been shown to act as membrane tethers with multiple cellular roles. As an update to previous comprehensive reviews of the GRASP family (Vinke et al., 2011 (Giuliani et al., 2011;Jarvela and Linstedt, 2012, we outline here the latest findings concerning their diverse roles. New insights into the mechanics of GRASP-mediated tethering come from recent crystal structures. The models of how GRASP65 and GRASP55 tether membranes relate directly to their role in Golgi ribbon formation in mammalian cells and the unlinking of the ribbon at the onset of mitosis. However, it is also clear that GRASPs act outside the Golgi with roles at the ER and ER exit sites (ERES. Furthermore, the proteins of this family display other roles upon cellular stress, especially in mediating unconventional secretion of both transmembrane proteins (Golgi bypass and cytoplasmic proteins (through secretory autophagosomes.

  9. Differential expression of granulopoiesis related genes in neutrophil subsets distinguished by membrane expression of CD177

    DEFF Research Database (Denmark)

    Hu, Nan; Mora-Jensen, Helena; Theilgaard-Mønch, Kim

    2014-01-01

    OBJECTIVE: Differential gene expression in CD177+ and CD177- neutrophils was investigated, in order to detect possible differences in neutrophil function which could be related to the pathogenesis of ANCA-associated Vasculitides (AAV). METHODS: Neutrophils were isolated from healthy controls (HC......) with high, negative or bimodal CD177 expression, and sorted into CD177+ and CD177- subpopulations. Total RNA was screened for expression of 24,000 probes with Illumina Ref-8 Beadchips. Genes showing differential expression between CD177+ and CD177- subsets in microarray analysis were re-assessed using...... quantitative-PCR. CD177 expression on neutrophil precursors in bone marrow was analyzed using quantitative PCR and flowcytometry. RESULTS: The proportion of CD177+ cells increased during neutrophil maturation in bone marrow. Fold change analysis of gene expression profile of sorted CD177+ and CD177...

  10. Membrane-tethered peptides patterned after the TRP domain (TRPducins) selectively inhibit TRPV1 channel activity.

    Science.gov (United States)

    Valente, Pierluigi; Fernández-Carvajal, Asia; Camprubí-Robles, María; Gomis, Ana; Quirce, Susana; Viana, Félix; Fernández-Ballester, Gregorio; González-Ros, José M; Belmonte, Carlos; Planells-Cases, Rosa; Ferrer-Montiel, Antonio

    2011-05-01

    The transient receptor potential vanilloid 1 (TRPV1) channel is a thermosensory receptor implicated in diverse physiological and pathological processes. The TRP domain, a highly conserved region in the C terminus adjacent to the internal channel gate, is critical for subunit tetramerization and channel gating. Here, we show that cell-penetrating, membrane-anchored peptides patterned after this protein domain are moderate and selective TRPV1 antagonists both in vitro and in vivo, blocking receptor activity in intact rat primary sensory neurons and their peripheral axons with mean decline time of 30 min. The most potent lipopeptide, TRP-p5, blocked all modes of TRPV1 gating with micromolar efficacy (IC(50)100 μM). TRP-p5 did not affect the capsaicin sensitivity of the vanilloid receptor. Our data suggest that TRP-p5 interferes with protein-protein interactions at the level of the TRP domain that are essential for the "conformational" change that leads to gate opening. Therefore, these palmitoylated peptides, which we termed TRPducins, are noncompetitive, voltage-independent, sequence-specific TRPV1 blockers. Our findings indicate that TRPducin-like peptides may embody a novel molecular strategy that can be exploited to generate a selective pharmacological arsenal for the TRP superfamily of ion channels.

  11. A central region in the minor capsid protein of papillomaviruses facilitates viral genome tethering and membrane penetration for mitotic nuclear entry.

    Directory of Open Access Journals (Sweden)

    Inci Aydin

    2017-05-01

    Full Text Available Incoming papillomaviruses (PVs depend on mitotic nuclear envelope breakdown to gain initial access to the nucleus for viral transcription and replication. In our previous work, we hypothesized that the minor capsid protein L2 of PVs tethers the incoming vDNA to mitotic chromosomes to direct them into the nascent nuclei. To re-evaluate how dynamic L2 recruitment to cellular chromosomes occurs specifically during prometaphase, we developed a quantitative, microscopy-based assay for measuring the degree of chromosome recruitment of L2-EGFP. Analyzing various HPV16 L2 truncation-mutants revealed a central chromosome-binding region (CBR of 147 amino acids that confers binding to mitotic chromosomes. Specific mutations of conserved motifs (IVAL286AAAA, RR302/5AA, and RTR313EEE within the CBR interfered with chromosomal binding. Moreover, assembly-competent HPV16 containing the chromosome-binding deficient L2(RTR313EEE or L2(IVAL286AAAA were inhibited for infection despite their ability to be transported to intracellular compartments. Since vDNA and L2 were not associated with mitotic chromosomes either, the infectivity was likely impaired by a defect in tethering of the vDNA to mitotic chromosomes. However, L2 mutations that abrogated chromatin association also compromised translocation of L2 across membranes of intracellular organelles. Thus, chromatin recruitment of L2 may in itself be a requirement for successful penetration of the limiting membrane thereby linking both processes mechanistically. Furthermore, we demonstrate that the association of L2 with mitotic chromosomes is conserved among the alpha, beta, gamma, and iota genera of Papillomaviridae. However, different binding patterns point to a certain variance amongst the different genera. Overall, our data suggest a common strategy among various PVs, in which a central region of L2 mediates tethering of vDNA to mitotic chromosomes during cell division thereby coordinating membrane

  12. The tissue-specific Rep8/UBXD6 tethers p97 to the endoplasmic reticulum membrane for degradation of misfolded proteins.

    Directory of Open Access Journals (Sweden)

    Louise Madsen

    Full Text Available The protein known as p97 or VCP in mammals and Cdc48 in yeast is a versatile ATPase complex involved in several biological functions including membrane fusion, protein folding, and activation of membrane-bound transcription factors. In addition, p97 plays a central role in degradation of misfolded secretory proteins via the ER-associated degradation pathway. This functional diversity of p97 depends on its association with various cofactors, and to further our understanding of p97 function it is important that these cofactors are identified and analyzed. Here, we isolate and characterize the human protein named Rep8 or Ubxd6 as a new cofactor of p97. Mouse Rep8 is highly tissue-specific and abundant in gonads. In testes, Rep8 is expressed in post-meiotic round spermatids, whereas in ovaries Rep8 is expressed in granulosa cells. Rep8 associates directly with p97 via its UBX domain. We show that Rep8 is a transmembrane protein that localizes to the ER membrane with its UBX domain facing the cytoplasm. Knock-down of Rep8 expression in human cells leads to a decreased association of p97 with the ER membrane and concomitantly a retarded degradation of misfolded ER-derived proteasome substrates. Thus, Rep8 tethers p97 to the ER membrane for efficient ER-associated degradation.

  13. The effect of particle size on the morphology and thermodynamics of diblock copolymer/tethered-particle membranes

    International Nuclear Information System (INIS)

    Zhang, Bo; Edwards, Brian J.

    2015-01-01

    A combination of self-consistent field theory and density functional theory was used to examine the effect of particle size on the stable, 3-dimensional equilibrium morphologies formed by diblock copolymers with a tethered nanoparticle attached either between the two blocks or at the end of one of the blocks. Particle size was varied between one and four tenths of the radius of gyration of the diblock polymer chain for neutral particles as well as those either favoring or disfavoring segments of the copolymer blocks. Phase diagrams were constructed and analyzed in terms of thermodynamic diagrams to understand the physics associated with the molecular-level self-assembly processes. Typical morphologies were observed, such as lamellar, spheroidal, cylindrical, gyroidal, and perforated lamellar, with the primary concentration region of the tethered particles being influenced heavily by particle size and tethering location, strength of the particle-segment energetic interactions, chain length, and copolymer radius of gyration. The effect of the simulation box size on the observed morphology and system thermodynamics was also investigated, indicating possible effects of confinement upon the system self-assembly processes

  14. The effect of particle size on the morphology and thermodynamics of diblock copolymer/tethered-particle membranes.

    Science.gov (United States)

    Zhang, Bo; Edwards, Brian J

    2015-06-07

    A combination of self-consistent field theory and density functional theory was used to examine the effect of particle size on the stable, 3-dimensional equilibrium morphologies formed by diblock copolymers with a tethered nanoparticle attached either between the two blocks or at the end of one of the blocks. Particle size was varied between one and four tenths of the radius of gyration of the diblock polymer chain for neutral particles as well as those either favoring or disfavoring segments of the copolymer blocks. Phase diagrams were constructed and analyzed in terms of thermodynamic diagrams to understand the physics associated with the molecular-level self-assembly processes. Typical morphologies were observed, such as lamellar, spheroidal, cylindrical, gyroidal, and perforated lamellar, with the primary concentration region of the tethered particles being influenced heavily by particle size and tethering location, strength of the particle-segment energetic interactions, chain length, and copolymer radius of gyration. The effect of the simulation box size on the observed morphology and system thermodynamics was also investigated, indicating possible effects of confinement upon the system self-assembly processes.

  15. The t-SNAREs syntaxin4 and SNAP23 but not v-SNARE VAMP2 are indispensable to tether GLUT4 vesicles at the plasma membrane in adipocyte

    International Nuclear Information System (INIS)

    Kawaguchi, Takayuki; Tamori, Yoshikazu; Kanda, Hajime; Yoshikawa, Mari; Tateya, Sanshiro; Nishino, Naonobu; Kasuga, Masato

    2010-01-01

    SNARE proteins (VAMP2, syntaxin4, and SNAP23) have been thought to play a key role in GLUT4 trafficking by mediating the tethering, docking and subsequent fusion of GLUT4-containing vesicles with the plasma membrane. The precise functions of these proteins have remained elusive, however. We have now shown that depletion of the vesicle SNARE (v-SNARE) VAMP2 by RNA interference in 3T3-L1 adipocytes inhibited the fusion of GLUT4 vesicles with the plasma membrane but did not affect tethering of the vesicles to the membrane. In contrast, depletion of the target SNAREs (t-SNAREs) syntaxin4 or SNAP23 resulted in impairment of GLUT4 vesicle tethering to the plasma membrane. Our results indicate that the t-SNAREs syntaxin4 and SNAP23 are indispensable for the tethering of GLUT4 vesicles to the plasma membrane, whereas the v-SNARE VAMP2 is not required for this step but is essential for the subsequent fusion event.

  16. The tissue-specific Rep8/UBXD6 tethers p97 to the endoplasmic reticulum membrane for degradation of misfolded proteins

    DEFF Research Database (Denmark)

    Madsen, Louise; Kriegenburg, Franziska; Lages Lino Vala, Andrea

    2011-01-01

    is a transmembrane protein that localizes to the ER membrane with its UBX domain facing the cytoplasm. Knock-down of Rep8 expression in human cells leads to a decreased association of p97 with the ER membrane and concomitantly a retarded degradation of misfolded ER-derived proteasome substrates. Thus, Rep8 tethers p......The protein known as p97 or VCP in mammals and Cdc48 in yeast is a versatile ATPase complex involved in several biological functions including membrane fusion, protein folding, and activation of membrane-bound transcription factors. In addition, p97 plays a central role in degradation of misfolded...... protein named Rep8 or Ubxd6 as a new cofactor of p97. Mouse Rep8 is highly tissue-specific and abundant in gonads. In testes, Rep8 is expressed in post-meiotic round spermatids, whereas in ovaries Rep8 is expressed in granulosa cells. Rep8 associates directly with p97 via its UBX domain. We show that Rep8...

  17. Hyperbranched-polyol-tethered poly (amic acid) electrospun nanofiber membrane with ultrahigh adsorption capacity for boron removal

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Zhe; Wu, Zhongyu; Zhang, Yufeng; Meng, Jianqiang, E-mail: jianqiang.meng@hotmail.com

    2017-04-30

    Highlights: • Electrospun nanofiber membranes were grafted with hyperbranched polyols. • The membrane had a maximum boron uptake of 5.68 mmol/g. • The membrane could adsorb 0.82 mmol/g boron from a 5 mg/L solution in 15 min. • The membrane obeyed the Langmuir and the pseudo-first-order kinetic model. • The regeneration efficiency remained over 90% after 10 cycled uses. - Abstract: The development of efficient adsorbents with high sorption capacity remains as a challenge for the removal of micropollutants occurred globally in water resources. In this work, poly (amic acid) (PAA) electrospun nanofiber membranes grafted with hyperbranched polyols were synthesized and used for boron removal. The PAA nanofiber was reacted with hyperbranched polyethylenimine (HPEI) and further with glycidol to introduce the vicinal hydroxyl groups. The chemical composition and surface characteristics of the obtained PAA-g-PG membranes were evaluated by FESEM, FTIR, XPS and water contact angles (WCA) measurements. The boron adsorption thermodynamics and kinetics were investigated systematically. The results showed that the PAA nanofiber spun from concentration of 15% had uniform morphology and narrow diameter distribution. The PAA-g-PG nanofiber membrane had a maximum boron uptake of 5.68 mmol/g and could adsorb 0.82 mmol/g boron from a 5 mg/L solution in 15 min. Both the high surface area of nanofibers and the hyperbranched structure should contribute to the high boron uptake and high adsorption rate. The nanofiber membrane obeyed the Langmuir adsorption model and the pseudo-first-order kinetic model. The regeneration efficiency of the nanofiber membrane remained 93.9% after 10 cycled uses, indicating good regenerability of the membrane.

  18. Aggressive re-warming at 38.5 degrees C following deep hypothermia at 21 degrees C increases neutrophil membrane bound elastase activity and pro-inflammatory factor release

    NARCIS (Netherlands)

    Tang, Min; Zhao, Xiao-gang; He, Yi; Gu, Yan; Mei, Ju

    2016-01-01

    Background: Cardiopulmonary bypass (CPB) is often performed under hypothermic condition. The effects of hypothermia and re-warming on neutrophil activity are unclear. This study aimed to compare the effects of different hypothermia and re-warming regimens on neutrophil membrane bound elastase (MBE)

  19. Increased Granulocyte Heparanase Activity in Neutrophils from Patients with Lupus Nephritis and Idiopathic Membranous Nephropathy.

    Science.gov (United States)

    Szymczak, Maciej; Kuźniar, Jakub; Kopeć, Wacław; Żabińska, Marcelina; Marchewka, Zofia; Kościelska-Kasprzak, Katarzyna; Klinger, Marian

    2017-02-01

    Heparanase is a β-glucuronidase that cleaves sugar chains of heparan sulfate proteoglycans. It is believed that heparanase may be involved in the pathogenesis of proteinuria. The aim of this study was to assess the significance of heparanase in the pathogenesis of particular glomerulonephritis types. The evaluation of heparanase activity in serum, urine, and granulocytes and superoxide dismutase (SOD) activity in granulocytes of patients with lupus nephritis (n = 17), membranous nephropathy (n = 11), IgA nephropathy (n = 12), focal and segmental glomerulosclerosis (n = 18), mesangiocapillary glomerulonephritis (n = 12) and in 19 healthy volunteers were performed. The heparanase activity in granulocytes of patients with lupus nephritis and membranous nephropathy was higher than heparanase activity in granulocytes in the control group (p = 0.02 in both cases). This is the first observation of this phenomenon. There was no difference between SOD activity in granulocytes of patients with all assessed types of glomerulonephritis and the control group. A positive correlation between heparanase activity in urine and double-strain DNA antibodies (r = 0.51; p = 0.04), and reverse correlations between heparanase in urine and hemolytic activity of the complement (r = -0.57; p = 0.03) in the lupus nephritis group, and between heparanase activity in granulocytes and serum total protein level (r = -0.69; p = 0.02) in membranous nephropathy were observed. Increase in heparanase activity without changes in superoxide dismutase activity in the granulocytes from patients with lupus nephritis and membranous nephropathy was observed. It may be used as one of the markers of these disease activities.

  20. The membrane tethered transcription factor EcbZIP17 from finger millet promotes plant growth and enhances tolerance to abiotic stresses.

    Science.gov (United States)

    Ramakrishna, Chopperla; Singh, Sonam; Raghavendrarao, Sangala; Padaria, Jasdeep C; Mohanty, Sasmita; Sharma, Tilak Raj; Solanke, Amolkumar U

    2018-02-01

    The occurrence of various stresses, as the outcome of global climate change, results in the yield losses of crop plants. Prospecting of genes in stress tolerant plant species may help to protect and improve their agronomic performance. Finger millet (Eleusine coracana L.) is a valuable source of superior genes and alleles for stress tolerance. In this study, we isolated a novel endoplasmic reticulum (ER) membrane tethered bZIP transcription factor from finger millet, EcbZIP17. Transgenic tobacco plants overexpressing this gene showed better vegetative growth and seed yield compared with wild type (WT) plants under optimal growth conditions and confirmed upregulation of brassinosteroid signalling genes. Under various abiotic stresses, such as 250 mM NaCl, 10% PEG6000, 400 mM mannitol, water withdrawal, and heat stress, the transgenic plants showed higher germination rate, biomass, primary and secondary root formation, and recovery rate, compared with WT plants. The transgenic plants exposed to an ER stress inducer resulted in greater leaf diameter and plant height as well as higher expression of the ER stress-responsive genes BiP, PDIL, and CRT1. Overall, our results indicated that EcbZIP17 improves plant growth at optimal conditions through brassinosteroid signalling and provide tolerance to various environmental stresses via ER signalling pathways.

  1. Mitochondrial membrane potential in human neutrophils is maintained by complex III activity in the absence of supercomplex organisation

    NARCIS (Netherlands)

    B.J. van Raam (Bram); W.J. Sluiter (Wim); F.R.C. de Wit (Frank); D. Roos (Dirk); A.J. Verhoeven (Arthur); T.W. Kuijpers (Taco W.)

    2008-01-01

    textabstractBackground: Neutrophils depend mainly on glycolysis for their enegry provision. Their mitochondria maintain a membrace potential (ΔΨm), which is usually generated by the repiratory chain complexes. We investigated the source of ΔΨm in neutrophils, as compared to peripheral blood

  2. Tethering factors as organizers of intracellular vesicular traffic.

    Science.gov (United States)

    Yu, I-Mei; Hughson, Frederick M

    2010-01-01

    Intracellular trafficking entails the budding, transport, tethering, and fusion of transport vesicles and other membrane carriers. Here we review recent progress toward a mechanistic understanding of vesicle tethering. The known tethering factors are large complexes important for one or more intracellular trafficking pathways and are capable of interacting directly with many of the other principal components of the cellular trafficking machinery. Our review emphasizes recent developments in the in vitro reconstitution of vesicle tethering and the structural characterization of multisubunit tethering factors. The combination of these and other approaches has led to exciting progress toward understanding how these essential nanomachines work.

  3. Membrane-Tethered Delta-Like 1 Homolog (DLK1) Restricts Adipose Tissue Size By Inhibiting Preadipocyte Proliferation

    DEFF Research Database (Denmark)

    Mortensen, Sussi B; Jensen, Charlotte H; Schneider, Mikael

    2012-01-01

    Adipocyte renewal from preadipocytes has been shown to occur throughout life and to contribute to obesity, yet very little is known about the molecular circuits that control preadipocyte expansion. The soluble form of the preadipocyte factor (also known as pref-1) delta-like 1 homolog (DLK1(S...... in vivo. Here, we demonstrate for the first time that only membrane-bound DLK1 (DLK1(M)) exhibits a substantial repression effect on preadipocyte proliferation. Thus, by independently manipulating DLK1 isoform levels, we established that DLK1(M) inhibits G1-to-S-phase cell cycle progression and thereby...

  4. Priming of the neutrophil NADPH oxidase activation: role of p47phox phosphorylation and NOX2 mobilization to the plasma membrane.

    Science.gov (United States)

    El-Benna, Jamel; Dang, Pham My-Chan; Gougerot-Pocidalo, Marie-Anne

    2008-07-01

    Neutrophils play an essential role in host defense against microbial pathogens and in the inflammatory reaction. Upon activation, neutrophils produce superoxide anion (O*2), which generates other reactive oxygen species (ROS) such as hydrogen peroxide (H2O2), hydroxyl radical (OH*) and hypochlorous acid (HOCl), together with microbicidal peptides and proteases. The enzyme responsible for O2* production is called the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase or respiratory burst oxidase. This multicomponent enzyme system is composed of two trans-membrane proteins (p22phox and gp91phox/NOX2, which form the cytochrome b558), three cytosolic proteins (p47phox, p67phox, p40phox) and a GTPase (Rac1 or Rac2), which assemble at membrane sites upon cell activation. NADPH oxidase activation in phagocytes can be induced by a large number of soluble and particulate factors. Three major events accompany NAPDH oxidase activation: (1) protein phosphorylation, (2) GTPase activation, and (3) translocation of cytosolic components to the plasma membrane to form the active enzyme. Actually, the neutrophil NADPH oxidase exists in different states: resting, primed, activated, or inactivated. The resting state is found in circulating blood neutrophils. The primed state can be induced by neutrophil adhesion, pro-inflammatory cytokines, lipopolysaccharide, and other agents and has been characterized as a "ready to go" state, which results in a faster and higher response upon exposure to a second stimulus. The active state is found at the inflammatory or infection site. Activation is induced by the pathogen itself or by pathogen-derived formylated peptides and other agents. Finally, inactivation of NADPH oxidase is induced by anti-inflammatory agents to limit inflammation. Priming is a "double-edged sword" process as it contributes to a rapid and efficient elimination of the pathogens but can also induce the generation of large quantities of toxic ROS by hyperactivation of

  5. Monitoring human neutrophil granule secretion by flow cytometry: secretion and membrane potential changes assessed by light scatter and a fluorescent probe of membrane potential

    International Nuclear Information System (INIS)

    Fletcher, M.P.; Seligmann, B.E.

    1985-01-01

    Purified human peripheral blood polymorphonuclear neutrophils (PMN) were incubated at 37 degrees C with the fluorescent membrane potential sensitive cyanine dye di-O-C(5)(3) and exposed to a number of stimulatory agents (N-formylmethionylleucylphenylalanine (FMLP), cytochalasin B (cyto B) + FMLP, phorbol myristate acetate (PMA). Flow cytometry was utilized to measure changes in forward light scatter (FS), orthogonal light scatter (90 degrees-SC), and fluorescence intensity of individual cells over time. A saturating (10(-6) M) dose of FMLP lead to a significant increase in the cells' FS without a change in 90 degrees-SC as well as a heterogeneous loss of di-O-C(5)(3) fluorescence. PMA (100 ng/ml) also caused an increase in FS but a uniform loss of dye fluorescence by all cells (apparent depolarization). Cyto B + FMLP produced an increase in FS, a marked loss of 90 degrees-SC, and a uniform loss of fluorescence. Secretion experiments under identical incubation conditions indicated a significantly positive relationship between loss of enzyme markers or cell granularity and orthogonal light scatter (r . 0.959, 0.998, and 0.989 for loss of 90 degrees-SC vs lysozyme, beta-glucuronidase, and granularity index, respectively). Flow cytometric light scatter measurements may yield important information on the extent of prior cell degranulation or activation

  6. Neurodegeneration and unfolded-protein response in mice expressing a membrane-tethered flexible tail of PrP.

    Directory of Open Access Journals (Sweden)

    Paolo Dametto

    Full Text Available The cellular prion protein (PrPC consists of a flexible N-terminal tail (FT, aa 23-128 hinged to a membrane-anchored globular domain (GD, aa 129-231. Ligation of the GD with antibodies induces rapid neurodegeneration, which is prevented by deletion or functional inactivation of the FT. Therefore, the FT is an allosteric effector of neurotoxicity. To explore its mechanism of action, we generated transgenic mice expressing the FT fused to a GPI anchor, but lacking the GD (PrPΔ141-225, or "FTgpi". Here we report that FTgpi mice develop a progressive, inexorably lethal neurodegeneration morphologically and biochemically similar to that triggered by anti-GD antibodies. FTgpi was mostly retained in the endoplasmic reticulum, where it triggered a conspicuous unfolded protein response specifically activating the PERK pathway leading to phosphorylation of eIF2α and upregulation of CHOP ultimately leading to neurodegeration similar to what was observed in prion infection.

  7. Tethering sockets and wrenches

    Science.gov (United States)

    Johnson, E. P.

    1990-01-01

    The tethering of sockets and wrenches was accomplished to improve the safety of working over motor segments. To accomplish the tethering of the sockets to the ratchets, a special design was implemented in which a groove was machined into each socket. Each socket was then fitted with a snap ring that can spin around the machined groove. The snap ring is tethered to the handle of the ratchet. All open end wrenches are also tethered to the ratchet or to the operator, depending upon the type. Tests were run to ensure that the modified tools meet torque requirements. The design was subsequently approved by Space Safety.

  8. Tethering sockets and wrenches

    Science.gov (United States)

    Johnson, E. P.

    1990-07-01

    The tethering of sockets and wrenches was accomplished to improve the safety of working over motor segments. To accomplish the tethering of the sockets to the ratchets, a special design was implemented in which a groove was machined into each socket. Each socket was then fitted with a snap ring that can spin around the machined groove. The snap ring is tethered to the handle of the ratchet. All open end wrenches are also tethered to the ratchet or to the operator, depending upon the type. Tests were run to ensure that the modified tools meet torque requirements. The design was subsequently approved by Space Safety.

  9. Coat/Tether Interactions—Exception or Rule?

    Science.gov (United States)

    Schröter, Saskia; Beckmann, Sabrina; Schmitt, Hans Dieter

    2016-01-01

    Coat complexes are important for cargo selection and vesicle formation. Recent evidence suggests that they may also be involved in vesicle targeting. Tethering factors, which form an initial bridge between vesicles and the target membrane, may bind to coat complexes. In this review, we ask whether these coat/tether interactions share some common mechanisms, or whether they are special adaptations to the needs of very specific transport steps. We compare recent findings in two multisubunit tethering complexes, the Dsl1 complex and the HOPS complex, and put them into context with the TRAPP I complex as a prominent example for coat/tether interactions. We explore where coat/tether interactions are found, compare their function and structure, and comment on a possible evolution from a common ancestor of coats and tethers. PMID:27243008

  10. Coat/Tether Interactions-Exception or Rule?

    Science.gov (United States)

    Schroeter, Saskia; Beckmann, Sabrina; Schmitt, Hans Dieter

    2016-01-01

    Coat complexes are important for cargo selection and vesicle formation. Recent evidence suggests that they may also be involved in vesicle targeting. Tethering factors, which form an initial bridge between vesicles and the target membrane, may bind to coat complexes. In this review, we ask whether these coat/tether interactions share some common mechanisms, or whether they are special adaptations to the needs of very specific transport steps. We compare recent findings in two multisubunit tethering complexes, the Dsl1 complex and the HOPS complex, and put them into context with the TRAPP I complex as a prominent example for coat/tether interactions. We explore where coat/tether interactions are found, compare their function and structure, and comment on a possible evolution from a common ancestor of coats and tethers.

  11. Coat/tether interactions – exceptions or rule?

    Directory of Open Access Journals (Sweden)

    Saskia eSchroeter

    2016-05-01

    Full Text Available Coat complexes are important for cargo selection and vesicle formation. Recent evidence suggests that they may also be involved in vesicle targeting. Tethering factors, which form an initial bridge between vesicles and the target membrane, may bind to coat complexes. In this review, we ask whether these coat/tether interactions share some common mechanisms, or whether they are special adaptations to the needs of very specific transport steps. We compare recent findings in two multisubunit tethering complexes, the Dsl1 complex and the HOPS complex, and put them into context with the TRAPP I complex as a prominent example for coat/tether interactions. We explore where coat/tether interactions are found, compare their function and structure, and comment on a possible evolution from a common ancestor of coats and tethers.

  12. Why Not Space Tethers?

    Science.gov (United States)

    Stone, Noble H.

    2007-01-01

    The Tethered Satellite System Space Shuttle missions, TSS-1 in 1993 and TSS-1R in 1996, were the height of space tether technology development. Since NASA's investment of some $200M and two Shuttle missions in those two pioneering missions, there have been several smaller tether flight experiments, but interest in this promising technology has waned within NASA as well as the DOD agencies. This is curious in view of the unique capabilities of space tether systems and the fact that they have been flight validated and shown to perform as, or better than, expected in earth orbit. While it is true that the TSS-1, TSS-1R and SEDS-2 missions experienced technical difficulties, the causes of these early developmental problems are now known to be design or materials flaws that are (1) unrelated to the basic viability of space tether technology, and (2) they are readily corrected. The purpose of this paper is to review the dynamic and electrodynamic fundamentals of space tethers and the unique capabilities they afford (that are enabling to certain types of space missions); to elucidate the nature, cause, and solution of the early developmental problems; and to provide an update on progress made in development of the technology. Finally, it is shown that (1) all problems experienced during early development of the technology now have solutions; and (2) the technology has been matured by advances made in strength and robustness of tether materials, high voltage engineering in the space environment, tether health and status monitoring, and the elimination of the broken tether hazard. In view of this, it is inexplicable why this flight-validated technology has not been utilized in the past decade, considering the powerful and unique capabilities that space tethers can afford that are, not only required to carryout, otherwise, unobtainable missions, but can also greatly reduce the cost of certain on-going space operations.

  13. Two Tethered Balloon Systems

    Science.gov (United States)

    Youngbluth, Otto; Owens, Thomas L.; Storey, Richard W.

    1990-01-01

    Systems take meteorological measurements for variety of research projects. Report describes work done by NASA Langley Research Center in atmospheric research using tethered balloon systems composed of commercially available equipment. Two separate tethered balloon systems described in report have payloads and configurations tailored to requirements of specific projects. Each system capable of measuring atmospheric parameter or species in situ and then telemetering this data in real time to ground station. Meteorological data and concentration of ozone typically measured. Indicates instrumented tethered balloon systems have distinct advantages over other systems for gathering data on troposphere.

  14. Membrane Transfer from Mononuclear Cells to Polymorphonuclear Neutrophils Transduces Cell Survival and Activation Signals in the Recipient Cells via Anti-Extrinsic Apoptotic and MAP Kinase Signaling Pathways.

    Science.gov (United States)

    Li, Ko-Jen; Wu, Cheng-Han; Shen, Chieh-Yu; Kuo, Yu-Min; Yu, Chia-Li; Hsieh, Song-Chou

    2016-01-01

    The biological significance of membrane transfer (trogocytosis) between polymorphonuclear neutrophils (PMNs) and mononuclear cells (MNCs) remains unclear. We investigated the biological/immunological effects and molecular basis of trogocytosis among various immune cells in healthy individuals and patients with active systemic lupus erythematosus (SLE). By flow cytometry, we determined that molecules in the immunological synapse, including HLA class-I and-II, CD11b and LFA-1, along with CXCR1, are exchanged among autologous PMNs, CD4+ T cells, and U937 cells (monocytes) after cell-cell contact. Small interfering RNA knockdown of the integrin adhesion molecule CD11a in U937 unexpectedly enhanced the level of total membrane transfer from U937 to PMN cells. Functionally, phagocytosis and IL-8 production by PMNs were enhanced after co-culture with T cells. Total membrane transfer from CD4+ T to PMNs delayed PMN apoptosis by suppressing the extrinsic apoptotic molecules, BAX, MYC and caspase 8. This enhancement of activities of PMNs by T cells was found to be mediated via p38- and P44/42-Akt-MAP kinase pathways and inhibited by the actin-polymerization inhibitor, latrunculin B, the clathrin inhibitor, Pitstop-2, and human immunoglobulin G, but not by the caveolin inhibitor, methyl-β-cyclodextrin. In addition, membrane transfer from PMNs enhanced IL-2 production by recipient anti-CD3/anti-CD28 activated MNCs, and this was suppressed by inhibitors of mitogen-activated protein kinase (PD98059) and protein kinase C (Rottlerin). Of clinical significance, decreased total membrane transfer from PMNs to MNCs in patients with active SLE suppressed mononuclear IL-2 production. In conclusion, membrane transfer from MNCs to PMNs, mainly at the immunological synapse, transduces survival and activation signals to enhance PMN functions and is dependent on actin polymerization, clathrin activation, and Fcγ receptors, while membrane transfer from PMNs to MNCs depends on MAP kinase and

  15. Membrane Transfer from Mononuclear Cells to Polymorphonuclear Neutrophils Transduces Cell Survival and Activation Signals in the Recipient Cells via Anti-Extrinsic Apoptotic and MAP Kinase Signaling Pathways.

    Directory of Open Access Journals (Sweden)

    Ko-Jen Li

    Full Text Available The biological significance of membrane transfer (trogocytosis between polymorphonuclear neutrophils (PMNs and mononuclear cells (MNCs remains unclear. We investigated the biological/immunological effects and molecular basis of trogocytosis among various immune cells in healthy individuals and patients with active systemic lupus erythematosus (SLE. By flow cytometry, we determined that molecules in the immunological synapse, including HLA class-I and-II, CD11b and LFA-1, along with CXCR1, are exchanged among autologous PMNs, CD4+ T cells, and U937 cells (monocytes after cell-cell contact. Small interfering RNA knockdown of the integrin adhesion molecule CD11a in U937 unexpectedly enhanced the level of total membrane transfer from U937 to PMN cells. Functionally, phagocytosis and IL-8 production by PMNs were enhanced after co-culture with T cells. Total membrane transfer from CD4+ T to PMNs delayed PMN apoptosis by suppressing the extrinsic apoptotic molecules, BAX, MYC and caspase 8. This enhancement of activities of PMNs by T cells was found to be mediated via p38- and P44/42-Akt-MAP kinase pathways and inhibited by the actin-polymerization inhibitor, latrunculin B, the clathrin inhibitor, Pitstop-2, and human immunoglobulin G, but not by the caveolin inhibitor, methyl-β-cyclodextrin. In addition, membrane transfer from PMNs enhanced IL-2 production by recipient anti-CD3/anti-CD28 activated MNCs, and this was suppressed by inhibitors of mitogen-activated protein kinase (PD98059 and protein kinase C (Rottlerin. Of clinical significance, decreased total membrane transfer from PMNs to MNCs in patients with active SLE suppressed mononuclear IL-2 production. In conclusion, membrane transfer from MNCs to PMNs, mainly at the immunological synapse, transduces survival and activation signals to enhance PMN functions and is dependent on actin polymerization, clathrin activation, and Fcγ receptors, while membrane transfer from PMNs to MNCs depends on

  16. Tether Deployer And Brake

    Science.gov (United States)

    Carroll, Joseph A.; Alexander, Charles M.

    1993-01-01

    Design concept promises speed, control, and reliability. Scheme for deploying tether provides for fast, free, and snagless payout and fast, dependable braking. Developed for small, expendable tethers in outer space, scheme also useful in laying transoceanic cables, deploying guidance wires to torpedoes and missiles, paying out rescue lines from ship to ship via rockets, deploying antenna wires, releasing communication and power cables to sonobuoys and expendable bathythermographs, and in reeling out lines from fishing rods.

  17. Modulation of the heterogeneous membrane potential response of neutrophils to N-formyl-methionyl-leucyl-phenylalanine (FMLP) by leukotriene B4: evidence for cell recruitment

    International Nuclear Information System (INIS)

    Fletcher, M.P.

    1986-01-01

    Individual human neutrophils (PMN) isolated by Hypaque-Ficoll gradient sedimentation, dextran sedimentation, or buffy coat preparation were assessed for the effects of leukotriene B4 (5S,12R dihydroxy 6,14-cis-8, 10 trans eicosatetraenoic acid (LTB4)-pretreatment on N-formylmethionyl-leucyl-phenylalanine (FMLP)-mediated membrane potential or oxidative responses by using flow cytometry and a lipophilic probe of membrane potential (di-pentyl-oxacarbocyanine, di-O-C(5)3), or the nitroblue tetrazolium dye (NBT) reduction test, respectively. Although exposure to LTB4 (10(-7) M) had no effect on the membrane potential of resting PMN and little effect on oxidant production, pretreating PMN with LTB4 followed by FMLP (10(-6) M) demonstrated a significant enhancement in the proportion of depolarizing PMN over that seen with FMLP alone (p = 0.0014, N = 9). This recruitment of previously unresponsive cells by LTB4 was dose and time dependent, with the maximal relative increase in the proportion of depolarizing cells occurring at LTB4 concentrations of 10(-8) to 10(-7) M and within 1 min of LTB4 addition. The recruitment effect persisted despite vigorous washing of the cells. LTB4 also increased the proportion of NBT-positive PMN in response to FMLP. Although LTB4 alone did not depolarize PMN it did induce a light scatter shift indicative of cell activation. 3 H-FMLP binding studied at 0 degree C comparing buffer and LTB4-treated PMN indicated no significant change in the number or affinity of FMLP binding. The data provide evidence for the recruitment of a greater proportion of cells into a FMLP-responsive state as a mechanism for the enhanced functional response of PMN pretreated with LTB4, as well as for a dissociation of the membrane potential and light scattering responses of cells to this pro-inflammatory LT

  18. Membrane fusion

    DEFF Research Database (Denmark)

    Bendix, Pól Martin

    2015-01-01

    At Stanford University, Boxer lab, I worked on membrane fusion of small unilamellar lipid vesicles to flat membranes tethered to glass surfaces. This geometry closely resembles biological systems in which liposomes fuse to plasma membranes. The fusion mechanism was studied using DNA zippering...... between complementary strands linked to the two apposing membranes closely mimicking the zippering mechanism of SNARE fusion complexes....

  19. Cytoplasmic lipid bodies of human neutrophilic leukocytes

    International Nuclear Information System (INIS)

    Weller, P.F.; Ackerman, S.J.; Nicholson-Weller, A.; Dvorak, A.M.

    1989-01-01

    The morphology and function of cytoplasmic lipid bodies in human neutrophils were evaluated. By transmission electron microscopy, neutrophil lipid bodies were cytoplasmic inclusions, usually several microns in diameter, that occasionally coalesced to attain a diameter up to 7 microM. Neutrophil lipid bodies were not enveloped by membrane but were often surrounded by a more electron-dense shell at their periphery. Normal peripheral blood neutrophils contained an average of approximately one lipid body per cell. Lipid bodies appeared in greater numbers in neutrophils from inflammatory lesions. Perturbation of neutrophils during conventional methods of cell isolation and purification modestly increased lipid body numbers in neutrophils, whereas incubation of neutrophils with 1 microM oleic acid rapidly induced lipid body formation over 30 to 60 minutes. After granulocytes were incubated for 2 hours with 3H-fatty acids, including arachidonic, oleic, and palmitic acids, electron microscopic autoradiography demonstrated that lipid bodies represented the predominant intracellular sites of localization of each of the three 3H-fatty acids. There was lesser labeling noted in the perinuclear cisterna, but not in cell membranes. Virtually all of each of the three 3H-fatty acids incorporated by the neutrophils were esterified into chromatographically resolved classes of neutral lipids or phospholipids. These findings indicate that cytoplasmic lipid bodies are more prominent in neutrophils in vivo engaged in inflammatory responses and that these organelles in human neutrophils function as sites of deposition of esterified, incorporated fatty acids

  20. Tethers in Space

    Science.gov (United States)

    Johnson, Les; Bilén, Sven G.; Gilchrist, Brian E.; Krause, Linda Habash

    2017-09-01

    This Special Section of Acta Astronautica contains several peer-reviewed papers selected from among those presented at the Fifth International Conference on Tethers in Space (TiS2016). After a hiatus of 21 years since the last Conference on Tethers in Space, TiS2016 brought together experts, practitioners, and other interested in space tethers and related fields. TiS2016 was held May 24-26, 2016 at The University of Michigan in Ann Arbor, Michigan, U.S.A. Leveraging the hard work of a great many volunteers, the conference co-chairs Prof. Brian Gilchrist and Prof. Sven Bilén welcomed an international contingent with authors from the U.S., Canada, Japan, Spain, China, Finland, Estonia, and Italy. The community provided updates on what has transpired since their last gathering by providing lessons learned; describing new technologies and subsystems; and proposing new tether missions and applications. Papers overviewed de-orbit systems, power generation, orbital maneuvering, momentum capture, debris removal, space tugs, space elevators, collision avoidance, and tether dynamics, among others.

  1. Nano- to microscale dynamics of P-selectin detachment from leukocyte interfaces. II. Tether flow terminated by P-selectin dissociation from PSGL-1.

    Science.gov (United States)

    Heinrich, Volkmar; Leung, Andrew; Evans, Evan

    2005-03-01

    We have used a biomembrane force probe decorated with P-selectin to form point attachments with PSGL-1 receptors on a human neutrophil (PMN) in a calcium-containing medium and then to quantify the forces experienced by the attachment during retraction of the PMN at fixed speed. From first touch to final detachment, the typical force history exhibited the following sequence of events: i), an initial linear-elastic displacement of the PMN surface, ii), an abrupt crossover to viscoplastic flow that signaled membrane separation from the interior cytoskeleton and the beginning of a membrane tether, and iii), the final detachment from the probe tip most often by one precipitous step of P-selectin:PSGL-1 dissociation. Analyzing the initial elastic response and membrane unbinding from the cytoskeleton in our companion article I, we focus in this article on the regime of tether extrusion that nearly always occurred before release of the extracellular adhesion bond at pulling speeds > or =1 microm/s. The force during tether growth appeared to approach a plateau at long times. Examined over a large range of pulling speeds up to 150 microm/s, the plateau force exhibited a significant shear thinning as indicated by a weak power-law dependence on pulling speed, f(infinity) = 60 pN(nu(pull)/microm/s)(0.25). Using this shear-thinning response to describe the viscous element in a nonlinear Maxwell-like fluid model, we show that a weak serial-elastic component with a stiffness of approximately 0.07 pN/nm provides good agreement with the time course of the tether force approach to the plateau under constant pulling speed.

  2. The membrane attack complex of complement contributes to plasmin-induced synthesis of platelet-activating factor by endothelial cells and neutrophils.

    Science.gov (United States)

    Lupia, Enrico; Del Sorbo, Lorenzo; Bergerone, Serena; Emanuelli, Giorgio; Camussi, Giovanni; Montrucchio, Giuseppe

    2003-08-01

    Thrombolytic agents, used to restore blood flow to ischaemic tissues, activate several enzymatic systems with pro-inflammatory effects, thus potentially contributing to the pathogenesis of ischaemia-reperfusion injury. Platelet-activating factor (PAF), a phospholipid mediator of inflammation, has been implicated in the pathogenesis of this process. We previously showed that the infusion of streptokinase (SK) induces the intravascular release of PAF in patients with acute myocardial infarction (AMI), and that cultured human endothelial cells (EC) synthesized PAF in response to SK and plasmin (PLN). In the present study, we investigated the role of the membrane attack complex (MAC) of complement in the PLN-induced synthesis of PAF. In vivo, we showed a correlation between the levels of soluble terminal complement components (sC5b-9) and the concentrations of PAF detected in blood of patients with AMI infused with SK. In vitro both EC and polymorphonuclear neutrophils (PMN), incubated in the presence of PLN and normal human serum, showed an intense staining for the MAC neoepitope, while no staining was detected when they were incubated with PLN in the presence of heat-inactivated normal human serum. Moreover, the insertion of MAC on EC and PMN plasmamembrane elicited the synthesis of PAF. In conclusion, our results elucidate the mechanisms involved in PAF production during the activation of the fibrinolytic system, showing a role for complement products in this setting. The release of PAF may increase the inflammatory response, thus limiting the beneficial effects of thrombolytic therapy. Moreover, it may have a pathogenic role in other pathological conditions, such as transplant rejection, tumoral angiogenesis, and septic shock, where fibrinolysis is activated.

  3. Regulation of formyl peptide receptor binding to rabbit neutrophil plasma membranes. Use of monovalent cations, guanine nucleotides, and bacterial toxins to discriminate among different states of the receptor

    International Nuclear Information System (INIS)

    Feltner, D.E.; Marasco, W.A.

    1989-01-01

    The regulation by monovalent cations, guanine nucleotides, and bacterial toxins of [3H]FMLP binding to rabbit neutrophil plasma membranes was studied by using dissociation techniques to identify regulatory effects on separate receptor states. Under conditions of low receptor occupancy (1 nM [3H]FMLP) and in both Na+ and K+ buffers, dissociation is heterogenous, displaying two distinct, statistically significant off rates. [3H]FMLP binding was enhanced by substituting other monovalent cations for Na+. In particular, enhanced binding in the presence of K+ relative to Na+ was caused by additional binding to both rapidly and slowly dissociating receptors. Three receptor dissociation rates, two of which appear to correspond to the two affinity states detected in equilibrium binding studies, were defined by specific GTP and pertussis toxin (PT) treatments. Neither GTP, nor PT or cholera toxins (CT) had an effect on the rate of dissociation of [3H]FMLP from the rapidly dissociating form of the receptor. Both 100 microM GTP and PT treatments increased the percentage of rapidly dissociating receptors, correspondingly decreasing the percentage of slowly dissociating receptors. The observed changes in the rapidly and slowly dissociating receptors after GTP, PT, and CT treatments were caused by an absolute decrease in the amount of binding to the slowly dissociating receptors. However, complete inhibition of slowly dissociating receptor binding by GTP, PT, or both was never observed. Both GTP and PT treatments, but not CT treatment, increased by two-fold the rate of dissociation of 1 nM [3H]FMLP from the slowly dissociating form of the receptor, resulting in a third dissociation rate. Thus, slowly dissociating receptors comprise two different receptor states, a G protein-associated guanine nucleotide and PT-sensitive state and a guanine nucleotide-insensitive state

  4. Effect of sevoflurane on human neutrophil apoptosis.

    LENUS (Irish Health Repository)

    Tyther, R

    2012-02-03

    BACKGROUND AND OBJECTIVE: Both chronic occupational exposure to volatile anaesthetic agents and acute in vitro exposure of neutrophils to isoflurane have been shown to inhibit the rate of apoptosis of human neutrophils. It is possible that inhibition of neutrophil apoptosis arises through delaying mitochondrial membrane potential collapse. We assessed mitochondrial depolarization and apoptosis in unexposed neutrophils and neutrophils exposed to sevoflurane in vivo. METHODS: A total of 20 mL venous blood was withdrawn pre- and postinduction of anaesthesia, the neutrophils isolated and maintained in culture. At 1, 12 and 24 h in culture, the percentage of neutrophil apoptosis was assessed by dual staining with annexin V-FITC and propidium iodide. Mitochondrial depolarization was measured using the dual emission styryl dye JC-1. RESULTS: Apoptosis was significantly inhibited in neutrophils exposed to sevoflurane in vivo at 24 (exposed: 38 (12)% versus control: 28 (11)%, P = 0.001), but not at 1 or 12 h, in culture. Mitochondrial depolarization was not delayed in neutrophils exposed to sevoflurane. CONCLUSIONS: The most important findings are that sevoflurane inhibits neutrophil apoptosis in vivo and that inhibition is not mediated primarily by an effect on mitochondrial depolarization.

  5. Superoxide anion production by human neutrophils activated by Trichomonas vaginalis.

    Science.gov (United States)

    Song, Hyun-Ouk; Ryu, Jae-Sook

    2013-08-01

    Neutrophils are the predominant inflammatory cells found in vaginal discharges of patients infected with Trichomonas vaginalis. In this study, we examined superoxide anion (O2 (.-)) production by neutrophils activated by T. vaginalis. Human neutrophils produced superoxide anions when stimulated with either a lysate of T. vaginalis, its membrane component (MC), or excretory-secretory product (ESP). To assess the role of trichomonad protease in production of superoxide anions by neutrophils, T. vaginalis lysate, ESP, and MC were each pretreated with a protease inhibitor cocktail before incubation with neutrophils. Superoxide anion production was significantly decreased by this treatment. Trichomonad growth was inhibited by preincubation with supernatants of neutrophils incubated for 3 hr with T. vaginalis lysate. Furthermore, myeloperoxidase (MPO) production by neutrophils was stimulated by live trichomonads. These results indicate that the production of superoxide anions and MPO by neutrophils stimulated with T. vaginalis may be a part of defense mechanisms of neutrophils in trichomoniasis.

  6. Space tether dynamics: an introduction

    Science.gov (United States)

    Denny, Mark

    2018-05-01

    The dynamics of orbiting tethers (space elevators and skyhooks) is developed from an unusual direction: Lagrangian rather than Newtonian mechanics. These basic results are derived among others: space elevator required length with and without counterweight, location and magnitude of maximum tether tension, skyhook orbital parameters and tether tension. These conceptual devices are being increasingly discussed as technologically feasible; here they make an interesting pedagogical application of Lagrangian mechanics suitable for undergraduate physics students.

  7. Nuclear pore complex tethers to the cytoskeleton.

    Science.gov (United States)

    Goldberg, Martin W

    2017-08-01

    The nuclear envelope is tethered to the cytoskeleton. The best known attachments of all elements of the cytoskeleton are via the so-called LINC complex. However, the nuclear pore complexes, which mediate the transport of soluble and membrane bound molecules, are also linked to the microtubule network, primarily via motor proteins (dynein and kinesins) which are linked, most importantly, to the cytoplasmic filament protein of the nuclear pore complex, Nup358, by the adaptor BicD2. The evidence for such linkages and possible roles in nuclear migration, cell cycle control, nuclear transport and cell architecture are discussed. Copyright © 2017. Published by Elsevier Ltd.

  8. Space Station tethered elevator system

    Science.gov (United States)

    Haddock, Michael H.; Anderson, Loren A.; Hosterman, K.; Decresie, E.; Miranda, P.; Hamilton, R.

    1989-01-01

    The optimized conceptual engineering design of a space station tethered elevator is presented. The tethered elevator is an unmanned, mobile structure which operates on a ten-kilometer tether spanning the distance between Space Station Freedom and a platform. Its capabilities include providing access to residual gravity levels, remote servicing, and transportation to any point along a tether. The report discusses the potential uses, parameters, and evolution of the spacecraft design. Emphasis is placed on the elevator's structural configuration and three major subsystem designs. First, the design of elevator robotics used to aid in elevator operations and tethered experimentation is presented. Second, the design of drive mechanisms used to propel the vehicle is discussed. Third, the design of an onboard self-sufficient power generation and transmission system is addressed.

  9. Neutrophil migration under normal and sepsis conditions.

    Science.gov (United States)

    Lerman, Yelena V; Kim, Minsoo

    2015-01-01

    Neutrophil migration is critical for pathogen clearance and host survival during severe sepsis. Interaction of neutrophil adhesion receptors with ligands on endothelial cells results in firm adhesion of the circulating neutrophils, followed by neutrophil activation and directed migration to sites of infection through the basement membrane and interstitial extracellular matrix. Proteolytic enzymes and reactive oxygen species are produced and released by neutrophils in response to a variety of inflammatory stimuli. Although these mediators are important for host defense, they also promote tissue damage. Excessive neutrophil migration during the early stages of sepsis may lead to an exaggerated inflammatory response with associated tissue damage and subsequent organ dysfunction. On the other hand, dysregulation of migration and insufficient migratory response that occurs during the latter stages of severe sepsis contributes to neutrophils' inability to contain and control infection and impaired wound healing. This review discusses the major steps and associated molecules involved in the balance of neutrophil trafficking, the precise regulation of which during sepsis spells life or death for the host.

  10. Tether Elevator Crawler Systems (TECS)

    Science.gov (United States)

    Swenson, Frank R.

    1987-01-01

    One of the needs of the experimenters on the space station is access to steady and controlled-variation microgravity environments. A method of providing these environments is to place the experiment on a tether attached to the space station. This provides a high degree of isolation from structural oscillations and vibrations. Crawlers can move these experiments along the tethers to preferred locations, much like an elevator. This report describes the motion control laws developed for these crawlers and the testing of laboratory models of these tether elevator crawlers.

  11. Human neutrophils in auto-immunity.

    Science.gov (United States)

    Thieblemont, Nathalie; Wright, Helen L; Edwards, Steven W; Witko-Sarsat, Véronique

    2016-04-01

    Human neutrophils have great capacity to cause tissue damage in inflammatory diseases via their inappropriate activation to release reactive oxygen species (ROS), proteases and other tissue-damaging molecules. Furthermore, activated neutrophils can release a wide variety of cytokines and chemokines that can regulate almost every element of the immune system. In addition to these important immuno-regulatory processes, activated neutrophils can also release, expose or generate neoepitopes that have the potential to break immune tolerance and result in the generation of autoantibodies, that characterise a number of human auto-immune diseases. For example, in vasculitis, anti-neutrophil cytoplasmic antibodies (ANCA) that are directed against proteinase 3 or myeloperoxidase are neutrophil-derived autoantigens and activated neutrophils are the main effector cells of vascular damage. In other auto-immune diseases, these neutrophil-derived neoepitopes may arise from a number of processes that include release of granule enzymes and ROS, changes in the properties of components of their plasma membrane as a result of activation or apoptosis, and via the release of Neutrophil Extracellular Traps (NETs). NETs are extracellular structures that contain chromatin that is decorated with granule enzymes (including citrullinated proteins) that can act as neo-epitopes to generate auto-immunity. This review therefore describes the processes that can result in neutrophil-mediated auto-immunity, and the role of neutrophils in the molecular pathologies of auto-immune diseases such as vasculitis, rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). We discuss the potential role of NETs in these processes and some of the debate in the literature regarding the role of this phenomenon in microbial killing, cell death and auto-immunity. Copyright © 2016 Elsevier Ltd. All rights reserved.

  12. Neutrophils at work

    DEFF Research Database (Denmark)

    Nauseef, William M; Borregaard, Niels

    2014-01-01

    In this Review we discuss data demonstrating recently recognized aspects of neutrophil homeostasis in the steady state, granulopoiesis in 'emergency' conditions and interactions of neutrophils with the adaptive immune system. We explore in vivo observations of the recruitment of neutrophils from ...

  13. The secret life of tethers: the role of tethering factors in SNARE complex regulation

    Directory of Open Access Journals (Sweden)

    Michelle L Dubuke

    2016-05-01

    Full Text Available Trafficking in eukaryotic cells is a tightly regulated process to ensure correct cargo delivery to the proper destination organelle or plasma membrane. In this review, we focus on how the vesicle fusion machinery, the SNARE complex, is regulated by the interplay of the multisubunit tethering complexes (MTC with the SNAREs and Sec1/Munc18 (SM proteins. Although these factors are used in different stages of membrane trafficking, e.g. Golgi to plasma membrane transport vs vacuolar fusion, and in a variety of diverse eukaryotic cell types, many commonalities between their functions are being revealed. We explore the various protein-protein interactions and findings from functional reconstitution studies in order to highlight both their common features and the differences in their modes of regulation. These studies serve as a starting point for mechanistic explorations in other systems.

  14. Physisorbed Polymer-Tethered Lipid Bilayer with Lipopolymer Gradient

    Directory of Open Access Journals (Sweden)

    Christoph A. Naumann

    2012-11-01

    Full Text Available Physisorbed polymer-tethered lipid bilayers consisting of phospholipids and lipopolymers represent an attractive planar model membrane platform, in which bilayer fluidity and membrane elastic properties can be regulated through lipopolymer molar concentration. Herein we report a method for the fabrication of such a planar model membrane system with a lateral gradient of lipopolymer density. In addition, a procedure is described, which leads to a sharp boundary between regions of low and high lipopolymer molar concentrations. Resulting gradients and sharp boundaries are visualized on the basis of membrane buckling structures at elevated lipopolymer concentrations using epifluorescence microscopy and atomic force microscopy. Furthermore, results from spot photobleaching experiments are presented, which provide insight into the lipid lateral fluidity in these model membrane architectures. The presented experimental data highlight a planar, solid-supported membrane characterized by fascinating length scale-dependent dynamics and elastic properties with remarkable parallels to those observed in cellular membranes.

  15. Experiments and Numerical Simulations of Electrodynamic Tether

    Science.gov (United States)

    Iki, Kentaro; Kawamoto, Satomi; Takahashi, Ayaka; Ishimoto, Tomori; Yanagida, Atsushi; Toda, Susumu

    As an effective means of suppressing space debris growth, the Aerospace Research and Development Directorate of the Japan Aerospace Exploration Agency (JAXA) has been investigating an active space debris removal system that employs highly efficient electrodynamic tether (EDT) technology for orbital transfer. This study investigates tether deployment dynamics by means of on-ground experiments and numerical simulations of an electrodynamic tether system. Some key parameters used in the numerical simulations, such as the elastic modulus and damping ratio of the tether, the spring constant of the coiling of the tether, and deployment friction, must be estimated, and various experiments are conducted to determine these values. As a result, the following values were obtained: The elastic modulus of the tether was 40 GPa, and the damping ratio of the tether was 0.02. The spring constant and the damping ratio of the tether coiling were 10-4 N/m and 0.025 respectively. The deployment friction was 0.038ν + 0.005 N. In numerical simulations using a multiple mass tether model, tethers with lengths of several kilometers are deployed and the attitude dynamics of satellites attached to the end of the tether and tether libration are calculated. As a result, the simulations confirmed successful deployment of the tether with a length of 500 m using the electrodynamic tether system.

  16. Chronic neutrophilic leukemia.

    Science.gov (United States)

    Bredeweg, Arthur; Burch, Micah; Krause, John R

    2018-01-01

    Chronic neutrophilic leukemia is a rare myeloproliferative disorder characterized by a sustained peripheral blood neutrophilia, absence of the BCR/ABL oncoprotein, bone marrow hypercellularity with less than 5% myeloblasts and normal neutrophil maturation, and no dysplasia. This leukemia has been associated with mutations in the colony-stimulating factor 3 receptor (CSF3R) that may activate this receptor, leading to the proliferation of neutrophils that are the hallmark of chronic neutrophilic leukemia. We present a case of chronic neutrophilic leukemia and discuss the criteria for diagnosis and the significance of mutations found in this leukemia.

  17. GROUP B STREPTOCOCCUS CIRCUMVENTS NEUTROPHILS AND NEUTROPHIL EXTRACELLULAR TRAPS DURING AMNIOTIC CAVITY INVASION AND PRETERM LABOR

    Science.gov (United States)

    Boldenow, Erica; Gendrin, Claire; Ngo, Lisa; Bierle, Craig; Vornhagen, Jay; Coleman, Michelle; Merillat, Sean; Armistead, Blair; Whidbey, Christopher; Alishetti, Varchita; Santana-Ufret, Veronica; Ogle, Jason; Gough, Michael; Srinouanprachanh, Sengkeo; MacDonald, James W; Bammler, Theo K; Bansal, Aasthaa; Liggitt, H. Denny; Rajagopal, Lakshmi; Waldorf, Kristina M Adams

    2016-01-01

    Preterm birth is a leading cause of neonatal morbidity and mortality. Although microbial invasion of the amniotic cavity (MIAC) is associated with the majority of early preterm births, the temporal events that occur during MIAC and preterm labor are not known. Group B Streptococci (GBS) are β-hemolytic, gram-positive bacteria, which commonly colonize the vagina but have been recovered from the amniotic fluid in preterm birth cases. To understand temporal events that occur during MIAC, we utilized a unique chronically catheterized nonhuman primate model that closely emulates human pregnancy. This model allows monitoring of uterine contractions, timing of MIAC and immune responses during pregnancy-associated infections. Here, we show that adverse outcomes such as preterm labor, MIAC, and fetal sepsis were observed more frequently during infection with hemolytic GBS when compared to nonhemolytic GBS. Although MIAC was associated with systematic progression in chorioamnionitis beginning with chorionic vasculitis and progressing to neutrophilic infiltration, the ability of the GBS hemolytic pigment toxin to induce neutrophil cell death and subvert killing by neutrophil extracellular traps (NETs) in placental membranes in vivo facilitated MIAC and fetal injury. Furthermore, compared to maternal neutrophils, fetal neutrophils exhibit decreased neutrophil elastase activity and impaired phagocytic functions to GBS. Collectively, our studies demonstrate how a unique bacterial hemolytic lipid toxin enables GBS to circumvent neutrophils and NETs in placental membranes to induce fetal injury and preterm labor. PMID:27819066

  18. Neutrophils in critical illness.

    Science.gov (United States)

    McDonald, Braedon

    2018-03-01

    During critical illness, dramatic alterations in neutrophil biology are observed including abnormalities of granulopoeisis and lifespan, cell trafficking and antimicrobial effector functions. As a result, neutrophils transition from powerful antimicrobial protectors into dangerous mediators of tissue injury and organ dysfunction. In this article, the role of neutrophils in the pathogenesis of critical illness (sepsis, trauma, burns and others) will be explored, including pathological changes to neutrophil function during critical illness and the utility of monitoring aspects of the neutrophil phenotype as biomarkers for diagnosis and prognostication. Lastly, we review findings from clinical trials of therapies that target the harmful effects of neutrophils, providing a bench-to-bedside perspective on neutrophils in critical illness.

  19. Vesicle fusion observed by content transfer across a tethered lipid bilayer.

    Science.gov (United States)

    Rawle, Robert J; van Lengerich, Bettina; Chung, Minsub; Bendix, Poul Martin; Boxer, Steven G

    2011-10-19

    Synaptic transmission is achieved by exocytosis of small, synaptic vesicles containing neurotransmitters across the plasma membrane. Here, we use a DNA-tethered freestanding bilayer as a target architecture that allows observation of content transfer of individual vesicles across the tethered planar bilayer. Tethering and fusion are mediated by hybridization of complementary DNA-lipid conjugates inserted into the two membranes, and content transfer is monitored by the dequenching of an aqueous content dye. By analyzing the diffusion profile of the aqueous dye after vesicle fusion, we are able to distinguish content transfer across the tethered bilayer patch from vesicle leakage above the patch. Copyright © 2011 Biophysical Society. Published by Elsevier Inc. All rights reserved.

  20. Tether applications for space station

    Science.gov (United States)

    Nobles, W.

    1986-01-01

    A wide variety of space station applications for tethers were reviewed. Many will affect the operation of the station itself while others are in the category of research or scientific platforms. One of the most expensive aspects of operating the space station will be the continuing shuttle traffic to transport logistic supplies and payloads to the space station. If a means can be found to use tethers to improve the efficiency of that transportation operation, it will increase the operating efficiency of the system and reduce the overall cost of the space station. The concept studied consists of using a tether to lower the shuttle from the space station. This results in a transfer of angular momentum and energy from the orbiter to the space station. The consequences of this transfer is studied and how beneficial use can be made of it.

  1. The Tethered Moon

    Science.gov (United States)

    Zahnle, Kevin; Lupu, Roxana Elena; Dubrovolskis, A. R.

    2014-01-01

    that the Moon's orbit evolves is limited by the modest radiative cooling rate of Earth's atmosphere, which in effect tethers the Moon to the Earth. Consequently the Moon's orbit evolves orders of magnitude more slowly than in conventional models. Slow orbital evolution promotes capture by orbital resonances that may have been important in the Earth-Moon system

  2. Enabling Tethered Exploration on Mars, Phase I

    Data.gov (United States)

    National Aeronautics and Space Administration — Strong science motivations exist for exploring hard to reach terrain on Mars and the leading systems proposed to do so require tethers. While tethers are used...

  3. Selected Tether Applications Cost Model

    Science.gov (United States)

    Keeley, Michael G.

    1988-01-01

    Diverse cost-estimating techniques and data combined into single program. Selected Tether Applications Cost Model (STACOM 1.0) is interactive accounting software tool providing means for combining several independent cost-estimating programs into fully-integrated mathematical model capable of assessing costs, analyzing benefits, providing file-handling utilities, and putting out information in text and graphical forms to screen, printer, or plotter. Program based on Lotus 1-2-3, version 2.0. Developed to provide clear, concise traceability and visibility into methodology and rationale for estimating costs and benefits of operations of Space Station tether deployer system.

  4. Atmospheric Electricity and Tethered Aerostats, Volume 1

    Science.gov (United States)

    1976-05-11

    CATALOG NUMBER AFETR -TR-76-07 __ 4. TITLE (and Subtitle) -. TYPE OF REPORT & PERIOD COVERED ATMOSPHERIC ELECTRICITY AND TETHERED AEROSTATS, FINAL. 1...Electricity Faraday Capes Balloons Lightning Effects , Protection, Warning Systems Conducting and Non-Conducting ’Tethers Potential Geadient Anomalies...and identifying feasible protective systems. After a brief introductory section math models of effects of tethered balloons on surrounding

  5. Swell activated chloride channel function in human neutrophils

    Energy Technology Data Exchange (ETDEWEB)

    Salmon, Michael D. [Leukocyte and Ion Channel Research Laboratory, School of Health and Biosciences, University of East London, Stratford Campus, London E15 4LZ (United Kingdom); Ahluwalia, Jatinder, E-mail: j.ahluwalia@uel.ac.uk [Leukocyte and Ion Channel Research Laboratory, School of Health and Biosciences, University of East London, Stratford Campus, London E15 4LZ (United Kingdom)

    2009-04-17

    Non-excitable cells such as neutrophil granulocytes are the archetypal inflammatory immune cell involved in critical functions of the innate immune system. The electron current generated (I{sub e}) by the neutrophil NADPH oxidase is electrogenic and rapidly depolarises the membrane potential. For continuous function of the NADPH oxidase, I{sub e} has to be balanced to preserve electroneutrality, if not; sufficient depolarisation would prevent electrons from leaving the cell and neutrophil function would be abrogated. Subsequently, the depolarisation generated by the neutrophil NADPH oxidase I{sub e} must be counteracted by ion transport. The finding that depolarisation required counter-ions to compensate electron transport was followed by the observation that chloride channels activated by swell can counteract the NADPH oxidase membrane depolarisation. In this mini review, we discuss the research findings that revealed the essential role of swell activated chloride channels in human neutrophil function.

  6. Mitochondria in neutrophil apoptosis

    NARCIS (Netherlands)

    van Raam, B. J.; Verhoeven, A. J.; Kuijpers, T. W.

    2006-01-01

    Central in the regulation of the short life span of neutrophils are their mitochondria. These organelles hardly contribute to the energy status of neutrophils but play a vital role in the apoptotic process. Not only do the mitochondria contain cytotoxic proteins that are released during apoptosis

  7. Tethered Satellite System Contingency Investigation Board

    Science.gov (United States)

    1992-11-01

    The Tethered Satellite System (TSS-1) was launched aboard the Space Shuttle Atlantis (STS-46) on July 31, 1992. During the attempted on-orbit operations, the Tethered Satellite System failed to deploy successfully beyond 256 meters. The satellite was retrieved successfully and was returned on August 6, 1992. The National Aeronautics and Space Administration (NASA) Associate Administrator for Space Flight formed the Tethered Satellite System (TSS-1) Contingency Investigation Board on August 12, 1992. The TSS-1 Contingency Investigation Board was asked to review the anomalies which occurred, to determine the probable cause, and to recommend corrective measures to prevent recurrence. The board was supported by the TSS Systems Working group as identified in MSFC-TSS-11-90, 'Tethered Satellite System (TSS) Contingency Plan'. The board identified five anomalies for investigation: initial failure to retract the U2 umbilical; initial failure to flyaway; unplanned tether deployment stop at 179 meters; unplanned tether deployment stop at 256 meters; and failure to move tether in either direction at 224 meters. Initial observations of the returned flight hardware revealed evidence of mechanical interference by a bolt with the level wind mechanism travel as well as a helical shaped wrap of tether which indicated that the tether had been unwound from the reel beyond the travel by the level wind mechanism. Examination of the detailed mission events from flight data and mission logs related to the initial failure to flyaway and the failure to move in either direction at 224 meters, together with known preflight concerns regarding slack tether, focused the assessment of these anomalies on the upper tether control mechanism. After the second meeting, the board requested the working group to complete and validate a detailed integrated mission sequence to focus the fault tree analysis on a stuck U2 umbilical, level wind mechanical interference, and slack tether in upper tether

  8. Two-Way Tether Gun

    Science.gov (United States)

    Sanger, George F.

    1994-01-01

    Safety-tether device enables crewmembers on spacecraft to retrieve crewmember drifting away from spacecraft. Alternatively, drifting crewmember who carries device uses it to grasp and return to spacecraft. Also used on Earth. For example, rescuer on vessel or pier uses it to retrieve and haul drowning or unconscious person to safety; drifting person or rescuer in water uses it to grasp and hold onto support.

  9. Space Environmental Effects on Coated Tether Materials

    Science.gov (United States)

    Gittemeier, Keith A.; Hawk, Clark W.; Finckenor, Miria M.; Watts, Ed

    2005-01-01

    The University of Alabama in Huntsville s Propulsion Research Center has teamed with NASA's Marshall Space Flight Center (MSFC) to research the effects of atomic oxygen (AO) bombardment on coated tether materials. Tethers Unlimited Inc. has provided several candidate tether materials with various coatings for AO exposure in MSFC s Atomic Oxygen Beam Facility. Additional samples were exposed to ultraviolet (UV) radiation at MSFC. AO erodes most organic materials, and ultraviolet radiation embrittles polymers. This test series was performed to determine the effect of AO and UV on the mechanical integrity of tether materials that were treated with AO-protective coatings, such as polyhedral oligomeric silsesquioxane (POSS) or metallization. Both TUI's Multi-Application Survivable Tether (MAST) Experiment and Marshall Space Flight Center s Momentum Exchange Electrodynamic Reboost (MXER) programs will benefit from this research by helping to determine tether materials and coatings that give the longest life with the lowest mass penalty.

  10. Atmospheric Electricity and Tethered Aerostats, Volume 2

    Science.gov (United States)

    1976-05-11

    EASTERN TEST RANGE PATRICK AIR FORCE BASE, FLORIDA 11 MAY 1976 028 099 AFETR -TR-76-07 ATMOSPHERIC ELECTRICITY AND ~TETHERED AEROSTATS, VOLUME 11 Range...number) Atmospheric Electricity Lightning- Effects , Protection, Warning Balloons Systems Conducting & Nonconducting Tethers Potential Gradient Anomalies...if necessary and Identify by block number) Part A, "Atmospheric Electrical Effects of and on Tethered Balloon Systems," by Latham includes airborne

  11. Autophagy Primes Neutrophils for Neutrophil Extracellular Trap Formation during Sepsis.

    Science.gov (United States)

    Park, So Young; Shrestha, Sanjeeb; Youn, Young-Jin; Kim, Jun-Kyu; Kim, Shin-Yeong; Kim, Hyun Jung; Park, So-Hee; Ahn, Won-Gyun; Kim, Shin; Lee, Myung Goo; Jung, Ki-Suck; Park, Yong Bum; Mo, Eun-Kyung; Ko, Yousang; Lee, Suh-Young; Koh, Younsuck; Park, Myung Jae; Song, Dong-Keun; Hong, Chang-Won

    2017-09-01

    Neutrophils are key effectors in the host's immune response to sepsis. Excessive stimulation or dysregulated neutrophil functions are believed to be responsible for sepsis pathogenesis. However, the mechanisms regulating functional plasticity of neutrophils during sepsis have not been fully determined. We investigated the role of autophagy in neutrophil functions during sepsis in patients with community-acquired pneumonia. Neutrophils were isolated from patients with sepsis and stimulated with phorbol 12-myristate 13-acetate (PMA). The levels of reactive oxygen species generation, neutrophil extracellular trap (NET) formation, and granule release, and the autophagic status were evaluated. The effect of neutrophil autophagy augmentation was further evaluated in a mouse model of sepsis. Neutrophils isolated from patients who survived sepsis showed an increase in autophagy induction, and were primed for NET formation in response to subsequent PMA stimulation. In contrast, neutrophils isolated from patients who did not survive sepsis showed dysregulated autophagy and a decreased response to PMA stimulation. The induction of autophagy primed healthy neutrophils for NET formation and vice versa. In a mouse model of sepsis, the augmentation of autophagy improved survival via a NET-dependent mechanism. These results indicate that neutrophil autophagy primes neutrophils for increased NET formation, which is important for proper neutrophil effector functions during sepsis. Our study provides important insights into the role of autophagy in neutrophils during sepsis.

  12. Autophagosomal membranes assemble at ER-plasma membrane contact sites.

    Science.gov (United States)

    Nascimbeni, Anna Chiara; Codogno, Patrice; Morel, Etienne

    2017-01-01

    The biogenesis of autophagosome, the double membrane bound organelle related to macro-autophagy, is a complex event requiring numerous key-proteins and membrane remodeling events. Our recent findings identify the extended synaptotagmins, crucial tethers of Endoplasmic Reticulum-plasma membrane contact sites, as key-regulators of this molecular sequence.

  13. Tether dynamics and control results for tethered satellite system's initial flight

    Science.gov (United States)

    Chapel, Jim D.; Flanders, Howard

    The recent Tethered Satellite System-1 (TSS-1) mission has provided a wealth of data concerning the dynamics of tethered systems in space and has demonstrated the effectiveness of operational techniques designed to control these dynamics. In this paper, we review control techniques developed for managing tether dynamics, and discuss the results of using these techniques for the Tethered Satellite System's maiden flight on STS-46. In particular, the flight results of controlling libration dynamics, string dynamics, and slack tether are presented. These results show that tether dynamics can be safely managed. The overall stability of the system was found to be surprisingly good even at relatively short tether lengths. In fact, the system operated in passive mode at a tether length of 256 meters for over 9 hours. Only monitoring of the system was required during this time. Although flight anomalies prevented the planned deployment to 20 km, the extended operations at shorter tether lengths have proven the viability of using tethers in space. These results should prove invaluable in preparing for future missions with tethered objects in space.

  14. Mobile tethering: Overview, perspectives and challengess

    NARCIS (Netherlands)

    Constantinescu, M.; Onur, E.; Durmus, Y.; Nikou, S.; Reuver, M. de; Bouwman, H.; Djurica, M.; Glatz, P.M.

    2014-01-01

    Purpose: The purpose of this paper is to analyze mobile tethering from technological and social perspectives. Mobile tethering allows us to share cellular data connection with others over WiFi, Bluetooth or USB. Although the technology is ready and has promising outcomes, service providers and the

  15. Differential Regulation of Synaptic Vesicle Tethering and Docking by UNC-18 and TOM-1.

    Science.gov (United States)

    Gracheva, Elena O; Maryon, Ed B; Berthelot-Grosjean, Martine; Richmond, Janet E

    2010-01-01

    The assembly of SNARE complexes between syntaxin, SNAP-25 and synaptobrevin is required to prime synaptic vesicles for fusion. Since Munc18 and tomosyn compete for syntaxin interactions, the interplay between these proteins is predicted to be important in regulating synaptic transmission. We explored this possibility, by examining genetic interactions between C. elegans unc-18(Munc18), unc-64(syntaxin) and tom-1(tomosyn). We have previously demonstrated that unc-18 mutants have reduced synaptic transmission, whereas tom-1 mutants exhibit enhanced release. Here we show that the unc-18 mutant release defect is associated with loss of two morphologically distinct vesicle pools; those tethered within 25 nm of the plasma membrane and those docked with the plasma membrane. In contrast, priming defective unc-13 mutants accumulate tethered vesicles, while docked vesicles are greatly reduced, indicating tethering is UNC-18-dependent and occurs in the absence of priming. C. elegans unc-64 mutants phenocopy unc-18 mutants, losing both tethered and docked vesicles, whereas overexpression of open syntaxin preferentially increases vesicle docking, suggesting UNC-18/closed syntaxin interactions are responsible for vesicle tethering. Given the competition between vertebrate tomosyn and Munc18, for syntaxin binding, we hypothesized that C. elegans TOM-1 may inhibit both UNC-18-dependent vesicle targeting steps. Consistent with this hypothesis, tom-1 mutants exhibit enhanced UNC-18 plasma membrane localization and a concomitant increase in both tethered and docked synaptic vesicles. Furthermore, in tom-1;unc-18 double mutants the docked, primed vesicle pool is preferentially rescued relative to unc-18 single mutants. Together these data provide evidence for the differential regulation of two vesicle targeting steps by UNC-18 and TOM-1 through competitive interactions with syntaxin.

  16. Differential regulation of synaptic vesicle tethering and docking by UNC-18 and TOM-1

    Directory of Open Access Journals (Sweden)

    Elena O Gracheva

    2010-10-01

    Full Text Available The assembly of SNARE complexes between syntaxin, SNAP-25 and synaptobrevin is required to prime synaptic vesicles for fusion. Since Munc18 and tomosyn compete for syntaxin interactions, the interplay between these proteins is predicted to be important in regulating synaptic transmission. We explored this possibility, by examining genetic interactions between C. elegans unc-18(Munc18, unc-64(syntaxin and tom-1(tomosyn. We have previously demonstrated that unc-18 mutants have reduced synaptic transmission, whereas tom-1 mutants exhibit enhanced release. Here we show that the unc-18 mutant release defect is associated with loss of two morphologically distinct vesicle pools; those tethered within 25nm of the plasma membrane and those docked with the plasma membrane. In contrast, priming defective unc-13 mutants accumulate tethered vesicles, while docked vesicles are greatly reduced, indicating tethering is UNC-18-dependent and occurs in the absence of priming. C. elegans unc-64 mutants phenocopy unc-18 mutants, losing both tethered and docked vesicles, whereas overexpression of open syntaxin preferentially increases vesicle docking, suggesting UNC-18/closed syntaxin interactions are responsible for vesicle tethering. Given the competition between vertebrate tomosyn and Munc18, for syntaxin binding, we hypothesized that C. elegans TOM-1 may inhibit both UNC-18-dependent vesicle targeting steps. Consistent with this hypothesis, tom-1 mutants exhibit enhanced UNC-18 plasma membrane localization and a concomitant increase in both tethered and docked synaptic vesicles. Furthermore, in tom-1;unc-18 double mutants the docked, primed vesicle pool is preferentially rescued relative to unc-18 single mutants. Together these data provide evidence for the differential regulation of two vesicle targeting steps by UNC-18 and TOM-1 through competitive interactions with syntaxin

  17. Staphylococcus aureus resistance to human defensins and evasion of neutrophil killing via the novel virulence factor MprF is based on modification of membrane lipids with L-lysine

    NARCIS (Netherlands)

    Peschel, A.; Jack, R.W.; Otto, M.; Collins, L.V.; Staubitz, P.; Nicholson, G.; Kalbacher, H.; Nieuwenhuizen, W.F.; Jung, G.; Tarkowski, A.; Kessel, K.P.M. van; Strijp, J.A.G. van

    2001-01-01

    Defensins, antimicrobial peptides of the innate immune system, protect human mucosal epithelia and skin against microbial infections and are produced in large amounts by neutrophils. The bacterial pathogen Staphylococcus aureus is insensitive to defensins by virtue of an unknown resistance

  18. Tethered Lubricants for Small Systems

    Energy Technology Data Exchange (ETDEWEB)

    Lynden A. Archer

    2006-01-09

    The objective of this research project is two-fold. First, to fundamentally understand friction and relaxation dynamics of polymer chains near surfaces; and second, to develop novel self-lubricated substrates suitable for MEMS devices. During the three-year performance period of this study the PI and his students have shown using theory and experiments that systematic introduction of disorder into tethered lubricant coatings (e.g. by using self-assembled monolayer (SAM) mixtures or SAMs with nonlinear, branched architectures) can be used to significantly reduce the friction coefficient of a surface. They have also developed a simple procedure based on dielectric spectroscopy for quantifying the effect of surface disorder on molecular relaxation in lubricant coatings. Details of research accomplishments in each area of the project are described in the body of the report.

  19. Theseus: tethered distributed robotics (TDR)

    Science.gov (United States)

    Digney, Bruce L.; Penzes, Steven G.

    2003-09-01

    The Defence Research and Development Canada's (DRDC) Autonomous Intelligent System's program conducts research to increase the independence and effectiveness of military vehicles and systems. DRDC-Suffield's Autonomous Land Systems (ALS) is creating new concept vehicles and autonomous control systems for use in outdoor areas, urban streets, urban interiors and urban subspaces. This paper will first give an overview of the ALS program and then give a specific description of the work being done for mobility in urban subspaces. Discussed will be the Theseus: Thethered Distributed Robotics (TDR) system, which will not only manage an unavoidable tether but exploit it for mobility and navigation. Also discussed will be the prototype robot called the Hedgehog, which uses conformal 3D mobility in ducts, sewer pipes, collapsed rubble voids and chimneys.

  20. Dynamic multibody modeling for tethered space elevators

    Science.gov (United States)

    Williams, Paul

    2009-08-01

    This paper presents a fundamental modeling strategy for dealing with powered and propelled bodies moving along space tethers. The tether is divided into a large number of discrete masses, which are connected by viscoelastic springs. The tether is subject to the full range of forces expected in Earth orbit in a relatively simple manner. Two different models of the elevator dynamics are presented. In order to capture the effect of the elevator moving along the tether, the elevator dynamics are included as a separate body in both models. One model treats the elevator's motion dynamically, where propulsive and friction forces are applied to the elevator body. The second model treats the elevator's motion kinematically, where the distance along the tether is determined by adjusting the lengths of tether on either side of the elevator. The tether model is used to determine optimal configurations for the space elevator. A modal analysis of two different configurations is presented which show that the fundamental mode of oscillation is a pendular one around the anchor point with a period on the order of 160 h for the in-plane motion, and 24 h for the out-of-plane motion. Numerical simulation results of the effects of the elevator moving along the cable are presented for different travel velocities and different elevator masses.

  1. The space station tethered elevator system

    Science.gov (United States)

    Anderson, Loren A.

    1989-01-01

    The optimized conceptual engineering design of a space station tethered elevator is presented. The elevator is an unmanned mobile structure which operates on a ten kilometer tether spanning the distance between the Space Station and a tethered platform. Elevator capabilities include providing access to residual gravity levels, remote servicing, and transportation to any point along a tether. The potential uses, parameters, and evolution of the spacecraft design are discussed. Engineering development of the tethered elevator is the result of work conducted in the following areas: structural configurations; robotics, drive mechanisms; and power generation and transmission systems. The structural configuration of the elevator is presented. The structure supports, houses, and protects all systems on board the elevator. The implementation of robotics on board the elevator is discussed. Elevator robotics allow for the deployment, retrieval, and manipulation of tethered objects. Robotic manipulators also aid in hooking the elevator on a tether. Critical to the operation of the tethered elevator is the design of its drive mechanisms, which are discussed. Two drivers, located internal to the elevator, propel the vehicle along a tether. These modular components consist of endless toothed belts, shunt-wound motors, regenerative power braking, and computer controlled linear actuators. The designs of self-sufficient power generation and transmission systems are reviewed. Thorough research indicates all components of the elevator will operate under power provided by fuel cells. The fuel cell systems will power the vehicle at seven kilowatts continuously and twelve kilowatts maximally. A set of secondary fuel cells provides redundancy in the unlikely event of a primary system failure. Power storage exists in the form of Nickel-Hydrogen batteries capable of powering the elevator under maximum loads.

  2. Tissue-transglutaminase contributes to neutrophil granulocyte differentiation and functions.

    Science.gov (United States)

    Balajthy, Zoltán; Csomós, Krisztián; Vámosi, György; Szántó, Attila; Lanotte, Michel; Fésüs, László

    2006-09-15

    Promyelocytic NB4 leukemia cells undergo differentiation to granulocytes following retinoic acid treatment. Here we report that tissue transglutaminase (TG2), a protein cross-linking enzyme, was induced, then partially translocated into the nucleus, and became strongly associated with the chromatin during the differentiation process. The transglutaminase-catalyzed cross-link content of both the cytosolic and the nuclear protein fractions increased while NB4 cells underwent cellular maturation. Inhibition of cross-linking activity of TG2 by monodansylcadaverin in these cells led to diminished nitroblue tetrazolium (NBT) positivity, production of less superoxide anion, and decreased expression of GP91PHOX, the membrane-associated subunit of NADPH oxidase. Neutrophils isolated from TG2(-/-) mice showed diminished NBT reduction capacity, reduced superoxide anion formation, and down-regulation of the gp91phox subunit of NADPH oxidase, compared with wild-type cells. It was also observed that TG2(-/-) mice exhibited increased neutrophil phagocytic activity, but had attenuated neutrophil chemotaxis and impaired neutrophil extravasation with higher neutrophil counts in their circulation during yeast extract-induced peritonitis. These results clearly suggest that TG2 may modulate the expression of genes related to neutrophil functions and is involved in several intracellular and extracellular functions of extravasating neutrophil.

  3. Phobos L1 Operational Tether Experiment (PHLOTE)

    Data.gov (United States)

    National Aeronautics and Space Administration — A sensor package that “floats” just above the surface of Phobos, suspended by a tether from a small spacecraft operating at the Mars/Phobos Lagrange 1 (L1) Point...

  4. Numerical modelling of elastic space tethers

    DEFF Research Database (Denmark)

    Kristiansen, Kristian Uldall; Palmer, P. L.; Roberts, R. M.

    2012-01-01

    In this paper the importance of the ill-posedness of the classical, non-dissipative massive tether model on an orbiting tether system is studied numerically. The computations document that via the regularisation of bending resistance a more reliable numerical integrator can be produced. Furthermo....... It is also shown that on the slow manifold the dynamics of the satellites are well-approximated by the finite dimensional slack-spring model....

  5. Trace gas measurements from tethered balloon platforms

    Science.gov (United States)

    Bandy, Alan R.; Bandy, Terese L.; Youngbluth, Otto; Owens, Thomas L.

    1987-01-01

    Instrumentation and chemical sampling and analysis procedures are described for making measurements of atmospheric carbon disulfide in the concentration range 1-1000 pptv from tethered balloon platforms. Results of a study on the CS2 composition of air downward of a saltwater marsh are reported. A method for obtaining the necessary data for solving the budget equations for surface fluxes, chemical formation rates and chemical destruction rates using data acquired from tethered balloon platforms is presented.

  6. A novel bacterial transport mechanism of Acinetobacter baumannii via activated human neutrophils through interleukin-8.

    Science.gov (United States)

    Kamoshida, Go; Tansho-Nagakawa, Shigeru; Kikuchi-Ueda, Takane; Nakano, Ryuichi; Hikosaka, Kenji; Nishida, Satoshi; Ubagai, Tsuneyuki; Higashi, Shouichi; Ono, Yasuo

    2016-12-01

    Hospital-acquired infections as a result of Acinetobacter baumannii have become problematic because of high rates of drug resistance. Although neutrophils play a critical role in early protection against bacterial infection, their interactions with A. baumannii remain largely unknown. To elucidate the interactions between A. baumannii and human neutrophils, we cocultured these cells and analyzed them by microscopy and flow cytometry. We found that A. baumannii adhered to neutrophils. We next examined neutrophil and A. baumannii infiltration into Matrigel basement membranes by an in vitro transmigration assay. Neutrophils were activated by A. baumannii, and invasion was enhanced. More interestingly, A. baumannii was transported together by infiltrating neutrophils. Furthermore, we observed by live cell imaging that A. baumannii and neutrophils moved together. In addition, A. baumannii-activated neutrophils showed increased IL-8 production. The transport of A. baumannii was suppressed by inhibiting neutrophil infiltration by blocking the effect of IL-8. A. baumannii appears to use neutrophils for transport by activating these cells via IL-8. In this study, we revealed a novel bacterial transport mechanism that A. baumannii exploits human neutrophils by adhering to and inducing IL-8 release for bacterial portage. This mechanism might be a new treatment target. © Society for Leukocyte Biology.

  7. Brownian motion of tethered nanowires.

    Science.gov (United States)

    Ota, Sadao; Li, Tongcang; Li, Yimin; Ye, Ziliang; Labno, Anna; Yin, Xiaobo; Alam, Mohammad-Reza; Zhang, Xiang

    2014-05-01

    Brownian motion of slender particles near a boundary is ubiquitous in biological systems and in nanomaterial assembly, but the complex hydrodynamic interaction in those systems is still poorly understood. Here, we report experimental and computational studies of the Brownian motion of silicon nanowires tethered on a substrate. An optical interference method enabled direct observation of microscopic rotations of the slender bodies in three dimensions with high angular and temporal resolutions. This quantitative observation revealed anisotropic and angle-dependent hydrodynamic wall effects: rotational diffusivity in inclined and azimuth directions follows different power laws as a function of the length, ∼ L(-2.5) and ∼ L(-3), respectively, and is more hindered for smaller inclined angles. In parallel, we developed an implicit simulation technique that takes the complex wire-wall hydrodynamic interactions into account efficiently, the result of which agreed well with the experimentally observed angle-dependent diffusion. The demonstrated techniques provide a platform for studying the microrheology of soft condensed matters, such as colloidal and biological systems near interfaces, and exploring the optimal self-assembly conditions of nanostructures.

  8. Cholesterol tethered bioresponsive polycation as a candidate for gene delivery

    Energy Technology Data Exchange (ETDEWEB)

    Zhu Ying [Second Affiliated Hospital, Medical College, Zhejiang University, Hangzhou 310009 (China); Wang Youxiang, E-mail: yx_wang@zju.edu.cn [Department of Polymer Science and Engineering, Zhejiang University, Hangzhou 310027 (China); Key Laboratory of Macromolecular Synthesis and Functionalization, Ministry of Education, Zhejiang University, Hangzhou 310027 (China); Hu Qiaoling; Shen Jiacong [Department of Polymer Science and Engineering, Zhejiang University, Hangzhou 310027 (China); Key Laboratory of Macromolecular Synthesis and Functionalization, Ministry of Education, Zhejiang University, Hangzhou 310027 (China)

    2009-04-30

    The efficient unpacking of viral protein shell gave the inspiration for the synthesized vectors. In this research, novel cholesterol tethered bioresponsive polyethylenimine (PEI) was specially designed via disulfide-containing cross-linker. The cholesterol lipid had proved to increase the permeability of gene vector through cell membrane. The acid-base titration indicated that the synthesized polycation possessed efficient proton sponge effect, which was suggested to increase endosomal release of pDNA complexes into the cytoplasm. The cholesterol tethered polycation could effectively induce DNA condensation and form spherical particles with diameter about 200 nm at N/P ratio of 10. At glutathione concentration of 3 mM, the polyplexes were unpacked due to the bioresponsive cleavage of the disulfide bonds. The in-vitro experiment indicated that the polyplexes showed efficient transfection efficiency to HEK293T cells. All the results indicated that the bioresponsive polycation could be served as an effective trigger to control the release of DNA at the intracellular environment. The novel bioresponsive polycation might have great potential in non-viral gene delivery research and application.

  9. Chemotactic Activity on Human Neutrophils to Streptococcus mutans

    Directory of Open Access Journals (Sweden)

    Tetiana Haniastuti

    2013-07-01

    Full Text Available Objective: The aim of this study was to evaluate chemotactic activity o neutrophil to S. mutans. Chemotaxis assay was performed in blind well chambers. Materials and Methods: Hanks balanced salt solution (HBSS containing 106 S. mutans,  108 S. mutans, 10-8 M fMLP, or HBSS alone were placed in the lower wells of the chamber and covered with polycorbonate membrane filter. Neutrophils suspension (2x105 cells was then placed in the upper compartment. After incubation for 60 mins at 37ºC in a humidified atmosphere with 5% CO2, the filters were removed and stained with Giemsa. Result: ANOVA revealed statistically significant differences among groups (p<0.05, indicating that S. mutans induced neutrophils chemotaxis. The number of neutrophils migration in response to 108 S. mutans and 106 S. mutans were signifiantly greater compared to fMLP (p<0.05. Conclusion: S. mutans may activate human neutrophils, resulting in the chemotaxis of the neutrophils.DOI: 10.14693/jdi.v16i2.99

  10. d(− Lactic Acid-Induced Adhesion of Bovine Neutrophils onto Endothelial Cells Is Dependent on Neutrophils Extracellular Traps Formation and CD11b Expression

    Directory of Open Access Journals (Sweden)

    Pablo Alarcón

    2017-08-01

    Full Text Available Bovine ruminal acidosis is of economic importance as it contributes to reduced milk and meat production. This phenomenon is mainly attributed to an overload of highly fermentable carbohydrate, resulting in increased d(− lactic acid levels in serum and plasma. Ruminal acidosis correlates with elevated acute phase proteins in blood, along with neutrophil activation and infiltration into various tissues leading to laminitis and aseptic polysynovitis. Previous studies in bovine neutrophils indicated that d(− lactic acid decreased expression of L-selectin and increased expression of CD11b to concentrations higher than 6 mM, suggesting a potential role in neutrophil adhesion onto endothelia. The two aims of this study were to evaluate whether d(− lactic acid influenced neutrophil and endothelial adhesion and to trigger neutrophil extracellular trap (NET production (NETosis in exposed neutrophils. Exposure of bovine neutrophils to 5 mM d(− lactic acid elevated NET release compared to unstimulated neutrophil negative controls. Moreover, this NET contains CD11b and histone H4 citrullinated, the latter was dependent on PAD4 activation, a critical enzyme in DNA decondensation and NETosis. Furthermore, NET formation was dependent on d(− lactic acid plasma membrane transport through monocarboxylate transporter 1 (MCT1. d(− lactic acid enhanced neutrophil adhesion onto endothelial sheets as demonstrated by in vitro neutrophil adhesion assays under continuous physiological flow conditions, indicating that cell adhesion was a NET- and a CD11b/ICAM-1-dependent process. Finally, d(− lactic acid was demonstrated for the first time to trigger NETosis in a PAD4- and MCT1-dependent manner. Thus, d(− lactic acid-mediated neutrophil activation may contribute to neutrophil-derived pro-inflammatory processes, such as aseptic laminitis and/or polysynovitis in animals suffering acute ruminal acidosis.

  11. α-1 Antitrypsin regulates human neutrophil chemotaxis induced by soluble immune complexes and IL-8.

    LENUS (Irish Health Repository)

    Bergin, David A

    2010-12-01

    Hereditary deficiency of the protein α-1 antitrypsin (AAT) causes a chronic lung disease in humans that is characterized by excessive mobilization of neutrophils into the lung. However, the reason for the increased neutrophil burden has not been fully elucidated. In this study we have demonstrated using human neutrophils that serum AAT coordinates both CXCR1- and soluble immune complex (sIC) receptor-mediated chemotaxis by divergent pathways. We demonstrated that glycosylated AAT can bind to IL-8 (a ligand for CXCR1) and that AAT-IL-8 complex formation prevented IL-8 interaction with CXCR1. Second, AAT modulated neutrophil chemotaxis in response to sIC by controlling membrane expression of the glycosylphosphatidylinositol-anchored (GPI-anchored) Fc receptor FcγRIIIb. This process was mediated through inhibition of ADAM-17 enzymatic activity. Neutrophils isolated from clinically stable AAT-deficient patients were characterized by low membrane expression of FcγRIIIb and increased chemotaxis in response to IL-8 and sIC. Treatment of AAT-deficient individuals with AAT augmentation therapy resulted in increased AAT binding to IL-8, increased AAT binding to the neutrophil membrane, decreased FcγRIIIb release from the neutrophil membrane, and normalization of chemotaxis. These results provide new insight into the mechanism underlying the effect of AAT augmentation therapy in the pulmonary disease associated with AAT deficiency.

  12. The investigation of tethered satellite system dynamics

    Science.gov (United States)

    Lorenzini, E. C.

    1986-01-01

    The analysis of the rotational dynamics of the satellite was focused on the rotational amplitude increase of the satellite, with respect to the tether, during retrieval. The dependence of the rotational amplitude upon the tether tension variation to the power 1/4 was thoroughly investigated. The damping of rotational oscillations achievable by reel control was also quantified while an alternative solution that makes use of a lever arm attached with a universal joint to the satellite was proposed. Comparison simulations between the Smithsonian Astrophysical Observatory and the Martin Marietta (MMA) computer code of reteival maneuvers were also carried out. The agreement between the two, completely independent, codes was extremely close, demonstrating the reliability of the models. The slack tether dynamics during reel jams was analytically investigated in order to identify the limits of applicability of the SLACK3 computer code to this particular case. Test runs with SLACK3 were also carried out.

  13. The PROPEL Electrodynamic Tether Demonstration Mission

    Science.gov (United States)

    Bilen, Sven G.; Johnson, C. Les; Wiegmann, Bruce M.; Alexander, Leslie; Gilchrist, Brian E.; Hoyt, Robert P.; Elder, Craig H.; Fuhrhop, Keith P.; Scadera, Michael

    2012-01-01

    The PROPEL ("Propulsion using Electrodynamics") mission will demonstrate the operation of an electrodynamic tether propulsion system in low Earth orbit and advance its technology readiness level for multiple applications. The PROPEL mission has two primary objectives: first, to demonstrate the capability of electrodynamic tether technology to provide robust and safe, near-propellantless propulsion for orbit-raising, de-orbit, plane change, and station keeping, as well as to perform orbital power harvesting and formation flight; and, second, to fully characterize and validate the performance of an integrated electrodynamic tether propulsion system, qualifying it for infusion into future multiple satellite platforms and missions with minimal modification. This paper provides an overview of the PROPEL system and design reference missions; mission goals and required measurements; and ongoing PROPEL mission design efforts.

  14. Tension waves in tethered satellite cables

    Science.gov (United States)

    Lallman, F. J.

    1984-01-01

    A one-degree-of-freedom simulation of the Tethered Satellite System (TSS) was programmed using a distributed system model of the tether based on the one-dimensional wave equation. This model represents the time varying tension profile along the tether as the sum of two traveling waves of tension moving in opposite directions. A control loop was devised which combines a deployment rate command with the measured tension at the deployer to produce a smooth, stable rate of deployment of the subsatellite. Simulation results show a buildup of periodic bursts of high frequency oscillation in tension. This report covers the mathematical modelling and simulation results and explains the reason for the observed oscillations. The design of a possible vibration damping device is discussed.

  15. Neutrophil extracellular traps - the dark side of neutrophils

    DEFF Research Database (Denmark)

    Sørensen, Ole E.; Borregaard, Niels

    2016-01-01

    Neutrophil extracellular traps (NETs) were discovered as extracellular strands of decondensed DNA in complex with histones and granule proteins, which were expelled from dying neutrophils to ensnare and kill microbes. NETs are formed during infection in vivo by mechanisms different from those ori...

  16. NASA Langley Research Center tethered balloon systems

    Science.gov (United States)

    Owens, Thomas L.; Storey, Richard W.; Youngbluth, Otto

    1987-01-01

    The NASA Langley Research Center tethered balloon system operations are covered in this report for the period of 1979 through 1983. Meteorological data, ozone concentrations, and other data were obtained from in situ measurements. The large tethered balloon had a lifting capability of 30 kilograms to 2500 meters. The report includes descriptions of the various components of the balloon systems such as the balloons, the sensors, the electronics, and the hardware. Several photographs of the system are included as well as a list of projects including the types of data gathered.

  17. Immunosenescence of Polymorphonuclear Neutrophils

    Directory of Open Access Journals (Sweden)

    Inga Wessels

    2010-01-01

    Full Text Available All immune cells are affected by aging, contributing to the high susceptibility to infections and increased mortality observed in the elderly. The effect of aging on cells of the adaptive immune system is well documented. In contrast, knowledge concerning age-related defects of polymorphonuclear neutrophils (PMN is limited. During the past decade, it has become evident that in addition to their traditional role as phagocytes, neutrophils are able to secrete a wide array of immunomodulating molecules. Their importance is underlined by the finding that genetic defects that lead to neutropenia increase susceptibility to infections. Whereas there is consistence about the constant circulating number of PMN throughout aging, the abilities of tissue infiltration, phagocytosis, and oxidative burst of PMN from aged donors are discussed controversially. Furthermore, there are numerous discrepancies between in vivo and in vitro results, as well as between results for murine and human PMN. Most of the reported functional changes can be explained by defective signaling pathways, but further research is required to get a detailed insight into the underlying molecular mechanisms. This could form the basis for drug development in order to prevent or treat age-related diseases, and thus to unburden the public health systems.

  18. Otolith tethering in the zebrafish otic vesicle requires Otogelin and α-Tectorin.

    Science.gov (United States)

    Stooke-Vaughan, Georgina A; Obholzer, Nikolaus D; Baxendale, Sarah; Megason, Sean G; Whitfield, Tanya T

    2015-03-15

    Otoliths are biomineralised structures important for balance and hearing in fish. Their counterparts in the mammalian inner ear, otoconia, have a primarily vestibular function. Otoliths and otoconia form over sensory maculae and are attached to the otolithic membrane, a gelatinous extracellular matrix that provides a physical coupling between the otolith and the underlying sensory epithelium. In this study, we have identified two proteins required for otolith tethering in the zebrafish ear, and propose that there are at least two stages to this process: seeding and maintenance. The initial seeding step, in which otolith precursor particles tether directly to the tips of hair cell kinocilia, fails to occur in the einstein (eis) mutant. The gene disrupted in eis is otogelin (otog); mutations in the human OTOG gene have recently been identified as causative for deafness and vestibular dysfunction (DFNB18B). At later larval stages, maintenance of otolith tethering to the saccular macula is dependent on tectorin alpha (tecta) function, which is disrupted in the rolling stones (rst) mutant. α-Tectorin (Tecta) is a major constituent of the tectorial membrane in the mammalian cochlea. Mutations in the human TECTA gene can cause either dominant (DFNA8/12) or recessive (DFNB21) forms of deafness. Our findings indicate that the composition of extracellular otic membranes is highly conserved between mammals and fish, reinforcing the view that the zebrafish is an excellent model system for the study of deafness and vestibular disease. © 2015. Published by The Company of Biologists Ltd.

  19. Ionic-Liquid-Tethered Nanoparticles: Hybrid Electrolytes

    KAUST Repository

    Moganty, Surya S.

    2010-10-22

    A new class of solventless electrolytes was created by tethering ionic liquids to hard inorganic ZrO2 nanostructures (see picture; NIM=nanoscale ionic material). These hybrid fluids exhibit exceptional redox stability windows, excellent thermal stability, good lithium transference numbers, long-term interfacial stability in the presence of a lithium anode and, when doped with lithium salt, reasonable ionic conductivities.

  20. Cooperative networks : The mobile tethering game

    NARCIS (Netherlands)

    Constantinescu, M.; Bouwman, H.; Djurica, M.; Durmus, Y.; Onur, E.; Reuver, M. de

    2012-01-01

    We propose an analysis of cooperation for data sharing and the behavioral aspects involved in the process of decision making. Starting with the tethering capabilities of recent devices we apply game theoretical principles and models, inquire what makes the cooperation work, and what are the

  1. Tethered "kiteplane" design for the Laddermill project

    NARCIS (Netherlands)

    Breukels, J.; Ockels, W.

    2005-01-01

    The Laddermill is an innovative concept for generating energy from wind using large kite-like wings on a tether. The wings are able to fly in both the regime of airplanes and kites. We therefore call these structures "kiteplanes". By providing a recurring motion with a large lift during ascending

  2. STICS: surface-tethered iterative carbohydrate synthesis.

    Science.gov (United States)

    Pornsuriyasak, Papapida; Ranade, Sneha C; Li, Aixiao; Parlato, M Cristina; Sims, Charles R; Shulga, Olga V; Stine, Keith J; Demchenko, Alexei V

    2009-04-14

    A new surface-tethered iterative carbohydrate synthesis (STICS) technology is presented in which a surface functionalized 'stick' made of chemically stable high surface area porous gold allows one to perform cost efficient and simple synthesis of oligosaccharide chains; at the end of the synthesis, the oligosaccharide can be cleaved off and the stick reused for subsequent syntheses.

  3. Calculating Payload for a Tethered Balloon System

    Science.gov (United States)

    Charles D. Tangren

    1980-01-01

    A graph method to calculate payload for a tethered balloon system, with the supporting helium lift and payload equations. is described. The balloon system is designed to collect emissions data during the convective-lift and no-convective-lift phases of a forest fire. A description of the balloon system and a list of factors affecting balloon selection are included....

  4. Tethered Aerostat Effects on Nearby Seismometers

    Energy Technology Data Exchange (ETDEWEB)

    Bowman, Daniel [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States)

    2017-12-01

    This report assesses seismic interference generated by a tethered aerostat. The study was motivated by a planned aerostat deployment within the footprint of the Dry Alluvium Geology seismic network. No evidence was found for seismic interference generated by the aerostat, and thus the e ects on the Dry Alluvium Geology sensors will be negligible.

  5. Targeting neutrophilic inflammation in severe neutrophilic asthma : can we target the disease-relevant neutrophil phenotype?

    NARCIS (Netherlands)

    Bruijnzeel, Piet L B; Uddin, Mohib; Koenderman, Leo

    2015-01-01

    In severe, neutrophilic asthma, neutrophils are thought to have an important role in both the maintenance of the disease and during exacerbations. These patients often display excessive, mucosal airway inflammation with unresolving neutrophilia. Because this variant of asthma is poorly controlled by

  6. Transitions of tethered chain molecules under tension.

    Science.gov (United States)

    Luettmer-Strathmann, Jutta; Binder, Kurt

    2014-09-21

    An applied tension force changes the equilibrium conformations of a polymer chain tethered to a planar substrate and thus affects the adsorption transition as well as the coil-globule and crystallization transitions. Conversely, solvent quality and surface attraction are reflected in equilibrium force-extension curves that can be measured in experiments. To investigate these effects theoretically, we study tethered chains under tension with Wang-Landau simulations of a bond-fluctuation lattice model. Applying our model to pulling experiments on biological molecules we obtain a good description of experimental data in the intermediate force range, where universal features dominate and finite size effects are small. For tethered chains in poor solvent, we observe the predicted two-phase coexistence at transitions from the globule to stretched conformations and also discover direct transitions from crystalline to stretched conformations. A phase portrait for finite chains constructed by evaluating the density of states for a broad range of solvent conditions and tensions shows how increasing tension leads to a disappearance of the globular phase. For chains in good solvents tethered to hard and attractive surfaces we find the predicted scaling with the chain length in the low-force regime and show that our results are well described by an analytical, independent-bond approximation for the bond-fluctuation model for the highest tensions. Finally, for a hard or slightly attractive surface the stretching of a tethered chain is a conformational change that does not correspond to a phase transition. However, when the surface attraction is sufficient to adsorb a chain it will undergo a desorption transition at a critical value of the applied force. Our results for force-induced desorption show the transition to be discontinuous with partially desorbed conformations in the coexistence region.

  7. TMBM: Tethered Micro-Balloons on Mars

    Science.gov (United States)

    Sims, M. H.; Greeley, R.; Cutts, J. A.; Yavrouian, A. H.; Murbach, M.

    2000-01-01

    The use of balloons/aerobots on Mars has been under consideration for many years. Concepts include deployment during entry into the atmosphere from a carrier spacecraft, deployment from a lander, use of super-pressurized systems for long duration flights, 'hot-air' systems, etc. Principal advantages include the ability to obtain high-resolution data of the surface because balloons provide a low-altitude platform which moves relatively slowly. Work conducted within the last few years has removed many of the technical difficulties encountered in deployment and operation of balloons/aerobots on Mars. The concept proposed here (a tethered balloon released from a lander) uses a relatively simple approach which would enable aspects of Martian balloons to be tested while providing useful and potentially unique science results. Tethered Micro-Balloons on Mars (TMBM) would be carried to Mars on board a future lander as a stand-alone experiment having a total mass of one to two kilograms. It would consist of a helium balloon of up to 50 cubic meters that is inflated after landing and initially tethered to the lander. Its primary instrumentation would be a camera that would be carried to an altitude of up to tens of meters above the surface. Imaging data would be transmitted to the lander for inclusion in the mission data stream. The tether would be released in stages allowing different resolutions and coverage. In addition during this staged release a lander camera system may observe the motion of the balloon at various heights above he lander. Under some scenarios upon completion of the primary phase of TMBM operations, the tether would be cut, allowing TMBM to drift away from the landing site, during which images would be taken along the ground.

  8. Membrane Contact Sites: Complex Zones for Membrane Association and Lipid Exchange

    Science.gov (United States)

    Quon, Evan; Beh, Christopher T.

    2015-01-01

    Lipid transport between membranes within cells involves vesicle and protein carriers, but as agents of nonvesicular lipid transfer, the role of membrane contact sites has received increasing attention. As zones for lipid metabolism and exchange, various membrane contact sites mediate direct associations between different organelles. In particular, membrane contact sites linking the plasma membrane (PM) and the endoplasmic reticulum (ER) represent important regulators of lipid and ion transfer. In yeast, cortical ER is stapled to the PM through membrane-tethering proteins, which establish a direct connection between the membranes. In this review, we consider passive and facilitated models for lipid transfer at PM–ER contact sites. Besides the tethering proteins, we examine the roles of an additional repertoire of lipid and protein regulators that prime and propagate PM–ER membrane association. We conclude that instead of being simple mediators of membrane association, regulatory components of membrane contact sites have complex and multilayered functions. PMID:26949334

  9. Anti-neutrophil cytoplasmic antibodies stimulate release of neutrophil microparticles.

    LENUS (Irish Health Repository)

    Hong, Ying

    2012-01-01

    The mechanisms by which anti-neutrophil cytoplasmic antibodies (ANCAs) may contribute to the pathogenesis of ANCA-associated vasculitis are not well understood. In this study, both polyclonal ANCAs isolated from patients and chimeric proteinase 3-ANCA induced the release of neutrophil microparticles from primed neutrophils. These microparticles expressed a variety of markers, including the ANCA autoantigens proteinase 3 and myeloperoxidase. They bound endothelial cells via a CD18-mediated mechanism and induced an increase in endothelial intercellular adhesion molecule-1 expression, production of endothelial reactive oxygen species, and release of endothelial IL-6 and IL-8. Removal of the neutrophil microparticles by filtration or inhibition of reactive oxygen species production with antioxidants abolished microparticle-mediated endothelial activation. In addition, these microparticles promoted the generation of thrombin. In vivo, we detected more neutrophil microparticles in the plasma of children with ANCA-associated vasculitis compared with that in healthy controls or those with inactive vasculitis. Taken together, these results support a role for neutrophil microparticles in the pathogenesis of ANCA-associated vasculitis, potentially providing a target for future therapeutics.

  10. Neutrophil programming dynamics and its disease relevance.

    Science.gov (United States)

    Ran, Taojing; Geng, Shuo; Li, Liwu

    2017-11-01

    Neutrophils are traditionally considered as first responders to infection and provide antimicrobial host defense. However, recent advances indicate that neutrophils are also critically involved in the modulation of host immune environments by dynamically adopting distinct functional states. Functionally diverse neutrophil subsets are increasingly recognized as critical components mediating host pathophysiology. Despite its emerging significance, molecular mechanisms as well as functional relevance of dynamically programmed neutrophils remain to be better defined. The increasing complexity of neutrophil functions may require integrative studies that address programming dynamics of neutrophils and their pathophysiological relevance. This review aims to provide an update on the emerging topics of neutrophil programming dynamics as well as their functional relevance in diseases.

  11. Cholesterol-Induced Buckling in Physisorbed Polymer-Tethered Lipid Monolayers

    Directory of Open Access Journals (Sweden)

    Christoph A. Naumann

    2013-04-01

    Full Text Available The influence of cholesterol concentration on the formation of buckling structures is studied in a physisorbed polymer-tethered lipid monolayer system using epifluorescence microscopy (EPI and atomic force microscopy (AFM. The monolayer system, built using the Langmuir-Blodgett (LB technique, consists of 3 mol % poly(ethylene glycol (PEG lipopolymers and various concentrations of the phospholipid, 1-stearoyl-2-oleoyl-sn-glycero-3-phosphocholine (SOPC, and cholesterol (CHOL. In the absence of CHOL, AFM micrographs show only occasional buckling structures, which is caused by the presence of the lipopolymers in the monolayer. In contrast, a gradual increase of CHOL concentration in the range of 0–40 mol % leads to fascinating film stress relaxation phenomena in the form of enhanced membrane buckling. Buckling structures are moderately deficient in CHOL, but do not cause any notable phospholipid-lipopolymer phase separation. Our experiments demonstrate that membrane buckling in physisorbed polymer-tethered membranes can be controlled through CHOL-mediated adjustment of membrane elastic properties. They further show that CHOL may have a notable impact on molecular confinement in the presence of crowding agents, such as lipopolymers. Our results are significant, because they offer an intriguing prospective on the role of CHOL on the material properties in complex membrane architecture.

  12. Dihydroxyoctadecamonoenoate esters inhibit the neutrophil ...

    Indian Academy of Sciences (India)

    PRAKASH

    that observed with arachidonic acid treatment (Li et al 1996). ..... An alternative possibility is that the methyl DiHOMEs .... nitric oxide-derived reactive species in vascular cells; Circ. ... necrosis factor 1-alpha-initiated neutrophil responses and.

  13. Proinflammatory mediators stimulate neutrophil-directed angiogenesis.

    LENUS (Irish Health Repository)

    McCourt, M

    2012-02-03

    BACKGROUND: Vascular endothelial growth factor (VEGF; vascular permeability factor) is one of the most potent proangiogenic cytokines, and it plays a central role in mediating the process of angiogenesis or new blood vessel formation. Neutrophils (PMNs) recently have been shown to produce VEGF. HYPOTHESIS: The acute inflammatory response is a potent stimulus for PMN-directed angiogenesis. METHODS: Neutrophils were isolated from healthy volunteers and stimulated with lipopolysaccharide (LPS), tumor necrosis factor alpha (TNF-alpha), interleukin 6 (IL-6), and anti-human Fas monoclonal antibody. Culture supernatants were assayed for VEGF using enzyme-linked immunosorbent assays. Culture supernatants from LPS- and TNF-alpha-stimulated PMNs were then added to human umbilical vein endothelial cells and human microvessel endothelial cells and assessed for endothelial cell proliferation using 5-bromodeoxyuridine labeling. Tubule formation was also assessed on MATRIGEL basement membrane matrix. Neutrophils were lysed to measure total VEGF release, and VEGF expression was detected using Western blot analysis. RESULTS: Lipopolysaccharide and TNF-alpha stimulation resulted in significantly increased release of PMN VEGF (532+\\/-49 and 484+\\/-80 pg\\/mL, respectively; for all, presented as mean +\\/- SEM) compared with control experiments (32+\\/-4 pg\\/mL). Interleukin 6 and Fas had no effect. Culture supernatants from LPS- and TNF-alpha-stimulated PMNs also resulted in significant increases (P<.005) in macrovascular and microvascular endothelial cell proliferation and tubule formation. Adding anti-human VEGF-neutralizing polyclonal antibody to stimulated PMN supernatant inhibited these effects. Total VEGF release following cell lysis and Western blot analysis suggests that the VEGF is released from an intracellular store. CONCLUSION: Activated human PMNs are directly angiogenic by releasing VEGF, and this has important implications for inflammation, capillary leak syndrome

  14. Imaging neutrophil migration dynamics using micro-optical coherence tomography (Conference Presentation)

    Science.gov (United States)

    Chu, Kengyeh K.; Yonker, Lael; Som, Avira; Pazos, Michael; Kusek, Mark E.; Hurley, Bryan P.; Tearney, Guillermo J.

    2016-03-01

    resistance (TEER), a measure of membrane integrity that decreases when neutrophils create openings in the epithelium to permit migration. Preliminary results (n = 2) using real-time TEER measurements indicate that TEER change in anti-CD18 migration (26% at 1 hour) is not lower compared to control (14% at 1 hour), suggesting that the neutrophil-epithelial interaction is not impaired. Combined µOCT+TEER will allow the relationship of neutrophil migration and epithelial interactions to be studied to help uncover the mechanisms of altered neutrophil behavior in patients with inflammatory and immune diseases.

  15. Tethered Forth system for FPGA applications

    Science.gov (United States)

    Goździkowski, Paweł; Zabołotny, Wojciech M.

    2013-10-01

    This paper presents the tethered Forth system dedicated for testing and debugging of FPGA based electronic systems. Use of the Forth language allows to interactively develop and run complex testing or debugging routines. The solution is based on a small, 16-bit soft core CPU, used to implement the Forth Virtual Machine. Thanks to the use of the tethered Forth model it is possible to minimize usage of the internal RAM memory in the FPGA. The function of the intelligent terminal, which is an essential part of the tethered Forth system, may be fulfilled by the standard PC computer or by the smartphone. System is implemented in Python (the software for intelligent terminal), and in VHDL (the IP core for FPGA), so it can be easily ported to different hardware platforms. The connection between the terminal and FPGA may be established and disconnected many times without disturbing the state of the FPGA based system. The presented system has been verified in the hardware, and may be used as a tool for debugging, testing and even implementing of control algorithms for FPGA based systems.

  16. Review of deployment technology for tethered satellite systems

    Science.gov (United States)

    Yu, B. S.; Wen, H.; Jin, D. P.

    2018-03-01

    Tethered satellite systems (TSSs) have attracted significant attention due to their potential and valuable applications for scientific research. With the development of various launched on-orbit missions, the deployment of tethers is considered a crucial technology for operation of a TSS. Both past orbiting experiments and numerical results have shown that oscillations of the deployed tether due to the Coriolis force and environmental perturbations are inevitable and that the impact between the space tether and end-body at the end of the deployment process leads to complicated nonlinear phenomena. Hence, a set of suitable control methods plays a fundamental role in tether deployment. This review article summarizes previous work on aspects of the dynamics, control, and ground-based experiments of tether deployment. The relevant basic principles, analytical expressions, simulation cases, and experimental results are presented as well.

  17. Lyapunov Orbits in the Jupiter System Using Electrodynamic Tethers

    Science.gov (United States)

    Bokelmann, Kevin; Russell, Ryan P.; Lantoine, Gregory

    2013-01-01

    Various researchers have proposed the use of electrodynamic tethers for power generation and capture from interplanetary transfers. The effect of tether forces on periodic orbits in Jupiter-satellite systems are investigated. A perturbation force is added to the restricted three-body problem model and a series of simplifications allows development of a conservative system that retains the Jacobi integral. Expressions are developed to find modified locations of equilibrium positions. Modified families of Lyapunov orbits are generated as functions of tether size and Jacobi integral. Zero velocity curves and stability analyses are used to evaluate the dynamical properties of tether-modified orbits.

  18. Passivity-Based Control of a Rigid Electrodynamic Tether

    DEFF Research Database (Denmark)

    Larsen, Martin Birkelund; Blanke, Mogens

    2011-01-01

    Electrodynamic tethers provide actuation for performing orbit correction of spacecrafts. When an electrodynamic tether system is orbiting the Earth in an inclined orbit, periodic changes in the magnetic field result in a family of unstable periodic solutions in the attitude motion. This paper shows...... how these periodic solutions can be stabilized by controlling only the current through the tether. A port-controlled Hamiltonian formulation is employed to describe the tethered satellite system and a passive input-output connection is utilized in the control design. The control law consists of two...

  19. The stochastic dynamics of tethered microcantilevers in a viscous fluid

    Energy Technology Data Exchange (ETDEWEB)

    Robbins, Brian A.; Paul, Mark R. [Department of Mechanical Engineering, Virginia Tech, Blacksburg, Virginia 24061 (United States); Radiom, Milad; Ducker, William A. [Department of Chemical Engineering, Virginia Tech, Blacksburg, Virginia 24061 (United States); Walz, John Y. [Department of Chemical Engineering, University of Kentucky, Lexington, Kentucky 40506 (United States)

    2014-10-28

    We explore and quantify the coupled dynamics of a pair of micron scale cantilevers immersed in a viscous fluid that are also directly tethered to one another at their tips by a spring force. The spring force, for example, could represent the molecular stiffness or elasticity of a biomolecule or material tethered between the cantilevers. We use deterministic numerical simulations with the fluctuation-dissipation theorem to compute the stochastic dynamics of the cantilever pair for the conditions of experiment when driven only by Brownian motion. We validate our approach by comparing directly with experimental measurements in the absence of the tether which shows excellent agreement. Using numerical simulations, we quantify the correlated dynamics of the cantilever pair over a range of tether stiffness. Our results quantify the sensitivity of the auto- and cross-correlations of equilibrium fluctuations in cantilever displacement to the stiffness of the tether. We show that the tether affects the magnitude of the correlations which can be used in a measurement to probe the properties of an attached tethering substance. For the configurations of current interest using micron scale cantilevers in water, we show that the magnitude of the fluid coupling between the cantilevers is sufficiently small such that the influence of the tether can be significant. Our results show that the cross-correlation is more sensitive to tether stiffness than the auto-correlation indicating that a two-cantilever measurement has improved sensitivity when compared with a measurement using a single cantilever.

  20. Orbital Propagation of Momentum Exchange Tether Systems

    Science.gov (United States)

    Westerhoff, John

    2002-01-01

    An advanced concept in in-space transportation currently being studied is the Momentum-Exchange/Electrodynamic Reboost Tether System (MXER). The system acts as a large momentum wheel, imparting a Av to a payload in low earth orbit (LEO) at the expense of its own orbital energy. After throwing a payload, the system reboosts itself using an electrodynamic tether to push against Earth's magnetic field and brings itself back up to an operational orbit to prepare for the next payload. The ability to reboost itself allows for continued reuse of the system without the expenditure of propellants. Considering the cost of lifting propellant from the ,ground to LEO to do the same Av boost at $10000 per pound, the system cuts the launch cost of the payload dramatically, and subsequently, the MXER system pays for itself after a small number of missions.1 One of the technical hurdles to be overcome with the MXER concept is the rendezvous maneuver. The rendezvous window for the capture of the payload is on the order of a few seconds, as opposed to traditional docking maneuvers, which can take as long ets necessary to complete a precise docking. The payload, therefore, must be able to match its orbit to meet up with the capture device on the end of the tether at a specific time and location in the future. In order to be able to determine that location, the MXER system must be numerically propagated forward in time to predict where the capture device will be at that instant. It should be kept in mind that the propagation computation must be done faster than real-time. This study focuses on the efforts to find and/or build the tools necessary to numerically propagate the motion of the MXER system as accurately as possible.

  1. Space webs based on rotating tethered formations

    Science.gov (United States)

    Palmerini, Giovanni B.; Sgubini, Silvano; Sabatini, Marco

    2009-07-01

    Several on-going studies indicate the interest for large, light orbiting structures, shaped as fish nets or webs: along the ropes of the web small spacecraft can move like spiders to position and re-locate, at will, pieces of hardware devoted to specific missions. The concept could be considered as an intermediate solution between the large monolithic structure, heavy and expensive to realize, but easy to control, and the formations of satellites, where all system members are completely free and should manoeuvre in order to acquire a desired configuration. Instead, the advantage of having a "hard-but-light" link among the different grids lays in the partition of the tasks among system components and in a possible overall reduction of the control system complexity and cost. Unfortunately, there is no stable configuration for an orbiting, two-dimensional web made by light, flexible tethers which cannot support compression forces. A possible solution is to make use of centrifugal forces to pull the net, with a reduced number of simple thrusters located at the tips of the tethers to initially acquire the required spin. In this paper a dynamic analysis of a simplified rotating web is performed, in order to evaluate the spinning velocity able to satisfy the requirement for the stability of the system. The model adopted overlaps simpler elements, each of them given by a tether (made up of a number of linear finite elements) connecting two extreme bodies accommodating the spinning thrusters. The combination of these "diameter-like" elements provides the web, shaped according to the specific requirements. The net is primarily considered as subjected to Keplerian attraction and J2 and drag perturbations only, but its behaviour under thermal inputs is also investigated.

  2. Endoplasmic Reticulum-Plasma Membrane Contact Sites.

    Science.gov (United States)

    Saheki, Yasunori; De Camilli, Pietro

    2017-06-20

    The endoplasmic reticulum (ER) has a broad localization throughout the cell and forms direct physical contacts with all other classes of membranous organelles, including the plasma membrane (PM). A number of protein tethers that mediate these contacts have been identified, and study of these protein tethers has revealed a multiplicity of roles in cell physiology, including regulation of intracellular Ca 2+ dynamics and signaling as well as control of lipid traffic and homeostasis. In this review, we discuss the cross talk between the ER and the PM mediated by direct contacts. We review factors that tether the two membranes, their properties, and their dynamics in response to the functional state of the cell. We focus in particular on the role of ER-PM contacts in nonvesicular lipid transport between the two bilayers mediated by lipid transfer proteins.

  3. Effects of ghrelin on the apoptosis of human neutrophils in vitro

    Science.gov (United States)

    Li, Bin; Zeng, Mian; Zheng, Haichong; Huang, Chunrong; He, Wanmei; Lu, Guifang; Li, Xia; Chen, Yanzhu; Xie, Ruijie

    2016-01-01

    Acute respiratory distress syndrome (ARDS) is characterized by lung inflammation and the diffuse infiltration of neutrophils into the alveolar space. Neutrophils are abundant, short-lived leukocytes that play a key role in immune defense against microbial infections. These cells die via apoptosis following the activation and uptake of microbes, and will also enter apoptosis spontaneously at the end of their lifespan if they do not encounter pathogens. Apoptosis is essential for the removal of neutrophils from inflamed tissues and for the timely resolution of neutrophilic inflammation. Ghrelin is an endogenous ligand for the growth hormone (GH) secretagogue receptor, produced and secreted mainly from the stomach. Previous studies have reported that ghrelin exerts anti-inflammatory effects in lung injury through the regulation of the apoptosis of different cell types; however, the ability of ghrelin to regulate alveolar neutrophil apoptosis remains largely undefined. We hypothesized that ghrelin may have the ability to modulate neutrophil apoptosis. In this study, to examine this hypothesis, we investigated the effects of ghrelin on freshly isolated neutrophils in vitro. Our findings demonstrated a decrease in the apoptotic ratio (as shown by flow cytometry), as well as in the percentage of cells with decreased mitochondrial membrane potential (ΔΨm) and in the terminal deoxynucleotidyl transferase (TdT)-mediated dUTP-biotin nick-end labeling-positive rate, accompanied by an increased B-cell lymphoma 2/Bax ratio and the downregulation of cleaved caspase-3 in neutrophils following exposure to lipopolysaccharide (100 ng/ml). However, pre-treatment with ghrelin at a physiological level (100 nM) did not have a notable influence on the neutrophils in all the aforementioned tests. Our findings suggest that ghrelin may not possess the ability to modulate the neutrophil lifespan in vitro. PMID:27431014

  4. Climber Motion Optimization for the Tethered Space Elevator

    NARCIS (Netherlands)

    Williams, P.; Ockels, W.J.

    The tethered space elevator could provide a revolutionary means for enabling cheap transportation to geostationary altitude and beyond. Assuming that such a system can be built, one of the dynamic design problems is determining a means of moving the elevator along the tether so as to minimize the

  5. Modeling and Simulation of a Tethered Harpoon for Comet Sampling

    Science.gov (United States)

    Quadrelli, Marco B.

    2014-01-01

    This paper describes the development of a dynamic model and simulation results of a tethered harpoon for comet sampling. This model and simulation was done in order to carry out an initial sensitivity analysis for key design parameters of the tethered system. The harpoon would contain a canister which would collect a sample of soil from a cometary surface. Both a spring ejected canister and a tethered canister are considered. To arrive in close proximity of the spacecraft at the end of its trajectory so it could be captured, the free-flying canister would need to be ejected at the right time and with the proper impulse, while the tethered canister must be recovered by properly retrieving the tether at a rate that would avoid an excessive amplitude of oscillatory behavior during the retrieval. The paper describes the model of the tether dynamics and harpoon penetration physics. The simulations indicate that, without the tether, the canister would still reach the spacecraft for collection, that the tether retrieval of the canister would be achievable with reasonable fuel consumption, and that the canister amplitude upon retrieval would be insensitive to variations in vertical velocity dispersion.

  6. Investigation of electrodynamic stabilization and control of long orbiting tethers

    Science.gov (United States)

    Colombo, G.; Arnold, D.

    1984-01-01

    The state-of-the-art in tether modelling among participants in the Tethered Satellite System (TSS) Program, the slack tether and its behavior, and certain advanced applications of the tether to problems in orbital mechanics are identified. The features and applications of the TSS software set are reviewed. Modelling the slack tether analytically with as many as 50 mass points and the application of this new model to a study of the behavior of a broken tether near the Shuttle are described. A reel control algorithm developed by SAO and examples of its use are described, including an example which also demonstrates the use of the tether in transferring a heavy payload from a low-orbiting Shuttle to a high circular orbit. Capture of a low-orbiting payload by a Space Station in high circular orbit is described. Energy transfer within a dumbbell-type spacecraft by cyclical reeling operations or gravitational effects on the natural elasticity of the connecting tether, it is shown, can circularize the orbit of the spacecraft.

  7. Attitude control analysis of tethered de-orbiting

    Science.gov (United States)

    Peters, T. V.; Briz Valero, José Francisco; Escorial Olmos, Diego; Lappas, V.; Jakowski, P.; Gray, I.; Tsourdos, A.; Schaub, H.; Biesbroek, R.

    2018-05-01

    The increase of satellites and rocket upper stages in low earth orbit (LEO) has also increased substantially the danger of collisions in space. Studies have shown that the problem will continue to grow unless a number of debris are removed every year. A typical active debris removal (ADR) mission scenario includes launching an active spacecraft (chaser) which will rendezvous with the inactive target (debris), capture the debris and eventually deorbit both satellites. Many concepts for the capture of the debris while keeping a connection via a tether, between the target and chaser have been investigated, including harpoons, nets, grapples and robotic arms. The paper provides an analysis on the attitude control behaviour for a tethered de-orbiting mission based on the ESA e.Deorbit reference mission, where Envisat is the debris target to be captured by a chaser using a net which is connected to the chaser with a tether. The paper provides novel insight on the feasibility of tethered de-orbiting for the various mission phases such as stabilization after capture, de-orbit burn (plus stabilization), stabilization during atmospheric pass, highlighting the importance of various critical mission parameters such as the tether material. It is shown that the selection of the appropriate tether material while using simple controllers can reduce the effort needed for tethered deorbiting and can safely control the attitude of the debris/chaser connected with a tether, without the danger of a collision.

  8. Tethered Contactless Mobile Nuclear Environment Monitoring Robot

    International Nuclear Information System (INIS)

    Choi, S. Y.; Lee, E. S.; Lee, Kun J.; Kim, Su H.; Rim, C. T.

    2013-01-01

    In fact, the nuclear environment monitoring is significantly crucial for early detection of NPP accident, radiological emergency, the estimation of radiation exposure to nearby residents as well as the long term radioactivity. In the UAE, the nuclear environment monitoring is, however, quite challenging because sampling locations are far from NPPs and the outdoor temperature and humidity are very high for NPP workers to collect soil, air, and water samples. Therefore, nuclear environment monitoring robots (Nubos) are strongly needed for the NPPs in the UAE. The Nubos can be remotely controlled to collect samples in extreme environment instead of NPP workers. Moreover, the Nubos can be unmanned ground vehicles (UGVs), unmanned aerial vehicles (UAVs) and unmanned marine vehicles (UMVs) to collect soil, air, and water samples, respectively. In this paper, the prototype development of UGV type Nubos using power cable for a long distance power delivery, called Tethered contactless mobile Nubo is introduced and validated by experiments. In this paper, the prototype development of Tethered Contactless Mobile (TeCoM) Nubo, which can be powered continuously within several km distance and avoid tangled cable, and the indoor test are finished. As further works, outdoor demonstration and a grand scale R and D proposal of practical Nubo will be proceeded

  9. Tethered Contactless Mobile Nuclear Environment Monitoring Robot

    Energy Technology Data Exchange (ETDEWEB)

    Choi, S. Y.; Lee, E. S.; Lee, Kun J.; Kim, Su H.; Rim, C. T. [Korea Advanced Institute of Science and Technology, Daejeon (Korea, Republic of)

    2013-05-15

    In fact, the nuclear environment monitoring is significantly crucial for early detection of NPP accident, radiological emergency, the estimation of radiation exposure to nearby residents as well as the long term radioactivity. In the UAE, the nuclear environment monitoring is, however, quite challenging because sampling locations are far from NPPs and the outdoor temperature and humidity are very high for NPP workers to collect soil, air, and water samples. Therefore, nuclear environment monitoring robots (Nubos) are strongly needed for the NPPs in the UAE. The Nubos can be remotely controlled to collect samples in extreme environment instead of NPP workers. Moreover, the Nubos can be unmanned ground vehicles (UGVs), unmanned aerial vehicles (UAVs) and unmanned marine vehicles (UMVs) to collect soil, air, and water samples, respectively. In this paper, the prototype development of UGV type Nubos using power cable for a long distance power delivery, called Tethered contactless mobile Nubo is introduced and validated by experiments. In this paper, the prototype development of Tethered Contactless Mobile (TeCoM) Nubo, which can be powered continuously within several km distance and avoid tangled cable, and the indoor test are finished. As further works, outdoor demonstration and a grand scale R and D proposal of practical Nubo will be proceeded.

  10. Monoclonal antibodies to antigens on human neutrophils, activated T lymphocytes, and acute leukemia blast cells

    International Nuclear Information System (INIS)

    Miterev, G.Yu.; Burova, G.F.; Puzhitskaya, M.S.; Danilevich, S.V.; Bulycheva, T.I.

    1987-01-01

    The authors describe the production of two mouse hybridomas secreting monoclonal antibodies to antigenic determinants of the surface membranes of human neutrophils, activated T lymphocytes, and acute leukemic blast cells. The degree of lymphocyte stimulation was estimated from incorporation of 3 H-thymidine with parallel microculture. Monoclonal antibodies of supernatants of hybridoma cultures shown here reacted in both immunofluorescence test and cytotoxicity test with surface membrane antigens on the majority of neutrophils and PHA-activated peripheral blood lymphocytes from healthy subjects, but did not give positive reactions with unactivated lymphocytes, adherent monocytes, erythrocytes, and alloantigen-stimulated lymphocytes

  11. Monoclonal antibodies to antigens on human neutrophils, activated T lymphocytes, and acute leukemia blast cells

    Energy Technology Data Exchange (ETDEWEB)

    Miterev, G.Yu.; Burova, G.F.; Puzhitskaya, M.S.; Danilevich, S.V.; Bulycheva, T.I.

    1987-11-01

    The authors describe the production of two mouse hybridomas secreting monoclonal antibodies to antigenic determinants of the surface membranes of human neutrophils, activated T lymphocytes, and acute leukemic blast cells. The degree of lymphocyte stimulation was estimated from incorporation of /sup 3/H-thymidine with parallel microculture. Monoclonal antibodies of supernatants of hybridoma cultures shown here reacted in both immunofluorescence test and cytotoxicity test with surface membrane antigens on the majority of neutrophils and PHA-activated peripheral blood lymphocytes from healthy subjects, but did not give positive reactions with unactivated lymphocytes, adherent monocytes, erythrocytes, and alloantigen-stimulated lymphocytes.

  12. Neutrophils, dendritic cells and Toxoplasma.

    Science.gov (United States)

    Denkers, Eric Y; Butcher, Barbara A; Del Rio, Laura; Bennouna, Soumaya

    2004-03-09

    Toxoplasma gondii rapidly elicits strong Type 1 cytokine-based immunity. The necessity for this response is well illustrated by the example of IFN-gamma and IL-12 gene knockout mice that rapidly succumb to the effects of acute infection. The parasite itself is skilled at sparking complex interactions in the innate immune system that lead to protective immunity. Neutrophils are one of the first cell types to arrive at the site of infection, and the cells release several proinflammatory cytokines and chemokines in response to Toxoplasma. Dendritic cells are an important source of IL-12 during infection with T. gondii and other microbial pathogens, and they are also specialized for high-level antigen presentation to T lymphocytes. Tachyzoites express at least two types of molecules that trigger innate immune cell cytokine production. One of these involves Toll-like receptor/MyD88 pathways common to many microbial pathogens. The second pathway is less conventional and involves molecular mimicry between a parasite cyclophilin and host CC chemokine receptor 5-binding ligands. Neutrophils, dendritic cells and Toxoplasma work together to elicit the immune response required for host survival. Cytokine and chemokine cross-talk between parasite-triggered neutrophils and dendritic cells results in recruitment, maturation and activation of the latter. Neutrophil-empowered dendritic cells possess properties expected of highly potent antigen presenting cells that drive T helper 1 generation.

  13. Immune modulation by neutrophil subsets

    NARCIS (Netherlands)

    Kamp, V.M.

    2013-01-01

    We show that human neutrophils can suppress T-cell proliferation in acute systemic inflammation and thus have anti-inflammatory functions, next to their well-known pro-inflammatory functions. The suppression is mediated by ROS production and integrin MAC-1, which are also important for the

  14. Assessing tether anchor labeling and usability in pickup trucks.

    Science.gov (United States)

    Klinich, Kathleen D; Manary, Miriam A; Malik, Laura A; Flannagan, Carol A; Jermakian, Jessica S

    2018-04-03

    The objective of this study was to investigate vehicle factors associated with child restraint tether use and misuse in pickup trucks and evaluate 4 labeling interventions designed to educate consumers on proper tether use. Volunteer testing was performed with 24 subjects and 4 different pickup trucks. Each subject performed 8 child restraint installations among the 4 pickups using 2 forward-facing restraints: a Britax Marathon G4.1 and an Evenflo Triumph. Vehicles were selected to represent 4 different implementations of tether anchors among pickups: plastic loop routers (Chevrolet Silverado), webbing routers (Ram), back wall anchors (Nissan Frontier), and webbing routers plus metal anchors (Toyota Tundra). Interventions included a diagram label, Quick Response (QR) Code linked to video instruction, coordinating text label, and contrasting text tag. Subjects used the child restraint tether in 93% of trials. However, tether use was completely correct in only 9% of trials. An installation was considered functional if the subject attached the tether to a tether anchor and had a tight installation (ignoring routing and head restraint position); 28% of subjects achieved a functional installation. The most common installation error was attaching the tether hook to the anchor/router directly behind the child restraint (near the top of the seatback) rather than placing the tether through the router and attaching it to the anchor in the adjacent seating position. The Nissan Frontier, with the anchor located on the back wall of the cab, had the highest rate of correct installations but also had the highest rate of attaching the tether to components other than the tether anchor (seat adjustor, child restraint storage hook, around head restraint). None of the labeling interventions had a significant effect on correct installation; not a single subject scanned the QR Code to access the video instruction. Subjects with the most successful installations spent extensive time

  15. Organic fouling behavior of superhydrophilic polyvinylidene fluoride (PVDF) ultrafiltration membranes functionalized with surface-tailored nanoparticles: Implications for organic fouling in membrane bioreactors

    KAUST Repository

    Liang, Shuai; Qi, Genggeng; Xiao, Kang; Sun, Jianyu; Giannelis, Emmanuel P.; Huang, Xia; Elimelech, Menachem

    2014-01-01

    This study systematically investigates the organic fouling behavior of a superhydrophilic polyvinylidene fluoride (PVDF) ultrafiltration membrane functionalized via post-fabrication tethering of surface-tailored silica nanoparticles to poly

  16. A conserved endoplasmic reticulum membrane protein complex (EMC facilitates phospholipid transfer from the ER to mitochondria.

    Directory of Open Access Journals (Sweden)

    Sujoy Lahiri

    2014-10-01

    Full Text Available Mitochondrial membrane biogenesis and lipid metabolism require phospholipid transfer from the endoplasmic reticulum (ER to mitochondria. Transfer is thought to occur at regions of close contact of these organelles and to be nonvesicular, but the mechanism is not known. Here we used a novel genetic screen in S. cerevisiae to identify mutants with defects in lipid exchange between the ER and mitochondria. We show that a strain missing multiple components of the conserved ER membrane protein complex (EMC has decreased phosphatidylserine (PS transfer from the ER to mitochondria. Mitochondria from this strain have significantly reduced levels of PS and its derivative phosphatidylethanolamine (PE. Cells lacking EMC proteins and the ER-mitochondria tethering complex called ERMES (the ER-mitochondria encounter structure are inviable, suggesting that the EMC also functions as a tether. These defects are corrected by expression of an engineered ER-mitochondrial tethering protein that artificially tethers the ER to mitochondria. EMC mutants have a significant reduction in the amount of ER tethered to mitochondria even though ERMES remained intact in these mutants, suggesting that the EMC performs an additional tethering function to ERMES. We find that all Emc proteins interact with the mitochondrial translocase of the outer membrane (TOM complex protein Tom5 and this interaction is important for PS transfer and cell growth, suggesting that the EMC forms a tether by associating with the TOM complex. Together, our findings support that the EMC tethers ER to mitochondria, which is required for phospholipid synthesis and cell growth.

  17. Biomaterial associated impairment of local neutrophil function.

    Science.gov (United States)

    Kaplan, S S; Basford, R E; Kormos, R L; Hardesty, R L; Simmons, R L; Mora, E M; Cardona, M; Griffith, B L

    1990-01-01

    The effect of biomaterials on neutrophil function was studied in vitro to determine if these materials activated neutrophils and to determine the subsequent response of these neutrophils to further stimulation. Two biomaterials--polyurethane, a commonly used substance, and Velcro pile (used in the Jarvik 7 heart)--were evaluated. Two control substances, polyethylene and serum-coated polystyrene, were used for comparison. Neutrophil superoxide release was measured following incubation with these materials for 10, 30, and 120 min in the absence of additional stimulation and after stimulation with formylmethionylleucylphenylalanine (fMLP) or phorbol myristate acetate (PMA). The authors observed that the incubation of neutrophils on both polyurethane and Velcro resulted in substantially increased superoxide release that was greater after the 10 min than after the 30 or 120 min association. These activated neutrophils exhibited a poor additional response to fMLP but responded well to PMA. The effect of implantation of the Novacor left ventricular assist device on peripheral blood neutrophil function was also evaluated. The peripheral blood neutrophils exhibited normal superoxide release and chemotaxis. These studies suggest that biomaterials may have a profound local effect on neutrophils, which may predispose the patient to periprosthetic infection, but that the reactivity of circulating neutrophils is unimpaired.

  18. Tamoxifen induces apoptotic neutrophil efferocytosis in horses.

    Science.gov (United States)

    Olave, C; Morales, N; Uberti, B; Henriquez, C; Sarmiento, J; Ortloff, A; Folch, H; Moran, G

    2018-03-01

    Macrophages and neutrophils are important cellular components in the process of acute inflammation and its subsequent resolution, and evidence increasingly suggests that they play important functions during the resolution of chronic, adaptive inflammatory processes. Exacerbated neutrophil activity can be harmful to surrounding tissues; this is important in a range of diseases, including allergic asthma and chronic obstructive pulmonary disease in humans, and equine asthma (also known as recurrent airway obstruction (RAO). Tamoxifen (TX) is a non-steroidal estrogen receptor modulator with effects on cell growth and survival. Previous studies showed that TX treatment in horses with induced acute pulmonary inflammation promoted early apoptosis of blood and BALF neutrophils, reduction of BALF neutrophils, and improvement in animals' clinical status. The aim of this study was to describe if TX induces in vitro efferocytosis of neutrophils by alveolar macrophages. Efferocytosis assay, myeloperoxidase (MPO) detection and translocation phosphatidylserine (PS) were performed on neutrophils isolated from peripheral blood samples from five healthy horses. In in vitro samples from heathy horses, TX treatment increases the phenomenon of efferocytosis of peripheral neutrophils by alveolar macrophages. Similar increases in supernatant MPO concentration and PS translocation were observed in TX-treated neutrophils, compared to control cells. In conclusion, these results confirm that tamoxifen has a direct effect on equine peripheral blood neutrophils, through stimulation of the engulfment of apoptotic neutrophils by alveolar macrophages.

  19. Neutrophils Compromise Retinal Pigment Epithelial Barrier Integrity

    Directory of Open Access Journals (Sweden)

    Jiehao Zhou

    2010-01-01

    Full Text Available We hypothesized that neutrophils and their secreted factors mediate breakdown of the integrity of the outer blood-retina-barrier by degrading the apical tight junctions of the retinal pigment epithelium (RPE. The effect of activated neutrophils or neutrophil cell lysate on apparent permeability of bovine RPE-Choroid explants was evaluated by measuring [H] mannitol flux in a modified Ussing chamber. The expression of matrix metalloproteinase- (MMP- 9 in murine peritoneal neutrophils, and the effects of neutrophils on RPE tight-junction protein expression were assessed by confocal microscopy and western blot. Our results revealed that basolateral incubation of explants with neutrophils decreased occludin and ZO-1 expression at 1 and 3 hours and increased the permeability of bovine RPE-Choroid explants by >3-fold (P<.05. Similarly, basolateral incubation of explants with neutrophil lysate decreased ZO-1 expression at 1 and 3 hours (P<.05 and increased permeability of explants by 75%. Further, we found that neutrophils prominently express MMP-9 and that incubation of explants with neutrophils in the presence of anti-MMP-9 antibody inhibited the increase in permeability. These data suggest that neutrophil-derived MMP-9 may play an important role in disrupting the integrity of the outer blood-retina barrier.

  20. Stationary Tether Device for Buoy Apparatus and System for Using

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — A rigid, neutrally buoyant hydrodynamicaly-faired tether and associated fastening hardware that loosely holds a bathymetric float at a predetermined distance from a...

  1. Hierarchical Structure in Semicrystalline Polymers Tethered to Nanospheres

    KAUST Repository

    Kim, Sung A; Archer, Lynden A.

    2014-01-01

    We report on structural and dynamic transitions of polymers tethered to nanoparticles. In particular, we use X-ray diffraction, vibrational spectroscopy, and thermal measurements to investigate multiscale structure and dynamic transitions of poly

  2. Crowded, Confined, and Frustrated: Dynamics of Molecules Tethered to Nanoparticles

    KAUST Repository

    Agarwal, Praveen; Kim, Sung A.; Archer, Lynden A.

    2012-01-01

    Above a critical chemistry-dependent molecular weight, all polymer molecules entangle and, as a result, exhibit slow dynamics, enhanced viscosity, and elasticity. Herein we report on the dynamics of low molecular weight polymers tethered

  3. FCAPD Protective Coating for Space Tethers, Phase I

    Data.gov (United States)

    National Aeronautics and Space Administration — Alameda Applied Sciences Corporation (AASC) proposes to demonstrate extended service lifetime of space tethers in the Low Earth Orbit (LEO) environment by using...

  4. Relaxation Dynamics of Nanoparticle-Tethered Polymer Chains

    KAUST Repository

    Kim, Sung A; Mangal, Rahul; Archer, Lynden A.

    2015-01-01

    © 2015 American Chemical Society. Relaxation dynamics of nanoparticle-tethered cis-1,4-polyisoprene (PI) are investigated using dielectric spectroscopy and rheometry. A model system composed of polymer chains densely grafted to spherical SiO2

  5. Tethered Nanoparticle–Polymer Composites: Phase Stability and Curvature

    KAUST Repository

    Srivastava, Samanvaya; Agarwal, Praveen; Archer, Lynden A.

    2012-01-01

    different small-angle X-ray scattering signatures in comparison to phase-separated composites comprised of bare or sparsely grafted nanoparticles. A general diagram for the dispersion state and phase stability of polymer tethered nanoparticle-polymer

  6. Fiber Optic Shape Sensing for Tethered Marsupial Rovers, Phase II

    Data.gov (United States)

    National Aeronautics and Space Administration — Building upon the successful proof of concept work in Phase I, Luna Innovations Incorporated is proposing to design, build, and test a sensing tether for marsupial...

  7. Neutrophil Responses to Sterile Implant Materials.

    Directory of Open Access Journals (Sweden)

    Siddharth Jhunjhunwala

    Full Text Available In vivo implantation of sterile materials and devices results in a foreign body immune response leading to fibrosis of implanted material. Neutrophils, one of the first immune cells to be recruited to implantation sites, have been suggested to contribute to the establishment of the inflammatory microenvironment that initiates the fibrotic response. However, the precise numbers and roles of neutrophils in response to implanted devices remains unclear. Using a mouse model of peritoneal microcapsule implantation, we show 30-500 fold increased neutrophil presence in the peritoneal exudates in response to implants. We demonstrate that these neutrophils secrete increased amounts of a variety of inflammatory cytokines and chemokines. Further, we observe that they participate in the foreign body response through the formation of neutrophil extracellular traps (NETs on implant surfaces. Our results provide new insight into neutrophil function during a foreign body response to peritoneal implants which has implications for the development of biologically compatible medical devices.

  8. Neutrophil Reverse Migration Becomes Transparent with Zebrafish

    Directory of Open Access Journals (Sweden)

    Taylor W. Starnes

    2012-01-01

    Full Text Available The precise control of neutrophil-mediated inflammation is critical for both host defense and the prevention of immunopathology. In vivo imaging studies in zebrafish, and more recently in mice, have made the novel observation that neutrophils leave a site of inflammation through a process called neutrophil reverse migration. The application of advanced imaging techniques to the genetically tractable, optically transparent zebrafish larvae was critical for these advances. Still, the mechanisms underlying neutrophil reverse migration and its effects on the resolution or priming of immune responses remain unclear. Here, we review the current knowledge of neutrophil reverse migration, its potential roles in host immunity, and the live imaging tools that make zebrafish a valuable model for increasing our knowledge of neutrophil behavior in vivo.

  9. Neutrophils in Tuberculosis: Heterogeneity Shapes the Way?

    Science.gov (United States)

    2017-01-01

    Infection with M. tuberculosis remains one of the most common infections in the world. The outcome of the infection depends on host ability to mount effective protection and balance inflammatory responses. Neutrophils are innate immune cells implicated in both processes. Accordingly, during M. tuberculosis infection, they play a dual role. Particularly, they contribute to the generation of effector T cells, participate in the formation of granuloma, and are directly involved in tissue necrosis, destruction, and infection dissemination. Neutrophils have a high bactericidal potential. However, data on their ability to eliminate M. tuberculosis are controversial, and the results of neutrophil depletion experiments are not uniform. Thus, the overall roles of neutrophils during M. tuberculosis infection and factors that determine these roles are not fully understood. This review analyzes data on neutrophil defensive and pathological functions during tuberculosis and considers hypotheses explaining the dualism of neutrophils during M. tuberculosis infection and tuberculosis disease. PMID:28626346

  10. Neutrophil Extracellular Traps in Ulcerative Colitis

    DEFF Research Database (Denmark)

    Bjerg Bennike, Tue; Carlsen, Thomas Gelsing; Ellingsen, Torkell

    2015-01-01

    microscopy and confocal microscopy. RESULTS: We identified and quantified 5711 different proteins with proteomics. The abundance of the proteins calprotectin and lactotransferrin in the tissue correlated with the degree of tissue inflammation as determined by histology. However, fecal calprotectin did...... not correlate. Forty-six proteins were measured with a statistically significant differences in abundances between the UC colon tissue and controls. Eleven of the proteins with increased abundances in the UC biopsies were associated with neutrophils and neutrophil extracellular traps. The findings were...... validated by microscopy, where an increased abundance of neutrophils and the presence of neutrophil extracellular traps by extracellular DNA present in the UC colon tissue were confirmed. CONCLUSIONS: Neutrophils, induced neutrophil extracellular traps, and several proteins that play a part in innate...

  11. Pulmonary endothelial activation caused by extracellular histones contributes to neutrophil activation in acute respiratory distress syndrome.

    Science.gov (United States)

    Zhang, Yanlin; Guan, Li; Yu, Jie; Zhao, Zanmei; Mao, Lijun; Li, Shuqiang; Zhao, Jinyuan

    2016-11-21

    During the acute respiratory distress syndrome (ARDS), neutrophils play a central role in the pathogenesis, and their activation requires interaction with the endothelium. Extracellular histones have been recognized as pivotal inflammatory mediators. This study was to investigate the role of pulmonary endothelial activation during the extracellular histone-induced inflammatory response in ARDS. ARDS was induced in male C57BL/6 mice by intravenous injection with lipopolysaccharide (LPS) or exogenous histones. Concurrent with LPS administration, anti-histone H4 antibody (anti-H4) or non-specific IgG was administered to study the role of extracellular histones. The circulating von Willebrand factor (vWF) and soluble thrombomodulin (sTM) were measured with ELISA kits at the preset time points. Myeloperoxidase (MPO) activity in lung tissue was measured with a MPO detection kit. The translocation of P-selectin and neutrophil infiltration were measured by immunohistochemical detection. For in vitro studies, histone H4 in the supernatant of mouse lung vascular endothelial cells (MLVECs) was measured by Western blot. The binding of extracellular histones with endothelial membrane was examined by confocal laser microscopy. Endothelial P-selectin translocation was measured by cell surface ELISA. Adhesion of neutrophils to MLVECs was assessed with a color video digital camera. The results showed that during LPS-induced ARDS extracellular histones caused endothelial and neutrophil activation, as seen by P-selectin translocation, release of vWF, an increase of circulating sTM, lung neutrophil infiltration and increased MPO activity. Extracellular histones directly bound and activated MLVECs in a dose-dependent manner. On the contrary, the direct stimulatory effect of exogenous histones on neutrophils was very limited, as measured by neutrophil adhesion and MPO activity. With the contribution of activated endothelium, extracellular histones could effectively activating

  12. The Natural Stilbenoid Piceatannol Decreases Activity and Accelerates Apoptosis of Human Neutrophils: Involvement of Protein Kinase C

    Directory of Open Access Journals (Sweden)

    Viera Jancinova

    2013-01-01

    Full Text Available Neutrophils are able to release cytotoxic substances and inflammatory mediators, which, along with their delayed apoptosis, have a potential to maintain permanent inflammation. Therefore, treatment of diseases associated with chronic inflammation should be focused on neutrophils; formation of reactive oxygen species and apoptosis of these cells represent two promising targets for pharmacological intervention. Piceatannol, a naturally occurring stilbenoid, has the ability to reduce the toxic action of neutrophils. This substance decreased the amount of oxidants produced by neutrophils both extra- and intracellularly. Radicals formed within neutrophils (fulfilling a regulatory role were reduced to a lesser extent than extracellular oxidants, potentially dangerous for host tissues. Moreover, piceatannol did not affect the phosphorylation of p40phox—a component of NADPH oxidase, responsible for the assembly of functional oxidase in intracellular (granular membranes. The stilbenoid tested elevated the percentage of early apoptotic neutrophils, inhibited the activity of protein kinase C (PKC—the main regulatory enzyme in neutrophils, and reduced phosphorylation of PKC isoforms α, βII, and δ on their catalytic region. The results indicated that piceatannol may be useful as a complementary medicine in states associated with persisting neutrophil activation and with oxidative damage of tissues.

  13. Lumbosacral arachnoid cyst with tethered cord: A rare case report

    Directory of Open Access Journals (Sweden)

    S K Jain

    2012-01-01

    Full Text Available Arachnoid cysts are cerebrospinal fluid collections in the spine that can present with neurological symptoms or be discovered accidentally. Intradural location of such cysts especially in the lumbosacral region is relatively rare. The association of such cysts with other congenital anomalies such as tethered cord lends evidence to the developmental origin of arachnoid cysts. We report a case of lumbosacral arachnoid cyst with tethered cord in a 6-year-old male child and discuss the etiopathogenesis and management options.

  14. Tethered catalysts for the hydration of carbon dioxide

    Science.gov (United States)

    Valdez, Carlos A; Satcher, Jr., Joe H; Aines, Roger D; Wong, Sergio E; Baker, Sarah E; Lightstone, Felice C; Stolaroff, Joshuah K

    2014-11-04

    A system is provided that substantially increases the efficiency of CO.sub.2 capture and removal by positioning a catalyst within an optimal distance from the air-liquid interface. The catalyst is positioned within the layer determined to be the highest concentration of carbon dioxide. A hydrophobic tether is attached to the catalyst and the hydrophobic tether modulates the position of the catalyst within the liquid layer containing the highest concentration of carbon dioxide.

  15. Complete identification of E-selectin ligands on neutrophils reveals distinct functions of PSGL-1, ESL-1, and CD44.

    Science.gov (United States)

    Hidalgo, Andrés; Peired, Anna J; Wild, Martin; Vestweber, Dietmar; Frenette, Paul S

    2007-04-01

    The selectins and their ligands are required for leukocyte extravasation during inflammation. Several glycoproteins have been suggested to bind to E-selectin in vitro, but the complete identification of its physiological ligands has remained elusive. Here, we showed that E-selectin ligand-1 (ESL-1), P-selectin glycoprotein ligand-1 (PSGL-1), and CD44 encompassed all endothelial-selectin ligand activity on neutrophils by using gene- and RNA-targeted loss of function. PSGL-1 played a major role in the initial leukocyte capture, whereas ESL-1 was critical for converting initial tethers into steady slow rolling. CD44 controlled rolling velocity and mediated E-selectin-dependent redistribution of PSGL-1 and L-selectin to a major pole on slowly rolling leukocytes through p38 signaling. These results suggest distinct and dynamic contributions of these three glycoproteins in selectin-mediated neutrophil adhesion and signaling.

  16. CD177 modulates human neutrophil migration through activation-mediated integrin and chemoreceptor regulation.

    Science.gov (United States)

    Bai, Ming; Grieshaber-Bouyer, Ricardo; Wang, Junxia; Schmider, Angela B; Wilson, Zachary S; Zeng, Liling; Halyabar, Olha; Godin, Matthew D; Nguyen, Hung N; Levescot, Anaïs; Cunin, Pierre; Lefort, Craig T; Soberman, Roy J; Nigrovic, Peter A

    2017-11-09

    CD177 is a glycosylphosphatidylinositol (GPI)-anchored protein expressed by a variable proportion of human neutrophils that mediates surface expression of the antineutrophil cytoplasmic antibody antigen proteinase 3. CD177 associates with β2 integrins and recognizes platelet endothelial cell adhesion molecule 1 (PECAM-1), suggesting a role in neutrophil migration. However, CD177 pos neutrophils exhibit no clear migratory advantage in vivo, despite interruption of in vitro transendothelial migration by CD177 ligation. We sought to understand this paradox. Using a PECAM-1-independent transwell system, we found that CD177 pos and CD177 neg neutrophils migrated comparably. CD177 ligation selectively impaired migration of CD177 pos neutrophils, an effect mediated through immobilization and cellular spreading on the transwell membrane. Correspondingly, CD177 ligation enhanced its interaction with β2 integrins, as revealed by fluorescence lifetime imaging microscopy, leading to integrin-mediated phosphorylation of Src and extracellular signal-regulated kinase (ERK). CD177-driven cell activation enhanced surface β2 integrin expression and affinity, impaired internalization of integrin attachments, and resulted in ERK-mediated attenuation of chemokine signaling. We conclude that CD177 signals in a β2 integrin-dependent manner to orchestrate a set of activation-mediated mechanisms that impair human neutrophil migration. © 2017 by The American Society of Hematology.

  17. The effects of tether placement on antibody stability on surfaces

    Science.gov (United States)

    Grawe, Rebecca W.; Knotts, Thomas A.

    2017-06-01

    Despite their potential benefits, antibody microarrays have fallen short of performing reliably and have not found widespread use outside of the research setting. Experimental techniques have been unable to determine what is occurring on the surface of an atomic level, so molecular simulation has emerged as the primary method of investigating protein/surface interactions. Simulations of small proteins have indicated that the stability of the protein is a function of the residue on the protein where a tether is placed. The purpose of this research is to see whether these findings also apply to antibodies, with their greater size and complexity. To determine this, 24 tethering locations were selected on the antibody Protein Data Bank (PDB) ID: 1IGT. Replica exchange simulations were run on two different surfaces, one hydrophobic and one hydrophilic, to determine the degree to which these tethering sites stabilize or destabilize the antibody. Results showed that antibodies tethered to hydrophobic surfaces were in general less stable than antibodies tethered to hydrophilic surfaces. Moreover, the stability of the antibody was a function of the tether location on hydrophobic surfaces but not hydrophilic surfaces.

  18. Flowing Plasma Interaction with an Electric Sail Tether Element

    Science.gov (United States)

    Schneider, Todd; Vaughn, Jason; Wright, Kenneth; Anderson, Allen; Stone, Nobie

    2017-01-01

    Harnessing the power of the solar wind, an Electric Sail, or E-sail, is a relatively new concept that promises to deliver high speed propellant-less propulsion. The electric sail is an invention made in 2006 at the Kumpula Space Centre in Finland by Pekka Janhunen [Janhunen and Sandroos, 2007]. At its core, an electric sail utilizes multiple positively biased tethers which exchange momentum with solar wind protons via the repelling electric field established around each tether, in other words, by reflecting the solar wind protons. Recognizing the solar wind is a plasma, the effective repelling area of each tether is increased significantly by the formation a plasma sheath around each tether. Fig. 1 shows schematically a spacecraft employing an electric sail. The positive voltage bias (greater than10kV) applied to each tether naturally results in electron collection. Therefore, the electric sail concept necessarily includes an electron source (electron gun) to return collected electrons to space and maintain the positive bias of the tether system.

  19. Impaired neutrophil function in intestinal lymphangiectasia.

    OpenAIRE

    Bolton, R P; Cotter, K L; Losowsky, M S

    1986-01-01

    Impaired neutrophil chemotaxis and phagocytosis were shown in three patients with intestinal lymphangiectasia. Abnormalities in cell associated and serum derived activity occurred, and possible mechanisms are suggested.

  20. Changes in neutrophil morphology and morphometry following exposure to cigarette smoke.

    Science.gov (United States)

    Lannan, S.; McLean, A.; Drost, E.; Gillooly, M.; Donaldson, K.; Lamb, D.; MacNee, W.

    1992-01-01

    Acute cigarette smoking delays neutrophils within the pulmonary circulation in some smokers. Evidence from an in-vitro Micropore filter model of the pulmonary capillaries indicates that this may be due to a smoke induced decrease in cell deformability. In order to determine whether changes in cell shape are associated with the observed decrease in neutrophil deformability following smoke exposure, cell morphology, using scanning electron microscopy, and morphometric measurements, made using transmission electron microscopy, were performed on aliquots of neutrophils harvested from whole blood in non-smoking subjects before and after exposure in vitro to cigarette smoke. Smoke exposure increased the maximum diameter and circumference of neutrophils, without changing their area. There was also a change in the maximum to minimum cell diameter ratio, which indicated that the cells had become less spherical. Scanning electron microscopy showed that smoke exposed cells had developed blebbing of their surface membranes, suggestive of an oxidative injury to the cell membrane rather than the shape changes associated with cell activation. These changes in the morphology and morphometry of smoke exposed neutrophils may contribute to the reduction in cell deformability induced by cigarette smoke. Images Fig. 3 Fig. 4 Fig. 5 PMID:1571278

  1. Complement Activation Induces Neutrophil Adhesion and Neutrophil-Platelet Aggregate Formation on Vascular Endothelial Cells

    Directory of Open Access Journals (Sweden)

    Magdalena Riedl

    2017-01-01

    Discussion: Therefore, our findings of (i neutrophils adhering to complement-activated endothelial cells, (ii the formation of neutrophil-platelet aggregates on endothelial cells, and (iii the ability of aHUS serum to induce similar effects identify a possible role for neutrophils in aHUS manifestation.

  2. DNA Electrochemistry with Tethered Methylene Blue

    Science.gov (United States)

    Pheeney, Catrina G.

    2012-01-01

    Methylene blue (MB′), covalently attached to DNA through a flexible C12 alkyl linker, provides a sensitive redox reporter in DNA electrochemistry measurements. Tethered, intercalated MB′ is reduced through DNA-mediated charge transport; the incorporation of a single base mismatch at position 3, 10, or 14 of a 17-mer causes an attenuation of the signal to 62 ± 3% of the well-matched DNA, irrespective of position in the duplex. The redox signal intensity for MB′–DNA is found to be least 3-fold larger than that of Nile blue (NB)–DNA, indicating that MB′ is even more strongly coupled to the π-stack. The signal attenuation due to an intervening mismatch does, however, depend on DNA film density and the backfilling agent used to passivate the surface. These results highlight two mechanisms for reduction of MB′ on the DNA-modified electrode: reduction mediated by the DNA base pair stack and direct surface reduction of MB′ at the electrode. These two mechanisms are distinguished by their rates of electron transfer that differ by 20-fold. The extent of direct reduction at the surface can be controlled by assembly and buffer conditions. PMID:22512327

  3. Interleukin-17 Promotes Neutrophil-Mediated Immunity by Activating Microvascular Pericytes and Not Endothelium

    Science.gov (United States)

    Liu, Rebecca; Lauridsen, Holly M.; Amezquita, Robert A.; Pierce, Richard W.; Jane-wit, Dan; Fang, Caodi; Pellowe, Amanda S.; Kirkiles-Smith, Nancy C.; Gonzalez, Anjelica L.; Pober, Jordan S.

    2016-01-01

    A classical hallmark of acute inflammation is neutrophil infiltration of tissues, a multi-step process that involves sequential cell-cell interactions of circulating leukocytes with interleukin (IL)-1- or tumor necrosis factor-α (TNF)-activated microvascular endothelial cells (ECs) and pericytes (PCs) that form the wall of the postcapillary venules. The initial infiltrating cells accumulate perivascularly in close proximity to PCs. IL-17, a pro-inflammatory cytokine that acts on target cells via a heterodimeric receptor formed by IL-17RA and IL-17RC subunits, also promotes neutrophilic inflammation but its effects on vascular cells are less clear. We report that both cultured human ECs and PCs strongly express IL-17RC and, while neither cell type expresses much IL-17RA, PCs express significantly more than ECs. IL-17, alone or synergistically with TNF, significantly alters inflammatory gene expression in cultured human PCs but not ECs. RNA-seq analysis identifies many IL-17-induced transcripts in PCs encoding proteins known to stimulate neutrophil-mediated immunity. Conditioned media (CM) from IL-17-activated PCs, but not ECs, induce pertussis toxin-sensitive neutrophil polarization, likely mediated by PC-secreted chemokines, and also stimulate neutrophil production of pro-inflammatory molecules, including TNF, IL-1α, IL-1β, and IL-8. Furthermore, IL-17-activated PCs but not ECs can prolong neutrophil survival by producing G-CSF and GM-CSF, delaying the mitochondria outer membrane permeabilization and caspase 9 activation. Importantly, neutrophils exhibit enhanced phagocytic capacity after activation by CM from IL-17-treated PCs. We conclude that PCs, not ECs, are the major target of IL-17 within the microvessel wall and that IL-17-activated PCs can modulate neutrophil functions within the perivascular tissue space. PMID:27534549

  4. Different innate neutrophil responses in controlled and uncontrolled asthma

    NARCIS (Netherlands)

    Tang, Francesca; Foxley, Gloria; Gibson, Peter; Burgess, Janette; Baines, Katherine; Oliver, Brian

    2015-01-01

    Introduction: Respiratory viruses are a major cause of asthma exacerbations. Neutrophilic inflammation occurs during infections and is associated with difficult to treat asthma. The role of neutrophils in viral infections and whether neutrophil dysfunction contributes to exacerbation pathogenesis

  5. Analytical investigation of the dynamics of tethered constellations in Earth orbit, phase 2

    Science.gov (United States)

    Lorenzini, Enrico C.; Gullahorn, Gordon E.; Cosmo, Mario L.; Estes, Robert D.; Grossi, Mario D.

    1994-01-01

    This final report covers nine years of research on future tether applications and on the actual flights of the Small Expendable Deployment System (SEDS). Topics covered include: (1) a description of numerical codes used to simulate the orbital and attitude dynamics of tethered systems during station keeping and deployment maneuvers; (2) a comparison of various tethered system simulators; (3) dynamics analysis, conceptual design, potential applications and propagation of disturbances and isolation from noise of a variable gravity/microgravity laboratory tethered to the Space Station; (4) stability of a tethered space centrifuge; (5) various proposed two-dimensional tethered structures for low Earth orbit for use as planar array antennas; (6) tethered high gain antennas; (7) numerical calculation of the electromagnetic wave field on the Earth's surface on an electrodynamically tethered satellite; (8) reentry of tethered capsules; (9) deployment dynamics of SEDS-1; (10) analysis of SEDS-1 flight data; and (11) dynamics and control of SEDS-2.

  6. [The significances of peripheral neutrophils CD(55) and myeloperoxidase expression in patients with myeloperoxidase-specific anti-neutrophil cytoplasmic antibody associated vasculitis].

    Science.gov (United States)

    Zhou, X L; Zheng, M J; Shuai, Z W; Zhang, L; Zhang, M M; Chen, S Y

    2017-06-01

    Objective: To investigate the expression of CD(55) and myeloperoxidase (MPO) on neutrophils in patients with MPO-specific anti-neutrophil cytoplasmic antibody associated vasculitis(MPO-AAV), and analyze the relationship between the expression and clinical manifestation. Methods: Forty untreated patients with active MPO-AAV (patient group) and 30 healthy volunteers (control group) were enrolled in this study. The CD(55) on neutrophils and both membrane and cytoplasmic MPO were detected by flow cytometry. Serum fragment-from the activated complement factor B(Ba) and MPO were measured by ELISA. The clinical activity of vasculitis was valued by Birmingham vasculitis activity score-version 3(BVAS-V3). The significance of laboratory data was evaluated by Spearman correlation test and multivariate linear regression analysis. Results: (1)The mean fluorescence intensity(MFI) of CD(55) expressed on neutrophils was significantly higher than that in control group[4 068.6±2 306.0 vs 2 999.5±1 504.9, P =0.033]. Similar results of serum MPO and Ba in patient group were found compared to controls [500.0(381.0, 612.7) IU/L vs 286.9(225.5, 329.1) IU/L, P <0.001; 35.2(25.2, 79.5) ng/L vs 18.0(15.0, 28.0) ng/L, P <0.001], respectively. However, MIF of cytoplasmic MPO in patients was significantly lower than that of control group(1 577.1±1 175.9 vs 3 105.3±2 323.0, P =0.003) . (2) In patient group, cytoplasmic intensity of MPO was negatively associated with the serum levels of MPO( r =-0.710, P <0.001) and Ba ( r =-0.589, P =0.001). Moreover, serum MPO was positively associated with serum Ba( r =0.691, P <0.001). Membrane intensity of CD(55) on neutrophils was positively correlated with patient age ( r =0.514, P =0.001), C reactive protein ( r =0.376, P =0.018), peripheral neutrophils count ( r =0.485, P =0.001) and BVAS-V3 ( r =0.484, P =0.002), whereas negative correlation between membrane CD(55) and disease duration was seen ( r =-0.403, P =0.01). (3) The result of multiple

  7. Oral neutrophil responses to acute prolonged exercise may not be representative of blood neutrophil responses.

    Science.gov (United States)

    Davison, Glen; Jones, Arwel Wyn

    2015-03-01

    Neutrophil numbers and function (oxidative burst) were assessed in peripheral blood and oral samples before and after prolonged exercise. Blood neutrophil count increased (∼3.5-fold, P < 0.001) and function decreased (30% ± 19% decrease, P = 0.005) postexercise. Oral neutrophil count (P = 0.392) and function (P = 0.334) were unchanged. Agreement between oral and blood neutrophil function responses to exercise was poor. These findings highlight the importance of studying neutrophils within various compartments/sample types.

  8. BST2/CD317 counteracts human coronavirus 229E productive infection by tethering virions at the cell surface

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Shiu-Mei [Department of Medical Research and Education, Taipei Veterans General Hospital and Institute of Clinical Medicine, Taipei 11217, Taiwan (China); Institute of Clinical Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan (China); Huang, Kuo-Jung [Department of Medical Research and Education, Taipei Veterans General Hospital and Institute of Clinical Medicine, Taipei 11217, Taiwan (China); Wang, Chin-Tien, E-mail: chintien@ym.edu.tw [Department of Medical Research and Education, Taipei Veterans General Hospital and Institute of Clinical Medicine, Taipei 11217, Taiwan (China); Institute of Clinical Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan (China)

    2014-01-20

    Bone marrow stromal antigen 2 (BST2), an interferon-inducible antiviral factor, has been shown to block the release of various enveloped viruses from cells. It has also been identified as an innate immune system component. Most enveloped viruses subject to BST2 restriction bud at the plasma membrane. Here we report our findings that (a) the production of human coronavirus 229E (HCoV-229E) progeny viruses, whose budding occurs at the ER-Golgi intermediate compartment (ERGIC), markedly decreases in the presence of BST2; and (b) BST2 knockdown expression results in enhanced HCoV-229E virion production. Electron microscopy analyses indicate that HCoV-229E virions are tethered to cell surfaces or intracellular membranes by BST2. Our results suggest that BST2 exerts a broad blocking effect against enveloped virus release, regardless of whether budding occurs at the plasma membrane or intracellular compartments. - Highlights: • BST2 knockdown expression results in enhanced HCoV-229E egress. • HCoV-229E virions are tethered to cell surfaces or intracellular membranes by BST2. • HCoV-229E infection at high MOI can significantly downregulate HeLa BST2 and rescue HIV-1 egress.

  9. Neutrophil heterogeneity: implications for homeostasis and pathogenesis

    NARCIS (Netherlands)

    Silvestre-Roig, Carlos; Hidalgo, Andres; Soehnlein, Oliver

    2016-01-01

    Neutrophils are polymorphonuclear leukocytes of the phagocytic system that act as first line of host defense against invading pathogens but are also important mediators of inflammation-induced injury. In contrast to other members of the innate immune system, neutrophils are classically considered a

  10. Candida albicans escapes from mouse neutrophils

    DEFF Research Database (Denmark)

    Ermert, David; Niemiec, Maria J; Röhm, Marc

    2013-01-01

    is the most widely used model organism. Neutrophils are essential immune cells to prevent opportunistic mycoses. To explore potential differences between the rodent infection model and the human host, we compared the interactions of C. albicans with neutrophil granulocytes from mice and humans. We revealed...

  11. Neutrophils: potential therapeutic targets in tularemia?

    Directory of Open Access Journals (Sweden)

    Lee-Ann H Allen

    2013-12-01

    Full Text Available The central role of neutrophils in innate immunity and host defense has long been recognized, and the ability of these cells to efficiently engulf and kill invading bacteria has been extensively studied, as has the role of neutrophil apoptosis in resolution of the inflammatory response. In the past few years additional immunoregulatory properties of neutrophils were discovered, and it is now clear that these cells play a much greater role in control of the immune response than was previously appreciated. In this regard, it is noteworthy that Francisella tularensis is one of relatively few pathogens that can successfully parasitize neutrophils as well as macrophages, DC and epithelial cells. Herein we will review the mechanisms used by F. tularensis to evade elimination by neutrophils. We will also reprise effects of this pathogen on neutrophil migration and lifespan as compared with other infectious and inflammatory disease states. In addition, we will discuss the evidence which suggests that neutrophils contribute to disease progression rather than effective defense during tularemia, and consider whether manipulation of neutrophil migration or turnover may be suitable adjunctive therapeutic strategies.

  12. Contribution of neutrophils to acute lung injury.

    Science.gov (United States)

    Grommes, Jochen; Soehnlein, Oliver

    2011-01-01

    Treatment of acute lung injury (ALI) and its most severe form, acute respiratory distress syndrome (ARDS), remain unsolved problems of intensive care medicine. ALI/ARDS are characterized by lung edema due to increased permeability of the alveolar-capillary barrier and subsequent impairment of arterial oxygenation. Lung edema, endothelial and epithelial injury are accompanied by an influx of neutrophils into the interstitium and broncheoalveolar space. Hence, activation and recruitment of neutrophils are regarded to play a key role in progression of ALI/ARDS. Neutrophils are the first cells to be recruited to the site of inflammation and have a potent antimicrobial armour that includes oxidants, proteinases and cationic peptides. Under pathological circumstances, however, unregulated release of these microbicidal compounds into the extracellular space paradoxically can damage host tissues. This review focuses on the mechanisms of neutrophil recruitment into the lung and on the contribution of neutrophils to tissue damage in ALI.

  13. The complex interplay between neutrophils and cancer.

    Science.gov (United States)

    Rakic, Andrea; Beaudry, Paul; Mahoney, Douglas J

    2018-03-01

    Neutrophils are the most abundant type of white blood cell, and are an essential component of the innate immune system. They characteristically arrive rapidly at sites of infection and injury, and release a variety of cytokines and toxic molecules to eliminate pathogens and elicit an acute inflammatory response. Research into the function of neutrophils in cancer suggest they have divergent roles. Indeed, while most studies have found neutrophils to be associated with cancer progression, others have also documented anticancer effects. In this review, we describe the investigations into neutrophil populations that have been implicated in promoting tumor growth and metastasis as well those demonstrating antitumor functions. The collective research suggests a complex role for neutrophils in cancer biology, which raises the prospect of their targeting for the treatment of cancer.

  14. Sonography compared with MR imaging in the evaluation of card tethering following myelomeningocele repair

    International Nuclear Information System (INIS)

    Newman, B.; Bowen, A.; Albright, L.

    1989-01-01

    This paper reports on MR imaging and videotaped US spine examinations to evaluate cord tethering were retrospectively compared in 12 children with prior myelomeningocele repair and correlated with clinical and surgical findings. Although US did not delineate normal or abnormal anatomy as well as MR imaging, both types of studies confirmed the presence of tethering in 10 patients. One child with a normal US examination and abnormal MR images had tethering confirmed surgically. A second child had a US study suggestive of tethering with equivocal MR images. Postoperative studies in eight patients correlated less well; US suggested persistent tethering in five patients and MR imaging indicated tethering in two

  15. Dynamic interactions of neutrophils and biofilms

    Directory of Open Access Journals (Sweden)

    Josefine Hirschfeld

    2014-12-01

    Full Text Available Background: The majority of microbial infections in humans are biofilm-associated and difficult to treat, as biofilms are highly resistant to antimicrobial agents and protect themselves from external threats in various ways. Biofilms are tenaciously attached to surfaces and impede the ability of host defense molecules and cells to penetrate them. On the other hand, some biofilms are beneficial for the host and contain protective microorganisms. Microbes in biofilms express pathogen-associated molecular patterns and epitopes that can be recognized by innate immune cells and opsonins, leading to activation of neutrophils and other leukocytes. Neutrophils are part of the first line of defense and have multiple antimicrobial strategies allowing them to attack pathogenic biofilms. Objective/design: In this paper, interaction modes of neutrophils with biofilms are reviewed. Antimicrobial strategies of neutrophils and the counteractions of the biofilm communities, with special attention to oral biofilms, are presented. Moreover, possible adverse effects of neutrophil activity and their biofilm-promoting side effects are discussed. Results/conclusion: Biofilms are partially, but not entirely, protected against neutrophil assault, which include the processes of phagocytosis, degranulation, and formation of neutrophil extracellular traps. However, virulence factors of microorganisms, microbial composition, and properties of the extracellular matrix determine whether a biofilm and subsequent microbial spread can be controlled by neutrophils and other host defense factors. Besides, neutrophils may inadvertently contribute to the physical and ecological stability of biofilms by promoting selection of more resistant strains. Moreover, neutrophil enzymes can degrade collagen and other proteins and, as a result, cause harm to the host tissues. These parameters could be crucial factors in the onset of periodontal inflammation and the subsequent tissue breakdown.

  16. Tethered Nanoparticle–Polymer Composites: Phase Stability and Curvature

    KAUST Repository

    Srivastava, Samanvaya

    2012-04-17

    Phase behavior of poly(ethylene glycol) (PEG) tethered silica nanoparticles dispersed in PEG hosts is investigated using small-angle X-ray scattering. Phase separation in dispersions of densely grafted nanoparticles is found to display strikingly different small-angle X-ray scattering signatures in comparison to phase-separated composites comprised of bare or sparsely grafted nanoparticles. A general diagram for the dispersion state and phase stability of polymer tethered nanoparticle-polymer composites incorporating results from this as well as various other contemporary studies is presented. We show that in the range of moderate to high grafting densities the dispersion state of nanoparticles in composites is largely insensitive to the grafting density of the tethered chains and chemistry of the polymer host. Instead, the ratio of the particle diameter to the size of the tethered chain and the ratio of the molecular weights of the host and tethered polymer chains (P/N) are shown to play a dominant role. Additionally, we find that well-functionalized nanoparticles form stable dispersions in their polymer host beyond the P/N limit that demarcates the wetting/dewetting transition in polymer brushes on flat substrates interacting with polymer melts. A general strategy for achieving uniform nanoparticle dispersion in polymers is proposed. © 2012 American Chemical Society.

  17. Tethered Pyrotechnic Apparatus for Acquiring a Ground Sample

    Science.gov (United States)

    Jones, Jack; Zimmerman, Wayne; Wu, Jiunn Jenq; Badescu, Mircea; Sherrit, Stewart

    2009-01-01

    A proposed alternative design for the balloon-borne ground-sampling system described in the immediately preceding article would not rely on free fall to drive a harpoonlike sample-collecting device into the ground. Instead, the harpoon-like sample-collecting device would be a pyrotechnically driven, tethered projectile. The apparatus would include a tripod that would be tethered to the gondola. A gun for shooting the projectile into the ground would be mounted at the apex of the tripod. The gun would include an electronic trigger circuit, a chamber at the breech end containing a pyrotechnic charge, and a barrel. A sabot would be placed in the barrel just below the pyrotechnic charge, and the tethered projectile would be placed in the barrel just below the sabot. The tripod feet would be equipped with contact sensors connected to the trigger circuit. In operation, the tripod would be lowered to the ground on its tether. Once contact with the ground was detected by the sensors on all three tripod feet, the trigger circuit would fire the pyrotechnic charge to drive the projectile into the ground. (Requiring contact among all three tripod feet and the ground would ensure that the projectile would be fired into the ground, rather than up toward the gondola or the balloon.) The tethered projectile would then be reeled back up to the gondola for analysis of the sample.

  18. Numerical Simulation of Tethered Underwater Kites for Power Generation

    Science.gov (United States)

    Ghasemi, Amirmahdi; Olinger, David; Tryggvason, Gretar

    2015-11-01

    An emerging renewable energy technology, tethered undersea kites (TUSK), which is used to extract hydrokinetic energy from ocean and tidal currents, is studied. TUSK systems consist of a rigid-winged ``kite,'' or glider, moving in an ocean current which is connected by tethers to a floating buoy on the ocean surface. The TUSK kite is a current speed enhancement device since the kite can move in high-speed, cross-current motion at 4-6 times the current velocity, thus producing more power than conventional marine turbines. A computational simulation is developed to simulate the dynamic motion of an underwater kite and extendable tether. A two-step projection method within a finite volume formulation, along with an Open MP acceleration method, is employed to solve the Navier-Stokes equations. An immersed boundary method is incorporated to model the fluid-structure interaction of the rigid kite (with NACA 0012 airfoil shape in 2D and NACA 0021 airfoil shape in 3D simulations) and the fluid flow. PID control methods are used to adjust the kite angle of attack during power (tether reel-out) and retraction (reel-in) phases. Two baseline simulations (for kite motions in two and three dimensions) are studied, and system power output, flow field vorticity, tether tension, and hydrodynamic coefficients (lift and drag) for the kite are determined. The simulated power output shows good agreement with established theoretical results for a kite moving in two-dimensions.

  19. Ectodomain Shedding by ADAM17: Its Role in Neutrophil Recruitment and the Impairment of This Process during Sepsis.

    Science.gov (United States)

    Mishra, Hemant K; Ma, Jing; Walcheck, Bruce

    2017-01-01

    Neutrophils are specialized at killing bacteria and are recruited from the blood in a rapid and robust manner during infection. A cascade of adhesion events direct their attachment to the vascular endothelium and migration into the underlying tissue. A disintegrin and metalloproteinase 17 (ADAM17) functions in the cell membrane of neutrophils and endothelial cells by cleaving its substrates, typically in a cis manner, at an extracellular site proximal to the cell membrane. This process is referred to as ectodomain shedding and it results in the downregulation of various adhesion molecules and receptors, and the release of immune regulating factors. ADAM17 sheddase activity is induced upon cell activation and rapidly modulates intravascular adhesion events in response to diverse environmental stimuli. During sepsis, an excessive systemic inflammatory response against infection, neutrophil migration becomes severely impaired. This involves ADAM17 as indicated by increased levels of its cleaved substrates in the blood of septic patients, and that ADAM17 inactivation improves neutrophil recruitment and bacterial clearance in animal models of sepsis. Excessive ADAM17 sheddase activity during sepsis thus appears to undermine in a direct and indirect manner the necessary balance between intravascular adhesion and de-adhesion events that regulate neutrophil migration into sites of infection. This review provides an overview of ADAM17 function and regulation and its potential contribution to neutrophil dysfunction during sepsis.

  20. Low Earth Orbit Environmental Effects on Space Tether Materials

    Science.gov (United States)

    Finckernor, Miria M.; Gitlemeier, Keith A.; Hawk, Clark W.; Watts, Ed

    2005-01-01

    Atomic oxygen (AO) and ultraviolet (UV) radiation erode and embrittle most polymeric materials. This research was designed to test several different materials and coatings under consideration for their application to space tethers, for resistance to these effects. The samples were vacuum dehydrated, weighed and then exposed to various levels of AO or UV radiation at the NASA Marshall Space Flight Center. They were then re-weighed to determine mass loss due to atomic oxygen erosion, inspected for damage and tensile tested to determine strength loss. The experiments determined that the Photosil coating process, while affording some protection, damaged the tether materials worse than the AO exposure. TOR-LM also failed to fully protect the materials, especially from UV radiation. The POSS and nickel coatings did provide some protection to the tethers, which survived the entire test regime. M5 was tested, uncoated, and survived AO exposure, though its brittleness prevented any tensile testing.

  1. Activation of bovine neutrophils by Brucella spp.

    Science.gov (United States)

    Keleher, Lauren L; Skyberg, Jerod A

    2016-09-01

    Brucellosis is a globally important zoonotic infectious disease caused by gram negative bacteria of the genus Brucella. While many species of Brucella exist, Brucella melitensis, Brucella abortus, and Brucella suis are the most common pathogens of humans and livestock. The virulence of Brucella is largely influenced by its ability to evade host factors, including phagocytic killing mechanisms, which are critical for the host response to infection. The aim of this study was to characterize the bovine neutrophil response to virulent Brucella spp. Here, we found that virulent strains of smooth B. abortus, B. melitensis, B. suis, and virulent, rough, strains of Brucella canis possess similar abilities to resist killing by resting, or IFN-γ-activated, bovine neutrophils. Bovine neutrophils responded to infection with a time-dependent oxidative burst that varied little between Brucella spp. Inhibition of TAK1, or SYK kinase blunted the oxidative burst of neutrophils in response to Brucella infection. Interestingly, Brucella spp. did not induce robust death of bovine neutrophils. These results indicate that bovine neutrophils respond similarly to virulent Brucella spp. In addition, virulent Brucella spp., including naturally rough strains of B. canis, have a conserved ability to resist killing by bovine neutrophils. Copyright © 2016 Elsevier B.V. All rights reserved.

  2. Tethered balloon-based measurements of meteorological variables and aerosols

    Science.gov (United States)

    Sentell, R. J.; Storey, R. W.; Chang, J. J. C.; Jacobsen, S. J.

    1976-01-01

    Tethered balloon based measurements of the vertical distributions of temperature, humidity, wind speed, and aerosol concentrations were taken over a 4-hour period beginning at sunrise on June 29, 1976, at Wallops Island, Virginia. Twelve consecutive profiles of each variable were obtained from ground to about 500 meters. These measurements were in conjuction with a noise propagation study on remotely arrayed acoustic range (ROMAAR) at Wallops Flight Center. An organized listing of these vertical soundings is presented. The tethered balloon system configuration utilized for these measurements is described.

  3. Use of top tethers with forward-facing child restraints: observations and driver interviews.

    Science.gov (United States)

    Eichelberger, Angela H; Decina, Lawrence E; Jermakian, Jessica S; McCartt, Anne T

    2014-02-01

    Despite the safety benefits, many parents do not use top tethers with forward-facing child restraints. Detailed information was collected about why parents are not using tethers. The sample included 479 drivers who had forward-facing child restraints installed in passenger vehicles equipped with tether anchors. The survey was conducted primarily at shopping centers, recreation facilities, child care facilities, car seat check events, and health care facilities in mostly suburban areas surrounding Philadelphia, Washington, DC, Fredericksburg (VA), and Seattle. Drivers were surveyed about their knowledge and use of tethers and experience with child restraints. Tether use was observed to verify whether tethers were being used correctly. Fifty-six percent of forward-facing child restraints were installed with the tether; 39% were installed with the tether used correctly. The tether was used with 71% of LATCH lower anchor installations and 33% of seat belt installations. Drivers who installed child restraints without tethers most often said they did not know about the tether or how to use it. Although the tether use rate was slightly higher in the current research than in previous studies, many parents and caregivers still use forward-facing child restraints without attaching the tether. Because the main problem is lack of awareness of the tether or how to use it, public education should focus specifically on the safety benefits of tethers and how to use them. Information about why caregivers fail to use top tethers is potentially useful to child restraint manufacturers, child passenger safety technicians, and others who work with parents to improve motor vehicle safety. Copyright © 2013 Elsevier Ltd and National Safety Council. All rights reserved.

  4. Neutrophil Lymphocyte Ratio Predicts Postoperative Pain after ...

    African Journals Online (AJOL)

    2018-02-07

    Feb 7, 2018 ... between preoperatively measured neutrophil-lymphocyte ratio (NLR) – as an inflammation ... analgesic (tenoxicam – as the first drug of choice, paracetamol, tramadol, or pethidine) usage ... fracture fixation). Age, sex, type of ...

  5. Investigation of urinary neutrophil gelatinase associated lipocalin ...

    African Journals Online (AJOL)

    Investigation of urinary neutrophil gelatinase associated lipocalin (NGAL) for early diagnosis of acute kidney ... African Journal of Urology ... Demographic and clinical data including surgical procedure were recorded in Excel and analyzed by ...

  6. Targeting Neutrophilic Inflammation using Polymersome-Mediated Cellular Delivery

    OpenAIRE

    Robertson, J.D.; Ward, J.R.; Avila-Olias, M.; Battaglia, G.; Renshaw, S.A.

    2017-01-01

    Neutrophils are key effector cells in inflammation and play an important role in neutralizing invading pathogens. During inflammation resolution, neutrophils undergo apoptosis before they are removed by macrophages, but if apoptosis is delayed, neutrophils can cause extensive tissue damage and chronic disease. Promotion of neutrophil apoptosis is a potential therapeutic approach for treating persistent inflammation, yet neutrophils have proven difficult cells to manipulate experimentally. In ...

  7. Cryptococcus neoformans modulates extracellular killing by neutrophils

    Directory of Open Access Journals (Sweden)

    Asfia eQureshi

    2011-09-01

    Full Text Available We recently established a key role for host sphingomyelin synthase (SMS in the regulation of the killing activity of neutrophils against Cryptococcus neoformans. In this work, we studied the effect of C. neoformans on the killing activity of neutrophils and whether SMS would still be a player against C. neoformans in immunocompromised mice lacking T and NK cells (Tgε26 mice. To this end, we analyzed whether C. neoformans would have any effect on neutrophil survival and killing in vitro and in vivo. We show that unlike C. albicans, neither the presence nor the capsule size of C. neoformans cells have any effect on neutrophil viability. Interestingly, melanized C. neoformans cells totally abrogated the killing activity of neutrophils. Next, we monitored how exposure of neutrophils to C. neoformans cells would interfere with any further killing activity of the medium and found that pre-incubation with live but not heat-killed fungal cells significantly inhibits further killing activity of the medium. We next studied whether activation of SMS at the site of C. neoformans infection is dependent on T and NK cells. Using matrix-assisted laser desorption-ionization (MALDI tissue imaging in infected lung we found that similarly to previous observations in the isogenic wild type CBA/J mice, SM 16:0 levels are significantly elevated at the site of infection in mice lacking T and NK cells but only at early time points. This study highlights that C. neoformans may negatively regulate the killing activity of neutrophils and that SMS activation in neutrophils appears to be partially independent of T and/or NK cells.

  8. Neutrophil extracellular trap formation in supragingival biofilms.

    Science.gov (United States)

    Hirschfeld, Josefine; Dommisch, Henrik; Skora, Philipp; Horvath, Gabor; Latz, Eicke; Hoerauf, Achim; Waller, Tobias; Kawai, Toshihisa; Jepsen, Søren; Deschner, James; Bekeredjian-Ding, Isabelle

    2015-01-01

    Oral biofilms are the causative agents of the highly prevalent oral diseases periodontitis and caries. Additionally, the host immune response is thought to play a critical role in disease onset. Neutrophils are known to be a key host response factor to bacterial challenge on host surfaces. Release of neutrophil extracellular traps (NETs) as a novel antimicrobial defense strategy has gained increasing attention in the past years. Here, we investigated the influx of neutrophils into the dental plaque and the ability of oral bacteria to trigger intra-biofilm release of NETs and intracellular proteins. Supragingival biofilms and whole saliva were sampled from systemically healthy subjects participating in an experimental gingivitis study. Biofilms were analysed by immunofluorescence followed by confocal and fluorescence microscopy. Moreover, concentrations of cytokines and immune-associated proteins in biofilm suspensions and saliva were assessed by ELISA. Neutrophils obtained from blood were stimulated with twelve bacterial species isolated from cultured biofilms or with lipopolysaccharide to monitor NET formation. Neutrophils, NETs, neutrophil-associated proteins (myeloperoxidase, elastase-2, cathepsin G, cathelicidin LL-37), interleukin-8, interleukin-1β and tumor necrosis factor were detected within plaque samples and saliva. All tested bacterial species as well as the polymicrobial samples isolated from the plaque of each donor induced release of NETs and interleukin-8. The degree of NET formation varied among different subjects and did not correlate with plaque scores or clinical signs of local inflammation. Our findings indicate that neutrophils are attracted towards dental biofilms, in which they become incorporated and where they are stimulated by microbes to release NETs and immunostimulatory proteins. Thus, neutrophils and NETs may be involved in host biofilm control, although their specific role needs to be further elucidated. Moreover, inter

  9. Hierarchical Structure in Semicrystalline Polymers Tethered to Nanospheres

    KAUST Repository

    Kim, Sung A

    2014-01-28

    We report on structural and dynamic transitions of polymers tethered to nanoparticles. In particular, we use X-ray diffraction, vibrational spectroscopy, and thermal measurements to investigate multiscale structure and dynamic transitions of poly(ethylene glycol) (PEG) chains densely grafted to SiO2 nanoparticles. The approach used for synthesizing these hybrid particles leads to homogeneous SiO2-PEG composites with polymer grafting densities as high as 1.5 chains/nm2, which allows the hybrid materials to exist as self-suspended suspensions with distinct hierarchical structure and thermal properties. On angstrom and nanometer length scales, the tethered PEG chains exhibit more dominant TTG conformations and helix unit cell structure, in comparison to the untethered polymer. The nanoparticle tethered PEG chains are also reported to form extended crystallites on tens of nanometers length scales and to exhibit more stable crystalline structure on small dimensions. On length scales comparable to the size of each hybrid SiO 2-PEG unit, the materials are amorphous presumably as a result of the difficulty fitting the nanoparticle anchors into the PEG crystal lattice. This structural change produces large effects on the thermal transitions of PEG molecules tethered to nanoparticles. © 2014 American Chemical Society.

  10. The Science and Applications Tethered Platform (SATP) project

    Science.gov (United States)

    Merlina, P.

    1986-01-01

    The capabilities of tether systems in orbit are going to be demonstrated by the first planned flights of the Tethered Satellite System (TSS). These test flights will investigate the properties of tether systems as low altitude atmospheric research facilities and as electric power generators. Studies are being conducted with the purpose of testing a variety of concepts and approaches. A comparative analysis of results will allow the choosing of the most promising ideas for further development. The broad range of applications presently under study include applications in electrodynamics, transportation, microgravity in addition to basic research. The SATP project definition study is now about midway through its first phase. The analyses conducted have led to an appraisal of users interest in the project and to a deeper understanding of the problems associated with large, long-lived tether systems in space. In addition, two specialized platform designs, devoted to microgravity and precise pointing applications, are being studied because of their potential usefulness and the promise of technical feasibility.

  11. 75 FR 47316 - Centennial Challenges 2010 Strong Tether Challenge

    Science.gov (United States)

    2010-08-05

    ... NATIONAL AERONAUTICS AND SPACE ADMINISTRATION Centennial Challenges 2010 Strong Tether Challenge... teams that wish to compete may register. Centennial Challenges is a program of prize competitions to..., please visit: http://www.spaceward.org/elevator2010-ts . For general information on the NASA Centennial...

  12. Position Control of an X4-Flyer Using a Tether

    Directory of Open Access Journals (Sweden)

    , Keigo Watanabe

    2014-10-01

    Full Text Available In Japan, aging of infrastructures, such as roads, bridges, and water and sewer services, etc. poses a problem, and it is required to extend the life-span of such infrastructures by maintenance. Among infrastructures, especially bridges are periodically inspected by short range visual observations, which check the damage and deterioration of the surface. However, since there are some cases where the short range visual observation is difficult, an alternative method is required so as to replace the short range visual observation with it. So, "X4-Flyer" is very attractive because of realizing a movement at high altitude easily. The objective of this study is to develop a tethered X4- Flyer, so that the conventional short range visual observation of bridges is replaced by it. In this paper, a method for the measurement and control of the position is described by using a tether for controlling the position of the X4-Flyer. In addition, it is checked whether the tethered X4-Flyer can control the position using the proposed method or not, letting it fly in a state in which a tether is being attached.

  13. T-Rex: A Japanese Space Tether Experiment

    Science.gov (United States)

    Johnson, Les

    2009-01-01

    Electrodynamic tether (EDT) thrusters work by virtue of the force a magnetic field exerts on a wire carrying an electrical current. The force, which acts on any charged particle moving through a magnetic field (including the electrons moving in a current-carrying wire), were concisely expressed by Lorentz in 1895 in an equation that now bears his name. The force acts in a direction perpendicular to both the direction of current flow and the magnetic field vector. Electric motors make use of this force: a wire loop in a magnetic field is made to rotate by the torque the Lorentz Force exerts on it due to an alternating current in the loop times so as to keep the torque acting in the same sense. The motion of the loop is transmitted to a shaft, thus providing work. Although the working principle of EDT thrusters is not new, its application to space transportation may be significant. In essence, an EDT thruster is just a clever way of getting an electrical current to flow in a long orbiting wire (the tether) so that the Earth s magnetic field will accelerate the wire and, consequently the payload attached to the wire. The direction of current flow in the tether, either toward or away from the Earth along the local vertical, determines whether the magnetic force will raise or lower the orbit. The bias voltage of a vertically deployed metal tether, which results just from its orbital motion (assumed eastward) through Earth s magnetic field, is positive with respect to the ambient plasma at the top and negative at the bottom. This polarization is due to the action of the Lorentz force on the electrons in the tether. Thus, the natural current flow is the result of negative electrons being attracted to the upper end and then returned to the plasma at the lower end. The magnetic force in this case has a component opposite to the direction of motion, and thus leads to a lowering of the orbit and eventually to re-entry. In this generator mode of operation the Lorentz Force

  14. Relaxation Dynamics of Nanoparticle-Tethered Polymer Chains

    KAUST Repository

    Kim, Sung A

    2015-09-08

    © 2015 American Chemical Society. Relaxation dynamics of nanoparticle-tethered cis-1,4-polyisoprene (PI) are investigated using dielectric spectroscopy and rheometry. A model system composed of polymer chains densely grafted to spherical SiO2 nanoparticles to form self-suspended suspensions facilitates detailed studies of slow global chain and fast segmental mode dynamics under surface and geometrical confinement-from experiments performed in bulk materials. We report that unentangled polymer molecules tethered to nanoparticles relax far more slowly than their tethered entangled counterparts. Specifically, at fixed grafting density we find, counterintuitively, that increasing the tethered polymer molecular weight up to values close to the entanglement molecular weight speeds up chain relaxation dynamics. Decreasing the polymer grafting density for a fixed molecular weight has the opposite effect: it dramatically slows down chain relaxation, increases interchain coupling, and leads to a transition in rheological response from simple fluid behavior to viscoelastic fluid behavior for tethered PI chains that are unentangled by conventional measures. Increasing the measurement temperature produces an even stronger elastic response and speeds up molecular relaxation at a rate that decreases with grafting density and molecular weight. These observations are discussed in terms of chain confinement driven by crowding between particles and by the existence of an entropic attractive force produced by the space-filling constraint on individual chains in a self-suspended material. Our results indicate that the entropic force between densely grafted polymer molecules couples motions of individual chains in an analogous manner to reversible cross-links in associating polymers.

  15. Modelling a tethered mammalian sperm cell undergoing hyperactivation

    KAUST Repository

    Curtis, M.P.

    2012-09-01

    The beat patterns of mammalian sperm flagella can be categorised into two different types. The first involves symmetric waves propagating down the flagellum with a net linear propulsion of the sperm cell. The second, hyperactive, waveform is classified by vigorous asymmetric waves of higher amplitude, lower wavenumber and frequency propagating down the flagellum resulting in highly curved trajectories. The latter beat pattern is part of the capacitation process whereby sperm prepare for the prospective penetration of the zona pellucida and fusion with the egg. Hyperactivation is often observed to initiate as sperm escape from epithelial and ciliary bindings formed within the isthmic regions of the female oviducts, leading to a conjecture in the literature that this waveform is mechanically important for sperm escape. Hence, we explore the mechanical effects of hyperactivation on a tethered sperm, focussing on a Newtonian fluid. Using a resistive force theory model we demonstrate that hyperactivation can indeed generate forces that pull the sperm away from a tethering point and consequently a hyperactivated sperm cell bound to an epithelial surface need not always be pushed by its flagellum. More generally, directions of the forces generated by tethered flagella are insensitive to reductions in beat frequency and the detailed flagellar responses depend on the nature of the binding at the tethering point. Furthermore, waveform asymmetry and amplitude increases enhance the tendency for a tethered flagellum to start tugging on its binding. The same is generally predicted to be true for reductions in the wavenumber of the flagellum beat, but not universally so, emphasising the dynamical complexity of flagellar force generation. Finally, qualitative observations drawn from experimental data of human sperm bound to excised female reproductive tract are also presented and are found to be consistent with the theoretical predictions. © 2012 Elsevier Ltd.

  16. Modelling a tethered mammalian sperm cell undergoing hyperactivation

    KAUST Repository

    Curtis, M.P.; Kirkman-Brown, J.C.; Connolly, T.J.; Gaffney, E.A.

    2012-01-01

    The beat patterns of mammalian sperm flagella can be categorised into two different types. The first involves symmetric waves propagating down the flagellum with a net linear propulsion of the sperm cell. The second, hyperactive, waveform is classified by vigorous asymmetric waves of higher amplitude, lower wavenumber and frequency propagating down the flagellum resulting in highly curved trajectories. The latter beat pattern is part of the capacitation process whereby sperm prepare for the prospective penetration of the zona pellucida and fusion with the egg. Hyperactivation is often observed to initiate as sperm escape from epithelial and ciliary bindings formed within the isthmic regions of the female oviducts, leading to a conjecture in the literature that this waveform is mechanically important for sperm escape. Hence, we explore the mechanical effects of hyperactivation on a tethered sperm, focussing on a Newtonian fluid. Using a resistive force theory model we demonstrate that hyperactivation can indeed generate forces that pull the sperm away from a tethering point and consequently a hyperactivated sperm cell bound to an epithelial surface need not always be pushed by its flagellum. More generally, directions of the forces generated by tethered flagella are insensitive to reductions in beat frequency and the detailed flagellar responses depend on the nature of the binding at the tethering point. Furthermore, waveform asymmetry and amplitude increases enhance the tendency for a tethered flagellum to start tugging on its binding. The same is generally predicted to be true for reductions in the wavenumber of the flagellum beat, but not universally so, emphasising the dynamical complexity of flagellar force generation. Finally, qualitative observations drawn from experimental data of human sperm bound to excised female reproductive tract are also presented and are found to be consistent with the theoretical predictions. © 2012 Elsevier Ltd.

  17. Autonomous Vision-Based Tethered-Assisted Rover Docking

    Science.gov (United States)

    Tsai, Dorian; Nesnas, Issa A.D.; Zarzhitsky, Dimitri

    2013-01-01

    Many intriguing science discoveries on planetary surfaces, such as the seasonal flows on crater walls and skylight entrances to lava tubes, are at sites that are currently inaccessible to state-of-the-art rovers. The in situ exploration of such sites is likely to require a tethered platform both for mechanical support and for providing power and communication. Mother/daughter architectures have been investigated where a mother deploys a tethered daughter into extreme terrains. Deploying and retracting a tethered daughter requires undocking and re-docking of the daughter to the mother, with the latter being the challenging part. In this paper, we describe a vision-based tether-assisted algorithm for the autonomous re-docking of a daughter to its mother following an extreme terrain excursion. The algorithm uses fiducials mounted on the mother to improve the reliability and accuracy of estimating the pose of the mother relative to the daughter. The tether that is anchored by the mother helps the docking process and increases the system's tolerance to pose uncertainties by mechanically aligning the mating parts in the final docking phase. A preliminary version of the algorithm was developed and field-tested on the Axel rover in the JPL Mars Yard. The algorithm achieved an 80% success rate in 40 experiments in both firm and loose soils and starting from up to 6 m away at up to 40 deg radial angle and 20 deg relative heading. The algorithm does not rely on an initial estimate of the relative pose. The preliminary results are promising and help retire the risk associated with the autonomous docking process enabling consideration in future martian and lunar missions.

  18. Learning characteristics of a space-time neural network as a tether skiprope observer

    Science.gov (United States)

    Lea, Robert N.; Villarreal, James A.; Jani, Yashvant; Copeland, Charles

    1993-01-01

    The Software Technology Laboratory at the Johnson Space Center is testing a Space Time Neural Network (STNN) for observing tether oscillations present during retrieval of a tethered satellite. Proper identification of tether oscillations, known as 'skiprope' motion, is vital to safe retrieval of the tethered satellite. Our studies indicate that STNN has certain learning characteristics that must be understood properly to utilize this type of neural network for the tethered satellite problem. We present our findings on the learning characteristics including a learning rate versus momentum performance table.

  19. One kilometer (1 km) electric solar wind sail tether produced automatically.

    Science.gov (United States)

    Seppänen, Henri; Rauhala, Timo; Kiprich, Sergiy; Ukkonen, Jukka; Simonsson, Martin; Kurppa, Risto; Janhunen, Pekka; Hæggström, Edward

    2013-09-01

    We produced a 1 km continuous piece of multifilament electric solar wind sail tether of μm-diameter aluminum wires using a custom made automatic tether factory. The tether comprising 90,704 bonds between 25 and 50 μm diameter wires is reeled onto a metal reel. The total mass of 1 km tether is 10 g. We reached a production rate of 70 m/24 h and a quality level of 1‰ loose bonds and 2‰ rebonded ones. We thus demonstrated that production of long electric solar wind sail tethers is possible and practical.

  20. Nontypeable Haemophilus influenzae initiates formation of neutrophil extracellular traps.

    Science.gov (United States)

    Juneau, Richard A; Pang, Bing; Weimer, Kristin E D; Armbruster, Chelsie E; Swords, W Edward

    2011-01-01

    Nontypeable Haemophilus influenzae (NTHI) is a leading cause of otitis media infections, which are often chronic and/or recurrent in nature. NTHI and other bacterial species persist in vivo within biofilms during otitis media and other persistent infections. These biofilms have a significant host component that includes neutrophil extracellular traps (NETs). These NETs do not mediate clearance of NTHI, which survives within NET structures by means of specific subpopulations of lipooligosaccharides on the bacterial surface that are determinants of biofilm formation in vitro. In this study, the ability of NTHI and NTHI components to initiate NET formation was examined using an in vitro model system. Both viable and nonviable NTHI strains were shown to promote NET formation, as did preparations of bacterial DNA, outer membrane proteins, and lipooligosaccharide (endotoxin). However, only endotoxin from a parental strain of NTHI exhibited equivalent potency in NET formation to that of NTHI. Additional studies showed that NTHI entrapped within NET structures is resistant to both extracellular killing within NETs and phagocytic killing by incoming neutrophils, due to oligosaccharide moieties within the lipooligosaccharides. Thus, we concluded that NTHI elicits NET formation by means of multiple pathogen-associated molecular patterns (most notably endotoxin) and is highly resistant to killing within NET structures. These data support the conclusion that, for NTHI, formation of NET structures may be a persistence determinant by providing a niche within the middle-ear chamber.

  1. Ca2+ response in neutrophils after exposure to bacterial N-formyl-methionyl-leucyl-phenylalanine: delayed response in ulcerative colitis

    DEFF Research Database (Denmark)

    Vainer, Ben; Lamberth, Kasper; Brimnes, Jens

    2003-01-01

    In acute stages of ulcerative colitis (UC), neutrophils migrate from the circulation into inflamed colonic tissue, initiated by yet unknown stimuli. The bacterial peptide N-formyl-methionyl-leucyl-phenylalanine (FMLP) is a component of the surface membrane of colonic bacteria such as Escherichia ...

  2. High Prevalence of Autoantibodies to hLAMP-2 in Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis

    NARCIS (Netherlands)

    Kain, Renate; Tadema, Henko; McKinney, Eoin F.; Benharkou, Alexandra; Brandes, Ricarda; Peschel, Andrea; Hubert, Virginie; Feenstra, Tjerk; Sengoelge, Guerkan; Stegeman, Coen; Heeringa, Peter; Lyons, Paul A.; Smith, Kenneth G. C.; Kallenberg, Cees; Rees, Andrew J.

    The involvement of autoantibodies to human lysosome-associated membrane protein-2 (hLAMP-2) in anti neutrophil cytoplasmic antibody (ANCA) associated vasculitis is controversial because of the absence of confirmatory data subsequent to the initial reports of their high prevalence in this disease. We

  3. Omega-3 Fatty acids and inflammation: novel interactions reveal a new step in neutrophil recruitment.

    Directory of Open Access Journals (Sweden)

    Samantha P Tull

    2009-08-01

    Full Text Available Inflammation is a physiological response to tissue trauma or infection, but leukocytes, which are the effector cells of the inflammatory process, have powerful tissue remodelling capabilities. Thus, to ensure their precise localisation, passage of leukocytes from the blood into inflamed tissue is tightly regulated. Recruitment of blood borne neutrophils to the tissue stroma occurs during early inflammation. In this process, peptide agonists of the chemokine family are assumed to provide a chemotactic stimulus capable of supporting the migration of neutrophils across vascular endothelial cells, through the basement membrane of the vessel wall, and out into the tissue stroma. Here, we show that, although an initial chemokine stimulus is essential for the recruitment of flowing neutrophils by endothelial cells stimulated with the inflammatory cytokine tumour necrosis factor-alpha, transit of the endothelial monolayer is regulated by an additional and downstream stimulus. This signal is supplied by the metabolism of the omega-6-polyunsaturated fatty acid (n-6-PUFA, arachidonic acid, into the eicosanoid prostaglandin-D(2 (PGD(2 by cyclooxygenase (COX enzymes. This new step in the neutrophil recruitment process was revealed when the dietary n-3-PUFA, eicosapentaenoic acid (EPA, was utilised as an alternative substrate for COX enzymes, leading to the generation of PGD(3. This alternative series eicosanoid inhibited the migration of neutrophils across endothelial cells by antagonising the PGD(2 receptor. Here, we describe a new step in the neutrophil recruitment process that relies upon a lipid-mediated signal to regulate the migration of neutrophils across endothelial cells. PGD(2 signalling is subordinate to the chemokine-mediated activation of neutrophils, but without the sequential delivery of this signal, neutrophils fail to penetrate the endothelial cell monolayer. Importantly, the ability of the dietary n-3-PUFA, EPA, to inhibit this process not

  4. Modeling and Control of Electrodynamic Tethers - an Energy and Topology Approach

    DEFF Research Database (Denmark)

    Larsen, Martin Birkelund

    A space tether is a cable used to connect spacecrafts in an orbiting structure. If an electrical current is lead through the tether, it can be utilized to provide propulsion for the spacecraft. In this case the cable is referred to as an electrodynamic tether. The system utilizes the magnetic field...... of the Earth for creating a Lorentz force along the tether which occur when a current carrying wire operates in a magnetic field. The use of electrodynamic tethers are interesting since they operate solely on electrical energy, which can be provided by solar panels of the spacecrafts. In this way the amount...... when using electrodynamic tethers is that the force created along the tether is based on an external uncontrollable condition, namely the magnetic field. Even whit a known model of the magnetic field, limitations to the creation of the Lorentz force still exists, since the force can only be generated...

  5. The golgin GMAP-210 is required for efficient membrane trafficking in the early secretory pathway

    OpenAIRE

    Roboti, Peristera; Sato, Keisuke; Lowe, Martin

    2015-01-01

    Golgins are coiled-coil proteins that participate in membrane-tethering events at the Golgi complex. Golgin-mediated tethering is thought to be important for vesicular trafficking and Golgi organization. However, the degree to which individual golgins contribute to these processes is poorly defined, and it has been proposed that golgins act in a largely redundant manner. Previous studies on the golgin GMAP-210 (also known as TRIP11), which is mutated in the rare skeletal disorder achondrogene...

  6. Neutrophils in Cancer: Two Sides of the Same Coin.

    Science.gov (United States)

    Uribe-Querol, Eileen; Rosales, Carlos

    2015-01-01

    Neutrophils are the most abundant leukocytes in blood and are considered to be the first line of defense during inflammation and infections. In addition, neutrophils are also found infiltrating many types of tumors. Tumor-associated neutrophils (TANs) have relevant roles in malignant disease. Indeed neutrophils may be potent antitumor effector cells. However, increasing clinical evidence shows TANs correlate with poor prognosis. The tumor microenvironment controls neutrophil recruitment and in turn TANs help tumor progression. Hence, TANs can be beneficial or detrimental to the host. It is the purpose of this review to highlight these two sides of the neutrophil coin in cancer and to describe recent studies that provide some light on the mechanisms for neutrophil recruitment to the tumor, for neutrophils supporting tumor progression, and for neutrophil activation to enhance their antitumor functions.

  7. Neutrophils in Cancer: Two Sides of the Same Coin

    Directory of Open Access Journals (Sweden)

    Eileen Uribe-Querol

    2015-01-01

    Full Text Available Neutrophils are the most abundant leukocytes in blood and are considered to be the first line of defense during inflammation and infections. In addition, neutrophils are also found infiltrating many types of tumors. Tumor-associated neutrophils (TANs have relevant roles in malignant disease. Indeed neutrophils may be potent antitumor effector cells. However, increasing clinical evidence shows TANs correlate with poor prognosis. The tumor microenvironment controls neutrophil recruitment and in turn TANs help tumor progression. Hence, TANs can be beneficial or detrimental to the host. It is the purpose of this review to highlight these two sides of the neutrophil coin in cancer and to describe recent studies that provide some light on the mechanisms for neutrophil recruitment to the tumor, for neutrophils supporting tumor progression, and for neutrophil activation to enhance their antitumor functions.

  8. Complete identification of E-selectin ligand activity on neutrophils reveals a dynamic interplay and distinct functions of PSGL-1, ESL-1 and CD44

    Science.gov (United States)

    Wild, Martin; Vestweber, Dietmar; Frenette, Paul S.

    2014-01-01

    SUMMARY The selectins and their ligands are required for leukocyte extravasation during inflammation. Several glycoproteins have been suggested to bind to E-selectin in vitro but the complete identification of its physiological ligands has remained elusive. Here, we show using gene- and RNA-targeted loss-of-function that E-selectin ligand-1 (ESL-1), PSGL-1 and CD44 encompass all endothelial selectin ligand activity on neutrophils. PSGL-1 plays a major role in the initial leukocyte capture, while ESL-1 is critical to convert initial tethers into steady slow rolling. CD44 controls rolling velocity and mediates E-selectin-dependent redistribution of PSGL-1 and L-selectin to a major pole on slowly rolling leukocytes through p38 signaling. These results suggest distinct and dynamic contributions of these three glycoproteins in selectin-mediated neutrophil adhesion and signaling. PMID:17442598

  9. Nano- to microscale dynamics of P-selectin detachment from leukocyte interfaces. I. Membrane separation from the cytoskeleton

    DEFF Research Database (Denmark)

    Evans, Evan; Heinrich, Volkmar; Leung, Andrew

    2005-01-01

    to final detachment, the typical force history exhibited the following sequence of events: i), an initial linear-elastic displacement of the PMN surface, ii), an abrupt crossover to viscoplastic flow that signaled membrane separation from the interior cytoskeleton and the beginning of a membrane tether......, and iii), the final detachment from the probe tip by usually one precipitous step of P-selectin:PSGL-1 dissociation. In this first article I, we focus on the initial elastic response and its termination by membrane separation from the cytoskeleton, initiating tether formation. Quantifying membrane...

  10. The control of neutrophil chemotaxis by inhibitors of cathepsin G and chymotrypsin.

    Science.gov (United States)

    Lomas, D A; Stone, S R; Llewellyn-Jones, C; Keogan, M T; Wang, Z M; Rubin, H; Carrell, R W; Stockley, R A

    1995-10-06

    Neutrophil chemotaxis plays an important role in the inflammatory response and when excessive or persistent may augment tissue damage. The effects of inhibitors indicated the involvement of one or more serine proteinases in human neutrophil migration and shape change in response to a chemoattractant. Monospecific antibodies, chloromethylketone inhibitors, and reactive-site mutants of alpha 1-antitrypsin and alpha 1-antichymotrypsin were used to probe the specificity of the proteinases involved in chemotaxis. Antibodies specific for cathepsin G inhibited chemotaxis. Moreover, rapid inhibitors of cathepsin G and alpha-chymotrypsin suppressed neutrophil chemotaxis to the chemoattractants N-formyl-L-methionyl-L-leucyl-L-phenylalanine (fMLP) and zymosan-activated serum in multiple blind well assays and to fMLP in migration assays under agarose. The concentrations of antichymotrypsin mutants that reduced chemotaxis by 50% would inactivate free cathepsin G with a half-life of 1.5-3 s, whereas the concentrations of chloromethylketones required to produce a similar inhibition of chemotaxis would inactivate cathepsin G with a half-life of 345 s. These data suggest different modes of action for these two classes of inhibitors. Indeed the chloromethylketone inhibitors of cathepsin G (Z-Gly-Leu-Phe-CMK) and to a lesser extent of chymotrypsin (Cbz-Gly-Gly-Phe-CMK) mediated their effect by preventing a shape change in the purified neutrophils exposed to fMLP. Antichymotrypsin did not affect shape change in response to fMLP even at concentrations that were able to reduce neutrophil chemotaxis by 50%. These results support the involvement of cell surface proteinases in the control of cell migration and show that antichymotrypsin and chloromethylketones have differing modes of action. This opens the possibility for the rational design of anti-inflammatory agents targeted at neutrophil membrane enzymes.

  11. Severe exercise and exercise training exert opposite effects on human neutrophil apoptosis via altering the redox status.

    Directory of Open Access Journals (Sweden)

    Guan-Da Syu

    Full Text Available Neutrophil spontaneous apoptosis, a process crucial for immune regulation, is mainly controlled by alterations in reactive oxygen species (ROS and mitochondria integrity. Exercise has been proposed to be a physiological way to modulate immunity; while acute severe exercise (ASE usually impedes immunity, chronic moderate exercise (CME improves it. This study aimed to investigate whether and how ASE and CME oppositely regulate human neutrophil apoptosis. Thirteen sedentary young males underwent an initial ASE and were subsequently divided into exercise and control groups. The exercise group (n = 8 underwent 2 months of CME followed by 2 months of detraining. Additional ASE paradigms were performed at the end of each month. Neutrophils were isolated from blood specimens drawn at rest and immediately after each ASE for assaying neutrophil spontaneous apoptosis (annexin-V binding on the outer surface along with redox-related parameters and mitochondria-related parameters. Our results showed that i the initial ASE immediately increased the oxidative stress (cytosolic ROS and glutathione oxidation, and sequentially accelerated the reduction of mitochondrial membrane potential, the surface binding of annexin-V, and the generation of mitochondrial ROS; ii CME upregulated glutathione level, retarded spontaneous apoptosis and delayed mitochondria deterioration; iii most effects of CME were unchanged after detraining; and iv CME blocked ASE effects and this capability remained intact even after detraining. Furthermore, the ASE effects on neutrophil spontaneous apoptosis were mimicked by adding exogenous H(2O(2, but not by suppressing mitochondrial membrane potential. In conclusion, while ASE induced an oxidative state and resulted in acceleration of human neutrophil apoptosis, CME delayed neutrophil apoptosis by maintaining a reduced state for long periods of time even after detraining.

  12. Tethered Ozonesonde Measurements During FRAPPE July-August 2014

    Science.gov (United States)

    Oltmans, S. J.; Johnson, B.; Sterling, C. W.; Cullis, P.; Hall, E. G.; Jordan, A. F.; Wendell, J.; Schnell, R. C.; McClure-Begley, A.; Thompson, A. M.

    2015-12-01

    O3 and temperature profiles were measured from tethered ozonesondes from surface to 400 m above ground level on 9 days during the summer of 2014 Colorado Front Range Air Pollution and Photochemistry Experiment (FRAPPE). The portable tethered ozonesonde system was set up at one of 3 sites located next to a Colorado Department of Public Health and Environment surface monitoring station. The day and site chosen were based on the previous day O3 and weather forecast. Measurements typically began at 8:30 AM and ended at 4:30 PM, averaging 40 profiles in one day. The ozonesonde when sampling at the surface consistently read within 0-3 ppbv of the surface monitor at each of the sites with a typical daytime range of 20-90 ppbv. The hourly values were averaged at 50 meter intervals showing O3 production rates were consistently around 8 ppbv per hour from 50 to 300 meters above ground level. On sunny, light wind days the O3 mixing ratio reached a maximum of 80-90 ppbv between 14:00 and 15:00 local time. The generally constant mixing ratio with height and highest mixing ratios above the surface indicate that photochemical O3 production was taking place throughout the profile. Continuous O3 profiles from a tall tower (5 and 300 m) and daily ozonesondes tracked O3 variability through the experiment. High O3 at each site was associated with different local wind directions. At Ft. Collins winds were generally out of the southeast, at Chatfield from the northeast, and at City Park Golf Course more variable. The tether system was developed at NOAA/ESRL to provide a cost effective method to measure O3 profiles on a continuous basis. The tether system consisted of a deep sea fishing pole, electric motor driving the reel with light-weight fishing line attached to the balloon ozonesonde, a tether control box, and laptop. The in house software package monitored data and controlled the tether speed and turn-around point based on real time GPS altitude from the transmitting radiosonde.

  13. SiMA: A simplified migration assay for analyzing neutrophil migration.

    Science.gov (United States)

    Weckmann, Markus; Becker, Tim; Nissen, Gyde; Pech, Martin; Kopp, Matthias V

    2017-07-01

    In lung inflammation, neutrophils are the first leukocytes migrating to an inflammatory site, eliminating pathogens by multiple mechanisms. The term "migration" describes several stages of neutrophil movement to reach the site of inflammation, of which the passage of the interstitium and basal membrane of the airway are necessary to reach the site of bronchial inflammation. Currently, several methods exist (e.g., Boyden Chamber, under-agarose assay, or microfluidic systems) to assess neutrophil mobility. However, these methods do not allow for parameterization on single cell level, that is, the individual neutrophil pathway analysis is still considered challenging. This study sought to develop a simplified yet flexible method to monitor and quantify neutrophil chemotaxis by utilizing commercially available tissue culture hardware, simple video microscopic equipment and highly standardized tracking. A chemotaxis 3D µ-slide (IBIDI) was used with different chemoattractants [interleukin-8 (IL-8), fMLP, and Leukotriene B4 (LTB 4 )] to attract neutrophils in different matrices like Fibronectin (FN) or human placental matrix. Migration was recorded for 60 min using phase contrast microscopy with an EVOS ® FL Cell Imaging System. The images were normalized and texture based image segmentation was used to generate neutrophil trajectories. Based on these spatio-temporal information a comprehensive parameter set is extracted from each time series describing the neutrophils motility, including velocity and directness and neutrophil chemotaxis. To characterize the latter one, a sector analysis was employed enabling the quantification of the neutrophils response to the chemoattractant. Using this hard- and software framework we were able to identify typical migration profiles of the chemoattractants IL-8, fMLP, and LTB 4 , the effect of the matrices FN versus HEM as well as the response to different medications (Prednisolone). Additionally, a comparison of four asthmatic and

  14. Neutrophil Leukocyte: Combustive Microbicidal Action and Chemiluminescence

    Directory of Open Access Journals (Sweden)

    Robert C. Allen

    2015-01-01

    Full Text Available Neutrophil leukocytes protect against a varied and complex array of microbes by providing microbicidal action that is simple, potent, and focused. Neutrophils provide such action via redox reactions that change the frontier orbitals of oxygen (O2 facilitating combustion. The spin conservation rules define the symmetry barrier that prevents direct reaction of diradical O2 with nonradical molecules, explaining why combustion is not spontaneous. In burning, the spin barrier is overcome when energy causes homolytic bond cleavage producing radicals capable of reacting with diradical O2 to yield oxygenated radical products that further participate in reactive propagation. Neutrophil mediated combustion is by a different pathway. Changing the spin quantum state of O2 removes the symmetry restriction to reaction. Electronically excited singlet molecular oxygen (O2*1 is a potent electrophilic reactant with a finite lifetime that restricts its radius of reactivity and focuses combustive action on the target microbe. The resulting exergonic dioxygenation reactions produce electronically excited carbonyls that relax by light emission, that is, chemiluminescence. This overview of neutrophil combustive microbicidal action takes the perspectives of spin conservation and bosonic-fermionic frontier orbital considerations. The necessary principles of particle physics and quantum mechanics are developed and integrated into a fundamental explanation of neutrophil microbicidal metabolism.

  15. Role of rab proteins in epithelial membrane traffic

    NARCIS (Netherlands)

    van Ijzendoorn, SCD; Mostov, KE; Hoekstra, D

    2003-01-01

    Small GTPase rab proteins play an important role in various aspects of membrane traffic, including cargo selection, vesicle budding, vesicle motility, tethering, docking, and fusion. Recent data suggest also that rabs, and their divalent effector proteins, organize organelle subdomains and as such

  16. Secretory vesicles in live cells are not free-floating but tethered to filamentous structures: A study using photonic force microscopy

    International Nuclear Information System (INIS)

    Abu-Hamdah, Rania; Cho, Won Jin; Hoerber, J.K.H.; Jena, Bhanu P.

    2006-01-01

    It is well established that actin and microtubule cytoskeletal systems are involved in organelle transport and membrane trafficking in cells. This is also true for the transport of secretory vesicles in neuroendocrine cells and neurons. It was however unclear whether secretory vesicles remain free-floating, only to associate with such cytoskeletal systems when needing transport. This hypothesis was tested using live pancreatic acinar cells in physiological buffer solutions, using the photonic force microscope (PFM). When membrane-bound secretory vesicles (0.2-1.2 μm in diameter) in live pancreatic acinar cells were trapped at the laser focus of the PFM and pulled, they were all found tethered to filamentous structures. Mild exposure of cells to nocodazole and cytochalasin B, disrupts the tether. Immunoblot analysis of isolated secretory vesicles, further demonstrated the association of actin, myosin V, and kinesin. These studies demonstrate for the first time that secretory vesicles in live pancreatic acinar cells are tethered and not free-floating, suggesting that following vesicle biogenesis, they are placed on their own railroad track, ready to be transported to their final destination within the cell when required. This makes sense, since precision and regulation are the hallmarks of all cellular process, and therefore would hold true for the transport and localization of subcellular organelles such as secretory vesicles

  17. Secretory vesicles in live cells are not free-floating but tethered to filamentous structures: A study using photonic force microscopy

    Energy Technology Data Exchange (ETDEWEB)

    Abu-Hamdah, Rania [Department of Physiology, Wayne State University School of Medicine, 5245 Scott Hall, 540 E. Canfield, Detroit, MI 48201 (United States); Cho, Won Jin [Department of Physiology, Wayne State University School of Medicine, 5245 Scott Hall, 540 E. Canfield, Detroit, MI 48201 (United States); Hoerber, J.K.H. [Department of Physics, University of Bristol, Bristol BS8 1TD (United Kingdom); Jena, Bhanu P. [Department of Physiology, Wayne State University School of Medicine, 5245 Scott Hall, 540 E. Canfield, Detroit, MI 48201 (United States)]. E-mail: bjena@med.wayne.edu

    2006-06-15

    It is well established that actin and microtubule cytoskeletal systems are involved in organelle transport and membrane trafficking in cells. This is also true for the transport of secretory vesicles in neuroendocrine cells and neurons. It was however unclear whether secretory vesicles remain free-floating, only to associate with such cytoskeletal systems when needing transport. This hypothesis was tested using live pancreatic acinar cells in physiological buffer solutions, using the photonic force microscope (PFM). When membrane-bound secretory vesicles (0.2-1.2 {mu}m in diameter) in live pancreatic acinar cells were trapped at the laser focus of the PFM and pulled, they were all found tethered to filamentous structures. Mild exposure of cells to nocodazole and cytochalasin B, disrupts the tether. Immunoblot analysis of isolated secretory vesicles, further demonstrated the association of actin, myosin V, and kinesin. These studies demonstrate for the first time that secretory vesicles in live pancreatic acinar cells are tethered and not free-floating, suggesting that following vesicle biogenesis, they are placed on their own railroad track, ready to be transported to their final destination within the cell when required. This makes sense, since precision and regulation are the hallmarks of all cellular process, and therefore would hold true for the transport and localization of subcellular organelles such as secretory vesicles.

  18. Neutrophils in Homeostasis, Immunity, and Cancer.

    Science.gov (United States)

    Nicolás-Ávila, José Ángel; Adrover, José M; Hidalgo, Andrés

    2017-01-17

    Neutrophils were among the first leukocytes described and visualized by early immunologists. Prominent effector functions during infection and sterile inflammation classically placed them low in the immune tree as rapid, mindless aggressors with poor regulatory functions. This view is currently under reassessment as we uncover new aspects of their life cycle and identify transcriptional and phenotypic diversity that endows them with regulatory properties that extend beyond their lifetime in the circulation. These properties are revealing unanticipated roles for neutrophils in supporting homeostasis, as well as complex disease states such as cancer. We focus this review on these emerging functions in order to define the true roles of neutrophils in homeostasis, immunity, and disease. Copyright © 2017 Elsevier Inc. All rights reserved.

  19. Long distance cell communication using spherical tether balloons

    Science.gov (United States)

    Manchanda, R. K.; Rajagopalan, Vasudevan; Vasudevan, Rajagopalan; Mehrotra, R. K.; Sreenivasan, S.; Pawaskar, M.; Subba Rao Jonnalagadda, Venkata; Buduru, Suneelkumar; Kulkarni, P. M.

    A proof-of-concept experiment was conducted for long-range cell communication for rural tele-phony and internet. We designed and fabricated a spherical tether balloon to carry the con-ventional micro base transceiver station (BTS) along with three slotted antenna to cover 2-pi radius. AC power and optical fiber were anchored along with the tether line. A special fre-quency license was obtained from Wireless Planning Commission (WPC) wing of Department of Telecommunication (DoT), India for the period of experiment so as not to affect the opera-tional networks. The experiments were carried out for different BTS heights up to 500 meter. Signal measurement both in data mode and voice quality were done in different quadrant using mobile vans. This paper describes the methodology (under patenting) and utility of technique for operational application.

  20. Tethered elevator: A unique opportunity for space processing

    Science.gov (United States)

    Monti, R.

    1986-01-01

    The latest fluid dynamic and material science experiments in the microgravity environment have emphasized the importance of the residual gravity level and of the g-jitter on fluid physics phenomena. The tethered elevator presents the possibility of providing variable g-levels (both steady and g-jitter) around a very low steady g-level (that can be realized when the elevator is near the center of mass of the space station-tether complex). When positioning a variable periodic oscillation to the payload a clean g-jitter disturbance can be obtained that would not be otherwise obtainable by other systems. These two possibilities make the elevator a facility to help resolve a number of still open questions that are preventing wider utilization of the space environment in the microgravity area.

  1. Stability control of a flexible maneuverable tethered space net robot

    Science.gov (United States)

    Zhang, Fan; Huang, Panfeng

    2018-04-01

    As a promising solution for active space debris capture and removal, a maneuverable Tethered Space Net Robot (TSNR) is proposed as an improved Space Tethered Net (TSN). In addition to the advantages inherit to the TSN, the TSNR's maneuverability expands the capture's potential. However, oscillations caused by the TSNR's flexibility and elasticity of make higher requests of the control scheme. Based on the dynamics model, a modified adaptive super-twisting sliding mode control scheme is proposed in this paper for TSNR stability control. The proposed continuous control force can effectively suppress oscillations. Theoretical verification and numerical simulations demonstrate that the desired trajectory can be tracked steadily and efficiently by employing the proposed control scheme.

  2. Synthesis and insertion chemistry of mixed tether uranium metallocene complexes

    Energy Technology Data Exchange (ETDEWEB)

    Siladke, Nathan A.; LeDuc, Jennifer; Ziller, Joseph W.; Evans, William J. [Department of Chemistry, University of California, Irvine, CA (United States)

    2012-11-12

    The synthesis of mixed tethered alkyl uranium metallocenes has been investigated by examining the reactivity of the bis(tethered alkyl) metallocene [(η{sup 5}-C{sub 5}Me{sub 4}SiMe{sub 2}CH{sub 2}-κC){sub 2}U] (1) with substrates that react with only one of the U-C linkages. The effect of these mixed tether coordination environments on the reactivity of the remaining U-C bond has been studied by using CO insertion chemistry. One equivalent of azidoadamantane (AdN{sub 3}) reacts with 1 to yield the mixed tethered alkyl triazenido complex [(η{sup 5}-C{sub 5}Me{sub 4}SiMe{sub 2}CH{sub 2}-κC)U(η{sup 5}-C{sub 5}Me{sub 4}SiMe{sub 2}-CH{sub 2}NNN-Ad-κ{sup 2}N{sup 1,3})]. Similarly, a single equivalent of CS{sub 2} reacts with 1 to form the mixed tethered alkyl dithiocarboxylate complex [(η{sup 5}-C{sub 5}Me{sub 4}SiMe{sub 2}CH{sub 2}-κC)U(η{sup 5}-C{sub 5}Me{sub 4}SiMe{sub 2}- CH{sub 2}C(S){sub 2}-κ{sup 2}S,S{sup '})], a reaction that constitutes the first example of CS{sub 2} insertion into a U{sup 4+}-C bond. Complex 1 reacts with one equivalent of pyridine N-oxide by C-H bond activation of the pyridine ring to form a mixed tethered alkyl cyclometalated pyridine N-oxide complex [(η{sup 5}-C{sub 5}Me{sub 4}SiMe{sub 2}CH{sub 2}-κC)(η{sup 5}-C{sub 5}Me{sub 4}SiMe{sub 3})U(C{sub 6}H{sub 4}NO-κ{sup 2} C,O)]. The remaining (η{sup 5}-C{sub 5}Me{sub 4}SiMe{sub 2}CH{sub 2}-κC){sup 2-} ligand in each of these mixed tethered species show reactivity towards CO and tethered enolate ligands form by insertion. Subsequent rearrangement have been identified in [(η{sup 5}-C{sub 5}Me{sub 4}SiMe{sub 3})U(C{sub 5}H{sub 4}NO-κ{sup 2}C,O)(η{sup 5}-C{sub 5}Me{sub 4}SiMe{sub 2}C(=CH{sub 2})O- κO)] and [(η{sup 5}-C{sub 5}Me{sub 4}SiMe{sub 2}CH{sub 2}NNN-Ad-κ{sup 2}N{sup 1,3})U(η{sup 5}-C{sub 5}Me{sub 4}SiMe{sub 2}C(=CH{sub 2})O-κO)]. (Copyright copyright 2012 WILEY-VCH Verlag GmbH and Co. KGaA, Weinheim)

  3. A simplified tether model for molecular motor transporting cargo

    International Nuclear Information System (INIS)

    Fang-Zhen, Li; Li-Chun, Jiang

    2010-01-01

    Molecular motors are proteins or protein complexes which function as transporting engines in biological cells. This paper models the tether between motor and its cargo as a symmetric linear potential. Different from Elston and Peskin's work for which performance of the system was discussed only in some limiting cases, this study produces analytic solutions of the problem for general cases by simplifying the transport system into two physical states, which makes it possible to discuss the dynamics of the motor–cargo system in detail. It turns out that the tether strength between motor and cargo should be greater than a threshold or the motor will fail to transport the cargo, which was not discussed by former researchers yet. Value of the threshold depends on the diffusion coefficients of cargo and motor and also on the strength of the Brownian ratchets dragging the system. The threshold approaches a finite constant when the strength of the ratchet tends to infinity. (general)

  4. Quantitative proteomics reveals differential biological processes in healthy neonatal cord neutrophils and adult neutrophils

    KAUST Repository

    Zhu, Jiang; Zhang, Huoming; Guo, Tiannan; Li, Wenying; Li, Huiyu; Zhu, Yi; Huang, Shiang

    2014-01-01

    Neonatal neutrophils are characterized by the immaturity of bactericidal mechanisms that contributes largely to neonatal mortality. However, underlying molecular mechanism associated with the immaturity remains incompletely understood. In this study, we performed comparative proteomic analysis on neonatal neutrophils derived from human cord blood and adult peripheral neutrophils. A total of 1332 proteins were identified and quantified, and 127 proteins were characterized as differentially expressed between adult and cord neutrophils. The differentially expressed proteins are mapped in KEGG pathways into five clusters and indicated impaired functions of neonatal neutrophils in proteasome, lysosome, phagosome, and leukocyte transendothelial migration. In particular, many proteins associated with NETosis, a critical mechanism for antimicrobial process and auto-clearance, were also found to be downregulated in cord neutrophils. This study represents a first comparative proteome profiling of neonatal and adult neutrophils, and provides a global view of differentially expressed proteome for enhancing our understanding of their various functional difference. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  5. Quantitative proteomics reveals differential biological processes in healthy neonatal cord neutrophils and adult neutrophils

    KAUST Repository

    Zhu, Jiang

    2014-06-11

    Neonatal neutrophils are characterized by the immaturity of bactericidal mechanisms that contributes largely to neonatal mortality. However, underlying molecular mechanism associated with the immaturity remains incompletely understood. In this study, we performed comparative proteomic analysis on neonatal neutrophils derived from human cord blood and adult peripheral neutrophils. A total of 1332 proteins were identified and quantified, and 127 proteins were characterized as differentially expressed between adult and cord neutrophils. The differentially expressed proteins are mapped in KEGG pathways into five clusters and indicated impaired functions of neonatal neutrophils in proteasome, lysosome, phagosome, and leukocyte transendothelial migration. In particular, many proteins associated with NETosis, a critical mechanism for antimicrobial process and auto-clearance, were also found to be downregulated in cord neutrophils. This study represents a first comparative proteome profiling of neonatal and adult neutrophils, and provides a global view of differentially expressed proteome for enhancing our understanding of their various functional difference. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  6. Crowded, Confined, and Frustrated: Dynamics of Molecules Tethered to Nanoparticles

    KAUST Repository

    Agarwal, Praveen

    2012-12-01

    Above a critical chemistry-dependent molecular weight, all polymer molecules entangle and, as a result, exhibit slow dynamics, enhanced viscosity, and elasticity. Herein we report on the dynamics of low molecular weight polymers tethered to nanoparticles and find that even conventionally unentangled chains manifest dynamical features similar to entangled, long-chain molecules. Our findings are shown to imply that crowding and confinement of polymers on particles produce topological constraints analogous to those in entangled systems. © 2012 American Physical Society.

  7. Advanced Electrodynamic Tether Systems: Modeling of Scattering and Unsteady Effects

    Science.gov (United States)

    2008-06-06

    spacecraft and satellites. A high altitude nuclear detonation would likely create a new high energy electron belt and increase the radiation risk to...our tether has no reason to roll, making O=0, and thus cosO =1. The y-component of the torque is thus expressed: < = < =< = FF cossin3 222 ’ (S...ions from the integral limits to manageable levels. Our goal is to isolate the permutations of initial velocities and impact parameters such that

  8. Pathogenic Bacterium Acinetobacter baumannii Inhibits the Formation of Neutrophil Extracellular Traps by Suppressing Neutrophil Adhesion

    Science.gov (United States)

    Kamoshida, Go; Kikuchi-Ueda, Takane; Nishida, Satoshi; Tansho-Nagakawa, Shigeru; Ubagai, Tsuneyuki; Ono, Yasuo

    2018-01-01

    Hospital-acquired infections caused by Acinetobacter baumannii have become problematic because of high rates of drug resistance. A. baumannii is usually harmless, but it may cause infectious diseases in an immunocompromised host. Although neutrophils are the key players of the initial immune response against bacterial infection, their interactions with A. baumannii remain largely unknown. A new biological defense mechanism, termed neutrophil extracellular traps (NETs), has been attracting attention. NETs play a critical role in bacterial killing by bacterial trapping and inactivation. Many pathogenic bacteria have been reported to induce NET formation, while an inhibitory effect on NET formation is rarely reported. In the present study, to assess the inhibition of NET formation by A. baumannii, bacteria and human neutrophils were cocultured in the presence of phorbol 12-myristate 13-acetate (PMA), and NET formation was evaluated. NETs were rarely observed during the coculture despite neutrophil PMA stimulation. Furthermore, A. baumannii prolonged the lifespan of neutrophils by inhibiting NET formation. The inhibition of NET formation by other bacteria was also investigated. The inhibitory effect was only apparent with live A. baumannii cells. Finally, to elucidate the mechanism of this inhibition, neutrophil adhesion was examined. A. baumannii suppressed the adhesion ability of neutrophils, thereby inhibiting PMA-induced NET formation. This suppression of cell adhesion was partly due to suppression of the surface expression of CD11a in neutrophils. The current study constitutes the first report on the inhibition of NET formation by a pathogenic bacterium, A. baumannii, and prolonging the neutrophil lifespan. This novel pathogenicity to inhibit NET formation, thereby escaping host immune responses might contribute to a development of new treatment strategies for A. baumannii infections. PMID:29467765

  9. Pathogenic Bacterium Acinetobacter baumannii Inhibits the Formation of Neutrophil Extracellular Traps by Suppressing Neutrophil Adhesion

    Directory of Open Access Journals (Sweden)

    Go Kamoshida

    2018-02-01

    Full Text Available Hospital-acquired infections caused by Acinetobacter baumannii have become problematic because of high rates of drug resistance. A. baumannii is usually harmless, but it may cause infectious diseases in an immunocompromised host. Although neutrophils are the key players of the initial immune response against bacterial infection, their interactions with A. baumannii remain largely unknown. A new biological defense mechanism, termed neutrophil extracellular traps (NETs, has been attracting attention. NETs play a critical role in bacterial killing by bacterial trapping and inactivation. Many pathogenic bacteria have been reported to induce NET formation, while an inhibitory effect on NET formation is rarely reported. In the present study, to assess the inhibition of NET formation by A. baumannii, bacteria and human neutrophils were cocultured in the presence of phorbol 12-myristate 13-acetate (PMA, and NET formation was evaluated. NETs were rarely observed during the coculture despite neutrophil PMA stimulation. Furthermore, A. baumannii prolonged the lifespan of neutrophils by inhibiting NET formation. The inhibition of NET formation by other bacteria was also investigated. The inhibitory effect was only apparent with live A. baumannii cells. Finally, to elucidate the mechanism of this inhibition, neutrophil adhesion was examined. A. baumannii suppressed the adhesion ability of neutrophils, thereby inhibiting PMA-induced NET formation. This suppression of cell adhesion was partly due to suppression of the surface expression of CD11a in neutrophils. The current study constitutes the first report on the inhibition of NET formation by a pathogenic bacterium, A. baumannii, and prolonging the neutrophil lifespan. This novel pathogenicity to inhibit NET formation, thereby escaping host immune responses might contribute to a development of new treatment strategies for A. baumannii infections.

  10. High-field MR imaging of tethered cord

    International Nuclear Information System (INIS)

    Sigal, R.; Bicetre, L.; Blass, C.; Doyon, D.; Pariente, D.

    1986-01-01

    MR imaging examinations of 12 patients with tethered cord syndrome have been performed on a 1.5-T MR imaging unit. Patients ranged in age from 3 to 60 years. MR findings were compared with those of myelography and metrizamide CT in all cases. Five patients underwent surgical control and postoperative MR imaging. Sagittal and axial sections were obtained using a spin-echo multisection, multiecho technique. T1-axial weighted images (SE 600/25) were sufficient to locate the position of the tip of the conus. They also allowed identification of extraspinal and intraspinal lipomas and clear-cut demarcation form associated tethered cord. Drawbacks of MR imaging were lack of precise depiction of the bone structures and the fact that clear identification of abnormal roots was problematic. The craniovertebral junction was always checked; two asymptomatic Chiari malformations were visualized. This study leads the authors to conclude that MR imaging should be used as the examination of first choice in the management of tethered cord syndrome

  11. Position Control of an X4-Flyer Using a Tether

    Directory of Open Access Journals (Sweden)

    Yusuke Ouchi

    2016-05-01

    Full Text Available In Japan, aging of infrastructures, such as roads,bridges, and water and sewer services, etc. poses a problem, andit is required to extend the life-span of such infrastructures bymaintenance. Among infrastructures, especially bridges areperiodically inspected by short range visual observations, whichcheck the damage and deterioration of the surface. However,since there are some cases where the short range visualobservation is difficult, an alternative method is required so as toreplace the short range visual observation with it. So, "X4-Flyer"is very attractive because of realizing a movement at high altitudeeasily. The objective of this study is to develop a tethered X4-Flyer, so that the conventional short range visual observation ofbridges is replaced by it. In this paper, a method for themeasurement and control of the position is described by using atether for controlling the position of the X4-Flyer. In addition, itis checked whether the tethered X4-Flyer can control the positionusing the proposed method or not, letting it fly in a state in whicha tether is being attached

  12. Results from a tethered rocket experiment (Charge-2)

    Science.gov (United States)

    Kawashima, N.; Sasaki, S.; Oyama, K. I.; Hirao, K.; Obayashi, T.; Raitt, W. J.; White, A. B.; Williamson, P. R.; Banks, P. M.; Sharp, W. F.

    A tethered payload experiment (Charge-2) was carried out as an international program between Japan and the USA using a NASA sounding rocket at White Sands Missile Range. The objective of the experiment was to perform a new type of active experiment in space by injecting an electron beam from a mother-daughter rocket system connected with a long tether wire. The electron beam with voltage and current up to 1 kV and 80 mA (nominal) was injected from the mother payload. An insulated conductive wire of 426 m length connected the two payloads, the longest tether system flown so far. The electron gun system and diagnostic instruments (plasma, optical, particle and wave) functioned correctly throughout the flight. The potential rise of the mother payload during the electron beam emission was measured with respect to the daughter payload. The beam trajectory was detected by a camera onboard the mother rocket. Wave generation and current induction in the wire during the beam emission were also studied.

  13. Phenotypic Diversity and Plasticity in Circulating Neutrophil Subpopulations in Cancer

    Directory of Open Access Journals (Sweden)

    Jitka Y. Sagiv

    2015-02-01

    Full Text Available Controversy surrounds neutrophil function in cancer because neutrophils were shown to provide both pro- and antitumor functions. We identified a heterogeneous subset of low-density neutrophils (LDNs that appear transiently in self-resolving inflammation but accumulate continuously with cancer progression. LDNs display impaired neutrophil function and immunosuppressive properties, characteristics that are in stark contrast to those of mature, high-density neutrophils (HDNs. LDNs consist of both immature myeloid-derived suppressor cells (MDSCs and mature cells that are derived from HDNs in a TGF-β-dependent mechanism. Our findings identify three distinct populations of circulating neutrophils and challenge the concept that mature neutrophils have limited plasticity. Furthermore, our findings provide a mechanistic explanation to mitigate the controversy surrounding neutrophil function in cancer.

  14. Dynamic analysis of the tether transportation system using absolute nodal coordinate formulation

    Science.gov (United States)

    Sun, Xin; Xu, Ming; Zhong, Rui

    2017-10-01

    Long space tethers are becoming a rising concern as an alternate way for transportation in space. It benefits from fuel economizing. This paper focuses on the dynamics of the tether transportation system, which consists of two end satellites connected by a flexible tether, and a movable vehicle driven by the actuator carried by itself. The Absolute Nodal Coordinate Formulation is applied to the establishment of the equation of motion, so that the influence caused by the distributed mass and elasticity of the tether is introduced. Moreover, an approximated method for accelerating the calculation of the generalized gravitational forces on the tether is proposed by substituting the volume integral every step into summation of finite terms. Afterwards, dynamic evolutions of such a system in different configurations are illustrated using numerical simulations. The deflection of the tether and the trajectory of the crawler during the transportation is investigated. Finally, the effect on the orbit of the system due to the crawler is revealed.

  15. Neutrophil beta-2 microglobulin: an inflammatory mediator

    DEFF Research Database (Denmark)

    Bjerrum, O W; Nissen, Mogens Holst; Borregaard, N

    1990-01-01

    Beta-2 microglobulin (beta 2m) constitutes the light invariant chain of HLA class I antigen, and is a constituent of mobilizable compartments of neutrophils. Two forms of beta 2m exist: native beta 2m and proteolytically modified beta 2m (Des-Lys58-beta 2m), which shows alpha mobility in crossed ...

  16. Neutrophils in atherosclerosis. A brief overview

    NARCIS (Netherlands)

    Hartwig, H.; Silvestre Roig, C.; Daemen, M.; Lutgens, E.; Soehnlein, O.

    2015-01-01

    Atherosclerosis is a chronic inflammation of the arterial wall and the continuous infiltration of leukocytes into the plaque enhances the progression of the lesion. Because of the scarce detection of neutrophils in atherosclerotic plaques compared to other immune cells, their contribution was

  17. Myeloperoxidase attracts neutrophils by physical forces

    Czech Academy of Sciences Publication Activity Database

    Klinke, A.; Nussbaum, C.; Kubala, Lukáš; Friedrichs, K.; Rudolph, T.K.; Rudolph, V.; Paust, H.-J.; Schröder, Ch.; Benten, D.; Lau, D.; Szocs, K.; Furtmüller, P.G.; Heeringa, P.; Sydow, K.; Duchstein, H.-J.; Ehmke, H.; Schumacher, U.; Meinertz, T.; Sperandio, M.; Baldus, S.

    2011-01-01

    Roč. 117, č. 4 (2011), s. 1350-1358 ISSN 0006-4971 Institutional research plan: CEZ:AV0Z50040507; CEZ:AV0Z50040702 Keywords : myeloperoxidase * polymorphonuclear neutrophils * glycocalyx Subject RIV: BO - Biophysics Impact factor: 9.898, year: 2011

  18. Rat Neutrophil Phagocytosis Following Feed Restriction

    Czech Academy of Sciences Publication Activity Database

    Slapničková, Martina; Berger, J.

    2002-01-01

    Roč. 11, č. 3 (2002), s. 172-177 ISSN 0938-7714 Institutional research plan: CEZ:AV0Z5052915 Keywords : circulating neutrophil * diet restriction * phagocytosis Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 0.167, year: 2001

  19. Selective inhibition of extracellular oxidants liberated from human neutrophils--A new mechanism potentially involved in the anti-inflammatory activity of hydroxychloroquine.

    Science.gov (United States)

    Jančinová, Viera; Pažoureková, Silvia; Lucová, Marianna; Perečko, Tomáš; Mihalová, Danica; Bauerová, Katarína; Nosáľ, Radomír; Drábiková, Katarína

    2015-09-01

    Hydroxychloroquine is used in the therapy of rheumatoid arthritis or lupus erythematosus. Although these diseases are often accompanied by activation of neutrophils, there are still few data relating to the impact of hydroxychloroquine on these cells. We investigated the effect of orally administered hydroxychloroquine on neutrophil oxidative burst in rats with adjuvant arthritis. In human neutrophils, extra- and intracellular formation of oxidants, mobilisation of intracellular calcium and the phosphorylation of proteins regulating NADPH oxidase assembly were analysed. Administration of hydroxychloroquine decreased the concentration of oxidants in blood of arthritic rats. The inhibition was comparable with the reference drug methotrexate, yet it was not accompanied by a reduction in neutrophil count. When both drugs were co-applied, the effect became more pronounced. In isolated human neutrophils, treatment with hydroxychloroquine resulted in reduced mobilisation of intracellular calcium, diminished concentration of external oxidants and in decreased phosphorylation of Ca(2+)-dependent protein kinase C isoforms PKCα and PKCβII, which regulate activation of NADPH oxidase on plasma membrane. On the other hand, no reduction was observed in intracellular oxidants or in the phosphorylation of p40(phox) and PKCδ, two proteins directing the oxidase assembly to intracellular membranes. Hydroxychloroquine reduced neutrophil-derived oxidants potentially involved in tissue damage and protected those capable to suppress inflammation. The observed effects may represent a new mechanism involved in the anti-inflammatory activity of this drug. Copyright © 2015 Elsevier B.V. All rights reserved.

  20. Changes in Neutrophil Functions in Astronauts

    Science.gov (United States)

    Kaur, Indreshpal; Simons, Elizabeth R.; Castro, Victoria; Pierson, Duane L.

    2002-01-01

    Neutrophil functions (phagocytosis, oxidative burst, degranulation) and expression of surface markers involved in these functions were studied in 25 astronauts before and after 4 space shuttle missions. Space flight duration ranged from 5 to 11 days. Blood specimens were obtained 10 days before launch (preflight or L-10), immediately after landing (landing or R+0), and again at 3 days after landing (postflight or R+3). Blood samples were also collected from 9 healthy low-stressed subjects at 3 time points simulating a 10-day shuttle mission. The number of neutrophils increased at landing by 85 percent when compared to the preflight numbers. Neutrophil functions were studied in whole blood using flow cytometric methods. Phagocytosis of E.coli-FITC and oxidative burst capacity of the neutrophils following the 9 to 11 day missions were lower at all three sampling points than the mean values for control subjects. Phagocytosis and oxidative burst capacity of the astronauts was decreased even 10-days before space flight. Mission duration appears to be a factor in phagocytic and oxidative functions. In contrast, following the short-duration (5-days) mission, these functions were unchanged from control values. No consistent changes in degranulation were observed following either short or medium length space missions. The expression of CD16, CD32, CD11a, CD11b, CD11c, L-selectin and CD36 was measured and found to be variable. Specifically, CD16 and CD32 did not correlate with the changes in oxidative burst and phagocytosis. We can conclude from this study that the stresses associated with space flight can alter the important functions of neutrophils.

  1. Tethered elevator and platforms as space station facilities: Systems studies and demonstrative experiments

    Science.gov (United States)

    1986-01-01

    Several key concepts of the science and applications tethered platforms were studied. Some conclusions reached are herein listed. Tether elevator and platform could improve the space station scientific and applicative capabilities. The space elevator presents unique characteristics as microgravity facility and as a tethered platform servicing vehicle. Pointing platforms could represent a new kind of observation facility for large class of payloads. The dynamical, control and technological complexity of these concepts advised demonstrative experiments. The on-going tethered satellite system offers the opportunity to perform such experiments. And feasibility studies are in progress.

  2. Dynamics Model for a Multi-Tethered Space-Based Interferometer

    National Research Council Canada - National Science Library

    Gates, Stephen

    2000-01-01

    .... Tether constitutive behavior is discussed. Prescribed motion of any system degrees of freedom is treated, and expressions for the corresponding constraint force/torque components are established.

  3. A Fiber-Optic Tether for the Hull Search UUV System Documentation

    National Research Council Canada - National Science Library

    Buescher, J. G

    2006-01-01

    ...) conducting ship hull inspection missions, defines the required specifications that will allow the integration and installation of a FO tether system on UUVs with ship hull inspection capability...

  4. Forces, energetics, and dynamics of conjugated-carbon ring tethers adhered to CNTs: a computational investigation.

    Science.gov (United States)

    Filla, Nicholas; Ramasamy, Ramaraja; Wang, Xianqiao

    2018-04-25

    The strength and nature of the interactions between carbon nanotubes (CNTs) and molecular tethers plays a vital role in technology such as CNT-enzyme sensors. Tethers that attach noncovalently to CNTs are ideal for retaining the electrical properties of the CNTs since they do not degrade the CNT surface and effect its electrical conductivity. However, leaching due to weak CNT-tether attachment is very common when using noncovalent tethers, and this has limited their use in commercial products including biosensors. Thus, understanding the fundamental mechanics governing the strength of CNT-tether adhesion is crucial for the design of highly sensitive, viable sensors. Here, we computationally investigate the adhesion strength of CNT-tether complexes with 8 different tethering molecules designed to adhere noncovalently to the CNT surface. We study the effects of CNT diameter, CNT chirality, and the size/geometry of the tethering molecule on the adhesion energy and force. Our results show an asymptotic relationship between adhesion strength and CNT diameter. Calculations show that noncovalent tethers tested here can reach adhesion forces and energies that are up to 21% and 54% of the strength of the carbon-carbon single bond force and bond energy respectively. We anticipate our results will help guide CNT-enzyme sensor design to produce sensors with high sensitivity and minimal leaching.

  5. Novel roaming and stationary tethered aerial robots for continuous mobile missions in nuclear power plants

    Energy Technology Data Exchange (ETDEWEB)

    Gu, Beom W.; Choi, Su Y.; Rim, Chun T. [Dept. of Nuclear and Quantum Engineering, KAIST, Daejeon (Korea, Republic of); Choi, Young Soo [Korea Atomic Energy Research Institute, Daejeon (Korea, Republic of); Cai, Guowei; Seneviratne, Lakmal [Dept. of Aerospace Engineering, Khalifa University, Abu Dhabi (United Arab Emirates)

    2016-08-15

    In this paper, new tethered aerial robots including roaming tethered aerial robots (RTARs) for radioactive material sampling and stationary tethered aerial robots (STARs) for environment monitoring are proposed to meet extremely-long-endurance missions of nuclear power plants. The flight of the proposed tethered aerial robots may last for a few days or even a few months as long as the tethered cable provides continuous power. A high voltage AC or DC power system was newly adopted to reduce the mass of the tethered cable. The RTAR uses a tethered cable spooled from the aerial robot and an aerial tension control system. The aerial tension control system provides the appropriate tension to the tethered cable, which is accordingly laid down on the ground as the RTAR roams. The STAR includes a tethered cable spooled from the ground and a ground tension control system, which enables the STAR to reach high altitudes. Prototypes of the RTAR and STAR were designed and successfully demonstrated in outdoor environments, where the load power, power type, operating frequency, and flight attitude of the RTAR and STAR were: 180 W, AC 100 kHz, and 20 m; and 300 W, AC or DC 100 kHz, and 80 m, respectively.

  6. Novel Roaming and Stationary Tethered Aerial Robots for Continuous Mobile Missions in Nuclear Power Plants

    Directory of Open Access Journals (Sweden)

    Beom W. Gu

    2016-08-01

    Full Text Available In this paper, new tethered aerial robots including roaming tethered aerial robots (RTARs for radioactive material sampling and stationary tethered aerial robots (STARs for environment monitoring are proposed to meet extremely-long-endurance missions of nuclear power plants. The flight of the proposed tethered aerial robots may last for a few days or even a few months as long as the tethered cable provides continuous power. A high voltage AC or DC power system was newly adopted to reduce the mass of the tethered cable. The RTAR uses a tethered cable spooled from the aerial robot and an aerial tension control system. The aerial tension control system provides the appropriate tension to the tethered cable, which is accordingly laid down on the ground as the RTAR roams. The STAR includes a tethered cable spooled from the ground and a ground tension control system, which enables the STAR to reach high altitudes. Prototypes of the RTAR and STAR were designed and successfully demonstrated in outdoor environments, where the load power, power type, operating frequency, and flight attitude of the RTAR and STAR were: 180 W, AC 100 kHz, and 20 m; and 300 W, AC or DC 100 kHz, and 80 m, respectively.

  7. Neutrophil transmigration mediated by the neutrophil-specific antigen CD177 is influenced by the endothelial S536N dimorphism of platelet endothelial cell adhesion molecule-1.

    Science.gov (United States)

    Bayat, Behnaz; Werth, Silke; Sachs, Ulrich J H; Newman, Debra K; Newman, Peter J; Santoso, Sentot

    2010-04-01

    The human neutrophil-specific adhesion molecule CD177 (also known as the NB1 alloantigen) becomes upregulated on the cell surface in a number of inflammatory settings. We recently showed that CD177 functions as a novel heterophilic counterreceptor for the endothelial junctional protein PECAM-1 (CD31), an interaction that is mediated by membrane-proximal PECAM-1 IgD 6, which is known to harbor an S(536)N single nucleotide polymorphism of two major isoforms V(98)N(536)G(643) and L(98)S(536)R(643) and a yet-to-be-determined region on CD177. In vitro transendothelial migration experiments revealed that CD177(+) neutrophils migrated significantly faster through HUVECs expressing the LSR, compared with the VNG, allelic variant of PECAM-1 and that this correlated with the decreased ability of anti-PECAM-1 Ab of ITIM tyrosine phosphorylation in HUVECs expressing the LSR allelic variant relative to the VNG allelic variant. Moreover, engagement of PECAM-1 with rCD177-Fc (to mimic heterophilic CD177 binding) suppressed Ab-induced tyrosine phosphorylation to a greater extent in cells expressing the LSR isoform compared with the VNG isoform, with a corresponding increased higher level of beta-catenin phosphorylation. These data suggest that heterophilic PECAM-1/CD177 interactions affect the phosphorylation state of PECAM-1 and endothelial cell junctional integrity in such a way as to facilitate neutrophil transmigration in a previously unrecognized allele-specific manner.

  8. Effect of moderate exercise on peritoneal neutrophils from juvenile rats.

    Science.gov (United States)

    Braz, Glauber Ruda; Ferreira, Diorginis Soares; Pedroza, Anderson Apolonio; da Silva, Aline Isabel; Sousa, Shirley Maria; Pithon-Curi, Tania Cristina; Lagranha, Claudia

    2015-09-01

    Previous studies showed that moderate exercise in adult rats enhances neutrophil function, although no studies were performed in juvenile rats. We evaluated the effects of moderate exercise on the neutrophil function in juvenile rats. Viability and neutrophils function were evaluated. Moderate exercise did not impair the viability and mitochondrial transmembrane potential of neutrophils, whereas there was greater reactive oxygen species production (164%; p < 0.001) and phagocytic capacity (29%; p < 0.05). Our results suggest that moderate exercise in juvenile rats improves neutrophil function, similar to adults.

  9. GSL-enriched membrane microdomains in innate immune responses.

    Science.gov (United States)

    Nakayama, Hitoshi; Ogawa, Hideoki; Takamori, Kenji; Iwabuchi, Kazuhisa

    2013-06-01

    Many pathogens target glycosphingolipids (GSLs), which, together with cholesterol, GPI-anchored proteins, and various signaling molecules, cluster on host cell membranes to form GSL-enriched membrane microdomains (lipid rafts). These GSL-enriched membrane microdomains may therefore be involved in host-pathogen interactions. Innate immune responses are triggered by the association of pathogens with phagocytes, such as neutrophils, macrophages and dendritic cells. Phagocytes express a diverse array of pattern-recognition receptors (PRRs), which sense invading microorganisms and trigger pathogen-specific signaling. PRRs can recognize highly conserved pathogen-associated molecular patterns expressed on microorganisms. The GSL lactosylceramide (LacCer, CDw17), which binds to various microorganisms, including Candida albicans, is expressed predominantly on the plasma membranes of human mature neutrophils and forms membrane microdomains together with the Src family tyrosine kinase Lyn. These LacCer-enriched membrane microdomains can mediate superoxide generation, migration, and phagocytosis, indicating that LacCer functions as a PRR in innate immunity. Moreover, the interactions of GSL-enriched membrane microdomains with membrane proteins, such as growth factor receptors, are important in mediating the physiological properties of these proteins. Similarly, we recently found that interactions between LacCer-enriched membrane microdomains and CD11b/CD18 (Mac-1, CR3, or αMβ2-integrin) are significant for neutrophil phagocytosis of non-opsonized microorganisms. This review describes the functional role of LacCer-enriched membrane microdomains and their interactions with CD11b/CD18.

  10. Targeting Neutrophilic Inflammation Using Polymersome-Mediated Cellular Delivery.

    Science.gov (United States)

    Robertson, James D; Ward, Jon R; Avila-Olias, Milagros; Battaglia, Giuseppe; Renshaw, Stephen A

    2017-05-01

    Neutrophils are key effector cells in inflammation and play an important role in neutralizing invading pathogens. During inflammation resolution, neutrophils undergo apoptosis before they are removed by macrophages, but if apoptosis is delayed, neutrophils can cause extensive tissue damage and chronic disease. Promotion of neutrophil apoptosis is a potential therapeutic approach for treating persistent inflammation, yet neutrophils have proven difficult cells to manipulate experimentally. In this study, we deliver therapeutic compounds to neutrophils using biocompatible, nanometer-sized synthetic vesicles, or polymersomes, which are internalized by binding to scavenger receptors and subsequently escape the early endosome through a pH-triggered disassembly mechanism. This allows polymersomes to deliver molecules into the cell cytosol of neutrophils without causing cellular activation. After optimizing polymersome size, we show that polymersomes can deliver the cyclin-dependent kinase inhibitor (R)-roscovitine into human neutrophils to promote apoptosis in vitro. Finally, using a transgenic zebrafish model, we show that encapsulated (R)-roscovitine can speed up inflammation resolution in vivo more efficiently than the free drug. These results show that polymersomes are effective intracellular carriers for drug delivery into neutrophils. This has important consequences for the study of neutrophil biology and the development of neutrophil-targeted therapeutics. Copyright © 2017 The Authors.

  11. Spontaneous neutrophil migration patterns during sepsis after major burns.

    Science.gov (United States)

    Jones, Caroline N; Moore, Molly; Dimisko, Laurie; Alexander, Andrew; Ibrahim, Amir; Hassell, Bryan A; Warren, H Shaw; Tompkins, Ronald G; Fagan, Shawn P; Irimia, Daniel

    2014-01-01

    Finely tuned to respond quickly to infections, neutrophils have amazing abilities to migrate fast and efficiently towards sites of infection and inflammation. Although neutrophils ability to migrate is perturbed in patients after major burns, no correlations have yet been demonstrated between altered migration and higher rate of infections and sepsis in these patients when compared to healthy individuals. To probe if such correlations exist, we designed microfluidic devices to quantify the neutrophil migration phenotype with high precision. Inside these devices, moving neutrophils are confined in channels smaller than the neutrophils and forced to make directional decisions at bifurcations and around posts. We employed these devices to quantify neutrophil migration across 18 independent parameters in 74 blood samples from 13 patients with major burns and 3 healthy subjects. Blinded, retrospective analysis of clinical data and neutrophil migration parameters revealed that neutrophils isolated from blood samples collected during sepsis migrate spontaneously inside the microfluidic channels. The spontaneous neutrophil migration is a unique phenotype, typical for patients with major burns during sepsis and often observed one or two days before the diagnosis of sepsis is confirmed. The spontaneous neutrophil migration phenotype is rare in patients with major burns in the absence of sepsis, and is not encountered in healthy individuals. Our findings warrant further studies of neutrophils and their utility for early diagnosing and monitoring sepsis in patients after major burns.

  12. The cystic fibrosis neutrophil: a specialized yet potentially defective cell.

    LENUS (Irish Health Repository)

    Hayes, Elaine

    2012-02-01

    Cystic fibrosis (CF) is one of the commonest genetically inherited diseases in the world. It is characterized by recurrent respiratory tract infections eventually leading to respiratory failure. One of the hallmarks of this disease is a persistent and predominantly neutrophil driven inflammation. Neutrophils provide the first line of defence by killing and digesting phagocytosed bacteria and fungi, yet despite advances in our understanding of the molecular and cellular basis of CF, there remains a paradox of why recruited CF neutrophils fail to eradicate bacterial infections in the lung. This review describes mechanisms involved in neutrophil migration, microbial killing and apoptosis leading to inflammatory resolution. We discuss dysregulated neutrophil activity and consider genetic versus inflammatory neutrophil reprogramming in CF and ultimately pharmacological modulation of the CF neutrophil for therapeutic intervention.

  13. The cystic fibrosis neutrophil: a specialized yet potentially defective cell.

    LENUS (Irish Health Repository)

    Hayes, Elaine

    2011-04-01

    Cystic fibrosis (CF) is one of the commonest genetically inherited diseases in the world. It is characterized by recurrent respiratory tract infections eventually leading to respiratory failure. One of the hallmarks of this disease is a persistent and predominantly neutrophil driven inflammation. Neutrophils provide the first line of defence by killing and digesting phagocytosed bacteria and fungi, yet despite advances in our understanding of the molecular and cellular basis of CF, there remains a paradox of why recruited CF neutrophils fail to eradicate bacterial infections in the lung. This review describes mechanisms involved in neutrophil migration, microbial killing and apoptosis leading to inflammatory resolution. We discuss dysregulated neutrophil activity and consider genetic versus inflammatory neutrophil reprogramming in CF and ultimately pharmacological modulation of the CF neutrophil for therapeutic intervention.

  14. Operator's Manual for SHEBA Powered Tether Balloon System

    Science.gov (United States)

    Lappen, Cara-Lyn; Randall, David A.

    1998-01-01

    The Surface Heat and Energy Budget of the Arctic (SHEBA) was an intensive field project which took place in the Arctic Ocean from October 1997 through October 1998. Its purpose was to measure as many facets of the Arctic environment as possible so that we would be able to better understand the interaction between the ice, atmosphere, and ocean and their interactions with global climate. One aspect of the atmospheric field component was launching tethered balloons to monitor the profiles of temperature, wind, pressure, and humidity, as well as examine the vertical structure of cloud droplet sizes and distributions. The tethered balloon that we used was one specially designed for use in freezing climates by SPEC Corporation in Boulder, Colorado. A special winch that was able to withstand Arctic temperature and weather became necessary when the testing of simple winch systems used in warmer climates failed under these extreme conditions. The purpose of this manual is to acquaint any new user to the powered tethered balloon system deployed at the The Surface Heat and Energy Budget of the Arctic (SHEBA ice camp. It includes a description of the preparations necessary to get ready for a launch, the mechanics of the actual launch, and an account of the proper procedure for taking down the equipment when finished. It will also include tips on how to minimize potential equipment failures, some trouble shooting, and some safety ideas. This manual is designed so that new operators can use the system with minimal previous training. At the end of this manual, the reader will find a quick checklist.

  15. Mechanism of subdural effusion evolves into chronic subdural hematoma: IL-8 inducing neutrophil oxidative burst.

    Science.gov (United States)

    Tao, Zhiqiang; Lin, Yingying; Hu, Maotong; Ding, Shenghong; Li, Jianwei; Qiu, Yongming

    2016-01-01

    Chronic subdural hematoma (CSDH) is still a mysterious disease. Though great success has been has achieved by neuro-surgery treatment, the origin and development of CSDH remains unknown. Tremendous clinical observations have found the correlation of subdural effusion (SDE) and CSDH. However, systematic elucidation of CSDH's origin and progression is lacking while almost all the current hypothesis only explained partial phenomenon. This hypothesis proposes Interleukin (IL)-8 inducing neutrophil respiratory burst is the crucial impact when SDE evolves into CSDH. IL-8 initially secreted by dural border layer cells, accumulates and the concentration of IL-8 rises in the SDE cavity. Accompanied by the formation of neo-membrane under the dura meninges, IL-8 firstly prompts to establish the neo-vasculature in it, and then attracts lymphocytes aggregation in the neo-membrane. Both the newly recruited lymphocytes and endothelial cells assist the further elevation of local IL-8 concentration. When the IL-8 concentration elevated to a particular level, it attracts neutrophils to the inner wall of neo-vessels and primes them to oxidative burst. Lysosomes and superoxide released by these neutrophils make the fragile neo-capillary became leaky, and subsequently the plasma and blood cells run into SDE. However, as long as the erythrocytes come into the cavity, they shall bind large quantity of IL-8 and decrease IL-8 concentration to a lower level relatively that reduce the neutrophils recruit. When this negative feedback is stagnancy, for example, the SDE space is so large in elder man who is experiencing brain atrophy, the neo-vessels have to release more erythrocytes to bind IL-8, the liquid cavity will expand and the high intracranial pressure symptoms appeared. Our hypothesis holds potential for the proper therapeutic intervention of CSDH. IL-8 antagonist and other anti-inflammation drugs like macrolides antibiotics, glucocorticoid and atorvastatin might be optional to resist

  16. Tethered Transition Metals Promoted Photocatalytic System for Efficient Hydrogen Evolutions

    KAUST Repository

    Takanabe, Kazuhiro; Isimjan, Tayirjan; Yu, Weili; Del Gobbo, Silvano; Xu, Wei

    2015-01-01

    The present invention is directed, at least in part, to a process for improving the efficiency of a photocatalyst (a semiconductor photocatalyst) by tethering (depositing) a metal (e.g., metal ions of a late transition metal, such as nickel) to the semiconductor (photocatalyst) surface through the use of an organic ligand. More specifically, 1,2-ethanedithiol (EDT) functions as an excellent molecular linker (organic ligand) to attach a transition metal complex (e.g., nickel (Ni.sup.2+ ions)) to the semiconductor surface, which can be in the form of a cadmium sulfide surface. The photocatalyst has particular utility in generating hydrogen from H.sub.2S.

  17. Tethered Transition Metals Promoted Photocatalytic System for Efficient Hydrogen Evolutions

    KAUST Repository

    Takanabe, Kazuhiro

    2015-03-05

    The present invention is directed, at least in part, to a process for improving the efficiency of a photocatalyst (a semiconductor photocatalyst) by tethering (depositing) a metal (e.g., metal ions of a late transition metal, such as nickel) to the semiconductor (photocatalyst) surface through the use of an organic ligand. More specifically, 1,2-ethanedithiol (EDT) functions as an excellent molecular linker (organic ligand) to attach a transition metal complex (e.g., nickel (Ni.sup.2+ ions)) to the semiconductor surface, which can be in the form of a cadmium sulfide surface. The photocatalyst has particular utility in generating hydrogen from H.sub.2S.

  18. Implementation Options for the PROPEL Electrodynamic Tether Demonstration Mission

    Science.gov (United States)

    Bilen, Sven G.; Johnson, C. Les; Gilchrist, Brian E.; Hoyt, Robert P.; Elder, Craig H.; Fuhrhop, Keith P.; Scadera, Michael; Stone, Nobie

    2014-01-01

    The PROPEL ("Propulsion using Electrodynamics") flight demonstration mission concept will demonstrate the use of an electrodynamic tether (EDT) for generating thrust, which will allow the propulsion system to overcome the limitations of the rocket equation. The mission concept has been developed by a team of government, industry, and academia partners led by NASA Marshall Space Flight Center (MSFC). PROPEL is being designed for versatility of the EDT system with multiple end users in mind and to be flexible with respect to platform. Previously, we reported on a comprehensive mission design for PROPEL with a mission duration of six months or longer with multiple mission goals including demonstration of significant boost, deboost, inclination change, and drag make-up activities. To explore a range of possible configurations, primarily driven by cost considerations, other mission concept designs have been pursued. In partnership with the NASA's Office of Chief Technologist (OCT) Game Changing Program, NASA MSFC Leadership, and the MSFC Advanced Concepts Office, a mission concept design was developed for a near-term EDT propulsion flight validation mission. The Electrodynamic Tether Propulsion Study (ETPS) defined an EDT propulsion system capable of very large delta-V for use on future missions developed by NASA, DoD, and commercial customers. To demonstrate the feasibility of an ETPS, the study focused on a space demonstration mission concept design with configuration of a pair of tethered satellite busses, one of which is the Japanese H-II Transfer Vehicle (HTV). The HTV would fly its standard ISS resupply mission. When resupply mission is complete, the ISS reconfigures and releases the HTV to perform the EDT experiment at safe orbital altitudes below the ISS. Though the focus of this particular mission concept design addresses a scenario involving the HTV or a similar vehicle, the propulsion system's capability is relevant to a number of applications, as noted above

  19. Fullerenic structures and such structures tethered to carbon materials

    Science.gov (United States)

    Goel, Anish; Howard, Jack B.; Vander Sande, John B.

    2010-01-05

    The fullerenic structures include fullerenes having molecular weights less than that of C.sub.60 with the exception of C.sub.36 and fullerenes having molecular weights greater than C.sub.60. Examples include fullerenes C.sub.50, C.sub.58, C.sub.130, and C.sub.176. Fullerenic structure chemically bonded to a carbon surface is also disclosed along with a method for tethering fullerenes to a carbon material. The method includes adding functionalized fullerene to a liquid suspension containing carbon material, drying the suspension to produce a powder, and heat treating the powder.

  20. A tethered balloon system for observation of atmospheric temperature inversion

    International Nuclear Information System (INIS)

    Hayashi, Takashi; Kakuta, Michio

    1979-05-01

    In environmental assessment of near-shore nuclear plants, information is often required on the development of internal boundary layer (IBL) and associated fumigation condition. Single tower data is not sufficient to clarify the site-dependent IBL structure that affects the atmospheric diffusion in shoreline-stack-site boundary complex. A tethered balloon system has been developed, which comprises a fixed point kitoon and a car-borne small balloon. The system enables us to measure the detailed time-space distribution of temperature without much man-power. The system and example of field observations with it are described. (author)

  1. Influence of exogenous leptin on redox homeostasis in neutrophils and lymphocytes cultured in synovial fluid isolated from patients with rheumatoid arthritis

    Directory of Open Access Journals (Sweden)

    Michał Gajewski

    2016-07-01

    Full Text Available Objectives : Leptin is an adipose cells derived hormone that regulates energy homeostasis within the body. Energy metabolism of immune cells influences their activity within numerous pathological states, but the effect of leptin on these cells in unclear. On the one hand, it was observed that leptin induces neutrophils chemotaxis and modulates phagocytosis. On the other hand, neutrophils exposed to leptin did not display detectable Ca 2+ ions mobilization or β 2 -integrin upregulation. In this study, we investigated the effect of leptin on the redox homeostasis in lymphocytes and neutrophils. Material and methods : Neutrophils and lymphocytes were isolated by density-gradient centrifugation of blood from healthy volunteers. Cells were cultured with or without leptin (100 ng/ml for lymphocytes and 500 ng/ml for neutrophils or with or without synovial fluid (85% for 0–72 h. Culture media were not changed during incubation. Cells were homogenized and homogenate was frozen until laboratory measurements. Redox homeostasis was assessed by the reduced glutathione (GSH vs. oxidized glutathione (GSSG ratio and membrane lipid peroxidation evaluation. Results : Lymphocytes cultured with leptin and synovial fluid showed a significant increase of the GSSG level. The GSSG/GSH ratio increased by 184 ±37%. In neutrophils incubated in a similar environment, the GSSG/GSH ratio increased by just 21 ±7%, and the effect was observed irrespectively of whether they were exposed to leptin or synovial fluid or both together. Neither leptin nor synovial fluid influenced lipid peroxidation in neutrophils, but in lymphocytes leptin intensified lipid peroxidation. Conclusions : Leptin altered the lymphocytes, but not neutrophils redox state. Because firstly neutrophils are anaerobic cells and have just a few mitochondria and secondly lymphocytes have typical aerobic metabolism, the divergence of our data supports the hypothesis that leptin induces oxidative stress by

  2. Effect of the dimetilsulfoxido in the response chemiluminescent and the consumption of oxygen of neutrophils activated human

    International Nuclear Information System (INIS)

    Garcia, J.

    2001-01-01

    Dimethylsulfoxide (DMSO), a hydroxyl radical scavenger, exerted a dose dependent inhibition on the luminol and lucigenin-enhanced chemiluminescent responses of human neutrophils activated with soluble and particulate stimulants. DMSO inhibition of the luminol chemiluminescense induced by calcium ionophore A23187 was probably due to OH scavenging, whereas inhibition of the lucigenin chemiluminescence suggested DMSO negatively affects the NADPH-dependent membrane oxidase of neutrophils. In agreement with this, DMSO moderately inhibited O2 consumption in PMN suspensions stimulated with chemotactic peptide and opsonized zymosan-induced luminol chemiluminescense was observed only when added before or in conjunction with stimulants, whereas A23187-induced chemiluminescense was inhibited by DMSO regardless of time of addition. Washing of DMSO-treated PMN resulted in increased luminol enhanced chemiluminescense in response to chemotactic peptide and opsonized zymosan. This is consistent with the idea that DMSO may be interfering with activation of the membrane subunits of the oxidase by translocation and docking of the cytoplasmic, regulatory subunits. These data imply that DMSO inhibits neutrophil chemiluminescense both by OH scavenging and interfering with oxidase activation. Key words:Dimethylsulfoxide, chemiluminescent, luminol, lucigenin,neutrophils [es

  3. Membrane elastic properties and cell function.

    Directory of Open Access Journals (Sweden)

    Bruno Pontes

    Full Text Available Recent studies indicate that the cell membrane, interacting with its attached cytoskeleton, is an important regulator of cell function, exerting and responding to forces. We investigate this relationship by looking for connections between cell membrane elastic properties, especially surface tension and bending modulus, and cell function. Those properties are measured by pulling tethers from the cell membrane with optical tweezers. Their values are determined for all major cell types of the central nervous system, as well as for macrophage. Astrocytes and glioblastoma cells, which are considerably more dynamic than neurons, have substantially larger surface tensions. Resting microglia, which continually scan their environment through motility and protrusions, have the highest elastic constants, with values similar to those for resting macrophage. For both microglia and macrophage, we find a sharp softening of bending modulus between their resting and activated forms, which is very advantageous for their acquisition of phagocytic functions upon activation. We also determine the elastic constants of pure cell membrane, with no attached cytoskeleton. For all cell types, the presence of F-actin within tethers, contrary to conventional wisdom, is confirmed. Our findings suggest the existence of a close connection between membrane elastic constants and cell function.

  4. Contribution of Neutrophils to Acute Lung Injury

    OpenAIRE

    Grommes, Jochen; Soehnlein, Oliver

    2010-01-01

    Treatment of acute lung injury (ALI) and its most severe form, acute respiratory distress syndrome (ARDS), remain unsolved problems of intensive care medicine. ALI/ARDS are characterized by lung edema due to increased permeability of the alveolar-capillary barrier and subsequent impairment of arterial oxygenation. Lung edema, endothelial and epithelial injury are accompanied by an influx of neutrophils into the interstitium and broncheoalveolar space. Hence, activation and recruitment of neut...

  5. Tumor Associated Neutrophils in Human Lung Cancer

    Science.gov (United States)

    2016-10-01

    tumor innate immune response. anti-tumor adaptive immune response, neutrophil and T cell interaction. ACCOMPLISHMENTS There were no significant...and by producing factors to recruit and acti- vate cells of the innate and adaptive immune system (Mantovani et al., 2011). Given these varying effects...vivo effects on neutro- phil activation (Figure 2, A and B) and cleavage of myeloid and lymphoid cell markers (Supplemental Figure 1, C–G). Once opti

  6. Acquisition of Ice-Tethered Profilers with Velocity (ITP-V) Instruments for Future Arctic Studies

    Science.gov (United States)

    2016-11-15

    San Diego, CA, IEEE Xplore . Toole, J. M., R. A. Krishfield, M.-L. Timmennans, and A. Proshutinsky, 2011: The Ice-Tethered Profiler: Argo ofthe Arctic, Oceanogr., 24, 126-135. 4 ...observations from Ice-Tethered Profilers, MTS/ IEEE Oceans’ 2015, Washington DC, 1-10. Krishfield, R., J. Toole, A. Proshutinsky, and M.-L. Timmennans, 2008

  7. Long-term evaluation of intraoperative neurophysiological monitoring-assisted tethered cord surgery

    NARCIS (Netherlands)

    Dulfer, S E; Drost, G; Lange, F; Journee, H L; Wapstra, F H; Hoving, E W

    2017-01-01

    PURPOSE: Patients with tethered spinal cord have been investigated for short-term effects after tethered spinal cord surgery in the past. However, little is known about the long-term effects in this patient group. In this retrospective, longitudinal, observational study, a patient sample of a

  8. Tethered balloon operation for wintering aerosol measurements in the lower troposphere at Syowa Station, Antarctica

    OpenAIRE

    Keiichiro Hara; Kazuo Osada; Takashi Yamanouchi

    2007-01-01

    The 46th Japanese Antarctic Research Expedition (JARE-46) carried out twenty seven tethered-balloon-borne aerosol measurements at Syowa Station for better understanding of aerosol chemical and physical properties in the lower troposphere from 6th January 2005 until 11 December 2005. This report summarizes the plan, preparation, field activities and some troubles/problems in the tethered-balloon observations.

  9. Tethered spinal cord: the effect of neurosurgery on the lower urinary tract and male sexual function

    NARCIS (Netherlands)

    Boemers, T. M.; van Gool, J. D.; de Jong, T. P.

    1995-01-01

    To determine the effect of neurosurgical untethering on the lower urinary tract and male sexual function, in patients with tethered spinal cord. Thirty-six children with tethered spinal cord due to neurospinal dysraphism were assessed clinically and urodynamically before and after surgical

  10. Leukotriene B4-Neutrophil Elastase Axis Drives Neutrophil Reverse Transendothelial Cell Migration In Vivo

    Science.gov (United States)

    Colom, Bartomeu; Bodkin, Jennifer V.; Beyrau, Martina; Woodfin, Abigail; Ody, Christiane; Rourke, Claire; Chavakis, Triantafyllos; Brohi, Karim; Imhof, Beat A.; Nourshargh, Sussan

    2015-01-01

    Summary Breaching endothelial cells (ECs) is a decisive step in the migration of leukocytes from the vascular lumen to the extravascular tissue, but fundamental aspects of this response remain largely unknown. We have previously shown that neutrophils can exhibit abluminal-to-luminal migration through EC junctions within mouse cremasteric venules and that this response is elicited following reduced expression and/or functionality of the EC junctional adhesion molecule-C (JAM-C). Here we demonstrate that the lipid chemoattractant leukotriene B4 (LTB4) was efficacious at causing loss of venular JAM-C and promoting neutrophil reverse transendothelial cell migration (rTEM) in vivo. Local proteolytic cleavage of EC JAM-C by neutrophil elastase (NE) drove this cascade of events as supported by presentation of NE to JAM-C via the neutrophil adhesion molecule Mac-1. The results identify local LTB4-NE axis as a promoter of neutrophil rTEM and provide evidence that this pathway can propagate a local sterile inflammatory response to become systemic. PMID:26047922

  11. Leukotriene B4-Neutrophil Elastase Axis Drives Neutrophil Reverse Transendothelial Cell Migration In Vivo.

    Science.gov (United States)

    Colom, Bartomeu; Bodkin, Jennifer V; Beyrau, Martina; Woodfin, Abigail; Ody, Christiane; Rourke, Claire; Chavakis, Triantafyllos; Brohi, Karim; Imhof, Beat A; Nourshargh, Sussan

    2015-06-16

    Breaching endothelial cells (ECs) is a decisive step in the migration of leukocytes from the vascular lumen to the extravascular tissue, but fundamental aspects of this response remain largely unknown. We have previously shown that neutrophils can exhibit abluminal-to-luminal migration through EC junctions within mouse cremasteric venules and that this response is elicited following reduced expression and/or functionality of the EC junctional adhesion molecule-C (JAM-C). Here we demonstrate that the lipid chemoattractant leukotriene B4 (LTB4) was efficacious at causing loss of venular JAM-C and promoting neutrophil reverse transendothelial cell migration (rTEM) in vivo. Local proteolytic cleavage of EC JAM-C by neutrophil elastase (NE) drove this cascade of events as supported by presentation of NE to JAM-C via the neutrophil adhesion molecule Mac-1. The results identify local LTB4-NE axis as a promoter of neutrophil rTEM and provide evidence that this pathway can propagate a local sterile inflammatory response to become systemic. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

  12. Piperidinium tethered nanoparticle-hybrid electrolyte for lithium metal batteries

    KAUST Repository

    Korf, Kevin S.

    2014-06-23

    We report on the synthesis of novel piperidinium-based ionic liquid tethered nanoparticle hybrid electrolytes and investigate their physical and electrochemical properties. Hybrid electrolytes based on the ionic liquid 1-methyl-1-propylpiperidinium bis(trifluoromethanesulfone) imide covalently tethered to silica nanoparticles (SiO2-PP-TFSI) were blended with propylene carbonate-1 M lithium bis(trifluoromethanesulfone) imide (LiTFSI). We employed NMR analysis to confirm the successful creation of the hybrid material. Dielectric and rheological measurements show that these electrolytes exhibit exceptional room-temperature DC ionic conductivity (10-2 to 10 -3 S cm-1) as well as high shear mechanical moduli (105 to 106 Pa). Lithium transference numbers were found to increase with particle loading and to reach values as high as 0.22 at high particle loadings where the particle jam to form a soft glassy elastic medium. Analysis of lithium electrodeposits obtained in the hybrid electrolytes using SEM and EDX spectra show that the SiO2-PP-TFSI nanoparticles are able to smooth lithium deposition and inhibit lithium dendrite proliferation in Li metal batteries. LTOSiO2-PP-TFSI/PC in 1 M LiTFSILi half-cells based on the SiO2-PP-TFSI hybrid electrolytes exhibit attractive voltage profiles and trouble-free extended cycling behavior over more than 1000 cycles of charge and discharge. This journal is © the Partner Organisations 2014.

  13. Isothermal pumping analysis for high-altitude tethered balloons.

    Science.gov (United States)

    Kuo, Kirsty A; Hunt, Hugh E M

    2015-06-01

    High-altitude tethered balloons have potential applications in communications, surveillance, meteorological observations and climate engineering. To maintain balloon buoyancy, power fuel cells and perturb atmospheric conditions, fluids could be pumped from ground level to altitude using the tether as a hose. This paper examines the pumping requirements of such a delivery system. Cases considered include delivery of hydrogen, sulfur dioxide (SO2) and powders as fluid-based slurries. Isothermal analysis is used to determine the variation of pressures and velocities along the pipe length. Results show that transport of small quantities of hydrogen to power fuel cells and maintain balloon buoyancy can be achieved at pressures and temperatures that are tolerable in terms of both the pipe strength and the current state of pumping technologies. To avoid solidification, transport of SO2 would require elevated temperatures that cannot be tolerated by the strength fibres in the pipe. While the use of particle-based slurries rather than SO2 for climate engineering can reduce the pipe size significantly, the pumping pressures are close to the maximum bursting pressure of the pipe.

  14. Prevention of vascular inflammation by nanoparticle targeting of adherent neutrophils

    Science.gov (United States)

    Wang, Zhenjia; Li, Jing; Cho, Jaehyung; Malik, Asrar B.

    2014-03-01

    Inflammatory diseases such as acute lung injury and ischaemic tissue injury are caused by the adhesion of a type of white blood cell--polymorphonuclear neutrophils--to the lining of the circulatory system or vascular endothelium and unchecked neutrophil transmigration. Nanoparticle-mediated targeting of activated neutrophils on vascular endothelial cells at the site of injury may be a useful means of directly inactivating neutrophil transmigration and hence mitigating vascular inflammation. Here, we report a method employing drug-loaded albumin nanoparticles, which efficiently deliver drugs into neutrophils adherent to the surface of the inflamed endothelium. Using intravital microscopy of tumour necrosis factor-α-challenged mouse cremaster post-capillary venules, we demonstrate that fluorescently tagged albumin nanoparticles are largely internalized by neutrophils adherent to the activated endothelium via cell surface Fcɣ receptors. Administration of albumin nanoparticles loaded with the spleen tyrosine kinase inhibitor, piceatannol, which blocks `outside-in' β2 integrin signalling in leukocytes, detached the adherent neutrophils and elicited their release into the circulation. Thus, internalization of drug-loaded albumin nanoparticles into neutrophils inactivates the pro-inflammatory function of activated neutrophils, thereby offering a promising approach for treating inflammatory diseases resulting from inappropriate neutrophil sequestration and activation.

  15. Sexy again: the renaissance of neutrophils in psoriasis.

    Science.gov (United States)

    Schön, Michael P; Broekaert, Sigrid M C; Erpenbeck, Luise

    2017-04-01

    Notwithstanding their prominent presence in psoriatic skin, the functional role of neutrophilic granulocytes still remains somewhat enigmatic. Sparked by exciting scientific discoveries regarding neutrophil functions within the last years, the interest in these short-lived cells of the innate immune system has been boosted recently. While it had been known for some time that neutrophils produce and respond to a number of inflammatory mediators, recent research has linked neutrophils with the pathogenic functions of IL-17, possibly in conjunction with the formation of NETs (neutrophil extracellular traps). Antipsoriatic therapies exert their effects, at least in part, through interference with neutrophils. Neutrophils also appear to connect psoriasis with comorbid diseases. However, directly tampering with neutrophil functions is not trivial as evinced by the failure of therapeutic approaches targeting redundantly regulated cellular communication networks. It has also become apparent that neutrophils link important pathogenic functions of the innate and the adaptive immune system and that they are intricately involved in regulatory networks underlying the pathophysiology of psoriasis. In order to advocate intensified research into the role of this interesting cell population, we here highlight some features of neutrophils and put them into perspective with our current view of the pathophysiology of psoriasis. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  16. Effect of Isolation Techniques on Viability of Bovine Blood Neutrophils

    Directory of Open Access Journals (Sweden)

    P. Sláma

    2006-01-01

    Full Text Available The effect of selected isolation methods on the viability of neutrophil granulocytes (neutrophils from the blood of healthy Holstein x Bohemian Red Pied crossbred heifers was evaluated. Two methods of neutrophil isolation were used: a neutrophil isolation on the basis of hypotonic erythrocyte lysis (in two variants: after the erythrocyte lysis proper, the cells were centrifuged at either 200 g or 1000 g, and b neutrophil isolation with FACS Lysing Solution as the lysing agent. The viability of the isolated neutrophils was evaluated on the basis of apoptosis and necrosis. The results obtained with flow cytometry (FCM suggest that, from the isolation techniques used, the method based on FACS Lysing Solution impaired the neutrophil viability least. After the application of this method, 5.36 ± 2.15% of neutrophils were apoptotic and 0.51 ± 0.12% were necrotic. In contrast, when the hypotonic erythrocyte lysis was used, the proportion of apoptotic neutrophils amounted to 42.14 ± 7.12% and 49.00 ± 14.70%, respectively, and 41.12 ± 5.55% and 36.91 ± 24.38% respectively of necrotic neutrophils (P < 0.01. This was also confirmed by the light microscopy. After the isolation with FASC Lysing Solution, 1.92 ± 1.74% of neutrophils were apoptotic and 1.05 ± 0.76% were necrotic, as distinct from after the hypotonic erythrocyte lysis where 9.43 ± 3.69% of neutrophils were apoptotic and 12.67 ± 4.74% of necrotic after centrifugation at 200 g, while 12.60 ± 4.35 were apoptotic and 14.96 ± 12.64% were necrotic after centrifugation at 1000 g. It follows from the above-mentioned data that hypotonic lysis is not a suitable method for the isolation of neutrophils, as the method itself markedly affects cell viability.

  17. Dynamics and stability of a tethered centrifuge in low earth orbit

    Science.gov (United States)

    Quadrelli, B. M.; Lorenzini, E. C.

    1992-01-01

    The three-dimensional attitude dynamics of a spaceborne tethered centrifuge for artificial gravity experiments in low earth orbit is analyzed using two different methods. First, the tethered centrifuge is modeled as a dumbbell with a straight viscoelastic tether, point tip-masses, and sophisticated environmental models such as nonspherical gravity, thermal perturbations, and a dynamic atmospheric model. The motion of the centrifuge during spin-up, de-spin, and steady-rotation is then simulated. Second, a continuum model of the tether is developed for analyzing the stability of lateral tether oscillations. Results indicate that the maximum fluctuation about the 1-g radial acceleration level is less than 0.001 g; the time required for spin-up and de-spin is less than one orbit; and lateral oscillations are stable for any practical values of the system parameters.

  18. Membrane dynamics

    DEFF Research Database (Denmark)

    Bendix, Pól Martin

    2015-01-01

    Current topics include membrane-protein interactions with regard to membrane deformation or curvature sensing by BAR domains. Also, we study the dynamics of membrane tubes of both cells and simple model membrane tubes. Finally, we study membrane phase behavior which has important implications...... for the lateral organization of membranes as wells as for physical properties like bending, permeability and elasticity...

  19. Characterization of Yersinia pestis Interactions with Human Neutrophils In vitro

    Directory of Open Access Journals (Sweden)

    Sophia C. Dudte

    2017-08-01

    Full Text Available Yersinia pestis is a gram-negative, zoonotic, bacterial pathogen, and the causative agent of plague. The bubonic form of plague occurs subsequent to deposition of bacteria in the skin by the bite of an infected flea. Neutrophils are recruited to the site of infection within the first few hours and interactions between neutrophils and Y. pestis have been demonstrated in vivo. In contrast to macrophages, neutrophils have been considered non-permissive to Y. pestis intracellular survival. Several studies have shown killing of the vast majority of Y. pestis ingested by human neutrophils. However, survival of 10–15% of Y. pestis after phagocytosis by neutrophils is consistently observed. Furthermore, these surviving bacteria eventually replicate within and escape from the neutrophils. We set out to further characterize the interactions between Y. pestis and human neutrophils by (1 determining the effects of known Y. pestis virulence factors on bacterial survival after uptake by neutrophils, (2 examining the mechanisms employed by the neutrophil to kill the majority of intracellular Y. pestis, (3 determining the activation phenotype of Y. pestis-infected neutrophils, and (4 characterizing the Y. pestis-containing phagosome in neutrophils. We infected human neutrophils in vitro with Y. pestis and assayed bacterial survival and uptake. Deletion of the caf1 gene responsible for F1 capsule production resulted in significantly increased uptake of Y. pestis. Surprisingly, while the two-component regulator PhoPQ system is important for survival of Y. pestis within neutrophils, pre-induction of this system prior to infection did not increase bacterial survival. We used an IPTG-inducible mCherry construct to distinguish viable from non-viable intracellular bacteria and determined the association of the Y. pestis-containing phagosome with neutrophil NADPH-oxidase and markers of primary, secondary and tertiary granules. Additionally, we show that inhibition of

  20. A novel neutrophil derived inflammatory biomarker of pulmonary exacerbation in cystic fibrosis.

    LENUS (Irish Health Repository)

    2012-02-01

    BACKGROUND: The focus of this study was to characterize a novel biomarker for cystic fibrosis (CF) that could reflect exacerbations of the disease and could be useful for therapeutic stratification of patients, or for testing of potential drug treatments. This study focused exclusively on a protein complex containing alpha-1 antitrypsin and CD16b (AAT:CD16b) which is released into the bloodstream from membranes of pro-inflammatory primed neutrophils. METHODS: Neutrophil membrane expression and extracellular levels of AAT and CD16b were quantified by flow cytometry, Western blot analysis and by 2D-PAGE. Interleukin-8 (IL-8), tumor necrosis factor-alpha (TNF-alpha) and AAT:CD16b complex were quantified in CF plasma (n=38), samples post antibiotic treatment for 14days (n=10), chronic obstructive pulmonary disease (n=10), AAT deficient (n=10) and healthy control (n=14) plasma samples by ELISA. RESULTS: Cell priming with IL-8 and TNF-alpha caused release of the AAT:CD16b complex from the neutrophil cell membrane. Circulating plasma levels of IL-8, TNF-alpha and AAT:CD16b complex were significantly higher in patients with CF than in the other patient groups or healthy controls (P<0.05). Antibiotic treatment of pulmonary exacerbation in patients with CF led to decreased plasma protein concentrations of AAT:CD16b complex with a significant correlation with improved FEV1 (r=0.81, P=0.003). CONCLUSION: The results of this study have shown that levels of AAT:CD16b complex present in plasma correlate to the inflammatory status of patients. The AAT:CD16b biomarker may become a useful addition to the clinical diagnosis of exacerbations in CF.

  1. ARF1 recruits RAC1 to leading edge in neutrophil chemotaxis.

    Science.gov (United States)

    Mazaki, Yuichi; Onodera, Yasuhito; Higashi, Tsunehito; Horinouchi, Takahiro; Oikawa, Tsukasa; Sabe, Hisataka

    2017-10-02

    The small GTPase ARF1 mediates membrane trafficking mostly from the Golgi, and is essential for the G protein-coupled receptor (GPCR)-mediated chemotaxis of neutrophils. In this process, ARF1 is activated by the guanine nucleotide exchanger GBF1, and is inactivated by the GTPase-activating protein GIT2. Neutrophils generate the Gβγ-PAK1-αPIX-GIT2 linear complex during GPCR-induced chemotaxis, in which αPIX activates RAC1/CDC42, which then employs PAK1. However, it has remained unclear as to why GIT2 is included in this complex. We investigated the association between ARF1 and RAC1/CDC42 during the fMLP-stimulated chemotaxis of HL60 cells. We found that the silencing of GBF1 significantly impaired the recruitment of RAC1 to the leading edges, but not PAK1, αPIX, RAC2, or CDC42. A significant population of RAC1 colocalized with ARF1 at the leading edges in stimulated cells, whereas fMLP activated both ARF1 and ARF5. Consistently, the silencing of ARF1, but not ARF5, impaired the recruitment of RAC1, whereas the silencing of RAC1 did not affect the recruitment of ARF1 to the leading edges. Our results indicated that the activation of ARF1 triggers the plasma membrane recruitment of RAC1 in GPCR-mediated chemotaxis, which is essential for cortical actin remodeling. Thus, membrane remodeling at the leading edges appears to precede actin remodeling in chemotaxis. Together with the fact that GIT2, which inactivates ARF1, is an integral component of the machinery activating RAC1, we proposed a model in which the ARF1-RAC1 linkage enables the regulation of ARF1 by repetitive on/off cycles during GPCR-mediated neutrophil chemotaxis.

  2. Advanced Role of Neutrophils in Common Respiratory Diseases

    Directory of Open Access Journals (Sweden)

    Jinping Liu

    2017-01-01

    Full Text Available Respiratory diseases, always being a threat towards the health of people all over the world, are most tightly associated with immune system. Neutrophils serve as an important component of immune defense barrier linking innate and adaptive immunity. They participate in the clearance of exogenous pathogens and endogenous cell debris and play an essential role in the pathogenesis of many respiratory diseases. However, the pathological mechanism of neutrophils remains complex and obscure. The traditional roles of neutrophils in severe asthma, chronic obstructive pulmonary diseases (COPD, pneumonia, lung cancer, pulmonary fibrosis, bronchitis, and bronchiolitis had already been reviewed. With the development of scientific research, the involvement of neutrophils in respiratory diseases is being brought to light with emerging data on neutrophil subsets, trafficking, and cell death mechanism (e.g., NETosis, apoptosis in diseases. We reviewed all these recent studies here to provide you with the latest advances about the role of neutrophils in respiratory diseases.

  3. Localization and Functionality of the Inflammasome in Neutrophils

    DEFF Research Database (Denmark)

    Bakele, Martina; Joos, Melanie; Burdi, Sofia

    2014-01-01

    Neutrophils represent the major fraction of circulating immune cells and are rapidly recruited to sites of infection and inflammation. The inflammasome is a multiprotein complex that regulates the generation of IL-1 family proteins. The precise subcellular localization and functionality...... of the inflammasome in human neutrophils are poorly defined. Here we demonstrate that highly purified human neutrophils express key components of the NOD-like receptor family, pyrin domain containing 3 (NLRP3), and absent in melanoma 2 (AIM2) inflammasomes, particularly apoptosis-associated speck-like protein...... and released as protein, highly purified neutrophils neither expressed nor released IL-1α at baseline or upon stimulation. Upon inflammasome activation, highly purified neutrophils released substantially lower levels of IL-1β protein compared with partially purified neutrophils. Serine proteases and caspases...

  4. Diverse novel functions of neutrophils in immunity, inflammation, and beyond

    OpenAIRE

    Mocsai, A.

    2013-01-01

    Neutrophils have long been considered simple suicide killers at the bottom of the hierarchy of the immune response. That view began to change 10–20 yr ago, when the sophisticated mechanisms behind how neutrophils locate and eliminate pathogens and regulate immunity and inflammation were discovered. The last few years witnessed a new wave of discoveries about additional novel and unexpected functions of these cells. Neutrophils have been proposed to participate in protection against intracellu...

  5. Neutrophilic dermatoses in a patient with collagenous colitis

    OpenAIRE

    Didac Barco; Maria A. Barnadas; Esther Roé; Francisco J. Sancho; Elena Ricart; Agustín Alomar

    2010-01-01

    We report the case of a 75-year old woman with collagenous colitis who presented with erythematous and edematous plaques on the periorbital and eyelid regions, accompanied by oral ulcers. Histopathology showed a dermal neutrophilic infiltrate plus mild septal and lobular panniculitis with lymphocytes, neutrophils and eosinophils. Five years earlier she had presented a flare of papules and vesicles on the trunk, together with oral ulcers; a skin biopsy revealed a neutrophilic dermal infiltrate...

  6. In vivo characterization of neutrophil extracellular traps in various organs of a murine sepsis model.

    Directory of Open Access Journals (Sweden)

    Koji Tanaka

    Full Text Available Neutrophil extracellular traps (NETs represent extracellular microbial trapping and killing. Recently, it has been implicated in thrombogenesis, autoimmune disease, and cancer progression. The aim of this study was to characterize NETs in various organs of a murine sepsis model in vivo and to investigate their associations with platelets, leukocytes, or vascular endothelium. NETs were classified as two distinct forms; cell-free NETs that were released away from neutrophils and anchored NETs that were anchored to neutrophils. Circulating cell-free NETs were characterized as fragmented or cotton-like structures, while anchored NETs were characterized as linear, reticular, membranous, or spot-like structures. In septic mice, both anchored and cell-free NETs were significantly increased in postcapillary venules of the cecum and hepatic sinusoids with increased leukocyte-endothelial interactions. NETs were also observed in both alveolar space and pulmonary capillaries of the lung. The interactions of NETs with platelet aggregates, leukocyte-platelet aggregates or vascular endothelium of arterioles and venules were observed in the microcirculation of septic mice. Microvessel occlusions which may be caused by platelet aggregates or leukocyte-platelet aggregates and heterogeneously decreased blood flow were also observed in septic mice. NETs appeared to be associated with the formation of platelet aggregates or leukocyte-platelet aggregates. These observational findings may suggest the adverse effect of intravascular NETs on the host during a sepsis.

  7. Neutrophils in traumatic brain injury (TBI): friend or foe?

    Science.gov (United States)

    Liu, Yang-Wuyue; Li, Song; Dai, Shuang-Shuang

    2018-05-17

    Our knowledge of the pathophysiology about traumatic brain injury (TBI) is still limited. Neutrophils, as the most abundant leukocytes in circulation and the first-line transmigrated immune cells at the sites of injury, are highly involved in the initiation, development, and recovery of TBI. Nonetheless, our understanding about neutrophils in TBI is obsolete, and mounting evidences from recent studies have challenged the conventional views. This review summarizes what is known about the relationships between neutrophils and pathophysiology of TBI. In addition, discussions are made on the complex roles as well as the controversial views of neutrophils in TBI.

  8. Hypoxia upregulates neutrophil degranulation and potential for tissue injury

    Science.gov (United States)

    Hoenderdos, Kim; Lodge, Katharine M; Hirst, Robert A; Chen, Cheng; Palazzo, Stefano G C; Emerenciana, Annette; Summers, Charlotte; Angyal, Adri; Porter, Linsey; Juss, Jatinder K; O'Callaghan, Christopher; Chilvers, Edwin R

    2016-01-01

    Background The inflamed bronchial mucosal surface is a profoundly hypoxic environment. Neutrophilic airway inflammation and neutrophil-derived proteases have been linked to disease progression in conditions such as COPD and cystic fibrosis, but the effects of hypoxia on potentially harmful neutrophil functional responses such as degranulation are unknown. Methods and results Following exposure to hypoxia (0.8% oxygen, 3 kPa for 4 h), neutrophils stimulated with inflammatory agonists (granulocyte-macrophage colony stimulating factor or platelet-activating factor and formylated peptide) displayed a markedly augmented (twofold to sixfold) release of azurophilic (neutrophil elastase, myeloperoxidase), specific (lactoferrin) and gelatinase (matrix metalloproteinase-9) granule contents. Neutrophil supernatants derived under hypoxic but not normoxic conditions induced extensive airway epithelial cell detachment and death, which was prevented by coincubation with the antiprotease α-1 antitrypsin; both normoxic and hypoxic supernatants impaired ciliary function. Surprisingly, the hypoxic upregulation of neutrophil degranulation was not dependent on hypoxia-inducible factor (HIF), nor was it fully reversed by inhibition of phospholipase C signalling. Hypoxia augmented the resting and cytokine-stimulated phosphorylation of AKT, and inhibition of phosphoinositide 3-kinase (PI3K)γ (but not other PI3K isoforms) prevented the hypoxic upregulation of neutrophil elastase release. Conclusion Hypoxia augments neutrophil degranulation and confers enhanced potential for damage to respiratory airway epithelial cells in a HIF-independent but PI3Kγ-dependent fashion. PMID:27581620

  9. Circular Orbit Target Capture Using Space Tether-Net System

    Directory of Open Access Journals (Sweden)

    Guang Zhai

    2013-01-01

    Full Text Available The space tether-net system for on-orbit capture is proposed in this paper. In order to research the dynamic behaviors during system deployment, both free and nonfree deployment dynamics in circular orbit are developed; the system motion with respect to Local Vertical and Local Horizontal frame is also researched with analysis and simulation. The results show that in the case of free deployment, the capture net follows curve trajectories due to the relative orbit dynamic perturbation, and the initial deployment velocities are planned by state transformation equations for static and floating target captures; in the case of non-free deployment, the system undergoes an altitude libration along the Local Vertical, and the analytical solutions that describe the attitude libration are obtained by using variable separation and integration. Finally, the dynamics of postdeployment system is also proved marginally stable if the critical initial conditions are satisfied.

  10. Kv7 channels can function without constitutive calmodulin tethering.

    Directory of Open Access Journals (Sweden)

    Juan Camilo Gómez-Posada

    Full Text Available M-channels are voltage-gated potassium channels composed of Kv7.2-7.5 subunits that serve as important regulators of neuronal excitability. Calmodulin binding is required for Kv7 channel function and mutations in Kv7.2 that disrupt calmodulin binding cause Benign Familial Neonatal Convulsions (BFNC, a dominantly inherited human epilepsy. On the basis that Kv7.2 mutants deficient in calmodulin binding are not functional, calmodulin has been defined as an auxiliary subunit of Kv7 channels. However, we have identified a presumably phosphomimetic mutation S511D that permits calmodulin-independent function. Thus, our data reveal that constitutive tethering of calmodulin is not required for Kv7 channel function.

  11. DOE Geothermal Data Repository - Tethering Data to Information: Preprint

    Energy Technology Data Exchange (ETDEWEB)

    Weers, J.; Anderson, A.

    2014-02-01

    Data are not inherently information. Without context, data are just numbers, figures, names, or points on a line. By assigning context to data, we can validate ideas, form opinions, and generate knowledge. This is an important distinction to information scientists, as we recognize that the context in which we keep our data plays a big part in generating its value. The mechanisms used to assign this context often include their own data, supplemental to the data being described and defining semantic relationships, commonly referred to as metadata. This paper provides the status of the DOE Geothermal Data Repository (DOE GDR), including recent efforts to tether data submissions to information, discusses the important distinction between data and information, outlines a path to generate useful knowledge from raw data, and details the steps taken in order to become a node on the National Geothermal Data System (NGDS).

  12. Heterobifunctional crosslinkers for tethering single ligand molecules to scanning probes

    International Nuclear Information System (INIS)

    Riener, Christian K.; Kienberger, Ferry; Hahn, Christoph D.; Buchinger, Gerhard M.; Egwim, Innocent O.C.; Haselgruebler, Thomas; Ebner, Andreas; Romanin, Christoph; Klampfl, Christian; Lackner, Bernd; Prinz, Heino; Blaas, Dieter; Hinterdorfer, Peter; Gruber, Hermann J.

    2003-01-01

    Single molecule recognition force microscopy (SMRFM) is a versatile atomic force microscopy (AFM) method to probe specific interactions of cognitive molecules on the single molecule level. It allows insights to be gained into interaction potentials and kinetic barriers and is capable of mapping interaction sites with nm positional accuracy. These applications require a ligand to be attached to the AFM tip, preferably by a distensible poly(ethylene glycol) (PEG) chain between the measuring tip and the ligand molecule. The PEG chain greatly facilitates specific binding of the ligand to immobile receptor sites on the sample surface. The present study contributes to tip-PEG-ligand tethering in three ways: (i) a convenient synthetic route was found to prepare NH 2 -PEG-COOH which is the key intermediate for long heterobifunctional crosslinkers; (ii) a variety of heterobifunctional PEG derivatives for tip-PEG-ligand linking were prepared from NH 2 -PEG-COOH; (iii) in particular, a new PEG crosslinker with one thiol-reactive end and one terminal nitrilotriacetic acid (NTA) group was synthesized and successfully used to tether His 6 -tagged protein molecules to AFM tips via noncovalent NTA-Ni 2+ -His 6 bridges. The new crosslinker was applied to link a recombinant His 6 -tagged fragment of the very-low density lipoprotein receptor to the AFM tip whereupon specific docking to the capsid of human rhinovirus particles was observed by force microscopy. In a parallel study, the specific interaction of the small GTPase Ran with the nuclear import receptor importin β1 was studied in detail by SMRFM, using the new crosslinker to link His 6 -tagged Ran to the measuring tip [Nat. Struct. Biol. (2003), 10, 553-557

  13. Elasticity of Hard-Spheres-And-Tether Systems

    International Nuclear Information System (INIS)

    Farago, O.; Kantor, Y.

    1999-01-01

    Physical properties of a large class of systems ranging from noble gases to polymers and rubber are primarily determined by entropy, while the internal energy plays a minor role. Such systems can be conveniently modeled and numerically studied using ''hard' (i.e., ''infinity-or-zero'') potentials, such as hard sphere repulsive interactions, or inextensible (''tether'') bonds which limit the distance between the bonded monomers, but have zero energy at all permitted distances. The knowledge of elastic constants is very important for understanding the behavior of entropy-dominated systems. Computational methods for determination of the elastic constants in such systems are broadly classified into ''strain'' methods and (fluctuation methods. In the former, the elastic constants are extracted from stress-strain relations, while in the latter they are determined from measurements of stress fluctuations. The fluctuation technique usually enables more accurate and well-controlled determination of the elastic constants since in this method the elastic constants are computed directly from simulations of the un strained system with no need to deform the simulation cell and perform numerical differentiations. For central forces systems, the original ''fluctuation'' formalism can be applied provided the pair potential is twice differentiable. We have extended this formalism to apply to hard-spheres-and-tether models in which this requirement is not fulfilled. We found that for such models the components of the tensor of elastic constants can be related to (two-, three- and four-point) probability densities of contacts between hard spheres and stretched bonds. We have tested our formalism on simple (phantom networks and three-dimensional hard spheres systems

  14. Minimally invasive tethered cord release in children: A technical note

    Directory of Open Access Journals (Sweden)

    S. Kağan Başarslan

    2014-03-01

    Full Text Available Tethered cord release is commonly performed in pediatric neurosurgery. Nowadays, minimally invasive procedures are created growing interest due to its highly tolerable nature for surgery. It has been main purpose a minimal damaging on access route and maximum protection of normal structures in surgery. We present a surgical treatment of tethered cord syndrome, by which is provided the cord releasing unlike the many methods being applied with tissue removal. The main advantage of performing this surgery through 2 cm hole is to avoid removing ligamentum flavum and bony structure like lamina in addition to reduce the length of the incision and the related scar tissue. J Clin Exp Invest 2014; 5 (1: 115-117 Technical note: the patient was taken on the operating table in the sitting-prone position, and L5-S1 distance was determined by fluoroscopy. The skin and subcutaneous tissues was passed via a 2 cm vertical incision settled in 0.5 cm laterally from midline. L5-S1 distance and its covering ligamentum flavum are displayed by the guidance of L5 lamina. Williams’s retractor was placed in the distance after fetching microscope. The foregoing procedures are the same with microdiscectomic surgery. By a vertical incision made on the flavum, its both layer was lifted up and hanged with simple suture on the back tissue for a comfortable exposure of the Dura. Thecal sac was opened by 0.5 cm long vertical incision on the Dura after obtaining secure CSF drainage with the help of yellow-tipped syringe needle. With finding by a nerve hook, the phylum was burned and released securely. Then the Dura was sutured primarily for the closure by means of microsurgery instruments, and flavum was laid on it again.

  15. Differential Use of Human Neutrophil Fcγ Receptors for Inducing Neutrophil Extracellular Trap Formation.

    Science.gov (United States)

    Alemán, Omar Rafael; Mora, Nancy; Cortes-Vieyra, Ricarda; Uribe-Querol, Eileen; Rosales, Carlos

    2016-01-01

    Neutrophils (PMN) are the most abundant leukocytes in the blood. PMN migrate from the circulation to sites of infection, where they are responsible for antimicrobial functions. PMN use phagocytosis, degranulation, and formation of neutrophil extracellular traps (NETs) to kill microbes. NETs are fibers composed of chromatin and neutrophil-granule proteins. Several pathogens, including bacteria, fungi, and parasites, and also some pharmacological stimuli such as phorbol 12-myristate 13-acetate (PMA) are efficient inducers of NETs. Antigen-antibody complexes are also capable of inducing NET formation. However the particular Fcγ receptor involved in triggering this function is a matter of controversy. In order to provide some insight into what Fcγ receptor is responsible for NET formation, each of the two human Fcγ receptors was stimulated individually by specific monoclonal antibodies and NET formation was evaluated. FcγRIIa cross-linking did not promote NET formation. Cross-linking other receptors such as integrins also did not promote NET formation. In contrast FcγRIIIb cross-linking induced NET formation similarly to PMA stimulation. NET formation was dependent on NADPH-oxidase, PKC, and ERK activation. These data show that cross-linking FcγRIIIb is responsible for NET formation by the human neutrophil.

  16. Differential Use of Human Neutrophil Fcγ Receptors for Inducing Neutrophil Extracellular Trap Formation

    Directory of Open Access Journals (Sweden)

    Omar Rafael Alemán

    2016-01-01

    Full Text Available Neutrophils (PMN are the most abundant leukocytes in the blood. PMN migrate from the circulation to sites of infection, where they are responsible for antimicrobial functions. PMN use phagocytosis, degranulation, and formation of neutrophil extracellular traps (NETs to kill microbes. NETs are fibers composed of chromatin and neutrophil-granule proteins. Several pathogens, including bacteria, fungi, and parasites, and also some pharmacological stimuli such as phorbol 12-myristate 13-acetate (PMA are efficient inducers of NETs. Antigen-antibody complexes are also capable of inducing NET formation. However the particular Fcγ receptor involved in triggering this function is a matter of controversy. In order to provide some insight into what Fcγ receptor is responsible for NET formation, each of the two human Fcγ receptors was stimulated individually by specific monoclonal antibodies and NET formation was evaluated. FcγRIIa cross-linking did not promote NET formation. Cross-linking other receptors such as integrins also did not promote NET formation. In contrast FcγRIIIb cross-linking induced NET formation similarly to PMA stimulation. NET formation was dependent on NADPH-oxidase, PKC, and ERK activation. These data show that cross-linking FcγRIIIb is responsible for NET formation by the human neutrophil.

  17. Rac1 deletion in mouse neutrophils has selective effects on neutrophil functions

    NARCIS (Netherlands)

    Glogauer, Michael; Marchal, Christophe C.; Zhu, Fei; Worku, Aelaf; Clausen, Björn E.; Foerster, Irmgard; Marks, Peter; Downey, Gregory P.; Dinauer, Mary; Kwiatkowski, David J.

    2003-01-01

    Defects in myeloid cell function in Rac2 knockout mice underline the importance of this isoform in activation of NADPH oxidase and cell motility. However, the specific role of Rac1 in neutrophil function has been difficult to assess since deletion of Rac1 results in embryonic lethality in mice. To

  18. In Vitro Evaluation of the Link Between Cell Activation State and Its Rheological Impact on the Microscale Flow of Neutrophil Suspensions

    Science.gov (United States)

    Akenhead, Michael L.; Horrall, Nolan M.; Rowe, Dylan; Sethu, Palaniappan; Shin, Hainsworth Y.

    2015-01-01

    Activated neutrophils have been reported to affect peripheral resistance, for example, by plugging capillaries or adhering to the microvasculature. In vivo and ex vivo data indicate that activated neutrophils circulating in the blood also influence peripheral resistance. We used viscometry and microvascular mimics for in vitro corroboration. The rheological impact of differentiated neutrophil-like HL-60 promyelocytes (dHL60s) or human neutrophil suspensions stimulated with 10 nM fMet-Leu-Phe (fMLP) was quantified using a cone-plate rheometer (450 s−1 shear rate). To evaluate their impact on microscale flow resistance, we used 10-μm Isopore® membranes to model capillaries as well as single 200 × 50 μm microchannels and networks of twenty 20 × 50 μm microfluidic channels to mimic noncapillary microvasculature. Stimulation of dHL60 and neutrophil populations significantly altered their flow behavior as evidenced by their impact on suspension viscosity. Notably, hematocrit abrogated the impact of leukocyte activation on blood cell suspension viscosity. In micropore filters, activated cell suspensions enhanced flow resistance. This effect was further enhanced by the presence of erythrocytes. The resistance of our noncapillary microvascular mimics to flow of activated neutrophil suspensions was significantly increased only with hematocrit. Notably, it was elevated to a higher extent within the micronetwork chambers compared to the single-channel chambers. Collectively, our findings provide supportive evidence that activated neutrophils passing through the microcirculation may alter hemodynamic resistance due to their altered rheology in the noncapillary microvasculature. This effect is another way neutrophil activation due to chronic inflammation may, at least in part, contribute to the elevated hemodynamic resistance associated with cardiovascular diseases (e.g., hypertension and hypercholesterolemia). PMID:26065495

  19. In Vitro Evaluation of the Link Between Cell Activation State and Its Rheological Impact on the Microscale Flow of Neutrophil Suspensions.

    Science.gov (United States)

    Akenhead, Michael L; Horrall, Nolan M; Rowe, Dylan; Sethu, Palaniappan; Shin, Hainsworth Y

    2015-09-01

    Activated neutrophils have been reported to affect peripheral resistance, for example, by plugging capillaries or adhering to the microvasculature. In vivo and ex vivo data indicate that activated neutrophils circulating in the blood also influence peripheral resistance. We used viscometry and microvascular mimics for in vitro corroboration. The rheological impact of differentiated neutrophil-like HL-60 promyelocytes (dHL60s) or human neutrophil suspensions stimulated with 10 nM fMet-Leu-Phe (fMLP) was quantified using a cone-plate rheometer (450 s(-1) shear rate). To evaluate their impact on microscale flow resistance, we used 10-μm Isopore® membranes to model capillaries as well as single 200 × 50 μm microchannels and networks of twenty 20 × 50 μm microfluidic channels to mimic noncapillary microvasculature. Stimulation of dHL60 and neutrophil populations significantly altered their flow behavior as evidenced by their impact on suspension viscosity. Notably, hematocrit abrogated the impact of leukocyte activation on blood cell suspension viscosity. In micropore filters, activated cell suspensions enhanced flow resistance. This effect was further enhanced by the presence of erythrocytes. The resistance of our noncapillary microvascular mimics to flow of activated neutrophil suspensions was significantly increased only with hematocrit. Notably, it was elevated to a higher extent within the micronetwork chambers compared to the single-channel chambers. Collectively, our findings provide supportive evidence that activated neutrophils passing through the microcirculation may alter hemodynamic resistance due to their altered rheology in the noncapillary microvasculature. This effect is another way neutrophil activation due to chronic inflammation may, at least in part, contribute to the elevated hemodynamic resistance associated with cardiovascular diseases (e.g., hypertension and hypercholesterolemia).

  20. Experiments and simulation of a net closing mechanism for tether-net capture of space debris

    Science.gov (United States)

    Sharf, Inna; Thomsen, Benjamin; Botta, Eleonora M.; Misra, Arun K.

    2017-10-01

    This research addresses the design and testing of a debris containment system for use in a tether-net approach to space debris removal. The tether-net active debris removal involves the ejection of a net from a spacecraft by applying impulses to masses on the net, subsequent expansion of the net, the envelopment and capture of the debris target, and the de-orbiting of the debris via a tether to the chaser spacecraft. To ensure a debris removal mission's success, it is important that the debris be successfully captured and then, secured within the net. To this end, we present a concept for a net closing mechanism, which we believe will permit consistently successful debris capture via a simple and unobtrusive design. This net closing system functions by extending the main tether connecting the chaser spacecraft and the net vertex to the perimeter and around the perimeter of the net, allowing the tether to actuate closure of the net in a manner similar to a cinch cord. A particular embodiment of the design in a laboratory test-bed is described: the test-bed itself is comprised of a scaled-down tether-net, a supporting frame and a mock-up debris. Experiments conducted with the facility demonstrate the practicality of the net closing system. A model of the net closure concept has been integrated into the previously developed dynamics simulator of the chaser/tether-net/debris system. Simulations under tether tensioning conditions demonstrate the effectiveness of the closure concept for debris containment, in the gravity-free environment of space, for a realistic debris target. The on-ground experimental test-bed is also used to showcase its utility for validating the dynamics simulation of the net deployment, and a full-scale automated setup would make possible a range of validation studies of other aspects of a tether-net debris capture mission.

  1. Simulations of momentum transfer process between solar wind plasma and bias voltage tethers of electric sail thruster

    Science.gov (United States)

    Xia, Guangqing; Han, Yajie; Chen, Liuwei; Wei, Yanming; Yu, Yang; Chen, Maolin

    2018-06-01

    The interaction between the solar wind plasma and the bias voltage of long tethers is the basic mechanism of the electric sail thruster. The momentum transfer process between the solar wind plasma and electric tethers was investigated using a 2D full particle PIC method. The coupled electric field distribution and deflected ion trajectory under different bias voltages were compared, and the influence of bias voltage on momentum transfer process was analyzed. The results show that the high potential of the bias voltage of long tethers will slow down, stagnate, reflect and deflect a large number of ions, so that ion cavities are formed in the vicinity of the tether, and the ions will transmit the axial momentum to the sail tethers to produce the thrust. Compared to the singe tether, double tethers show a better thrust performance.

  2. Gβ1 is required for neutrophil migration in zebrafish.

    Science.gov (United States)

    Ke, Wenfan; Ye, Ding; Mersch, Kacey; Xu, Hui; Chen, Songhai; Lin, Fang

    2017-08-01

    Signaling mediated by G protein-coupled receptors (GPCRs) is essential for the migration of cells toward chemoattractants. The recruitment of neutrophils to injured tissues in zebrafish larvae is a useful model for studying neutrophil migration and trafficking in vivo. Indeed, the study of this process led to the discovery that PI3Kγ is required for the polarity and motility of neutrophils, features that are necessary for the directed migration of these cells to wounds. However, the mechanism by which PI3Kγ is activated remains to be determined. Here we show that signaling by specifically the heterotrimeric G protein subunit Gβ1 is critical for neutrophil migration in response to wounding. In embryos treated with small-molecule inhibitors of Gβγ signaling, neutrophils failed to migrate to wound sites. Although both the Gβ1 and Gβ4 isoforms are expressed in migrating neutrophils, only deficiency for the former (morpholino-based knockdown) interfered with the directed migration of neutrophils towards wounds. The Gβ1 deficiency also impaired the ability of cells to change cell shape and reduced their general motility, defects that are similar to those in neutrophils deficient for PI3Kγ. Transplantation assays showed that the requirement for Gβ1 in neutrophil migration is cell autonomous. Finally, live imaging revealed that Gβ1 is required for polarized activation of PI3K, and for the actin dynamics that enable neutrophil migration. Collectively, our data indicate that Gβ1 signaling controls proper neutrophil migration by activating PI3K and modulating actin dynamics. Moreover, they illustrate a role for a specific Gβ isoform in chemotaxis in vivo. Copyright © 2017 Elsevier Inc. All rights reserved.

  3. Hidden truth of circulating neutrophils (polymorphonuclear neutrophil function in periodontally healthy smoker subjects

    Directory of Open Access Journals (Sweden)

    Chitra Agarwal

    2016-01-01

    Full Text Available Context: Tobacco smoking is considered to be a major risk factor associated with periodontal disease. Smoking exerts a major effect on the protective elements of the immune response, resulting in an increase in the extent and severity of periodontal destruction. Aims: The aim of the present study was to assess viability and phagocytic function of neutrophils in circulating blood of the smokers and nonsmokers who are periodontally healthy. Settings and Design: Two hundred subjects in the mean range of 20–30 years of age were included in the study population. It was a retrospective study carried out for 6 months. Materials and Methods: Two hundred subjects were divided into four groups: 50 nonsmokers, 50 light smokers (15 cigarettes/day. Full mouth plaque index, sulcus bleeding index, and probing depths were measured. Percentage viability of circulating neutrophils and average number of phagocytosed Candida albicans were recorded. Statistical Analysis Used: Means and standard deviations were calculated from data obtained within the groups. Comparison between the smokers and nonsmokers was performed by Kruskal–Wallis ANOVA analysis. Comparison between smoker groups was performed using Mann–Whitney–Wilcoxon test. Results: Percentage viability of neutrophils was significantly less in heavy smokers (66.9 ± 4.0, moderate (76.6 ± 4.2, light smokers (83.1 ± 2.5 as compared to nonsmokers (92.3 ± 2.6 (P < 0.01. The ability of neutrophils to phagocytose, i.e., mean particle number was significantly less in light smokers (3.5 ± 0.5, moderate smokers (2.3 ± 0.5, and heavy smokers (1.4 ± 0.5 compared to nonsmokers (4.9 ± 0.7 (P < 0.01 with evidence of dose-response effect. Conclusions: Smoking significantly affects neutrophils viability and phagocytic function in periodontally healthy population.

  4. The Tethered Balloon Current Generator - A space shuttle-tethered subsatellite for plasma studies and power generation

    Science.gov (United States)

    Williamson, P. R.; Banks, P. M.

    1976-01-01

    The objectives of the Tethered Balloon Current Generator experiment are to: (1) generate relatively large regions of thermalized, field-aligned currents, (2) produce controlled-amplitude Alfven waves, (3) study current-driven electrostatic plasma instabilities, and (4) generate substantial amounts of power or propulsion through the MHD interaction. A large balloon (a diameter of about 30 m) will be deployed with a conducting surface above the space shuttle at a distance of about 10 km. For a generally eastward directed orbit at an altitude near 400 km, the balloon, connected to the shuttle by a conducting wire, will be positive with respect to the shuttle, enabling it to collect electrons. At the same time, the shuttle will collect positive ions and, upon command, emit an electron beam to vary current flow in the system.

  5. The novel 2Fe–2S outer mitochondrial protein mitoNEET displays conformational flexibility in its N-terminal cytoplasmic tethering domain

    International Nuclear Information System (INIS)

    Conlan, Andrea R.; Paddock, Mark L.; Axelrod, Herbert L.; Cohen, Aina E.; Abresch, Edward C.; Wiley, Sandra; Roy, Melinda; Nechushtai, Rachel; Jennings, Patricia A.

    2009-01-01

    The crystal structure of the anti-diabetic drug target mitoNEET obtained from a GFP fusion construct (1.4 Å resolution, R factor = 20.2%) shows that the CDGSH 2Fe–2S binding domains are superimposable with previously determined non-fused constructs. However, there is considerable flexibility in the position of the outer mitochondrial tethering arms resulting in two different conformations in the crystal structure. A primary role for mitochondrial dysfunction is indicated in the pathogenesis of insulin resistance. A widely used drug for the treatment of type 2 diabetes is pioglitazone, a member of the thiazolidinedione class of molecules. MitoNEET, a 2Fe–2S outer mitochondrial membrane protein, binds pioglitazone [Colca et al. (2004 ▶), Am. J. Physiol. Endocrinol. Metab.286, E252–E260]. The soluble domain of the human mitoNEET protein has been expressed C-terminal to the superfolder green fluorescent protein and the mitoNEET protein has been isolated. Comparison of the crystal structure of mitoNEET isolated from cleavage of the fusion protein (1.4 Å resolution, R factor = 20.2%) with other solved structures shows that the CDGSH domains are superimposable, indicating proper assembly of mitoNEET. Furthermore, there is considerable flexibility in the position of the cytoplasmic tethering arms, resulting in two different conformations in the crystal structure. This flexibility affords multiple orientations on the outer mitochondrial membrane

  6. Diverse novel functions of neutrophils in immunity, inflammation, and beyond.

    Science.gov (United States)

    Mócsai, Attila

    2013-07-01

    Neutrophils have long been considered simple suicide killers at the bottom of the hierarchy of the immune response. That view began to change 10-20 yr ago, when the sophisticated mechanisms behind how neutrophils locate and eliminate pathogens and regulate immunity and inflammation were discovered. The last few years witnessed a new wave of discoveries about additional novel and unexpected functions of these cells. Neutrophils have been proposed to participate in protection against intracellular pathogens such as viruses and mycobacteria. They have been shown to intimately shape the adaptive immune response at various levels, including marginal zone B cells, plasmacytoid dendritic cells and T cell populations, and even to control NK cell homeostasis. Neutrophils have been shown to mediate an alternative pathway of systemic anaphylaxis and to participate in allergic skin reactions. Finally, neutrophils were found to be involved in physiological and pathological processes beyond the immune system, such as diabetes, atherosclerosis, and thrombus formation. Many of those functions appear to be related to their unique ability to release neutrophil extracellular traps even in the absence of pathogens. This review summarizes those novel findings on versatile functions of neutrophils and how they change our view of neutrophil biology in health and disease.

  7. Regulation of calcium homeostasis in activated human neutrophils ...

    African Journals Online (AJOL)

    Objectives. The objectives of the current study were to: (i) present an integrated model for the restoration of calcium homeostasis in activated human neutrophils based on current knowledge and recent research; and (ii) identify potential targets for the modulation of calcium fluxes in activated neutrophils based on this model ...

  8. Azurophil granule proteins constitute the major mycobactericidal proteins in human neutrophils and enhance the killing of mycobacteria in macrophages.

    Directory of Open Access Journals (Sweden)

    Prajna Jena

    Full Text Available Pathogenic mycobacteria reside in, and are in turn controlled by, macrophages. However, emerging data suggest that neutrophils also play a critical role in innate immunity to tuberculosis, presumably by their different antibacterial granule proteins. In this study, we purified neutrophil azurophil and specific granules and systematically analyzed the antimycobacterial activity of some purified azurophil and specific granule proteins against M. smegmatis, M. bovis-BCG and M. tuberculosis H37Rv. Using gel overlay and colony forming unit assays we showed that the defensin-depleted azurophil granule proteins (AZP were more active against mycobacteria compared to other granule proteins and cytosolic proteins. The proteins showing antimycobacterial activity were identified by MALDI-TOF mass spectrometry. Electron microscopic studies demonstrate that the AZP disintegrate bacterial cell membrane resulting in killing of mycobacteria. Exogenous addition of AZP to murine macrophage RAW 264.7, THP-1 and peripheral blood monocyte-derived macrophages significantly reduced the intracellular survival of mycobacteria without exhibiting cytotoxic activity on macrophages. Immunofluorescence studies showed that macrophages actively endocytose neutrophil granular proteins. Treatment with AZP resulted in increase in co-localization of BCG containing phagosomes with lysosomes but not in increase of autophagy. These data demonstrate that neutrophil azurophil proteins may play an important role in controlling intracellular survival of mycobacteria in macrophages.

  9. Neutrophilic dermatoses in a patient with collagenous colitis

    Directory of Open Access Journals (Sweden)

    Didac Barco

    2010-01-01

    Full Text Available We report the case of a 75-year old woman with collagenous colitis who presented with erythematous and edematous plaques on the periorbital and eyelid regions, accompanied by oral ulcers. Histopathology showed a dermal neutrophilic infiltrate plus mild septal and lobular panniculitis with lymphocytes, neutrophils and eosinophils. Five years earlier she had presented a flare of papules and vesicles on the trunk, together with oral ulcers; a skin biopsy revealed a neutrophilic dermal infiltrate and Sweet’s syndrome was diagnosed. Both the neutrophilic panniculitis and the Sweet’s syndrome were accompanied by fever, malaise and diarrhea. Cutaneous and intestinal symptoms disappeared with corticoid therapy. The two types of neutrophilic dermatoses that appeared in periods of colitis activity suggest that intestinal and cutaneous manifestations may be related.

  10. Alternate Fuel Cell Membranes for Energy Independence

    Energy Technology Data Exchange (ETDEWEB)

    Storey, Robson, F.; Mauritz, Kenneth, A.; Patton, Derek, L.; Savin, Daniel, A.

    2012-12-18

    The overall objective of this project was the development and evaluation of novel hydrocarbon fuel cell (FC) membranes that possess high temperature performance and long term chemical/mechanical durability in proton exchange membrane (PEM) fuel cells (FC). The major research theme was synthesis of aromatic hydrocarbon polymers of the poly(arylene ether sulfone) (PAES) type containing sulfonic acid groups tethered to the backbone via perfluorinated alkylene linkages and in some cases also directly attached to the phenylene groups along the backbone. Other research themes were the use of nitrogen-based heterocyclics instead of acid groups for proton conduction, which provides high temperature, low relative humidity membranes with high mechanical/thermal/chemical stability and pendant moieties that exhibit high proton conductivities in the absence of water, and synthesis of block copolymers consisting of a proton conducting block coupled to poly(perfluorinated propylene oxide) (PFPO) blocks. Accomplishments of the project were as follows: 1) establishment of a vertically integrated program of synthesis, characterization, and evaluation of FC membranes, 2) establishment of benchmark membrane performance data based on Nafion for comparison to experimental membrane performance, 3) development of a new perfluoroalkyl sulfonate monomer, N,N-diisopropylethylammonium 2,2-bis(p-hydroxyphenyl) pentafluoropropanesulfonate (HPPS), 4) synthesis of random and block copolymer membranes from HPPS, 5) synthesis of block copolymer membranes containing high-acid-concentration hydrophilic blocks consisting of HPPS and 3,3'-disulfonate-4,4'-dichlorodiphenylsulfone (sDCDPS), 6) development of synthetic routes to aromatic polymer backbones containing pendent 1H-1,2,3-triazole moieties, 7) development of coupling strategies to create phase-separated block copolymers between hydrophilic sulfonated prepolymers and commodity polymers such as PFPO, 8) establishment of basic

  11. Materials for advancement of MXER tether design (1000-371), Phase I

    Data.gov (United States)

    National Aeronautics and Space Administration — There exist a need to develop, identify, and classify various materials that can be used in the fabrication of electrodynamic tethers for various applications. These...

  12. UV-Curable Hybrid Nanocomposite Coating to Protect Tether Polymer Materials, Phase I

    Data.gov (United States)

    National Aeronautics and Space Administration — To address the NASA need for coatings to protect and strengthen tether materials for Momentum-exchange Electrodynamic Reboost (MXER) technology, Luminit, LLC,...

  13. Development of a Tethered Formation Flight Testbed for ISS, Phase I

    Data.gov (United States)

    National Aeronautics and Space Administration — The development of a testbed for the development and demonstration of technologies needed by tethered formation flying satellites is proposed. Such a testbed would...

  14. Significance of relative velocity in drag force or drag power estimation for a tethered float

    Digital Repository Service at National Institute of Oceanography (India)

    Vethamony, P.; Sastry, J.S.

    There is difference in opinion regarding the use of relative velocity instead of particle velocity alone in the estimation of drag force or power. In the present study, a tethered spherical float which undergoes oscillatory motion in regular waves...

  15. The motion and control of a complex three-body space tethered system

    Science.gov (United States)

    Shi, Gefei; Zhu, Zhanxia; Chen, Shiyu; Yuan, Jianping; Tang, Biwei

    2017-11-01

    This paper is mainly devoted to investigating the dynamics and stability control of a three body-tethered satellite system which contains a main satellite and two subsatellites connected by two straight, massless and inextensible tethers. Firstly, a detailed mathematical model is established in the central gravitational field. Then, the dynamic characteristics of the established system are investigated and analyzed. Based on the dynamic analysis, a novel sliding mode prediction model (SMPM) control strategy is proposed to suppress the motion of the built tethered system. The numerical results show that the proposed underactuated control law is highly effective in suppressing the attitude/libration motion of the underactuated three-body tethered system. Furthermore, cases of different target angles are also examined and analyzed. The simulation results reveal that even if the final equilibrium states differ from different selections of the target angles, the whole system can still be maintained in acceptable areas.

  16. An Effective Approach Control Scheme for the Tethered Space Robot System

    Directory of Open Access Journals (Sweden)

    Zhongjie Meng

    2014-09-01

    Full Text Available The tethered space robot system (TSR, which is composed of a platform, a gripper and a space tether, has great potential in future space missions. Given the relative motion among the platform, tether, gripper and the target, an integrated approach model is derived. Then, a novel coordinated approach control scheme is presented, in which the tether tension, thrusters and the reaction wheel are all utilized. It contains the open-loop trajectory optimization, the feedback trajectory control and attitude control. The numerical simulation results show that the rendezvous between TSR and the target can be realized by the proposed coordinated control scheme, and the propellant consumption is efficiently reduced. Moreover, the control scheme performs well in the presence of the initial state's perturbations, actuator characteristics and sensor errors.

  17. Myocardial Infarction Alters Adaptation of the Tethered Mitral Valve

    NARCIS (Netherlands)

    Dal-Bianco, Jacob P; Aikawa, Elena; Bischoff, Joyce; Guerrero, J Luis; Hjortnaes, Jesper; Beaudoin, Jonathan; Szymanski, Catherine; Bartko, Philipp E; Seybolt, Margo M; Handschumacher, Mark D; Sullivan, Suzanne; Garcia, Michael L; Mauskapf, Adam; Titus, James S; Wylie-Sears, Jill; Irvin, Whitney S; Chaput, Miguel; Messas, Emmanuel; Hagège, Albert A; Carpentier, Alain; Levine, Robert A

    2016-01-01

    BACKGROUND: In patients with myocardial infarction (MI), leaflet tethering by displaced papillary muscles induces mitral regurgitation (MR), which doubles mortality. Mitral valves (MVs) are larger in such patients but fibrosis sets in counterproductively. The investigators previously reported that

  18. Electron Emitter for small-size Electrodynamic Space Tether using MEMS Technology

    DEFF Research Database (Denmark)

    Fleron, René A. W.; Blanke, Mogens

    2004-01-01

    Adjustment of the orbit of a spacecraft using the forces created by an electro-dynamic space-tether has been shown as a theoretic possibility in recent literature. Practical implementation is being pursued for larger scale missions where a hot filament device controls electron emission...... and the current flowing in the electrodynamic space tether. Applications to small spacecraft, or space debris in the 1–10 kg range, possess difficulties with electron emission technology, as low power emitting devices are needed. This paper addresses the system concepts of a small spacecraft electrodynamic tether...... system with focus on electron emitter design and manufacture using micro-electro-mechanical- system (MEMS) technology. The paper addresses the system concepts of a small size electrodynamic tether mission and shows a novel electron emitter for the 1-2 mA range where altitude can be effectively affected...

  19. Investigation of electrodynamic stabilization and control of long orbiting tethers. [space shuttle payloads

    Science.gov (United States)

    Arnold, D. A.; Dobrowolny, M.

    1981-01-01

    An algorithm for using electric currents to control pendular oscillations induced by various perturbing forces on the Skyhook wire is considered. Transverse and vertical forces on the tether; tether instability modes and causes during retrieval by space shuttle; simple and spherical pendulum motion and vector damping; and current generation and control are discussed. A computer program for numerical integration of the in-plane and out-of-plane displacements of the tether vs time was developed for heuristic study. Some techniques for controlling instabilities during payload retrieval and methods for employing the tether for launching satellites from the space shuttle are considered. Derivations and analyses of a general nature used in all of the areas studied are included.

  20. Regulation of neutrophil senescence by microRNAs.

    Directory of Open Access Journals (Sweden)

    Jon R Ward

    2011-01-01

    Full Text Available Neutrophils are rapidly recruited to sites of tissue injury or infection, where they protect against invading pathogens. Neutrophil functions are limited by a process of neutrophil senescence, which renders the cells unable to respond to chemoattractants, carry out respiratory burst, or degranulate. In parallel, aged neutrophils also undergo spontaneous apoptosis, which can be delayed by factors such as GMCSF. This is then followed by their subsequent removal by phagocytic cells such as macrophages, thereby preventing unwanted inflammation and tissue damage. Neutrophils translate mRNA to make new proteins that are important in maintaining functional longevity. We therefore hypothesised that neutrophil functions and lifespan might be regulated by microRNAs expressed within human neutrophils. Total RNA from highly purified neutrophils was prepared and subjected to microarray analysis using the Agilent human miRNA microarray V3. We found human neutrophils expressed a selected repertoire of 148 microRNAs and that 6 of these were significantly upregulated after a period of 4 hours in culture, at a time when the contribution of apoptosis is negligible. A list of predicted targets for these 6 microRNAs was generated from http://mirecords.biolead.org and compared to mRNA species downregulated over time, revealing 83 genes targeted by at least 2 out of the 6 regulated microRNAs. Pathway analysis of genes containing binding sites for these microRNAs identified the following pathways: chemokine and cytokine signalling, Ras pathway, and regulation of the actin cytoskeleton. Our data suggest that microRNAs may play a role in the regulation of neutrophil senescence and further suggest that manipulation of microRNAs might represent an area of future therapeutic interest for the treatment of inflammatory disease.

  1. Neutrophils, a candidate biomarker and target for radiation therapy?

    Science.gov (United States)

    Schernberg, Antoine; Blanchard, Pierre; Chargari, Cyrus; Deutsch, Eric

    2017-11-01

    Neutrophils are the most abundant blood-circulating white blood cells, continuously generated in the bone marrow. Growing evidence suggests they regulate the innate and adaptive immune system during tumor evolution. This review will first summarize the recent findings on neutrophils as a key player in cancer evolution, then as a potential biomarker, and finally as therapeutic targets, with respective focuses on the interplay with radiation therapy. A complex interplay: Neutrophils have been associated with tumor progression through multiple pathways. Ionizing radiation has cytotoxic effects on cancer cells, but the sensitivity to radiation therapy in vivo differ from isolated cancer cells in vitro, partially due to the tumor microenvironment. Different microenvironmental states, whether baseline or induced, can modulate or even attenuate the effects of radiation, with consequences for therapeutic efficacy. Inflammatory biomarkers: Inflammation-based scores have been widely studied as prognostic biomarkers in cancer patients. We have performed a large retrospective cohort of patients undergoing radiation therapy (1233 patients), with robust relationship between baseline blood neutrophil count and 3-year's patient's overall survival in patients with different cancer histologies. (Pearson's correlation test: p = .001, r = -.93). Therapeutic approaches: Neutrophil-targeting agents are being developed for the treatment of inflammatory and autoimmune diseases. Neutrophils either can exert antitumoral (N1 phenotype) or protumoral (N2 phenotype) activity, depending on the Tumor Micro Environment. Tumor associated N2 neutrophils are characterized by high expression of CXCR4, VEGF, and gelatinase B/MMP9. TGF-β within the tumor microenvironment induces a population of TAN with a protumor N2 phenotype. TGF-β blockade slows tumor growth through activation of CD8 + T cells, macrophages, and tumor associated neutrophils with an antitumor N1 phenotype. This supports

  2. Multifunctional-layered materials for creating membrane-restricted nanodomains and nanoscale imaging

    Energy Technology Data Exchange (ETDEWEB)

    Srinivasan, P., E-mail: prasri@ece.ucsb.edu, E-mail: srinivasan@lifesci.ucsb.edu [Department of Electrical and Computer Engineering, University of California, Santa Barbara, California 93106, USA and Neuroscience Research Institute, University of California, Santa Barbara, California 93106 (United States)

    2016-01-18

    Experimental platform that allows precise spatial positioning of biomolecules with an exquisite control at nanometer length scales is a valuable tool to study the molecular mechanisms of membrane bound signaling. Using micromachined thin film gold (Au) in layered architecture, it is possible to add both optical and biochemical functionalities in in vitro. Towards this goal, here, I show that docking of complementary DNA tethered giant phospholiposomes on Au surface can create membrane-restricted nanodomains. These nanodomains are critical features to dissect molecular choreography of membrane signaling complexes. The excited surface plasmon resonance modes of Au allow label-free imaging at diffraction-limited resolution of stably docked DNA tethered phospholiposomes, and lipid-detergent bicelle structures. Such multifunctional building block enables realizing rigorously controlled in vitro set-up to model membrane anchored biological signaling, besides serving as an optical tool for nanoscale imaging.

  3. Visceral leishmaniasis patients display altered composition and maturity of neutrophils as well as impaired neutrophil effector functions

    Directory of Open Access Journals (Sweden)

    Endalew Yizengaw

    2016-11-01

    Full Text Available Immunologically, active visceral leishmaniasis (VL is characterised by profound immunosuppression, severe systemic inflammatory responses and an impaired capacity to control parasite replication. Neutrophils are highly versatile cells, which play a crucial role in the induction as well as the resolution of inflammation, the control of pathogen replication and the regulation of immune responses. Neutrophil functions have been investigated in human cutaneous leishmaniasis, however, their role in human visceral leishmaniasis is poorly understood.In the present study we evaluated the activation status and effector functions of neutrophils in patients with active VL and after successful anti-leishmanial treatment. Our results show that neutrophils are highly activated and have degranulated; high levels of arginase, myeloperoxidase and elastase, all contained in neutrophils’ granules, were found in the plasma of VL patients. In addition, we show that a large proportion of these cells are immature. We also analysed effector functions of neutrophils that are essential for pathogen clearance and show that neutrophils have an impaired capacity to release neutrophil extracellular traps, produce reactive oxygen species and phagocytose bacterial particles, but not Leishmania parasites.Our results suggest that impaired effector functions, increased activation and immaturity of neutrophils play a key role in the pathogenesis of VL.

  4. Acquisition of Human Operation Characteristics for Kite-based Tethered Flying Robot using Human Operation Data

    OpenAIRE

    Todoroki, Chiaki; Takahashi, Yasutake; Nakamura, Takayuki

    2015-01-01

    This paper shows human skill acquisition systems to control the kite-based tethered flying robot. The kite-based tethered flying robot has been proposed as a flying observation system with long-term activity capability[1]. It is a relatively new system and aimed to complement other information gathering systems using a balloon or an air vehicle. This paper shows some approaches of human operation characteristics acquisition based on fuzzy learning controller, knearest neighbor algorithm, and ...

  5. Tethered balloon operation for wintering aerosol measurements in the lower troposphere at Syowa Station, Antarctica

    Directory of Open Access Journals (Sweden)

    Keiichiro Hara

    2007-03-01

    Full Text Available The 46th Japanese Antarctic Research Expedition (JARE-46 carried out twenty seven tethered-balloon-borne aerosol measurements at Syowa Station for better understanding of aerosol chemical and physical properties in the lower troposphere from 6th January 2005 until 11 December 2005. This report summarizes the plan, preparation, field activities and some troubles/problems in the tethered-balloon observations.

  6. Mobility of tethering factor EEA1 on endosomes is decreased upon stimulation of EGF receptor endocytosis in HeLa cells

    International Nuclear Information System (INIS)

    Kosheverova, Vera V.; Kamentseva, Rimma S.; Gonchar, Ilya V.; Kharchenko, Marianna V.; Kornilova, Elena S.

    2016-01-01

    Tethering factor EEA1, mediating homotypic fusion of early endosomes, was shown to be localized in membrane-bound state both in serum-deprived and stimulated for EGF receptor endocytosis cells. However, it is not known whether dynamics behavior of EEA1 is affected by EGF stimulation. We investigated EEA1 cytosol-to-membrane exchange rate in interphase HeLa cells by FRAP analysis. The data obtained fitted two-states binding model, with the bulk of membrane-associated EEA1 protein represented by the mobile fraction both in serum-starved and EGF-stimulated cells. Fast recovery state had similar half-times in the two cases: about 1.6 s and 2.8 s, respectively. However, the recovery half-time of slowly cycled EEA1 fraction significantly increased in EGF-stimulated comparing to serum-starved cells (from 21 to 99 s). We suppose that the retardation of EEA1 fluorescence recovery upon EGF-stimulation may be due to the increase of activated Rab5 on endosomal membranes, the growth of the number of tethering events between EEA1-positive vesicles and their clustering. - Highlights: • EEA1 mobility was compared in serum-starved and EGF-stimulated interphase HeLa cells. • FRAP analysis revealed fast and slow components of EEA1 recovery in both cases. • Stimulation of EGFR endocytosis did not affect fast EEA1 turnover. • EGF stimulation significantly increased half-time of slowly exchanged EEA1 fraction.

  7. Mobility of tethering factor EEA1 on endosomes is decreased upon stimulation of EGF receptor endocytosis in HeLa cells

    Energy Technology Data Exchange (ETDEWEB)

    Kosheverova, Vera V., E-mail: kosheverova_vera@incras.ru [Institute of Cytology of RAS, 4, Tikhoretsky Ave, St. Petersburg, 194064 (Russian Federation); Kamentseva, Rimma S., E-mail: rkamentseva@yandex.ru [Institute of Cytology of RAS, 4, Tikhoretsky Ave, St. Petersburg, 194064 (Russian Federation); St. Petersburg State University, 7-9, Universitetskaya nab, St. Petersburg, 199034 (Russian Federation); Gonchar, Ilya V., E-mail: ample@mail.ru [Institute of Cytology of RAS, 4, Tikhoretsky Ave, St. Petersburg, 194064 (Russian Federation); Kharchenko, Marianna V., E-mail: mariannakharchenko@gmail.com [Institute of Cytology of RAS, 4, Tikhoretsky Ave, St. Petersburg, 194064 (Russian Federation); Kornilova, Elena S., E-mail: lenkor@mail.cytspb.rssi.ru [Institute of Cytology of RAS, 4, Tikhoretsky Ave, St. Petersburg, 194064 (Russian Federation); St. Petersburg State University, 7-9, Universitetskaya nab, St. Petersburg, 199034 (Russian Federation); Department of Medical Physics, Peter the Great St. Petersburg Polytechnic University, 29, Polytechnicheskaya, St.Petersburg, 195251 (Russian Federation)

    2016-04-22

    Tethering factor EEA1, mediating homotypic fusion of early endosomes, was shown to be localized in membrane-bound state both in serum-deprived and stimulated for EGF receptor endocytosis cells. However, it is not known whether dynamics behavior of EEA1 is affected by EGF stimulation. We investigated EEA1 cytosol-to-membrane exchange rate in interphase HeLa cells by FRAP analysis. The data obtained fitted two-states binding model, with the bulk of membrane-associated EEA1 protein represented by the mobile fraction both in serum-starved and EGF-stimulated cells. Fast recovery state had similar half-times in the two cases: about 1.6 s and 2.8 s, respectively. However, the recovery half-time of slowly cycled EEA1 fraction significantly increased in EGF-stimulated comparing to serum-starved cells (from 21 to 99 s). We suppose that the retardation of EEA1 fluorescence recovery upon EGF-stimulation may be due to the increase of activated Rab5 on endosomal membranes, the growth of the number of tethering events between EEA1-positive vesicles and their clustering. - Highlights: • EEA1 mobility was compared in serum-starved and EGF-stimulated interphase HeLa cells. • FRAP analysis revealed fast and slow components of EEA1 recovery in both cases. • Stimulation of EGFR endocytosis did not affect fast EEA1 turnover. • EGF stimulation significantly increased half-time of slowly exchanged EEA1 fraction.

  8. Discovery of dual-action membrane-anchored modulators of incretin receptors.

    Directory of Open Access Journals (Sweden)

    Jean-Philippe Fortin

    Full Text Available The glucose-dependent insulinotropic polypeptide (GIP and the glucagon-like peptide-1 (GLP-1 receptors are considered complementary therapeutic targets for type 2 diabetes. Using recombinant membrane-tethered ligand (MTL technology, the present study focused on defining optimized modulators of these receptors, as well as exploring how local anchoring influences soluble peptide function.Serial substitution of residue 7 in membrane-tethered GIP (tGIP led to a wide range of activities at the GIP receptor, with [G(7]tGIP showing enhanced efficacy compared to the wild type construct. In contrast, introduction of G(7 into the related ligands, tGLP-1 and tethered exendin-4 (tEXE4, did not affect signaling at the cognate GLP-1 receptor. Both soluble and tethered GIP and GLP-1 were selective activators of their respective receptors. Although soluble EXE4 is highly selective for the GLP-1 receptor, unexpectedly, tethered EXE4 was found to be a potent activator of both the GLP-1 and GIP receptors. Diverging from the pharmacological properties of soluble and tethered GIP, the newly identified GIP-R agonists, (i.e. [G(7]tGIP and tEXE4 failed to trigger cognate receptor endocytosis. In an attempt to recapitulate the dual agonism observed with tEXE4, we conjugated soluble EXE4 to a lipid moiety. Not only did this soluble peptide activate both the GLP-1 and GIP receptors but, when added to receptor expressing cells, the activity persists despite serial washes.These findings suggest that conversion of a recombinant MTL to a soluble membrane anchored equivalent offers a means to prolong ligand function, as well as to design agonists that can simultaneously act on more than one therapeutic target.

  9. Biomimicry enhances sequential reactions of tethered glycolytic enzymes, TPI and GAPDHS.

    Directory of Open Access Journals (Sweden)

    Chinatsu Mukai

    Full Text Available Maintaining activity of enzymes tethered to solid interfaces remains a major challenge in developing hybrid organic-inorganic devices. In nature, mammalian spermatozoa have overcome this design challenge by having glycolytic enzymes with specialized targeting domains that enable them to function while tethered to a cytoskeletal element. As a step toward designing a hybrid organic-inorganic ATP-generating system, we implemented a biomimetic site-specific immobilization strategy to tether two glycolytic enzymes representing different functional enzyme families: triose phosphoisomerase (TPI; an isomerase and glyceraldehyde 3-phosphate dehydrogenase (GAPDHS; an oxidoreductase. We then evaluated the activities of these enzymes in comparison to when they were tethered via classical carboxyl-amine crosslinking. Both enzymes show similar surface binding regardless of immobilization method. Remarkably, specific activities for both enzymes were significantly higher when tethered using the biomimetic, site-specific immobilization approach. Using this biomimetic approach, we tethered both enzymes to a single surface and demonstrated their function in series in both forward and reverse directions. Again, the activities in series were significantly higher in both directions when the enzymes were coupled using this biomimetic approach versus carboxyl-amine binding. Our results suggest that biomimetic, site-specific immobilization can provide important functional advantages over chemically specific, but non-oriented attachment, an important strategic insight given the growing interest in recapitulating entire biological pathways on hybrid organic-inorganic devices.

  10. Biomimicry enhances sequential reactions of tethered glycolytic enzymes, TPI and GAPDHS.

    Science.gov (United States)

    Mukai, Chinatsu; Gao, Lizeng; Bergkvist, Magnus; Nelson, Jacquelyn L; Hinchman, Meleana M; Travis, Alexander J

    2013-01-01

    Maintaining activity of enzymes tethered to solid interfaces remains a major challenge in developing hybrid organic-inorganic devices. In nature, mammalian spermatozoa have overcome this design challenge by having glycolytic enzymes with specialized targeting domains that enable them to function while tethered to a cytoskeletal element. As a step toward designing a hybrid organic-inorganic ATP-generating system, we implemented a biomimetic site-specific immobilization strategy to tether two glycolytic enzymes representing different functional enzyme families: triose phosphoisomerase (TPI; an isomerase) and glyceraldehyde 3-phosphate dehydrogenase (GAPDHS; an oxidoreductase). We then evaluated the activities of these enzymes in comparison to when they were tethered via classical carboxyl-amine crosslinking. Both enzymes show similar surface binding regardless of immobilization method. Remarkably, specific activities for both enzymes were significantly higher when tethered using the biomimetic, site-specific immobilization approach. Using this biomimetic approach, we tethered both enzymes to a single surface and demonstrated their function in series in both forward and reverse directions. Again, the activities in series were significantly higher in both directions when the enzymes were coupled using this biomimetic approach versus carboxyl-amine binding. Our results suggest that biomimetic, site-specific immobilization can provide important functional advantages over chemically specific, but non-oriented attachment, an important strategic insight given the growing interest in recapitulating entire biological pathways on hybrid organic-inorganic devices.

  11. The mechanics of motorised momentum exchange tethers when applied to active debris removal from LEO

    Energy Technology Data Exchange (ETDEWEB)

    Caldecott, Ralph; Kamarulzaman, Dayangku N. S.; Kirrane, James P.; Cartmell, Matthew P.; Ganilova, Olga A. [Department of Mechanical Engineering, University of Sheffield, Mappin St., Sheffield, S1 3JD, England (United Kingdom)

    2014-12-10

    The concept of momentum exchange when applied to space tethers for propulsion is well established, and a considerable body of literature now exists on the on-orbit modelling, the dynamics, and also the control of a large range of tether system applications. The authors consider here a new application for the Motorised Momentum Exchange Tether by highlighting three key stages of development leading to a conceptualisation that can subsequently be developed into a technology for Active Debris Removal. The paper starts with a study of the on-orbit mechanics of a full sized motorised tether in which it is shown that a laden and therefore highly massasymmetrical tether can still be forced to spin, and certainly to librate, thereby confirming its possible usefulness for active debris removal (ADR). The second part of the paper concentrates on the modelling of the centripetal deployment of a symmetrical MMET in order to get it initialized for debris removal operations, and the third and final part of the paper provides an entry into scale modelling for low cost mission design and testing. It is shown that the motorised momentum exchange tether offers a potential solution to the removal of large pieces of orbital debris, and that dynamic methodologies can be implemented to in order to optimise the emergent design.

  12. The mechanics of motorised momentum exchange tethers when applied to active debris removal from LEO

    International Nuclear Information System (INIS)

    Caldecott, Ralph; Kamarulzaman, Dayangku N. S.; Kirrane, James P.; Cartmell, Matthew P.; Ganilova, Olga A.

    2014-01-01

    The concept of momentum exchange when applied to space tethers for propulsion is well established, and a considerable body of literature now exists on the on-orbit modelling, the dynamics, and also the control of a large range of tether system applications. The authors consider here a new application for the Motorised Momentum Exchange Tether by highlighting three key stages of development leading to a conceptualisation that can subsequently be developed into a technology for Active Debris Removal. The paper starts with a study of the on-orbit mechanics of a full sized motorised tether in which it is shown that a laden and therefore highly massasymmetrical tether can still be forced to spin, and certainly to librate, thereby confirming its possible usefulness for active debris removal (ADR). The second part of the paper concentrates on the modelling of the centripetal deployment of a symmetrical MMET in order to get it initialized for debris removal operations, and the third and final part of the paper provides an entry into scale modelling for low cost mission design and testing. It is shown that the motorised momentum exchange tether offers a potential solution to the removal of large pieces of orbital debris, and that dynamic methodologies can be implemented to in order to optimise the emergent design

  13. On the mechanism of oscillations in neutrophils

    DEFF Research Database (Denmark)

    Brasen, Jens Christian; Barington, Torben; Olsen, Lars Folke

    2010-01-01

    We have investigated the regulation of the oscillatory generation of H(2)O(2) and oscillations in shape and size in neutrophils in suspension. The oscillations are independent of cell density and hence do not represent a collective phenomena. Furthermore, the oscillations are independent...... of the external glucose concentration and the oscillations in H(2)O(2) production are 180 degrees out of phase with the oscillations in NAD(P)H. Cytochalasin B blocked the oscillations in shape and size whereas it increased the period of the oscillations in H(2)O(2) production. 1- and 2-butanol also blocked...... the oscillations in shape and size, but only 1-butanol inhibited the oscillations in H(2)O(2) production. We conjecture that the oscillations are likely to be due to feedback regulations in the signal transduction cascade involving phosphoinositide 3-kinases (PI3K). We have tested this using a simple mathematical...

  14. Flow structures around a beetle in a tethered flight

    Science.gov (United States)

    Lee, Boogeon; Oh, Sehyeong; Park, Hyungmin; Choi, Haecheon

    2017-11-01

    In the present study, through a wind-tunnel experiment, we visualize the flow in a tethered flight of a rhinoceros beetle using a smoke-wire visualization technique. Measurements are done at five side planes along the wind span while varying the body angle (angle between the horizontal and the body axis) to investigate the influence of the stroke plane angle that was observed to change depending on the flight mode such as hovering, forward and takeoff flights so on. Observing that a large attached leading-edge vortex is only found on the hindwing, it is inferred that most of the aerodynamic forces would be generated by hindwings (flexible inner wings) compared to the elytra (hard outer wings). In addition, it is observed to use unsteady lift-generating mechanisms such as clap-and-fling, wing-wing interaction and wake capture. Finally, we discuss the relation between the advance ratio and Strouhal number by adjusting free-stream velocity and the body angle (i.e., angle of wake-induced flow). Supported by a Grant to Bio-Mimetic Robot Research Center Funded by Defense Acquisition Program Administration, and by ADD, Korea (UD130070ID).

  15. Lipoproteins tethered dendrimeric nanoconstructs for effective targeting to cancer cells

    Science.gov (United States)

    Jain, Anupriya; Jain, Keerti; Mehra, Neelesh Kumar; Jain, N. K.

    2013-10-01

    In the present investigation, poly (propylene imine) dendrimers up to fifth generation (PPI G5.0) were synthesized using ethylene diamine and acrylonitrile. Lipoproteins (high-density lipoprotein; HDL and low-density lipoprotein; LDL) were isolated from human plasma by discontinuous density gradient ultracentrifugation, characterized and tethered to G5.0 PPI dendrimers to construct LDL- and HDL-conjugated dendrimeric nanoconstructs for tumor-specific delivery of docetaxel. Developed formulations showed sustained release characteristics in in vitro drug release and in vivo pharmacokinetic studies. The cancer targeting potential of lipoprotein coupled dendrimers was investigated by ex vivo cytotoxicity and cell uptake studies using human hepatocellular carcinoma cell lines (HepG2 cells) and biodistribution studies in albino rats of Sprague-Dawley strain. Lipoprotein anchored dendrimeric nanoconstructs showed significant uptake by cancer cells as well as higher biodistribution of docetaxel to liver and spleen. It is concluded that these precisely synthesized engineered dendrimeric nanoconstructs could serve as promising drug carrier for fighting with the fatal disease, i.e., cancer, attributed to their defined targeting and therapeutic potential.

  16. Lipoproteins tethered dendrimeric nanoconstructs for effective targeting to cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Jain, Anupriya; Jain, Keerti, E-mail: keertijain02@gmail.com; Mehra, Neelesh Kumar, E-mail: neelesh81mph@gmail.com; Jain, N. K., E-mail: dr.jnarendr@gmail.com [Dr. H. S. Gour University, Pharmaceutics Research Laboratory, Department of Pharmaceutical Sciences (India)

    2013-10-15

    In the present investigation, poly (propylene imine) dendrimers up to fifth generation (PPI G5.0) were synthesized using ethylene diamine and acrylonitrile. Lipoproteins (high-density lipoprotein; HDL and low-density lipoprotein; LDL) were isolated from human plasma by discontinuous density gradient ultracentrifugation, characterized and tethered to G5.0 PPI dendrimers to construct LDL- and HDL-conjugated dendrimeric nanoconstructs for tumor-specific delivery of docetaxel. Developed formulations showed sustained release characteristics in in vitro drug release and in vivo pharmacokinetic studies. The cancer targeting potential of lipoprotein coupled dendrimers was investigated by ex vivo cytotoxicity and cell uptake studies using human hepatocellular carcinoma cell lines (HepG2 cells) and biodistribution studies in albino rats of Sprague-Dawley strain. Lipoprotein anchored dendrimeric nanoconstructs showed significant uptake by cancer cells as well as higher biodistribution of docetaxel to liver and spleen. It is concluded that these precisely synthesized engineered dendrimeric nanoconstructs could serve as promising drug carrier for fighting with the fatal disease, i.e., cancer, attributed to their defined targeting and therapeutic potential.

  17. Pseudomonas aeruginosa ExoU augments neutrophil transepithelial migration.

    Science.gov (United States)

    Pazos, Michael A; Lanter, Bernard B; Yonker, Lael M; Eaton, Alex D; Pirzai, Waheed; Gronert, Karsten; Bonventre, Joseph V; Hurley, Bryan P

    2017-08-01

    Excessive neutrophil infiltration of the lungs is a common contributor to immune-related pathology in many pulmonary disease states. In response to pathogenic infection, airway epithelial cells produce hepoxilin A3 (HXA3), initiating neutrophil transepithelial migration. Migrated neutrophils amplify this recruitment by producing a secondary gradient of leukotriene B4 (LTB4). We sought to determine whether this two-step eicosanoid chemoattractant mechanism could be exploited by the pathogen Pseudomonas aeruginosa. ExoU, a P. aeruginosa cytotoxin, exhibits phospholipase A2 (PLA2) activity in eukaryotic hosts, an enzyme critical for generation of certain eicosanoids. Using in vitro and in vivo models of neutrophil transepithelial migration, we evaluated the impact of ExoU expression on eicosanoid generation and function. We conclude that ExoU, by virtue of its PLA2 activity, augments and compensates for endogenous host neutrophil cPLA2α function, leading to enhanced transepithelial migration. This suggests that ExoU expression in P. aeruginosa can circumvent immune regulation at key signaling checkpoints in the neutrophil, resulting in exacerbated neutrophil recruitment.

  18. Pseudomonas aeruginosa ExoU augments neutrophil transepithelial migration.

    Directory of Open Access Journals (Sweden)

    Michael A Pazos

    2017-08-01

    Full Text Available Excessive neutrophil infiltration of the lungs is a common contributor to immune-related pathology in many pulmonary disease states. In response to pathogenic infection, airway epithelial cells produce hepoxilin A3 (HXA3, initiating neutrophil transepithelial migration. Migrated neutrophils amplify this recruitment by producing a secondary gradient of leukotriene B4 (LTB4. We sought to determine whether this two-step eicosanoid chemoattractant mechanism could be exploited by the pathogen Pseudomonas aeruginosa. ExoU, a P. aeruginosa cytotoxin, exhibits phospholipase A2 (PLA2 activity in eukaryotic hosts, an enzyme critical for generation of certain eicosanoids. Using in vitro and in vivo models of neutrophil transepithelial migration, we evaluated the impact of ExoU expression on eicosanoid generation and function. We conclude that ExoU, by virtue of its PLA2 activity, augments and compensates for endogenous host neutrophil cPLA2α function, leading to enhanced transepithelial migration. This suggests that ExoU expression in P. aeruginosa can circumvent immune regulation at key signaling checkpoints in the neutrophil, resulting in exacerbated neutrophil recruitment.

  19. Biomaterial-induced alterations of neutrophil superoxide production.

    Science.gov (United States)

    Kaplan, S S; Basford, R E; Mora, E; Jeong, M H; Simmons, R L

    1992-08-01

    Because periprosthetic infection remains a vexing problem for patients receiving implanted devices, we evaluated the effect of several materials on neutrophil free radical production. Human peripheral blood neutrophils were incubated with several sterile, lipopolysaccharide (LPS)-free biomaterials used in surgically implantable prosthetic devices: polyurethane, woven dacron, and velcro. Free radical formation as the superoxide (O2-) anion was evaluated by cytochrome c reduction in neutrophils that were exposed to the materials and then removed and in neutrophils allowed to remain in association with the materials. Neutrophils exposed to polyurethane or woven dacron for 30 or 60 min and then removed consistently exhibited an enhanced release of O2- after simulation via receptor engagement with formyl methionyl-leucyl-phenylalanine. Enhanced reactivity to stimulation via protein kinase C with phorbol myristate acetate, however, was not consistently observed. The cells evaluated for O2- release during continuous association with the biomaterials showed enhanced metabolic activity during short periods of association (especially with polyurethane and woven dacron). Although O2- release by neutrophils in association with these materials decreased with longer periods of incubation, it was not obliterated. These studies, therefore, show that several commonly used biomaterials activate neutrophils soon after exposure and that this activated state diminishes with prolonged exposure but nevertheless remains measurable. The diminishing level of activity with prolonged exposure, however, suggests that ultimately a depletion of reactivity may occur and may result in increased susceptibility to periprosthetic infection.

  20. Neutrophils in oral paracoccidioidomycosis and the involvement of Nrf2.

    Directory of Open Access Journals (Sweden)

    Vera Cavalcanti Araújo

    Full Text Available Neutrophils have been implicated in granuloma formation in several infectious diseases, in addition to their main phagocytic and pathogen destruction role. It has been demonstrated that Nrf2 regulates antioxidant protection in neutrophils, attenuating inflammation without compromising the hosts bacterial defense. In this study, we analyzed the presence of neutrophils in Paracoccidioides brasiliensis mycosis (PCM, as well as the immunoexpression of Nrf2. Thirty-nine cases of oral PCM were classified according to quantity of fungi and to the presence of loose or well-organized granulomas and microabscesses. An Nrf2 antibody was used for immunohistochemical analysis. The results showed that neutrophils are present in microabscesses and loose granulomas, but were absent in structured granulomas. A greater quantity of fungi was shown in cases with only loose granulomas when compared to loose and well organized granulomas. Nrf2 was observed in the nuclei of neutrophils of loose granulomas and abscesses, with its expression in loose granulomas maintained despite the additional presence of well organized granulomas in the same specimen. This study suggests that neutrophils participate in P. brasiliensis granuloma formation and that Nrf2 has a possible role in neutrophil survival, via modulation of the inflammatory response.

  1. Activated signature of antiphospholipid syndrome neutrophils reveals potential therapeutic target

    Science.gov (United States)

    Knight, Jason S.; Meng, He; Coit, Patrick; Yalavarthi, Srilakshmi; Sule, Gautam; Gandhi, Alex A.; Grenn, Robert C.; Mazza, Levi F.; Ali, Ramadan A.; Renauer, Paul; Wren, Jonathan D.; Bockenstedt, Paula L.; Wang, Hui; Eitzman, Daniel T.; Sawalha, Amr H.

    2017-01-01

    Antiphospholipid antibodies, present in one-third of lupus patients, increase the risk of thrombosis. We recently reported a key role for neutrophilsneutrophil extracellular traps (NETs), in particular — in the thrombotic events that define antiphospholipid syndrome (APS). To further elucidate the role of neutrophils in APS, we performed a comprehensive transcriptome analysis of neutrophils isolated from patients with primary APS. Moreover, APS-associated venous thrombosis was modeled by treating mice with IgG prepared from APS patients, followed by partial restriction of blood flow through the inferior vena cava. In patients, APS neutrophils demonstrated a proinflammatory signature with overexpression of genes relevant to IFN signaling, cellular defense, and intercellular adhesion. For in vivo studies, we focused on P-selectin glycoprotein ligand-1 (PSGL-1), a key adhesion molecule overexpressed in APS neutrophils. The introduction of APS IgG (as compared with control IgG) markedly potentiated thrombosis in WT mice, but not PSGL-1–KOs. PSGL-1 deficiency was also associated with reduced leukocyte vessel wall adhesion and NET formation. The thrombosis phenotype was restored in PSGL-1–deficient mice by infusion of WT neutrophils, while an anti–PSGL-1 monoclonal antibody inhibited APS IgG–mediated thrombosis in WT mice. PSGL-1 represents a potential therapeutic target in APS. PMID:28931754

  2. Phenotypic changes in neutrophils related to anti-inflammatory therapy.

    Science.gov (United States)

    Barton, A E; Bayley, D L; Mikami, M; Llewellyn-Jones, C G; Stockley, R A

    2000-01-03

    Previous work from the group has shown that non-steroidal anti-inflammatory agents given to volunteers and patients inhibit PMN function possibly by affecting the developing neutrophil during the differentiation process. In this study indomethacin treatment in vivo reduced neutrophil chemotaxis and proteolytic degradation of fibronectin, with a maximal effect after 14 days. Stimulated neutrophil adherence to fibronectin was also reduced but this was not due to quantitative changes in beta(2) integrin expression or function. L-Selectin expression on resting and stimulated neutrophils was increased after 14 days and there was a small decrease in plasma levels of soluble L-selectin. These effects, however, could not be reproduced by treatment of neutrophils with indomethacin in vitro, suggesting they are due to effects on differentiating/maturing PMNs. In an attempt to interpret these changes, studies were performed with dexamethasone, which is known to alter neutrophil function and kinetics. Dexamethasone treatment reduced chemotaxis and increased superoxide generation after 1 day and was associated with increased expression of activated beta(2) integrins and reduced L-selectin expression on resting neutrophils. This suggests the appearance of mainly 'activated' cells as a result of demargination and indicates that the effects of indomethacin are distinctive and not related to changes in compartmentalisation.

  3. Neutrophil adhesion and chemotaxis depend on substrate mechanics

    International Nuclear Information System (INIS)

    Jannat, Risat A; Hammer, Daniel A; Robbins, Gregory P; Ricart, Brendon G; Dembo, Micah

    2010-01-01

    Neutrophil adhesion to the vasculature and chemotaxis within tissues play critical roles in the inflammatory response to injury and pathogens. Unregulated neutrophil activity has been implicated in the progression of numerous chronic and acute diseases such as rheumatoid arthritis, asthma and sepsis. Cell migration of anchorage-dependent cells is known to depend on both chemical and mechanical interactions. Although neutrophil responses to chemical cues have been well characterized, little is known about the effect of underlying tissue mechanics on neutrophil adhesion and migration. To address this question, we quantified neutrophil migration and traction stresses on compliant hydrogel substrates with varying elasticity in a micromachined gradient chamber in which we could apply either a uniform concentration or a precise gradient of the bacterial chemoattractant fMLP. Neutrophils spread more extensively on substrates of greater stiffness. In addition, increasing the stiffness of the substrate leads to a significant increase in the chemotactic index for each fMLP gradient tested. As the substrate becomes stiffer, neutrophils generate higher traction forces without significant changes in cell speed. These forces are often displayed in pairs and focused in the uropod. Increases in the mean fMLP concentration beyond the K D of the receptor lead to a decrease in chemotactic index on all surfaces. Blocking with an antibody against β 2 -integrins leads to a significant reduction, but not an elimination, of directed motility on stiff materials, but no change in motility on soft materials, suggesting neutrophils can display both integrin-dependent and integrin-independent motility. These findings are critical for understanding how neutrophil migration may change in different mechanical environments in vivo and can be used to guide the design of migration inhibitors that more efficiently target inflammation.

  4. Heterogeneity in Neutrophil Microparticles Reveals Distinct Proteome and Functional Properties*

    Science.gov (United States)

    Dalli, Jesmond; Montero-Melendez, Trinidad; Norling, Lucy V; Yin, Xiaoke; Hinds, Charles; Haskard, Dorian; Mayr, Manuel; Perretti, Mauro

    2013-01-01

    Altered plasma neutrophil microparticle levels have recently been implicated in a number of vascular and inflammatory diseases, yet our understanding of their actions is very limited. Herein, we investigate the proteome of neutrophil microparticles in order to shed light on their biological actions. Stimulation of human neutrophils, either in suspension or adherent to an endothelial monolayer, led to the production of microparticles containing >400 distinct proteins with only 223 being shared by the two subsets. For instance, postadherent microparticles were enriched in alpha-2 macroglobulin and ceruloplasmin, whereas microparticles produced by neutrophils in suspension were abundant in heat shock 70 kDa protein 1. Annexin A1 and lactotransferrin were expressed in both microparticle subsets. We next determined relative abundance of these proteins in three types of human microparticle samples: healthy volunteer plasma, plasma of septic patients and skin blister exudates finding that these proteins were differentially expressed on neutrophil microparticles from these samples reflecting in part the expression profiles we found in vitro. Functional assessment of the neutrophil microparticles subsets demonstrated that in response to direct stimulation neutrophil microparticles produced reactive oxygen species and leukotriene B4 as well as locomoted toward a chemotactic gradient. Finally, we investigated the actions of the two neutrophil microparticles subsets described herein on target cell responses. Microarray analysis with human primary endothelial cells incubated with either microparticle subset revealed a discrete modulation of endothelial cell gene expression profile. These findings demonstrate that neutrophil microparticles are heterogenous and can deliver packaged information propagating the activation status of the parent cell, potentially exerting novel and fundamental roles both under homeostatic and disease conditions. PMID:23660474

  5. Neutrophil adhesion and chemotaxis depend on substrate mechanics

    Energy Technology Data Exchange (ETDEWEB)

    Jannat, Risat A; Hammer, Daniel A [Department of Bioengineering, University of Pennsylvania, 240 Skirkanich Hall, 210 South 33rd Street, Philadelphia, PA 19104 (United States); Robbins, Gregory P; Ricart, Brendon G [Department of Chemical and Biomolecular Engineering, University of Pennsylvania, 311A Towne Building, 220 South 33rd Street, Philadelphia, PA 19104 (United States); Dembo, Micah, E-mail: hammer@seas.upenn.ed [Department of Biomedical Engineering, Boston University, 44 Cummington Street, Boston, MA 02215 (United States)

    2010-05-19

    Neutrophil adhesion to the vasculature and chemotaxis within tissues play critical roles in the inflammatory response to injury and pathogens. Unregulated neutrophil activity has been implicated in the progression of numerous chronic and acute diseases such as rheumatoid arthritis, asthma and sepsis. Cell migration of anchorage-dependent cells is known to depend on both chemical and mechanical interactions. Although neutrophil responses to chemical cues have been well characterized, little is known about the effect of underlying tissue mechanics on neutrophil adhesion and migration. To address this question, we quantified neutrophil migration and traction stresses on compliant hydrogel substrates with varying elasticity in a micromachined gradient chamber in which we could apply either a uniform concentration or a precise gradient of the bacterial chemoattractant fMLP. Neutrophils spread more extensively on substrates of greater stiffness. In addition, increasing the stiffness of the substrate leads to a significant increase in the chemotactic index for each fMLP gradient tested. As the substrate becomes stiffer, neutrophils generate higher traction forces without significant changes in cell speed. These forces are often displayed in pairs and focused in the uropod. Increases in the mean fMLP concentration beyond the K{sub D} of the receptor lead to a decrease in chemotactic index on all surfaces. Blocking with an antibody against {beta}{sub 2}-integrins leads to a significant reduction, but not an elimination, of directed motility on stiff materials, but no change in motility on soft materials, suggesting neutrophils can display both integrin-dependent and integrin-independent motility. These findings are critical for understanding how neutrophil migration may change in different mechanical environments in vivo and can be used to guide the design of migration inhibitors that more efficiently target inflammation.

  6. Intracellular accumulation of potent amiloride analogues by human neutrophils

    International Nuclear Information System (INIS)

    Simchowitz, L.; Woltersdorf, O.W. Jr.; Cragoe, E.J. Jr.

    1987-01-01

    The mechanism of uptake of a series of amiloride derivatives by human neutrophils was investigated using [ 14 C]amiloride and the 14 C-labeled 5-(1-hexahydroazepinyl)-6-bromo analogue (BrMM) which is approximately 500-fold more potent than the parent compound at inhibiting Na+/H+ exchange. At an external concentration of 2 microM, the influx of BrMM at 37 degrees C was rapid, reaching a steady state by approximately 20 min. The rate of BrMM uptake (approximately 25 mumol/liter.min) was approximately 90-fold faster than for the same concentration of amiloride, a finding which correlates with differences in lipid partitioning of the two compounds. Uptake was unrelated to specific binding to Na+/H+ exchange transport sites: influx of either drug was nonsaturable whereas amiloride- and BrMM-mediated inhibition of Na+/H+ countertransport obeyed Michaelis-Menten kinetics with apparent Ki values of approximately 75 and approximately 0.2 microM. Entry occurred exclusively via the neutral (uncharged) forms (pK'a 8.40-8.55). Influx was markedly pH-dependent: it was enhanced by extracellular alkalinization and reduced by acidification. Influx was, however, insensitive to large changes in membrane voltage, thereby implying the protonated (charged) species to be impermeant. About 75% of the total intracellular pool of amiloride, but only approximately 25% of BrMM, is contained within the lysosomes, an expected consequence of the partitioning and subsequent trapping of a weak base within this strongly acidic subcellular compartment. With BrMM, there was a relative approximately 60-fold enrichment in the internal/external water concentration ratio of the drug; the value for amiloride was much less, approximately 4. This disparity is consistent with substantial binding of BrMM to internal constituents, presumably to proteins and/or nucleic acids

  7. A Liver Capsular Network of Monocyte-Derived Macrophages Restricts Hepatic Dissemination of Intraperitoneal Bacteria by Neutrophil Recruitment.

    Science.gov (United States)

    Sierro, Frederic; Evrard, Maximilien; Rizzetto, Simone; Melino, Michelle; Mitchell, Andrew J; Florido, Manuela; Beattie, Lynette; Walters, Shaun B; Tay, Szun Szun; Lu, Bo; Holz, Lauren E; Roediger, Ben; Wong, Yik Chun; Warren, Alessandra; Ritchie, William; McGuffog, Claire; Weninger, Wolfgang; Le Couteur, David G; Ginhoux, Florent; Britton, Warwick J; Heath, William R; Saunders, Bernadette M; McCaughan, Geoffrey W; Luciani, Fabio; MacDonald, Kelli P A; Ng, Lai Guan; Bowen, David G; Bertolino, Patrick

    2017-08-15

    The liver is positioned at the interface between two routes traversed by pathogens in disseminating infection. Whereas blood-borne pathogens are efficiently cleared in hepatic sinusoids by Kupffer cells (KCs), it is unknown how the liver prevents dissemination of peritoneal pathogens accessing its outer membrane. We report here that the hepatic capsule harbors a contiguous cellular network of liver-resident macrophages phenotypically distinct from KCs. These liver capsular macrophages (LCMs) were replenished in the steady state from blood monocytes, unlike KCs that are embryonically derived and self-renewing. LCM numbers increased after weaning in a microbiota-dependent process. LCMs sensed peritoneal bacteria and promoted neutrophil recruitment to the capsule, and their specific ablation resulted in decreased neutrophil recruitment and increased intrahepatic bacterial burden. Thus, the liver contains two separate and non-overlapping niches occupied by distinct resident macrophage populations mediating immunosurveillance at these two pathogen entry points to the liver. Copyright © 2017 Elsevier Inc. All rights reserved.

  8. Azurophil granule proteins constitute the major mycobactericidal proteins in human neutrophils and enhance the killing of mycobacteria in macrophages

    DEFF Research Database (Denmark)

    Jena, Prajna; Mohanty, Soumitra; Mohanty, Tirthankar

    2012-01-01

    Pathogenic mycobacteria reside in, and are in turn controlled by, macrophages. However, emerging data suggest that neutrophils also play a critical role in innate immunity to tuberculosis, presumably by their different antibacterial granule proteins. In this study, we purified neutrophil azurophil...... and specific granules and systematically analyzed the antimycobacterial activity of some purified azurophil and specific granule proteins against M. smegmatis, M. bovis-BCG and M. tuberculosis H37Rv. Using gel overlay and colony forming unit assays we showed that the defensin-depleted azurophil granule...... proteins (AZP) were more active against mycobacteria compared to other granule proteins and cytosolic proteins. The proteins showing antimycobacterial activity were identified by MALDI-TOF mass spectrometry. Electron microscopic studies demonstrate that the AZP disintegrate bacterial cell membrane...

  9. Predictors of neutrophilic airway inflammation in young smokers with asthma

    DEFF Research Database (Denmark)

    Westergaard, Christian Grabow; Munck, Christian; Helby, Jens

    2014-01-01

    by a higher degree of neutrophilic inflammation than in non-smokers. A state of neutrophilic inflammation may lead to increased steroid resistance and an accelerated loss of lung function owing to tissue destruction. The aim of this study was to elucidate predictors of neutrophilic inflammation in young...... asthmatic smokers not on steroid treatment, including analysis of tobacco history and bacterial colonization. Methods: In a cross-sectional study, 52 steroid-free, current smokers with asthma were examined with induced sputum, fractional exhaled nitric oxide (FeNO), lung function, ACQ6 score, mannitol...... smokers, neutrophilia may be induced when a certain threshold of tobacco consumption is reached....

  10. Fcγ and Complement Receptors and Complement Proteins in Neutrophil Activation in Rheumatoid Arthritis: Contribution to Pathogenesis and Progression and Modulation by Natural Products

    Directory of Open Access Journals (Sweden)

    Adriana Balbina Paoliello-Paschoalato

    2015-01-01

    Full Text Available Rheumatoid arthritis (RA is a highly disabling disease that affects all structures of the joint and significantly impacts on morbidity and mortality in RA patients. RA is characterized by persistent inflammation of the synovial membrane lining the joint associated with infiltration of immune cells. Eighty to 90% of the leukocytes infiltrating the synovia are neutrophils. The specific role that neutrophils play in the onset of RA is not clear, but recent studies have evidenced that they have an important participation in joint damage and disease progression through the release of proteolytic enzymes, reactive oxygen species (ROS, cytokines, and neutrophil extracellular traps, in particular during frustrated phagocytosis of immune complexes (ICs. In addition, the local and systemic activation of the complement system contributes to the pathogenesis of RA and other IC-mediated diseases. This review discusses (i the participation of Fcγ and complement receptors in mediating the effector functions of neutrophils in RA; (ii the contribution of the complement system and ROS-dependent and ROS-independent mechanisms to joint damage in RA; and (iii the use of plant extracts, dietary compounds, and isolated natural compounds in the treatment of RA, focusing on modulation of the effector functions of neutrophils and the complement system activity and/or activation.

  11. Tasting Pseudomonas aeruginosa biofilms.Human neutrophils express the bitter receptor T2R38 as sensor for the quorum sensing molecule N-(3-oxododecanoyl-L-homoserine lactone

    Directory of Open Access Journals (Sweden)

    Susanne eMaurer

    2015-07-01

    Full Text Available Bacteria communicate with each other via specialized signalling molecules, known as quorum sensing molecules or autoinducers. The Pseudomonas aeruginosa-derived quorum sensing molecule N-(3-oxododecanoyl-L-homoserine lactone (AHL-12, however, also activates mammalian cells. As shown previously, AHL-12 induced chemotaxis, up-regulated CD11b expression, and enhanced phagocytosis of polymorphonuclear neutrophils (PMN. Circumstantial evidence concurred with a receptor for AHL-12, which so far has been elusive. We investigated the bitter receptor T2R38 as a potential candidate. Although identified as a taste receptor, cells outside the gustatory system express T2R38, for example epithelial cells in the lung. We now detected T2R38 in peripheral blood neutrophils, monocytes and lymphocytes on the cell membrane, but also intracellular. In neutrophils, T2R38 was located in vesicles with characteristics of lipid droplets, and super-resolution microscopy showed a co-localisation with the lipid droplet membrane. Neutrophils take up AHL-12, and it co-localized with T2R38 as seen by laser scan microscopy. Binding of AHL-12 to T2R28 was confirmed by pull-down assays using biotin-coupled AHL-12 as bait. A commercially available antibody to T2R38 inhibited binding of AHL-12 to neutrophils, and this antibody by itself stimulated neutrophils, similarly to AHL-12. In conclusion, our data provide evidence for expression of functional T2R38 on neutrophils, and are compatible with the notion that T2R38 is the receptor for AHL-12 on neutrophils.

  12. Application of the NASCAP Spacecraft Simulation Tool to Investigate Electrodynamic Tether Current Collection in LEO

    Science.gov (United States)

    Adams, Mitzi; HabashKrause, Linda

    2012-01-01

    Recent interest in using electrodynamic tethers (EDTs) for orbital maneuvering in Low Earth Orbit (LEO) has prompted the development of the Marshall ElectroDynamic Tether Orbit Propagator (MEDTOP) model. The model is comprised of several modules which address various aspects of EDT propulsion, including calculation of state vectors using a standard orbit propagator (e.g., J2), an atmospheric drag model, realistic ionospheric and magnetic field models, space weather effects, and tether librations. The natural electromotive force (EMF) attained during a radially-aligned conductive tether results in electrons flowing down the tether and accumulating on the lower-altitude spacecraft. The energy that drives this EMF is sourced from the orbital energy of the system; thus, EDTs are often proposed as de-orbiting systems. However, when the current is reversed using satellite charged particle sources, then propulsion is possible. One of the most difficult challenges of the modeling effort is to ascertain the equivalent circuit between the spacecraft and the ionospheric plasma. The present study investigates the use of the NASA Charging Analyzer Program (NASCAP) to calculate currents to and from the tethered satellites and the ionospheric plasma. NASCAP is a sophisticated set of computational tools to model the surface charging of three-dimensional (3D) spacecraft surfaces in a time-varying space environment. The model's surface is tessellated into a collection of facets, and NASCAP calculates currents and potentials for each one. Additionally, NASCAP provides for the construction of one or more nested grids to calculate space potential and time-varying electric fields. This provides for the capability to track individual particles orbits, to model charged particle wakes, and to incorporate external charged particle sources. With this study, we have developed a model of calculating currents incident onto an electrodynamic tethered satellite system, and first results are shown

  13. Proteomic analysis of GPI-anchored membrane proteins

    DEFF Research Database (Denmark)

    Jung, Hye Ryung; Jensen, Ole Nørregaard

    2006-01-01

    Glycosyl-phosphatidyl-inositol-anchored proteins (GPI-APs) represent a subset of post-translationally modified proteins that are tethered to the outer leaflet of the plasma membrane via a C-terminal GPI anchor. GPI-APs are found in a variety of eukaryote species, from pathogenic microorganisms...... to humans. GPI-APs confer important cellular functions as receptors, enzymes and scaffolding molecules. Specific enzymes and detergent extraction methods combined with separation technologies and mass spectrometry permit proteomic analysis of GPI-APs from plasma membrane preparations to reveal cell...

  14. Antifouling Ultrafiltration Membranes via Post-Fabrication Grafting of Biocidal Nanomaterials

    KAUST Repository

    Mauter, Meagan S.; Wang, Yue; Okemgbo, Kaetochi C.; Osuji, Chinedum O.; Giannelis, Emmanuel P.; Elimelech, Menachem

    2011-01-01

    Figure Presented: Ultrafiltration (UF) membranes perform critical pre-treatment functions in advanced water treatment processes. In operational systems, however, biofouling decreases membrane performance and increases the frequency and cost of chemical cleaning. The present work demonstrates a novel technique for covalently or ionically tethering antimicrobial nanoparticles to the surface of UF membranes. Silver nanoparticles (AgNPs) encapsulated in positively charged polyethyleneimine (PEI) were reacted with an oxygen plasma modified polysulfone UF membrane with and without 1-ethyl-3-(3- dimethylaminopropyl) carbodiimide hydrochloride (EDC) present. The nucleophilic primary amines of the PEI react with the electrophilic carboxyl groups on the UF membrane surface to form electrostatic and covalent bonds. The irreversible modification process imparts significant antimicrobial activity to the membrane surface. Post-synthesis functionalization methods, such as the one presented here, maximize the density of nanomaterials at the membrane surface and may provide a more efficient route for fabricating diverse array of reactive nanocomposite membranes. © 2011 American Chemical Society.

  15. Antifouling Ultrafiltration Membranes via Post-Fabrication Grafting of Biocidal Nanomaterials

    KAUST Repository

    Mauter, Meagan S.

    2011-08-24

    Figure Presented: Ultrafiltration (UF) membranes perform critical pre-treatment functions in advanced water treatment processes. In operational systems, however, biofouling decreases membrane performance and increases the frequency and cost of chemical cleaning. The present work demonstrates a novel technique for covalently or ionically tethering antimicrobial nanoparticles to the surface of UF membranes. Silver nanoparticles (AgNPs) encapsulated in positively charged polyethyleneimine (PEI) were reacted with an oxygen plasma modified polysulfone UF membrane with and without 1-ethyl-3-(3- dimethylaminopropyl) carbodiimide hydrochloride (EDC) present. The nucleophilic primary amines of the PEI react with the electrophilic carboxyl groups on the UF membrane surface to form electrostatic and covalent bonds. The irreversible modification process imparts significant antimicrobial activity to the membrane surface. Post-synthesis functionalization methods, such as the one presented here, maximize the density of nanomaterials at the membrane surface and may provide a more efficient route for fabricating diverse array of reactive nanocomposite membranes. © 2011 American Chemical Society.

  16. Revisiting the tethered ureteral stents in children: a novel modification.

    Science.gov (United States)

    Kajbafzadeh, Abdol-Mohammad; Nabavizadeh, Behnam; Keihani, Sorena; Hosseini Sharifi, Seyed Hossein

    2015-06-01

    To propose a simple noninvasive method for ureteral stent retrieval using an extraction string sutured to the skin in children. A retrospective chart review was performed to gather relevant data from December 2005 to February 2013. After the surgeries, if indicated, a tethered double-J stent was placed in the ureter. A 5-0 non-absorbable Prolene stitch was used as an extraction string passing through the urethra and was sutured to subcoronal skin in boys or inner surface of labia majora in girls. For stent removal, a small amount of 2 % lidocaine jelly was pushed into the urethra 5 min before the procedure. The string was then pulled by continuous and gentle force until the entire stent was out. The suture was then cut to release the stent. No sedation or anesthesia was needed. A total of 378 double-J stents with extraction strings were inserted for a total of 325 patients (61.2 % male). Of the 53 patients with bilateral ureteral stents, one male patient (1.88 %) experienced early stent protrusion from urethral meatus. Two of 272 patients (0.73 %) with unilateral ureteral stent (one male and one female) encountered the same problem. All other stents were extracted successfully using the extraction string without any complications. No upward stent migration or suture site reaction was encountered. This method is a safe, easy-to-use, feasible and noninvasive alternative for cystoscopic stent removal with high success rate and minimal complications. This can lead to considerable saving in time and costs for patients, families and healthcare system.

  17. Turbulence measurements using tethered balloon instrumentation during FIRE 1987

    Science.gov (United States)

    Hignett, Phillip

    1990-01-01

    As part of the surface-based observations conducted on San Nicolas Island, the U.K. Meteorological Office operated a set of turbulence probes attached to a balloon tether cable. Typically six probes were used, each capable of measuring momentum, heat, and humidity fluxes. Two probes were fitted with net radiometers, one positioned above cloud and the other below; a third probe carried a Lyman-alpha hygrometer fitted with a pre-heater for the measurement of total water content. Some preliminary results are presented from the 14th July describing the variation in structure of the cloudy boundary layer during the daytime. This day was characterized by a complete cloud cover, an inversion height of approximately 600 m. and north-westerly winds of approximately 6 m.s(-1). As an illustration the equivalent potential temperature derived from a profile ascent made between approximately 0830 and 0930 (PDT) is shown. The data has been smoothed to a height resolution of about 4 metres. At this time the cloud base was approximately 200 m. and very light drizzle was reaching the surface. The vertical velocity variance and potential temperature flux for two periods are shown; the first (shown by full lines) immediately follows the profile and the second (shown by dashed lines) is central around 1400 (PDT). The data have been normalized by their maximum values in the first period. Cloud base has now risen to approximately 300 m. There is a marked variation during the morning, particularly in sigma w. The net radiative flux above cloud top has by now reached its maximum value.

  18. Low-Cost Propellant Launch From a Tethered Balloon

    Science.gov (United States)

    Wilcox, Brian

    2006-01-01

    A document presents a concept for relatively inexpensive delivery of propellant to a large fuel depot in low orbit around the Earth, for use in rockets destined for higher orbits, the Moon, and for remote planets. The propellant is expected to be at least 85 percent of the mass needed in low Earth orbit to support the NASA Exploration Vision. The concept calls for the use of many small ( 10 ton) spin-stabilized, multistage, solid-fuel rockets to each deliver 250 kg of propellant. Each rocket would be winched up to a balloon tethered above most of the atmospheric mass (optimal altitude 26 2 km). There, the rocket would be aimed slightly above the horizon, spun, dropped, and fired at a time chosen so that the rocket would arrive in orbit near the depot. Small thrusters on the payload (powered, for example, by boil-off gases from cryogenic propellants that make up the payload) would precess the spinning rocket, using data from a low-cost inertial sensor to correct for small aerodynamic and solid rocket nozzle misalignment torques on the spinning rocket; would manage the angle of attack and the final orbit insertion burn; and would be fired on command from the depot in response to observations of the trajectory of the payload so as to make small corrections to bring the payload into a rendezvous orbit and despin it for capture by the depot. The system is low-cost because the small rockets can be mass-produced using the same techniques as those to produce automobiles and low-cost munitions, and one or more can be launched from a U.S. territory on the equator (Baker or Jarvis Islands in the mid-Pacific) to the fuel depot on each orbit (every 90 minutes, e.g., any multiple of 6,000 per year).

  19. Biogenic nonmethane hydrocarbon emissions estimated from tethered balloon observations

    Science.gov (United States)

    Davis, K. J.; Lenschow, D. H.; Zimmerman, P. R.

    1994-01-01

    A new technique for estimating surface fluxes of trace gases, the mixed-layer gradient technique, is used to calculate isoprene and terpene emissions from forests. The technique is applied to tethered balloon measurements made over the Amazon forest and a pine-oak forest in Alabama at altitudes up to 300 m. The observations were made during the dry season Amazon Boundary Layer Experiment (ABLE 2A) and the Rural Oxidants in the Southern Environment 1990 experiment (ROSE I). Results from large eddy simulations of scalar transport in the clear convective boundary layer are used to infer fluxes from the balloon profiles. Profiles from the Amazon give a mean daytime emission of 3630 +/- 1400 micrograms isoprene sq m/h, where the uncertainty represents the standard deviation of the mean of eight flux estimates. Twenty profiles from Alabama give emissions of 4470 +/- 3300 micrograms isoprene sq m/h, 1740 +/- 1060 micrograms alpha-pinene sq m/h, and 790 +/- 560 micrograms beta-pinene sq m/h, respectively. These results are in agreement with emissions derived from chemical budgets. The emissions may be overestimated because of uncertainty about how to incorporate the effects of the canopy on the mixed-layer gradients. The large variability in these emission estimates is probably due to the relatively short sampling times of the balloon profiles, though spatially heterogeneous emissions may also play a role. Fluxes derived using this technique are representative of an upwind footprint of several kilometers and are independent of hydrocarbon oxidation rate and mean advection.

  20. Characterization of neutrophil adhesion to different titanium surfaces

    Indian Academy of Sciences (India)

    Scanning electron microscopy and flow cytometry were used to measure .... discs containing neutrophils were inverted and placed in a tube assembly that ... Representative AFM images of smooth (a) and rough (b) Ti surfaces. The arithmetic ...

  1. Neutrophil evasion strategies by Streptococcus pneumoniae and Staphylococcus aureus.

    Science.gov (United States)

    Lewis, Megan L; Surewaard, Bas G J

    2018-03-01

    Humans are well equipped to defend themselves against bacteria. The innate immune system employs diverse mechanisms to recognize, control and initiate a response that can destroy millions of different microbes. Microbes that evade the sophisticated innate immune system are able to escape detection and could become pathogens. The pathogens Streptococcus pneumoniae and Staphylococcus aureus are particularly successful due to the development of a wide variety of virulence strategies for bacterial pathogenesis and they invest significant efforts towards mechanisms that allow for neutrophil evasion. Neutrophils are a primary cellular defense and can rapidly kill invading microbes, which is an indispensable function for maintaining host health. This review compares the key features of Streptococcus pneumoniae and Staphylococcus aureus in epidemiology, with a specific focus on virulence mechanisms utilized to evade neutrophils in bacterial pathogenesis. It is important to understand the complex interactions between pathogenic bacteria and neutrophils so that we can disrupt the ability of pathogens to cause disease.

  2. Systems biology of neutrophil differentiation and immune response

    DEFF Research Database (Denmark)

    Theilgaard-Mönch, Kim; Porse, Bo T; Borregaard, Niels

    2005-01-01

    Systems biology has emerged as a new scientific field, which aims at investigating biological processes at the genomic and proteomic levels. Recent studies have unravelled aspects of neutrophil differentiation and immune responses at the systems level using high-throughput technologies. These stu......Systems biology has emerged as a new scientific field, which aims at investigating biological processes at the genomic and proteomic levels. Recent studies have unravelled aspects of neutrophil differentiation and immune responses at the systems level using high-throughput technologies....... These studies have identified a plethora of novel effector proteins stored in the granules of neutrophils. In addition, these studies provide evidence that neutrophil differentiation and immune response are governed by a highly coordinated transcriptional programme that regulates cellular fate and function...

  3. Cryptococcal capsular glucuronoxylomannan reduces ischaemia-related neutrophil influx

    NARCIS (Netherlands)

    Ellerbroek, PM; Schoemaker, RG; van Veghel, R; Hoepelman, AIM; Coenjaerts, FEJ

    Background The capsular polysaccharide glucuronoxylomannan (GXM) of Cryptococcus neoformans interferes with the chemotaxis and transendothelial migration of neutrophils. Intravenous administration of purified GXM has been shown to reduce the influx of inflammatory cells in an animal model of

  4. Effects of Acrolein on Leukotriene Biosynthesis in Human Neutrophils

    OpenAIRE

    Zemski Berry, Karin A.; Henson, Peter M.; Murphy, Robert C.

    2008-01-01

    Acrolein is a toxic, highly reactive α,β-unsaturated aldehyde that is present in high concentrations in cigarette smoke. In the current study, the effect of acrolein on eicosanoid synthesis in stimulated human neutrophils was examined. Eicosanoid synthesis in neutrophils was initiated by priming with granulocyte-macrophage colony-stimulating factor (GM-CSF) and subsequent stimulation with formyl-methionyl-leucyl-phenylalanine (fMLP) and 5-LO products in addition to small amounts of COX produc...

  5. Disentangling the effects of tocilizumab on neutrophil survival and function.

    Science.gov (United States)

    Gaber, Timo; Hahne, Martin; Strehl, Cindy; Hoff, Paula; Dörffel, Yvonne; Feist, Eugen; Burmester, Gerd-Rüdiger; Buttgereit, Frank

    2016-06-01

    The synovial tissue in rheumatoid arthritis (RA) represents a hypoxic environment with up-regulated pro-inflammatory cytokines and cellular infiltrates including neutrophils. Although inhibition of the interleukin (IL)6 receptor pathway by tocilizumab is a potent treatment option for RA, it may also cause adverse effects such as an occasionally high-grade neutropenia. We analysed the impact of tocilizumab on survival, mediator secretion, oxidative burst, phagocytosis and energy availability of high-dose toll-like receptor (TLR)2/4-stimulated neutrophils (to mimic an arthritis flare) under normoxic versus hypoxic conditions. Human neutrophils were purified, pre-treated with varying doses of tocilizumab, dexamethasone or human IgG1 and high-dose-stimulated with lipopolysaccharide (LPS) alone-triggering TLR2/4-, LPS plus IL6, or left unstimulated. Cells were then incubated under normoxic (18 % O2) or hypoxic (1 % O2) conditions and subsequently analysed. Neutrophil survival and energy availability were significantly decreased by tocilizumab in a dose-dependent manner in high-dose TLR2/4-stimulated cells, but to a greater extent under normoxia as compared to hypoxia. We also found high-dose LPS-stimulated oxidative burst and phagocytosis of neutrophils to be higher under hypoxic versus normoxic conditions, but this difference was reduced by tocilizumab. Finally, we observed that tocilizumab affected neutrophil mediator secretion as a function of oxygen availability. Tocilizumab is known for both beneficial effects and a higher incidence of neutropenia when treating RA patients. Our results suggest that both effects can at least in part be explained by a reduction in neutrophil survival, a dose-dependent inhibition of hypoxia-induced NADPH oxidase-mediated oxidative burst and phagocytosis of infiltrating hypoxic neutrophils and an alteration of mediator secretion.

  6. Template-directed ligation of tethered mononucleotides by t4 DNA ligase for kinase ribozyme selection.

    Directory of Open Access Journals (Sweden)

    David G Nickens

    Full Text Available BACKGROUND: In vitro selection of kinase ribozymes for small molecule metabolites, such as free nucleosides, will require partition systems that discriminate active from inactive RNA species. While nucleic acid catalysis of phosphoryl transfer is well established for phosphorylation of 5' or 2' OH of oligonucleotide substrates, phosphorylation of diffusible small molecules has not been demonstrated. METHODOLOGY/PRINCIPAL FINDINGS: This study demonstrates the ability of T4 DNA ligase to capture RNA strands in which a tethered monodeoxynucleoside has acquired a 5' phosphate. The ligation reaction therefore mimics the partition step of a selection for nucleoside kinase (deoxyribozymes. Ligation with tethered substrates was considerably slower than with nicked, fully duplex DNA, even though the deoxynucleotides at the ligation junction were Watson-Crick base paired in the tethered substrate. Ligation increased markedly when the bridging template strand contained unpaired spacer nucleotides across from the flexible tether, according to the trends: A(2>A(1>A(3>A(4>A(0>A(6>A(8>A(10 and T(2>T(3>T(4>T(6 approximately T(1>T(8>T(10. Bridging T's generally gave higher yield of ligated product than bridging A's. ATP concentrations above 33 microM accumulated adenylated intermediate and decreased yields of the gap-sealed product, likely due to re-adenylation of dissociated enzyme. Under optimized conditions, T4 DNA ligase efficiently (>90% joined a correctly paired, or TratioG wobble-paired, substrate on the 3' side of the ligation junction while discriminating approximately 100-fold against most mispaired substrates. Tethered dC and dG gave the highest ligation rates and yields, followed by tethered deoxyinosine (dI and dT, with the slowest reactions for tethered dA. The same kinetic trends were observed in ligase-mediated capture in complex reaction mixtures with multiple substrates. The "universal" analog 5-nitroindole (dNI did not support ligation when

  7. Thrust Control During Towing of Space Debris using an Elastic Tether

    Directory of Open Access Journals (Sweden)

    A. D. Ledkov

    2014-01-01

    Full Text Available The paper considers a maneuver for deorbiting the large space debris using an active spacecraft connected with the debris by an elastic tether. Tether slacking during the maneuver can lead to the tether rupture, kinking, and winding on the descending object. Therefore it is important to prevent slacking. The objective of this work is to find the law of thrust force control of the active spacecraft to ensure a continuously strained tether during the maneuver.Using Lagrange formalism a mathematical model to describe the system plane motion is developed. This model considers the active spacecraft as a mass point, the space debris as a rigid body, and the tether as a weightless elastic rod. A thrust force is directed along the local horizon of the spacecraft. Linearization of nonlinear differential equation describing longitudinal oscillations of the tether length is performed. Its phase portrait is analyzed. An approximate expression describing the position of the center on the phase portrait is obtained. A time-optimal control with full feedback to ensure that the tether is in the strained state is found by solving the Bellman equation. To use the obtained optimal law it is necessary to set the measuring equipment on the spacecraft, which is capable of accurate measuring a distance to the space debris and its relative velocity. An alternative control law, which is simpler in terms of the practical implementation, is proposed. As an example, the descent from an orbit of nonfunctioning Soviet satellite Meteor-2 is considered. It is shown that both proposed laws provide continuous strain of the tether during deorbiting of the satellite. Moreover, slack does not occur even at the first period of oscillation of the tether length. It is shown that the use of the proposed control laws leads to slight increase of deorbiting time as compared to the case of using the constant thrust.The results can be used to develop the control systems of small spacecrafts

  8. Live Brugia malayi microfilariae inhibit transendothelial migration of neutrophils and monocytes.

    Directory of Open Access Journals (Sweden)

    Jan-Hendrik Schroeder

    Full Text Available Lymphatic filariasis is a major tropical disease caused by the parasite Brugia malayi. Microfilariae (Mf circulate in the peripheral blood for 2-3 hours in synchronisation with maximal feeding of the mosquito vector. When absent from the peripheral blood, Mf sequester in the capillaries of the lungs. Mf are therefore in close contact with vascular endothelial cells (EC and may induce EC immune function and/or wound repair mechanisms such as angiogenesis. In this study, Mf were co-cultured with human umbilical vein EC (HUVEC or human lung microvascular EC (HLMVEC and the transendothelial migration of leukocyte subsets was analysed. In addition, the protein and/or mRNA expression of chemokine, cytokine and angiogenic mediators in endothelial cells in the presence of live microfilariae were measured by a combination of cDNA arrays, protein arrays, ELISA and fluorescence antibody tests.Surprisingly, our findings indicate that Mf presence partially blocked transendothelial migration of monocytes and neutrophils, but not lymphocytes. However, Mf exposure did not result in altered vascular EC expression of key mediators of the tethering stage of extravasation, such as ICAM-1, VCAM-1 and various chemokines. To further analyse the immunological function of vascular EC in the presence of Mf, we measured the mRNA and/or protein expression of a number of pro-inflammatory mediators. We found that expression levels of the mediators tested were predominantly unaltered upon B. malayi Mf exposure. In addition, a comparison of angiogenic mediators induced by intact Mf and Wolbachia-depleted Mf revealed that even intact Mf induce the expression of remarkably few angiogenic mediators in vascular EC. Our study suggests that live microfilariae are remarkably inert in their induction and/or activation of vascular cells in their immediate local environment. Overall, this work presents important insights into the immunological function of the vascular endothelium during

  9. The shear flow processing of controlled DNA tethering and stretching for organic molecular electronics.

    Science.gov (United States)

    Yu, Guihua; Kushwaha, Amit; Lee, Jungkyu K; Shaqfeh, Eric S G; Bao, Zhenan

    2011-01-25

    DNA has been recently explored as a powerful tool for developing molecular scaffolds for making reproducible and reliable metal contacts to single organic semiconducting molecules. A critical step in the process of exploiting DNA-organic molecule-DNA (DOD) array structures is the controlled tethering and stretching of DNA molecules. Here we report the development of reproducible surface chemistry for tethering DNA molecules at tunable density and demonstrate shear flow processing as a rationally controlled approach for stretching/aligning DNA molecules of various lengths. Through enzymatic cleavage of λ-phage DNA to yield a series of DNA chains of various lengths from 17.3 μm down to 4.2 μm, we have investigated the flow/extension behavior of these tethered DNA molecules under different flow strengths in the flow-gradient plane. We compared Brownian dynamic simulations for the flow dynamics of tethered λ-DNA in shear, and found our flow-gradient plane experimental results matched well with our bead-spring simulations. The shear flow processing demonstrated in our studies represents a controllable approach for tethering and stretching DNA molecules of various lengths. Together with further metallization of DNA chains within DOD structures, this bottom-up approach can potentially enable efficient and reliable fabrication of large-scale nanoelectronic devices based on single organic molecules, therefore opening opportunities in both fundamental understanding of charge transport at the single molecular level and many exciting applications for ever-shrinking molecular circuits.

  10. Disaster Coverage Predication for the Emerging Tethered Balloon Technology: Capability for Preparedness, Detection, Mitigation, and Response.

    Science.gov (United States)

    Alsamhi, Saeed H; Samar Ansari, Mohd; Rajput, Navin S

    2018-04-01

    A disaster is a consequence of natural hazards and terrorist acts, which have significant potential to disrupt the entire wireless communication infrastructure. Therefore, the essential rescue squads and recovery operations during a catastrophic event will be severely debilitated. To provide efficient communication services, and to reduce casualty mortality and morbidity during the catastrophic events, we proposed the Tethered Balloon technology for disaster preparedness, detection, mitigation, and recovery assessment. The proposed Tethered Balloon is applicable to any type of disaster except for storms. The Tethered Balloon is being actively researched and developed as a simple solution to improve the performance of rescues, facilities, and services of emergency medical communication in the disaster area. The most important requirement for rescue and relief teams during or after the disaster is a high quality of service of delivery communication services to save people's lives. Using our proposed technology, we report that the Tethered Balloon has a large disaster coverage area. Therefore, the rescue and research teams are given higher priority, and their performance significantly improved in the particular coverage area. Tethered Balloon features made it suitable for disaster preparedness, mitigation, and recovery. The performance of rescue and relief teams was effective and efficient before and after the disaster as well as can be continued to coordinate the relief teams until disaster recovery. (Disaster Med Public Health Preparedness. 2018;12:222-231).

  11. Refining the tethering of American oysters (Crassostrea virginica) to measure the effects of two environmental stressors.

    Science.gov (United States)

    Poirier, Luke A; Gilbert, Shane T C; St-Hilaire, Sophie; Davidson, Jeff; Cox, Ruth; Quijón, Pedro A

    2018-02-01

    Tethering assays, or the physical restraint of test organisms, has been used in the past to measure selected organisms' response to stressors while removing the observer from the experimental setting. Although informative for monitoring and hypothesis testing, these assays often used microfilaments that have been found to be too invasive or prone to biases given their effects on test organisms' behavior. Here, we describe a new variation of tethering using American oysters (Crassostrea virginica) and illustrate its use in the study of their mortality rates as a result of two stressors: siltation and predation by a non-indigenous species. Our protocol identified a resistant (non-toxic) glue that could be used to attach oysters to stone slabs, thus partially mimicking the natural cementation of the shell to natural substrates. This variation of tethering was harmless and maintained oysters' body position and natural ability to filter feed. Using tethered oysters in separate two-week field cage experiments, we also show how siltation and predation by a non-indigenous species (the European green crab, Carcinus maenas), caused a gradual, easily measurable increase in oyster mortality rates. We argue that this variation of tethering is a cost-effective and advantageous way to monitor or test the effects of these and other stressors on oysters and similar species. Copyright © 2017 Elsevier Ltd. All rights reserved.

  12. Observing Formation of Flux Rope by Tether-cutting Reconnection in the Sun

    Energy Technology Data Exchange (ETDEWEB)

    Xue, Zhike; Yan, Xiaoli; Yang, Liheng; Wang, Jincheng; Zhao, Li, E-mail: zkxue@ynao.ac.cn [Yunnan Observatories, Chinese Academy of Sciences, Kunming Yunnan 650216 (China)

    2017-05-10

    Tether-cutting reconnection is considered as one mechanism for the formation of a flux rope. It has been proposed for more than 30 years; however, so far, direct observations of it are very rare. In this Letter, we present observations of the formation of a flux rope via tether-cutting reconnection in NOAA AR 11967 on 2014 February 2 by combining observations with the New Vacuum Solar Telescope and the Solar Dynamic Observatory . The tether-cutting reconnection occurs between two sets of highly sheared magnetic arcades. Comprehensive observational evidence of the reconnection is as follows: changes of the connections between the arcades, brightenings at the reconnection site, hot outflows, formation of a flux rope, slow-rise motion of the flux rope, and flux cancelation. The outflows are along three directions from the reconnection site to the footpoints with the velocities from 24 ± 1 km s{sup −1} to 69 ± 5 km s{sup −1}. Additionally, it is found that the newly formed flux rope connects far footpoints and has a left-handed twisted structure with many fine threads and a concave-up-shape structure in the middle. All the observations are in agreement with the tether-cutting model and provide evidence that tether-cutting reconnection leads to the formation of the flux rope associated with flux shear flow and cancelation.

  13. Tumor-Associated Macrophages and Neutrophils in Tumor Microenvironment

    Directory of Open Access Journals (Sweden)

    Jaehong Kim

    2016-01-01

    Full Text Available Distinct tumor microenvironment forms in each progression step of cancer and has diverse capacities to induce both adverse and beneficial consequences for tumorigenesis. It is now known that immune cells can be activated to favor tumor growth and progression, most probably influenced by the tumor microenvironment. Tumor-associated macrophages and tumor-associated neutrophils can exert protumoral functions, enhancing tumor cell invasion and metastasis, angiogenesis, and extracellular matrix remodeling, while inhibiting the antitumoral immune surveillance. Considering that neutrophils in inflammatory environments recruit macrophages and that recruited macrophages affect neutrophil functions, there may be various degrees of interaction between tumor-associated macrophages and tumor-associated neutrophils. Platelets also play an important role in the recruitment and regulation of monocytic and granulocytic cells in the tumor tissues, suggesting that platelet function may be essential for generation of tumor-associated macrophages and tumor-associated neutrophils. In this review, we will explore the biology of tumor-associated macrophages and tumor-associated neutrophils and their possible interactions in the tumor microenvironment. Special attention will be given to the recruitment and activation of these tumor-associated cells and to the roles they play in maintenance of the tumor microenvironment and progression of tumors.

  14. Pathophysiology of neutrophil-mediated extracellular redox reactions.

    Science.gov (United States)

    Jaganjac, Morana; Cipak, Ana; Schaur, Rudolf Joerg; Zarkovic, Neven

    2016-01-01

    Neutrophil granulocyte leukocytes (neutrophils) play fundamental role in the innate immune response. In the presence of adequate stimuli, neutrophils release excessive amount of reactive oxygen species (ROS) that may induce cell and tissue injury. Oxidative burst of neutrophils acts as a double-edged sword. It may contribute to the pathology of atherosclerosis and brain injury but is also necessary in resolving infections. Moreover, neutrophil-derived ROS may also have both a tumor promoting and tumor suppressing role. ROS have a specific activities and diffusion distance, which is related to their short lifetime. Therefore, the manner in which ROS will act depends on the cells targeted and the intra- and extracellular levels of individual ROS, which can further cause production of reactive aldehydes like 4-hydroxynonenal (HNE) that act as a second messengers of ROS. In this review we discuss the influence of neutrophil mediated extracellular redox reactions in ischemia reperfusion injury, transplant rejection and chronic diseases (atherosclerosis, inflammatory bowel diseases and cancer). At the end a brief overview of cellular mechanisms to maintain ROS homeostasis is given.

  15. Granule protein processing and regulated secretion in neutrophils

    Directory of Open Access Journals (Sweden)

    Avinash eSheshechalam

    2014-09-01

    Full Text Available Neutrophils are part of a family of granulocytes that, together with eosinophils and basophils, play an essential role in innate immunity. Neutrophils are the most abundant circulating leukocytes and are vital for rapid immune responses, being recruited to sites of injury or infection within minutes, where they can act as specialized phagocytic cells. However, another prominent function of neutrophils is the release of pro-inflammatory compounds, including cytokines, chemokines and digestive enzymes, which are stored in intracellular compartments and released through regulated exocytosis. Hence, an important feature that contributes to rapid immune responses is capacity of neutrophils to synthesize and store pre-formed pro-inflammatory mediators in specialized intracellular vesicles and thus no new synthesis is required. This review will focus on advancement in three topics relevant to neutrophil secretion. First we will examine what is known about basal level pro-inflammatory mediator synthesis, trafficking and storage in secretory compartments. Second, we will review recent advancements in the mechanisms that control vesicle mobilization and the release of pre-formed mediators. Third, we will examine the upregulation and de novo synthesis of pro-inflammatory mediators by neutrophils engaged at sites of infection.

  16. Suppressed neutrophil function in children with acute lymphoblastic leukemia.

    Science.gov (United States)

    Tanaka, Fumiko; Goto, Hiroaki; Yokosuka, Tomoko; Yanagimachi, Masakatsu; Kajiwara, Ryosuke; Naruto, Takuya; Nishimaki, Shigeru; Yokota, Shumpei

    2009-10-01

    Infection is a major obstacle in cancer chemotherapy. Neutropenia has been considered to be the most important risk factor for severe infection; however, other factors, such as impaired neutrophil function, may be involved in susceptibility to infection in patients undergoing chemotherapy. In this study, we analyzed neutrophil function in children with acute lymphoblastic leukemia (ALL). Whole blood samples were obtained from 16 children with ALL at diagnosis, after induction chemotherapy, and after consolidation chemotherapy. Oxidative burst and phagocytic activity of neutrophils were analyzed by flow cytometry. Oxidative burst of neutrophils was impaired in ALL patients. The percentage of neutrophils with normal oxidative burst after PMA stimulation was 59.0 +/- 13.2 or 70.0 +/- 21.0% at diagnosis or after induction chemotherapy, respectively, which was significantly lower compared with 93.8 +/- 6.1% in healthy control subjects (P = 0.00004, or 0.002, respectively); however, this value was normal after consolidation chemotherapy. No significant differences were noted in phagocytic activity in children with ALL compared with healthy control subjects. Impaired oxidative burst of neutrophils may be one risk factor for infections in children with ALL, especially in the initial periods of treatment.

  17. Arabidopsis EXO70A1 recruits Patellin3 to the cell membrane independent of its role as an exocyst subunit

    NARCIS (Netherlands)

    Wu, C.; Tan, L.; van Hooren, M.; Tan, X.; Liu, F.; Li, Y.; Zhao, Y.; Li, B.; Rui, Q.; Munnik, T.; Bao, Y.

    2017-01-01

    The exocyst is a well-known complex which tethers vesicles at the cell membrane before fusion. Whether an individual subunit can execute a unique function is largely unknown. Using yeast-two-hybrid (Y2H) analysis, we found that EXO70A1 interacted with the GOLD domain of Patellin3 (PATL3). The direct

  18. Roles of the TRAPP-II Complex and the Exocyst in Membrane Deposition during Fission Yeast Cytokinesis.

    Directory of Open Access Journals (Sweden)

    Ning Wang

    2016-04-01

    Full Text Available The cleavage-furrow tip adjacent to the actomyosin contractile ring is believed to be the predominant site for plasma-membrane insertion through exocyst-tethered vesicles during cytokinesis. Here we found that most secretory vesicles are delivered by myosin-V on linear actin cables in fission yeast cytokinesis. Surprisingly, by tracking individual exocytic and endocytic events, we found that vesicles with new membrane are deposited to the cleavage furrow relatively evenly during contractile-ring constriction, but the rim of the cleavage furrow is the main site for endocytosis. Fusion of vesicles with the plasma membrane requires vesicle tethers. Our data suggest that the transport particle protein II (TRAPP-II complex and Rab11 GTPase Ypt3 help to tether secretory vesicles or tubulovesicular structures along the cleavage furrow while the exocyst tethers vesicles at the rim of the division plane. We conclude that the exocyst and TRAPP-II complex have distinct localizations at the division site, but both are important for membrane expansion and exocytosis during cytokinesis.

  19. Human neutrophils facilitate tumor cell transendothelial migration.

    LENUS (Irish Health Repository)

    Wu, Q D

    2012-02-03

    Tumor cell extravasation plays a key role in tumor metastasis. However, the precise mechanisms by which tumor cells migrate through normal vascular endothelium remain unclear. In this study, using an in vitro transendothelial migration model, we show that human polymorphonuclear neutrophils (PMN) assist the human breast tumor cell line MDA-MB-231 to cross the endothelial barrier. We found that tumor-conditioned medium (TCM) downregulated PMN cytocidal function, delayed PMN apoptosis, and concomitantly upregulated PMN adhesion molecule expression. These PMN treated with TCM attached to tumor cells and facilitated tumor cell migration through different endothelial monolayers. In contrast, MDA-MB-231 cells alone did not transmigrate. FACScan analysis revealed that these tumor cells expressed high levels of intercellular adhesion molecule-1 (ICAM-1) but did not express CD11a, CD11b, or CD18. Blockage of CD11b and CD18 on PMN and of ICAM-1 on MDA-MB-231 cells significantly attenuated TCM-treated, PMN-mediated tumor cell migration. These tumor cells still possessed the ability to proliferate after PMN-assisted transmigration. These results indicate that TCM-treated PMN may serve as a carrier to assist tumor cell transendothelial migration and suggest that tumor cells can exploit PMN and alter their function to facilitate their extravasation.

  20. A Scalable Method toward Superhydrophilic and Underwater Superoleophobic PVDF Membranes for Effective Oil/Water Emulsion Separation.

    Science.gov (United States)

    Yuan, Tao; Meng, Jianqiang; Hao, Tingyu; Wang, Zihong; Zhang, Yufeng

    2015-07-15

    A superhydrophilic and underwater superoleophobic PVDF membrane (PVDFAH) has been prepared by surface-coating of a hydrogel onto the membrane surface, and its superior performance for oil/water emulsion separation has been demonstrated. The coated hydrogel was constructed by an interfacial polymerization based on the thiol-epoxy reaction of pentaerythritol tetrakis (3-mercaptopropionate) (PETMP) with diethylene glycol diglycidyl ether (PEGDGE) and simultaneously tethered on an alkaline-treated commercial PVDF membrane surface via the thio-ene reaction. The PVDFAH membranes can be fabricated in a few minutes under mild conditions and show superhydrophilic and underwater superoleophobic properties for a series of organic solvents. Energy dispersive X-ray (EDX) analysis shows that the hydrogel coating was efficient throughout the pore lumen. The membrane shows superior oil/water emulsion separation performance, including high water permeation, quantitative oil rejection, and robust antifouling performance in a series oil/water emulsions, including that prepared from crude oil. In addition, a 24 h Soxhlet-extraction experiment with ethanol/water solution (50:50, v/v) was conducted to test the tethered hydrogel stability. We see that the membrane maintained the water contact angle below 5°, indicating the covalent tethering stability. This technique shows great promise for scalable fabrication of membrane materials for handling practical oil emulsion purification.

  1. Age is the work of art? Impact of neutrophil and organism age on neutrophil extracellular trap formation.

    Science.gov (United States)

    Ortmann, Weronika; Kolaczkowska, Elzbieta

    2018-03-01

    Neutrophil extracellular traps or NETs are released by highly activated neutrophils in response to infectious agents, sterile inflammation, autoimmune stimuli and cancer. In the cells, the nuclear envelop disintegrates and decondensation of chromatin occurs that depends on peptidylarginine deiminase 4 (PAD4) and neutrophil elastase (NE). Subsequently, proteins from neutrophil granules (e.g., NE, lactoferrin and myeloperoxidase) and the nucleus (histones) bind to decondensed DNA and the whole structure is ejected from the cell. The DNA decorated with potent antimicrobials and proteases can act to contain dissemination of infection and in sterile inflammation NETs were shown to degrade cytokines and chemokines via serine proteases. On the other hand, overproduction of NETs, or their inadequate removal and prolonged presence in vasculature or tissues, can lead to bystander damage or even initiation of diseases. Considering the pros and cons of NET formation, it is of relevance if the stage of neutrophil maturation (immature, mature and senescent cells) affects the capacity to produce NETs as the cells of different age-related phenotypes dominate in given (pathological) conditions. Moreover, the immune system of neonates and elderly individuals is weaker than in adulthood. Is the same pattern followed when it comes to NETs? The overall importance of individual and neutrophil age on the capacity to release NETs is reviewed in detail and the significance of these facts is discussed.

  2. Zinc and magnesium ions synergistically inhibit superoxide generation by cultured human neutrophils--a promising candidate formulation for amnioinfusion fluid.

    Science.gov (United States)

    Uchida, Toshiyuki; Itoh, Hiroaki; Nakamura, Yuki; Kobayashi, Yukiko; Hirai, Kyuya; Suzuki, Kazunao; Sugihara, Kazuhiro; Kanayama, Naohiro; Hiramatsu, Mitsuo

    2010-06-01

    Oligohydramnios is often caused by the premature rupturing of membranes and subsequent intrauterine infections, such as chorioamnionitis, in which event oxidative stress is hypothesized to be closely associated with the damage to the fetal organs. The clinical efficiency of amnioinfusion using warmed saline in cases of premature rupture of membranes is still controversial, especially concerning the prognosis for the fetus. In the present study, we found that human amniotic fluid per se suppresses the release of superoxide from cultured human neutrophils, suggesting an acute or chronic shortage of amniotic fluid in cases of premature rupture of membranes can affect the shielding of intrauterine organs from oxidative stress. The aim of this study was to propose a formula of zinc and magnesium ions in saline for amnioinfusion, by assessing antioxidative activities. A combination of 5 microM zinc and 5mM magnesium in saline synergistically inhibited superoxide production by cultured human neutrophils, equivalent to human amniotic fluid. The intraperitoneal administration of this formula significantly improved the survival rate in a rat model of peritonitis compared to the saline control (46.7% vs. 10%). The combination of these metals with saline may thus be a promising formula for an amnioinfusion fluid with the capacity to protect fetal organs from oxidative stress. Copyright (c) 2010 Elsevier Ireland Ltd. All rights reserved.

  3. DioxolaneA3-phosphatidylethanolamines are generated by human platelets and stimulate neutrophil integrin expression

    Directory of Open Access Journals (Sweden)

    Maceler Aldrovandi

    2017-04-01

    Full Text Available Activated platelets generate an eicosanoid proposed to be 8-hydroxy-9,10-dioxolane A3 (DXA3. Herein, we demonstrate that significant amounts of DXA3 are rapidly attached to phosphatidylethanolamine (PE forming four esterified eicosanoids, 16:0p, 18:0p, 18:1p and 18:0a/DXA3-PEs that can activate neutrophil integrin expression. These lipids comprise the majority of DXA3 generated by platelets, are formed in ng amounts (24.3±6.1 ng/2×108 and remain membrane bound. Pharmacological studies revealed DXA3-PE formation involves cyclooxygenase-1 (COX, protease-activated receptors (PAR 1 and 4, cytosolic phospholipase A2 (cPLA2, phospholipase C and intracellular calcium. They are generated primarily via esterification of newly formed DXA3, but can also be formed in vitro via co-oxidation of PE during COX-1 co-oxidation of arachidonate. All four DXA3-PEs were detected in human clots. Purified platelet DXA3-PE activated neutrophil Mac-1 expression, independently of its hydrolysis to the free eicosanoid. This study demonstrates the structures and cellular synthetic pathway for a family of leukocyte-activating platelet phospholipids generated on acute activation, adding to the growing evidence that enzymatic PE oxidation is a physiological event in innate immune cells.

  4. Neutrophil Extracellular Trap-Related Extracellular Histones Cause Vascular Necrosis in Severe GN.

    Science.gov (United States)

    Kumar, Santhosh V R; Kulkarni, Onkar P; Mulay, Shrikant R; Darisipudi, Murthy N; Romoli, Simone; Thomasova, Dana; Scherbaum, Christina R; Hohenstein, Bernd; Hugo, Christian; Müller, Susanna; Liapis, Helen; Anders, Hans-Joachim

    2015-10-01

    Severe GN involves local neutrophil extracellular trap (NET) formation. We hypothesized a local cytotoxic effect of NET-related histone release in necrotizing GN. In vitro, histones from calf thymus or histones released by neutrophils undergoing NETosis killed glomerular endothelial cells, podocytes, and parietal epithelial cells in a dose-dependent manner. Histone-neutralizing agents such as antihistone IgG, activated protein C, or heparin prevented this effect. Histone toxicity on glomeruli ex vivo was Toll-like receptor 2/4 dependent, and lack of TLR2/4 attenuated histone-induced renal thrombotic microangiopathy and glomerular necrosis in mice. Anti-glomerular basement membrane GN involved NET formation and vascular necrosis, whereas blocking NET formation by peptidylarginine inhibition or preemptive anti-histone IgG injection significantly reduced all aspects of GN (i.e., vascular necrosis, podocyte loss, albuminuria, cytokine induction, recruitment or activation of glomerular leukocytes, and glomerular crescent formation). To evaluate histones as a therapeutic target, mice with established GN were treated with three different histone-neutralizing agents. Anti-histone IgG, recombinant activated protein C, and heparin were equally effective in abrogating severe GN, whereas combination therapy had no additive effects. Together, these results indicate that NET-related histone release during GN elicits cytotoxic and immunostimulatory effects. Furthermore, neutralizing extracellular histones is still therapeutic when initiated in established GN. Copyright © 2015 by the American Society of Nephrology.

  5. Diamond surface functionalization with biomimicry – Amine surface tether and thiol moiety for electrochemical sensors

    Energy Technology Data Exchange (ETDEWEB)

    Sund, James B., E-mail: jim@jamessund.com [Department of Electrical and Computer Engineering, Duke University, Durham, NC (United States); Causey, Corey P. [Departments of Chemistry and Biochemistry, Duke University, Durham, NC (United States); Wolter, Scott D. [Department of Physics, Elon University, Elon, NC 27244 (United States); Parker, Charles B., E-mail: charles.parker@duke.edu [Department of Electrical and Computer Engineering, Duke University, Durham, NC (United States); Stoner, Brian R. [Department of Electrical and Computer Engineering, Duke University, Durham, NC (United States); Research Triangle Institute (RTI) International, Research Triangle Park, NC (United States); Toone, Eric J. [Departments of Chemistry and Biochemistry, Duke University, Durham, NC (United States); Glass, Jeffrey T. [Department of Electrical and Computer Engineering, Duke University, Durham, NC (United States)

    2014-05-01

    Highlights: • Diamond surfaces were functionalized with organic molecules using a novel approach. • Used biomimicry to select a molecule to bind NO, similar to the human body. • Molecular orbital theory predicted the molecule-analyte oxidation behavior. • A thiol moiety was attached to an amine surface tether on the diamond surface. • XPS analysis verified each surface functionalization step. - Abstract: The surface of conducting diamond was functionalized with a terminal thiol group that is capable of binding and detecting nitrogen–oxygen species. The functionalization process employed multiple steps starting with doped diamond films grown by plasma enhanced chemical vapor deposition followed by hydrogen termination and photochemical attachment of a chemically protected amine alkene. The surface tether was deprotected to reveal the amine functionality, which enabled the tether to be extended with surface chemistry to add a terminal thiol moiety for electrochemical sensing applications. Each step of the process was validated using X-ray photoelectron spectroscopy analysis.

  6. Diamond surface functionalization with biomimicry – Amine surface tether and thiol moiety for electrochemical sensors

    International Nuclear Information System (INIS)

    Sund, James B.; Causey, Corey P.; Wolter, Scott D.; Parker, Charles B.; Stoner, Brian R.; Toone, Eric J.; Glass, Jeffrey T.

    2014-01-01

    Highlights: • Diamond surfaces were functionalized with organic molecules using a novel approach. • Used biomimicry to select a molecule to bind NO, similar to the human body. • Molecular orbital theory predicted the molecule-analyte oxidation behavior. • A thiol moiety was attached to an amine surface tether on the diamond surface. • XPS analysis verified each surface functionalization step. - Abstract: The surface of conducting diamond was functionalized with a terminal thiol group that is capable of binding and detecting nitrogen–oxygen species. The functionalization process employed multiple steps starting with doped diamond films grown by plasma enhanced chemical vapor deposition followed by hydrogen termination and photochemical attachment of a chemically protected amine alkene. The surface tether was deprotected to reveal the amine functionality, which enabled the tether to be extended with surface chemistry to add a terminal thiol moiety for electrochemical sensing applications. Each step of the process was validated using X-ray photoelectron spectroscopy analysis

  7. Measurement of calcium influx in tethered rings of rabbit aorta under tension

    International Nuclear Information System (INIS)

    Gleason, M.M.; Ratz, P.H.; Flaim, S.F.

    1985-01-01

    Calcium (Ca) influx in vascular smooth muscle is routinely measured in untethered preparations not under passive stretch, and Ca influx data are correlated with data for steady-state isometric tension obtained under parallel conditions from tethered preparations under passive stretch. The validity of this method was tested by simultaneous measurement of Ca influx and tension in tethered rings of rabbit thoracic aorta. Ca influx ( 45 Ca 3-min pulse) and tension were measured at 3 and 30 min after norepinephrine (NE) or KCl and under control (no agonist) conditions. Active tension was significantly altered by variations in passive tension. Ca influx was unaffected by passive tension under control, NE, or KCl conditions, and results were similar at 3 and 30 min. The results confirm the validity of correlating Ca influx data from untethered rings with steady-state contractile response data obtained from tethered rings under similar experimental conditions

  8. Manipulating neuronal circuits with endogenous and recombinant cell-surface tethered modulators

    Directory of Open Access Journals (Sweden)

    Mandë Holford

    2009-10-01

    Full Text Available Neuronal circuits depend on the precise regulation of cell-surface receptors and ion channels. An ongoing challenge in neuroscience research is deciphering the functional contribution of specific receptors and ion channels using engineered modulators. A novel strategy, termed “tethered toxins”, was recently developed to characterize neuronal circuits using the evolutionary derived selectivity of venom peptide toxins and endogenous peptide ligands, such as lynx1 prototoxins. Herein, the discovery and engineering of cell-surface tethered peptides is reviewed, with particular attention given to their cell-autonomy, modular composition, and genetic targeting in different model organisms. The relative ease with which tethered peptides can be engineered, coupled with the increasing number of neuroactive venom toxins and ligand peptides being discovered, imply a multitude of potentially innovative applications for manipulating neuronal circuits and tissue-specific cell networks, including treatment of disorders caused by malfunction of receptors and ion channels.

  9. Stability analysis and trend study of a balloon tethered in a wind, with experimental comparisons

    Science.gov (United States)

    Redd, L. T.; Bland, S. R.; Bennett, R. M.

    1973-01-01

    A stability analysis and trend study for a balloon tethered in a steady wind are presented. The linearized, stability-derivative type analysis includes balloon aerodynamics, buoyancy, mass (including apparent mass), and static forces resulting from the tether cable. The analysis has been applied to a balloon 7.64 m in length, and the results are compared with those from tow tests of this balloon. This comparison shows that the analysis gives reasonable predictions for the damping, frequencies, modes of motion, and stability boundaries exhibited by the balloon. A trend study for the 7.64-m balloon was made to illustrate how the stability boundaries are affected by changes in individual stability parameters. The trends indicated in this study may also be applicable to many other tethered-balloon systems.

  10. Computer Programs for Calculating and Plotting the Stability Characteristics of a Balloon Tethered in a Wind

    Science.gov (United States)

    Bennett, R. M.; Bland, S. R.; Redd, L. T.

    1973-01-01

    Computer programs for calculating the stability characteristics of a balloon tethered in a steady wind are presented. Equilibrium conditions, characteristic roots, and modal ratios are calculated for a range of discrete values of velocity for a fixed tether-line length. Separate programs are used: (1) to calculate longitudinal stability characteristics, (2) to calculate lateral stability characteristics, (3) to plot the characteristic roots versus velocity, (4) to plot the characteristic roots in root-locus form, (5) to plot the longitudinal modes of motion, and (6) to plot the lateral modes for motion. The basic equations, program listings, and the input and output data for sample cases are presented, with a brief discussion of the overall operation and limitations. The programs are based on a linearized, stability-derivative type of analysis, including balloon aerodynamics, apparent mass, buoyancy effects, and static forces which result from the tether line.

  11. Unilateral pedicle screws asymmetric tethering: an innovative method to create idiopathic deformity

    Directory of Open Access Journals (Sweden)

    Zhang Xuesong

    2007-10-01

    Full Text Available Abstract Objective To evaluate the feasibility of the method that unilateral pedicle screws asymmetric tethering in concave side in combination with convex rib resection for creating idiopathic deformity. Summary of background data Various methods are performed to create idiopathic deformity. Among these methods, posterior asmmetric tethering of the spine shows satisfying result, but some drawbacks related to the current posterior asymmetric tether were still evident. Materials and methods Unilateral pedicle screws asymmetric tethering was performed to 14 female goats (age: 5–8 week-old, weight: 6–8 kg in concave side in combination with convex rib resection. Dorsoventral and lateral plain radiographs were taken of each thoracic spine in the frontal and sagittal planes right after the surgery and later every 4 weeks. Results All animals ambulated freely after surgery. For technical reasons, 2 goats were excluded (one animal died for anesthetic during the surgery, and one animal was lost for instrumental fail due to postoperative infection. Radiography showed that 11 goats exhibited scoliosis with convex toward to the right side, and as the curve increased with time, only 1 goat showed nonprogressive. The initial scoliosis generated in the progressors after the procedures measured 29.0° on average (range 23.0°–38.5° and increased to 43.0° on average (range 36.0°–58.0° over 8 to 10 weeks. The average progression of 14.0° was measured. The curvature immediately after tethering surgery (the initial Cobb angle did have a highly significant correlation with the final curvature (p Conclusion Unilateral pedicle screws asymmetric tethering is a practical method to create experimental scoliosis, especially for those who would like to study the correction of this deformity.

  12. Membrane Biophysics

    CERN Document Server

    Ashrafuzzaman, Mohammad

    2013-01-01

    Physics, mathematics and chemistry all play a vital role in understanding the true nature and functioning of biological membranes, key elements of living processes. Besides simple spectroscopic observations and electrical measurements of membranes we address in this book the phenomena of coexistence and independent existence of different membrane components using various theoretical approaches. This treatment will be helpful for readers who want to understand biological processes by applying both simple observations and fundamental scientific analysis. It provides a deep understanding of the causes and effects of processes inside membranes, and will thus eventually open new doors for high-level pharmaceutical approaches towards fighting membrane- and cell-related diseases.

  13. Effects of acrolein on leukotriene biosynthesis in human neutrophils.

    Science.gov (United States)

    Berry, Karin A Zemski; Henson, Peter M; Murphy, Robert C

    2008-12-01

    Acrolein is a toxic, highly reactive alpha,beta-unsaturated aldehyde that is present in high concentrations in cigarette smoke. In the current study, the effect of acrolein on eicosanoid synthesis in stimulated human neutrophils was examined. Eicosanoid synthesis in neutrophils was initiated by priming with granulocyte-macrophage colony-stimulating factor (GM-CSF) and subsequent stimulation with formyl-methionyl-leucyl-phenylalanine (fMLP) and 5-lipoxygenase (5-LO) products in addition to small amounts of cyclooxygenase (COX) products were detected using LC/MS/MS. A dose-dependent decrease in the formation of 5-LO products was observed in GM-CSF/fMLP-stimulated neutrophils when acrolein (0-50 microM) was present with almost complete inhibition at > or = 25 microM acrolein. The production of COX products was not affected by acrolein in these cells. The effect of acrolein was examined on key parts of the eicosanoid pathway, such as arachidonic acid release, intracellular calcium ion concentration, and adenosine production. In addition, the direct effect of acrolein on 5-LO enzymatic activity was probed using a recombinant enzyme. Some of these factors were affected by acrolein but did not completely explain the almost complete inhibition of 5-LO product formation in GM-CSF/fMLP-treated cells with acrolein. In addition, the effect of acrolein on different stimuli that initiate the 5-LO pathway [platelet-activating factor (PAF)/fMLP, GM-CSF/PAF, opsonized zymosan, and A23187] was examined. Acrolein had no significant effect on the leukotriene production in neutrophils stimulated with PAF/fMLP, GM-CSF/ PAF, or OPZ. Additionally, 50% inhibition of the 5-LO pathway was observed in A23187-stimulated neutrophils. Our results suggest that acrolein has a profound effect on the 5-LO pathway in neutrophils, which may have implications in disease states, such as chronic obstructive pulmonary disease and other pulmonary disease, where both activated neutrophils and acrolein are

  14. Platelet modulation of human neutrophil functions

    Energy Technology Data Exchange (ETDEWEB)

    McGarrity, S.T.; Hyers, T.M.; Webster, R.O.

    1986-03-01

    The combined presence of platelets (PLTS) and neutrophils (PMN) at inflammatory sites has led to examination of the hypothesis that interaction of these cells modulates their responses to stimuli. Gel-filtered human PLTS (GFP) were found to inhibit N-formyl-met-leu-phe (FMLP) and phorbol myristate acetate (PMA) stimulated PMN O/sub 2//sup -/ generation in a concentration-dependent fashion. The heat-stable inhibitory activity was present in the supernatants of GFP after incubation with FMLP (10/sup -7/M), thrombin (0.5 U/ml) or ADP (20 ..mu..M), suggesting a role for PLT release products. PLT lysates added to PMN produced up to 80% inhibition of O/sub 2//sup -/ generation for PMA and 40% for FMLP. Like GFP, lysates failed to scavenge O/sub 2/..pi.. produced by xanthine oxidase-hypoxanthine. The inhibitory activity could not be ascribed to serotonin or adenosine. PLT lysates failed to compete with /sup 3/H-FMLP for binding to PMN. Sephadex G-200 fractionation of PLT lysates releaved two peaks of inhibitory activity with apparent Mr > 200,000 and < 14,000 Daltons. Pretreatment of PMN with PLT lysates also results in a concentration-dependent inhibition of degranulation provoked by FMLP (2 x 10/sup -7/M) or PMA (2 ng/ml) and PMN chemotaxis to FMLP (10/sup -8/M). These studies indicate that preformed PLT mediator(s) released in response to physiological stimuli may limit tissue damage by PMN at sites of inflammation.

  15. Diamond surface functionalization with biomimicry - Amine surface tether and thiol moiety for electrochemical sensors

    Science.gov (United States)

    Sund, James B.; Causey, Corey P.; Wolter, Scott D.; Parker, Charles B.; Stoner, Brian R.; Toone, Eric J.; Glass, Jeffrey T.

    2014-05-01

    The surface of conducting diamond was functionalized with a terminal thiol group that is capable of binding and detecting nitrogen-oxygen species. The functionalization process employed multiple steps starting with doped diamond films grown by plasma enhanced chemical vapor deposition followed by hydrogen termination and photochemical attachment of a chemically protected amine alkene. The surface tether was deprotected to reveal the amine functionality, which enabled the tether to be extended with surface chemistry to add a terminal thiol moiety for electrochemical sensing applications. Each step of the process was validated using X-ray photoelectron spectroscopy analysis.

  16. Electromechanical engineering in SnO2 nanoparticle tethered hybrid ionic liquid

    Science.gov (United States)

    Deb, Debalina; Bhattacharya, Subhratanu

    2017-05-01

    Challenge of developing electrolytes comprising synergic properties of high mechanical strength with superior electrical and electrochemical properties has so far been unmet towards the application of secondary storage devices. In this research, we have engineered the electromechanical properties of 2-(trimethylamino) ethyl methacrylate bis(trifluoromethylsulfonyl) imide [TMEM]TFSI ionic liquid by tethering silane modified SnO2 nanoparticles within it. Different percentages of tethering are employed to achieve improved ionic conductivity, better discharge/ charging ratio (40%) along with gel like mechanical properties. Our findings appear to provide an optimal solution towards the future prospects in application in a number of areas, notably in energy-related technologies.

  17. Calculating the electromagnetic field on the earth due to an electrodynamic tethered system in the ionosphere

    Science.gov (United States)

    Estes, Robert D.

    1989-01-01

    A method is presented for calculating the electromagnetic wave field on the earth's surface associated with the operation of an electrodynamic tethered satellite system of constant or slowly varying current in the upper ionosphere. The wave field at the ionospheric boundary and on the earth's surface is obtained by numerical integration. The results suggest that the ionospheric waves do not propagate into the atmosphere and that the image of the Alfven wings from a steady-current tether should be greatly broadened on the earth's surface.

  18. Stabilization of periodic solutions in a tethered satellite system by damping injection

    DEFF Research Database (Denmark)

    Larsen, Martin Birkelund; Blanke, Mogens

    2009-01-01

    presents a control design for stabilizing these periodic solutions. The design consists of a control law for stabilizing the open-loop equilibrium and a bias term which forces the system trajectory away from the equilibrium. The tether needs to be positioned away from open-loop equilibrium for the tether...... to affect the orbit parameters. An approximation of the periodic solutions of the closed loop system is found as a series expansion in the parameter plane spanned by the controller gain and the bias term. The stability of the solutions is investigated using linear Floquet analysis of the variational...

  19. Towing Asteroids with Gravity Tractors Enhanced by Tethers and Solar Sails

    Science.gov (United States)

    Shen, Haijun; Roithmayr, Carlos M.

    2015-01-01

    Material collected from an asteroid's surface can be used to increase gravitational attraction between the asteroid and a Gravity Tractor (GT); the spacecraft therefore operates more effectively and is referred to as an Enhanced Gravity Tractor (EGT). The use of tethers and solar sails to further improve effectiveness and simplify operations is investigated. By employing a tether, the asteroidal material can be placed close to the asteroid while the spacecraft is stationed farther away, resulting in a better safety margin and improved thruster efficiency. A solar sail on a spacecraft can naturally provide radial offset and inter-spacecraft separation required for multiple EGTs.

  20. Phase 3 study of selected tether applications in space. Volume 2: Study results

    Science.gov (United States)

    1986-01-01

    Engineering designs were developed relative to a tethered launch assist from the Shuttle for payloads up to 10,000 kg mass and the tethering of a 15,000 kg science platform from the space station. These designs are used for a cost benefit analysis which assesses the feasibility of using such systems as a practical alternative to what would otherwise be accomplished by conventional means. The term conventional as related to both these applications is intended to apply to the use of some form(s) of chemical propulsion system.

  1. Neutrophil labeling with [99mTc]-technetium stannous colloid is complement receptor 3-mediated and increases the neutrophil priming response to lipopolysaccharide

    International Nuclear Information System (INIS)

    Gallagher, Hayley; Ramsay, Stuart C.; Barnes, Jodie; Maggs, Jacqueline; Cassidy, Nathan; Ketheesan, Natkunam

    2006-01-01

    Introduction: [ 99m Tc]-technetium stannous colloid (TcSnC)-labeled white cells are used to image inflammation. Neutrophil labeling with TcSnC is probably phagocytic, but the phagocytic receptor involved is not known. We hypothesised that complement receptor 3 (CR3) plays a key role. Phagocytic labeling could theoretically result in neutrophil activation or priming, affecting the behaviour of labeled cells. Fluorescence-activated cell sorter (FACS) analysis side scatter measurements can assess neutrophil activation and priming. Methods: We tested whether TcSnC neutrophil labeling is CR3-mediated by assessing if neutrophil uptake of TcSnC was inhibited by a monoclonal antibody (mAb) directed at the CD11b component of CR3. We tested if TcSnC-labeled neutrophils show altered activation or priming status, comparing FACS side scatter in labeled and unlabeled neutrophils and examining the effect of lipopolysaccharide (LPS), a known priming agent. Results: Anti-CD11b mAb reduced neutrophil uptake of TcSnC in a dose-dependent fashion. Labeled neutrophils did not show significantly increased side scatter compared to controls. LPS significantly increased side scatter in control cells and labeled neutrophils. However, the increase was significantly greater in labeled neutrophils than unlabeled cells. Conclusions: Neutrophil labeling with TcSnC is related to the function of CR3, a receptor which plays a central role in phagocytosis. TcSnC labeling did not significantly activate or prime neutrophils. However, labeled neutrophils showed a greater priming response to LPS. This could result in labeled neutrophils demonstrating increased adhesion on activated endothelium at sites of infection

  2. Neutrophil labeling with [{sup 99m}Tc]-technetium stannous colloid is complement receptor 3-mediated and increases the neutrophil priming response to lipopolysaccharide

    Energy Technology Data Exchange (ETDEWEB)

    Gallagher, Hayley [School of Veterinary and Biomedical Sciences, James Cook University, Townsville, Queensland 4811 (Australia); Ramsay, Stuart C. [School of Medicine, James Cook University, Townsville, Queensland (Australia) and Townsville Nuclear Medicine, Mater Hospital, Townsville, Queensland 4812 (Australia)]. E-mail: stuart.ramsey@jcu.edu.au; Barnes, Jodie [School of Veterinary and Biomedical Sciences, James Cook University, Townsville, Queensland 4811 (Australia); Maggs, Jacqueline [Department of Nuclear Medicine, Townsville Hospital, Townsville, Queensland 4814 (Australia); Cassidy, Nathan [Townsville Nuclear Medicine, Mater Hospital, Townsville, Queensland 4812 (Australia); Ketheesan, Natkunam [School of Veterinary and Biomedical Sciences, James Cook University, Townsville, Queensland 4811 (Australia); School of Medicine, James Cook University, Townsville, Queensland (Australia)

    2006-04-15

    Introduction: [{sup 99m}Tc]-technetium stannous colloid (TcSnC)-labeled white cells are used to image inflammation. Neutrophil labeling with TcSnC is probably phagocytic, but the phagocytic receptor involved is not known. We hypothesised that complement receptor 3 (CR3) plays a key role. Phagocytic labeling could theoretically result in neutrophil activation or priming, affecting the behaviour of labeled cells. Fluorescence-activated cell sorter (FACS) analysis side scatter measurements can assess neutrophil activation and priming. Methods: We tested whether TcSnC neutrophil labeling is CR3-mediated by assessing if neutrophil uptake of TcSnC was inhibited by a monoclonal antibody (mAb) directed at the CD11b component of CR3. We tested if TcSnC-labeled neutrophils show altered activation or priming status, comparing FACS side scatter in labeled and unlabeled neutrophils and examining the effect of lipopolysaccharide (LPS), a known priming agent. Results: Anti-CD11b mAb reduced neutrophil uptake of TcSnC in a dose-dependent fashion. Labeled neutrophils did not show significantly increased side scatter compared to controls. LPS significantly increased side scatter in control cells and labeled neutrophils. However, the increase was significantly greater in labeled neutrophils than unlabeled cells. Conclusions: Neutrophil labeling with TcSnC is related to the function of CR3, a receptor which plays a central role in phagocytosis. TcSnC labeling did not significantly activate or prime neutrophils. However, labeled neutrophils showed a greater priming response to LPS. This could result in labeled neutrophils demonstrating increased adhesion on activated endothelium at sites of infection.

  3. TFG facilitates outer coat disassembly on COPII transport carriers to promote tethering and fusion with ER-Golgi intermediate compartments.

    Science.gov (United States)

    Hanna, Michael G; Block, Samuel; Frankel, E B; Hou, Feng; Johnson, Adam; Yuan, Lin; Knight, Gavin; Moresco, James J; Yates, John R; Ashton, Randolph; Schekman, Randy; Tong, Yufeng; Audhya, Anjon

    2017-09-12

    The conserved coat protein complex II (COPII) mediates the initial steps of secretory protein trafficking by assembling onto subdomains of the endoplasmic reticulum (ER) in two layers to generate cargo-laden transport carriers that ultimately fuse with an adjacent ER-Golgi intermediate compartment (ERGIC). Here, we demonstrate that Trk-fused gene (TFG) binds directly to the inner layer of the COPII coat. Specifically, the TFG C terminus interacts with Sec23 through a shared interface with the outer COPII coat and the cargo receptor Tango1/cTAGE5. Our findings indicate that TFG binding to Sec23 outcompetes these other associations in a concentration-dependent manner and ultimately promotes outer coat dissociation. Additionally, we demonstrate that TFG tethers vesicles harboring the inner COPII coat, which contributes to their clustering between the ER and ERGIC in cells. Together, our studies define a mechanism by which COPII transport carriers are retained locally at the ER/ERGIC interface after outer coat disassembly, which is a prerequisite for fusion with ERGIC membranes.

  4. Formation of neutrophil extracellular traps under low oxygen level

    Directory of Open Access Journals (Sweden)

    Katja Branitzki-Heinemann

    2016-11-01

    Full Text Available Since their discovery, neutrophil extracellular traps (NETs have been characterized as a fundamental host innate immune defense mechanism. Conversely, excessive NET release may have a variety of detrimental consequences for the host. A fine balance between NET formation and elimination is necessary to sustain a protective effect during an infectious challenge. Our own recently published data revealed that stabilization of hypoxia inducible factor 1α (HIF-1α by the iron chelating HIF-1α-agonist desferoxamine or AKB-4924 enhanced the release of phagocyte extracellular traps. Since HIF-1α is a global regulator of the cellular response to low oxygen, we hypothesized that NET formation may be similarly increased under low oxygen conditions. Hypoxia occurs in tissues during infection or inflammation, mostly due to overconsumption of oxygen by pathogens and recruited immune cells. Therefore, experiments were performed to characterize the formation of NETs under hypoxic oxygen conditions compared to normoxia. Human blood-derived neutrophils were isolated and incubated under normoxic (21% oxygen level and compared to hypoxic (1% conditions. Dissolved oxygen levels were monitored in the primary cell culture using a Fibox4-PSt3 measurement system. The formation of NETs was quantified by fluorescence microscopy in response to the known NET-inducer phorbol 12-myristate 13-acetate (PMA or S. aureus wildtype and a nuclease-deficient mutant. In contrast to our hypothesis, spontaneous NET formation of neutrophils incubated under hypoxia was distinctly reduced compared to control neutrophils incubated under normoxia. Furthermore, neutrophils incubated under hypoxia showed significantly reduced formation of NETs in response to PMA. Gene expression analysis revealed that mRNA level of hif-1α as well as hif-1α target genes was not altered. However, in good correlation to the decreased NET formation under hypoxia, the cholesterol content of the neutrophils was

  5. Biomechanical simulations of costo-vertebral and anterior vertebral body tethers for the fusionless treatment of pediatric scoliosis.

    Science.gov (United States)

    Aubin, Carl-Éric; Clin, Julien; Rawlinson, Jeremy

    2018-01-01

    Compression-based fusionless tethers are an alternative to conventional surgical treatments of pediatric scoliosis. Anterior approaches place an anterior (ANT) tether on the anterolateral convexity of the deformed spine to modify growth. Posterior, or costo-vertebral (CV), approaches have not been assessed for biomechanical and corrective effectiveness. The objective was to biomechanically assess CV and ANT tethers using six patient-specific, finite element models of adolescent scoliotic patients (11.9 ± 0.7 years, Cobb 34° ± 10°). A validated algorithm simulated the growth and Hueter-Volkmann growth modulation over a period of 2 years with the CV and ANT tethers at two initial tensions (100, 200 N). The models without tethering also simulated deformity progression with Cobb angle increasing from 34° to 56°, axial rotation 11° to 13°, and kyphosis 28° to 32° (mean values). With the CV tether, the Cobb angle was reduced to 27° and 20° for tensions of 100 and 200 N, respectively, kyphosis to 21° and 19°, and no change in axial rotation. With the ANT tether, Cobb was reduced to 32° and 9° for 100 and 200 N, respectively, kyphosis unchanged, and axial rotation to 3° and 0°. While the CV tether mildly corrected the coronal curve over a 2-year growth period, it had sagittal lordosing effect, particularly with increasing initial axial rotation (>15°). The ANT tether achieved coronal correction, maintained kyphosis, and reduced the axial rotation, but over-correction was simulated at higher initial tensions. This biomechanical study captured the differences between a CV and ANT tether and indicated the variability arising from the patient-specific characteristics. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:254-264, 2018. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

  6. Demodex-associated bacterial proteins induce neutrophil activation.

    LENUS (Irish Health Repository)

    2012-02-01

    Background: Patients with rosacea demonstrate a higher density of Demodex mites in their skin than controls. A bacterium isolated from a Demodex mite from a patient with papulopustular rosacea (PPR) was previously shown to provoke an immune response in patients with PPR or ocular rosacea thus suggesting a possible role for bacterial proteins in the etiology of this condition. Objectives: To examine the response of neutrophils to proteins derived from a bacterium isolated from a Demodex mite. Methods: Bacterial cells were lysed and proteins were partially purified by AKTA-FPLC. Isolated neutrophils were exposed to bacterial proteins and monitored for alterations in migration, degranulation and cytokine production. Results: Neutrophils exposed to proteins from Bacillus cells demonstrated increased levels of migration and elevated release of MMP-9, an enzyme known to degrade collagen and cathelicidin, an antimicrobial peptide. In addition neutrophils exposed to the bacterial proteins demonstrated elevated rates of Il-8 and TNF-alpha production. Conclusions: Proteins produced by a bacterium isolated from a Demodex mite have the ability to increase the migration, degranulation and cytokine production abilities of neutrophils. These results suggest that bacteria may play a role in the inflammatory erythema associated with rosacea.

  7. Burn injury reduces neutrophil directional migration speed in microfluidic devices.

    Directory of Open Access Journals (Sweden)

    Kathryn L Butler

    2010-07-01

    Full Text Available Thermal injury triggers a fulminant inflammatory cascade that heralds shock, end-organ failure, and ultimately sepsis and death. Emerging evidence points to a critical role for the innate immune system, and several studies had documented concurrent impairment in neutrophil chemotaxis with these post-burn inflammatory changes. While a few studies suggest that a link between neutrophil motility and patient mortality might exist, so far, cumbersome assays have prohibited exploration of the prognostic and diagnostic significance of chemotaxis after burn injury. To address this need, we developed a microfluidic device that is simple to operate and allows for precise and robust measurements of chemotaxis speed and persistence characteristics at single-cell resolution. Using this assay, we established a reference set of migration speed values for neutrophils from healthy subjects. Comparisons with samples from burn patients revealed impaired directional migration speed starting as early as 24 hours after burn injury, reaching a minimum at 72-120 hours, correlated to the size of the burn injury and potentially serving as an early indicator for concurrent infections. Further characterization of neutrophil chemotaxis using this new assay may have important diagnostic implications not only for burn patients but also for patients afflicted by other diseases that compromise neutrophil functions.

  8. Increased lung neutrophil apoptosis and inflammation resolution in nonresponding pneumonia.

    Science.gov (United States)

    Moret, I; Lorenzo, M J; Sarria, B; Cases, E; Morcillo, E; Perpiñá, M; Molina, J M; Menéndez, R

    2011-11-01

    Neutrophil activation state and its relationship with an inflammatory environment in community-acquired pneumonia (CAP) remain insufficiently elucidated. We aimed to evaluate the neutrophil apoptosis and cytokine pattern in CAP patients after 72 h of treatment, and their impact on infection resolution. Apoptosis of blood and bronchoalveolar lavage (BAL) neutrophils was measured in nonresponding CAP (NCAP), in responding CAP (blood only) and in patients without infection (control). Pro-inflammatory (interleukin (IL)-6, IL-8) and anti-inflammatory (IL-10) cytokines were measured. Main outcomes were clinical stability and days of hospitalisation. Basal neutrophil apoptosis was higher in the BAL and blood of NCAP, whereas spontaneous apoptosis (after 24 h culture) was lower. Cytokines in NCAP were higher than in responding CAP and control: IL-6 was increased in BAL and blood, IL-8 in BAL and IL-10 in blood. An increased basal apoptosis (≥20%) in BAL of NCAP was associated with lower systemic IL-10 (p<0.01), earlier clinical stability (p=0.05) and shorter hospital stay (p=0.02). A significant correlation was found for systemic IL-6 and IL-10 with days to reach stability and length of stay. After 72 h of treatment, an increased basal alveolar neutrophil apoptosis might contribute to downregulation of inflammation and to faster clinical stability.

  9. Peptide secreted by human alveolar macrophages releases neutrophil granule contents

    International Nuclear Information System (INIS)

    MacArthur, C.K.; Miller, E.J.; Cohen, A.B.

    1987-01-01

    A monoclonal antibody was developed against an 8000-kDa enzyme-releasing peptide (ERP) released from human alveolar macrophages. ERP was isolated on an immunoaffinity column containing the antibody bound to staphylococcal protein A-Sepharose, and by autoradiography. Release of ERP from the macrophages is not changed by plastic adherence, phagocytosis, calcium ionophore, or phorbol esters. The peptide was not antigenically similar to interferon-γ, tumor necrosis factor, or interleukin lα or 1β. The release of constituents from azurophilic and specific granules was the main identified biologic function of ERP. ERP was a more effective secretagogue in the untreated neutrophils and f-met-leu-phe was more effective in the cytochalasin B-treated neutrophils. Absorption of ERP from macrophage-conditioned medium removed a small amount of the chemotactic activity; however, the immunopurified peptide was not chemotactic or chemokinetic for neutrophils, and at high concentrations, it suppressed base line chemokinesis. Treatment of washed macrophages with trypsin released active ERP of approximately the same m.w. of spontaneously secreted ERP. These studies showed that human alveolar macrophages release a peptide which is a secretagogue for human neutrophils under conditions which may be encountered in the lungs during certain disease states. Proteolytic enzymes which are free in the lungs may release the peptide and lead to the secretion of neutrophil enzymes

  10. Infusion of hypertonic saline (7.5%) does not change neutrophil oxidative burst or expression of endothelial adhesion molecules after abdominal hysterectomy

    DEFF Research Database (Denmark)

    Kølsen-Petersen, Jens Aage; Rasmussen, Torsten Bøgh; Krog, Jan

    2006-01-01

    of leukocyte and differential count, neutrophil membrane expression of endothelial adhesion molecules by flow cytometry, and O2- -generation by superoxide dismutase-inhibitable reduction of cytochrome C. RESULTS: Surgery induced well-known changes in the number and distribution of white blood cells, reduced...... the expression of adhesion molecules, and halved the superoxide production unrelated to the tonicity or volume of the infused fluids. CONCLUSION: Infusion of a clinically relevant dose of hypertonic saline has no detectable effect on the membrane expression of endothelial adhesion molecules or O2- -generation...

  11. Neutrophil Protease Cleavage of Von Willebrand Factor in Glomeruli – An Anti-thrombotic Mechanism in the Kidney

    Directory of Open Access Journals (Sweden)

    Ramesh Tati

    2017-02-01

    Full Text Available Adequate cleavage of von Willebrand factor (VWF prevents formation of thrombi. ADAMTS13 is the main VWF-cleaving protease and its deficiency results in development of thrombotic microangiopathy. Besides ADAMTS13 other proteases may also possess VWF-cleaving activity, but their physiological importance in preventing thrombus formation is unknown. This study investigated if, and which, proteases could cleave VWF in the glomerulus. The content of the glomerular basement membrane (GBM was studied as a reflection of processes occurring in the subendothelial glomerular space. VWF was incubated with human GBMs and VWF cleavage was assessed by multimer structure analysis, immunoblotting and mass spectrometry. VWF was cleaved into the smallest multimers by the GBM, which contained ADAMTS13 as well as neutrophil proteases, elastase, proteinase 3 (PR3, cathepsin-G and matrix-metalloproteinase 9. The most potent components of the GBM capable of VWF cleavage were in the serine protease or metalloprotease category, but not ADAMTS13. Neutralization of neutrophil serine proteases inhibited GBM-mediated VWF-cleaving activity, demonstrating a marked contribution of elastase and/or PR3. VWF-platelet strings formed on the surface of primary glomerular endothelial cells, in a perfusion system, were cleaved by both elastase and the GBM, a process blocked by elastase inhibitor. Ultramorphological studies of the human kidney demonstrated neutrophils releasing elastase into the GBM. Neutrophil proteases may contribute to VWF cleavage within the subendothelium, adjacent to the GBM, and thus regulate thrombus size. This anti-thrombotic mechanism would protect the normal kidney during inflammation and could also explain why most patients with ADAMTS13 deficiency do not develop severe kidney failure.

  12. Class IA phosphoinositide 3-kinase β and δ regulate neutrophil oxidase activation in response to Aspergillus fumigatus hyphae.

    Science.gov (United States)

    Boyle, Keith B; Gyori, David; Sindrilaru, Anca; Scharffetter-Kochanek, Karin; Taylor, Philip R; Mócsai, Attila; Stephens, Len R; Hawkins, Phillip T

    2011-03-01

    An effective immune response to the ubiquitous fungus Aspergillus fumigatus is dependent upon production of reactive oxygen species (ROS) by the NADPH oxidase. This is evidenced by the acute sensitivity of oxidase-deficient humans and mice to invasive aspergillosis. Neutrophils are recruited to the lungs shortly postinfection and respond by phagocytosing conidia and mediating extracellular killing of germinated hyphae in a ROS-dependent manner. However, the signaling mechanisms regulating the generation of ROS in response to hyphae are poorly understood. PI3Ks are important regulators of numerous cellular processes, with much recent work describing unique roles for the different class I PI3K isoforms. We showed by live-cell imaging that the lipid products of class I PI3Ks accumulated at the hyphal-bound neutrophil plasma membrane. Further, we used pharmacological and genetic approaches to demonstrate essential, but overlapping, roles for PI3Kβ and PI3Kδ in the ROS and spreading responses of murine neutrophils to Aspergillus hyphae. Hyphal-induced ROS responses were substantially inhibited by deletion of the common β2-integrin subunit CD18, with only a minor, redundant role for Dectin-1. However, addition of soluble algal glucans plus the genetic deletion of CD18 were required to significantly inhibit activation of the PI3K-effector protein kinase B. Hyphal ROS responses were also totally dependent on the presence of Syk, but not its ITAM-containing adaptor proteins FcRγ or DAP12, and the Vav family of Rac-guanine nucleotide exchange factors. These results start to define the signaling network controlling neutrophil ROS responses to A. fumigatus hyphae.

  13. Neutrophils to the ROScue: Mechanisms of NADPH Oxidase Activation and Bacterial Resistance

    Directory of Open Access Journals (Sweden)

    Giang T. Nguyen

    2017-08-01

    Full Text Available Reactive oxygen species (ROS generated by NADPH oxidase play an important role in antimicrobial host defense and inflammation. Their deficiency in humans results in recurrent and severe bacterial infections, while their unregulated release leads to pathology from excessive inflammation. The release of high concentrations of ROS aids in clearance of invading bacteria. Localization of ROS release to phagosomes containing pathogens limits tissue damage. Host immune cells, like neutrophils, also known as PMNs, will release large amounts of ROS at the site of infection following the activation of surface receptors. The binding of ligands to G-protein-coupled receptors (GPCRs, toll-like receptors, and cytokine receptors can prime PMNs for a more robust response if additional signals are encountered. Meanwhile, activation of Fc and integrin directly induces high levels of ROS production. Additionally, GPCRs that bind to the bacterial-peptide analog fMLP, a neutrophil chemoattractant, can both prime cells and trigger low levels of ROS production. Engagement of these receptors initiates intracellular signaling pathways, resulting in activation of downstream effector proteins, assembly of the NADPH oxidase complex, and ultimately, the production of ROS by this complex. Within PMNs, ROS released by the NADPH oxidase complex can activate granular proteases and induce the formation of neutrophil extracellular traps (NETs. Additionally, ROS can cross the membranes of bacterial pathogens and damage their nucleic acids, proteins, and cell membranes. Consequently, in order to establish infections, bacterial pathogens employ various strategies to prevent restriction by PMN-derived ROS or downstream consequences of ROS production. Some pathogens are able to directly prevent the oxidative burst of phagocytes using secreted effector proteins or toxins that interfere with translocation of the NADPH oxidase complex or signaling pathways needed for its activation

  14. Radiation-induced muscositis and neutrophil granulocytes in oral mucosa; Strahleninduzierte Mukositis und neutrophile Granulozyten in der Mundschleimhaut

    Energy Technology Data Exchange (ETDEWEB)

    Schmidberger, H.; Rave-Fraenk, M.; Kim, S.; Hille, A.; Pradier, O.; Hess, C.F. [Klinik fuer Strahlentherapie und Radioonkologie, Univ. Goettingen (Germany)

    2003-10-01

    Background: Chemotherapy-induced mucositis can be related to a decrease in oral neutrophils. We tested the relationship between radiation-induced mucositis and oral neutrophil counts. Patients and Methods: Oral neutrophil counts were obtained for ten patients with head and neck cancer who received radiotherapy of the pharynx and oral cavity. Four patients received additional chemotherapy (5-FU, Mitomycin). Counts were obtained before and during treatment; four healthy volunteers were included in the study as well. For evaluation, a quantitative mouth rinse assay, including neutrophil-staining with acridin-orange, was applied. Results: We observed large inter-individual variations with respect to neutrophil counts for patients and control persons (Table 1). During treatment (irradiation or chemoirradiation), large intra-individual variations were seen additionally (Figure 1). We found a correlation between neutrophil counts and clinical reaction grade. Neutrophil counts increased with increasing mucositis (Figure 2). This increase was more pronounced for patients treated with chemoirradiation compared to radiation alone. Treatment breaks at weekends had no clear influence on neutrophil counts. Conclusions: We observed a weak correlation between neutrophil counts and clinical reaction grade. However, the variations in neutrophil counts are too large to utilize this parameter as a surrogate for clinical mucositis grading. The assumption that a decrease in oral neutrophils is associated with radiation-induced mucositis was clearly negated. (orig.) [German] Hintergrund: Die chemotherapieinduzierte Mukositis kann mit einer Verarmung der Mundschleimhaut an neutrophilen Granulozyten vergesellschaftet sein. Wir ueberprueften den Zusammenhang zwischen der radiogenen Mukositis und der Anzahl neutrophiler Granulozyten. Patienten und Methoden: Bei zehn Patienten mit Tumoren der Kopf-Hals-Region, die sich einer Strahlentherapie unterzogen, wurde die Anzahl enoraler neutrophiler

  15. Cell activation and cellular-cellular interactions during hemodialysis: effect of dialyzer membrane.

    Science.gov (United States)

    Sirolli, V; Ballone, E; Di Stante, S; Amoroso, L; Bonomini, M

    2002-06-01

    During hemodialysis (HD), circulating blood cells can be activated and also engage in dynamic interplay. These phenomena may be important factors behind dialysis membrane bio(in)compatibility. In the present prospective cross-over study, we have used flow cytometry to evaluate the influence of different dialysis membranes on the activation of circulating blood cells (leukocytes, platelets) and their dynamic interactions (formation of circulating platelet-leukocyte and platelet-erythrocyte aggregates) during in vivo HD. Each patient (n = 10) was treated with dialyzers containing membranes of cellulose diacetate, polysulfone and ethylenevinylalcohol (EVAL) in a randomized order. Upregulation of adhesion receptor expression (CD15s, CD11b/CD18) occurred mainly with the cellulosic membrane, though an increase in CD11b/CD18 circulating on neutrophils was also found with both synthetic membranes. Circulating activated platelets (P-selectin/CD63-positive platelets) increased during HD sessions with cellulose diacetate and polysulfone. An increased formation of platelet-neutrophil aggregates was found at 15 and 30 min during dialysis with cellulose diacetate and polysulfone but not with EVAL. Platelet-erythrocyte aggregates also increased with cellulose diacetate and at 15 min with polysulfone as well. Generally in concomitance with the increase in platelet-neutrophil coaggregates, there was an increased hydrogen peroxide production by neutrophils. The results of this study indicate that cellular mechanisms can be activated during HD largely depending on the membrane material, EVAL causing less reactivity than the other two membranes. It appears that each dialysis membrane has multiple and different characteristics that may contribute to interactions with blood components. Our results also indicate that derivatizing cellulose (cellulose diacetate) may be a useful way to improve the biocompatibility of the cellulose polymer and that there may be great variability in the

  16. Doxycycline induced photodamage to human neutrophils and tryptophan

    International Nuclear Information System (INIS)

    Sandberg, S.; Glette, J.; Hopen, G.; Solberg, C.O.

    1984-01-01

    Neutrophil function were studied following irradiation (340-380 nm) of the cells in the presence of 22 μM doxycycline. At increasing light fluence the locomotion, chemiluminescence and glucose oxidation (by the hexose monophosphate shunt) of the neutrophils steadily decreased. The photodamage increased with increasing preincubation temperature and time and was enhanced in D 2 O, reduced in azide and abolished in anaerobiosis. Superoxide dismutase, catalase or mannitol did not influence the photodamage. Photooxidation of tryptophan in the presence of doxycycline was increased 9-10-fold in D 2 O and nearly abolished in the presence of 0.25 mM NaN 3 , indicating that singlet oxygen is the most important reactive oxygen species in the doxycycline-induced photodamage. The results may explain some of the features of tetracycline-induced photosensitivity and why other authors have obtained diverging results when studying the influence of tetracyclines on neutrophil functions. (author)

  17. Accelerated apoptosis of neutrophils in familial Mediterranean fever

    DEFF Research Database (Denmark)

    Manukyan, Gayane; Aminov, Rustam; Hakobyan, Gagik

    2015-01-01

    The causative mutations for familial Mediterranean fever (FMF) are located in the MEFV gene, which encodes pyrin. Pyrin modulates the susceptibility to apoptosis via its PYD domain, but how the mutated versions of pyrin affect apoptotic processes are poorly understood. Spontaneous and induced rates...... of systemic neutrophil apoptosis as well as the levels of proteins involved in apoptosis were investigated ex vivo in patients with FMF using flow cytometry and RT-qPCR. The freshly collected neutrophils from the patients in FMF remission displayed a significantly larger number of cells spontaneously entering...... apoptosis compared to control (6.27 ± 2.14 vs. 1.69 ± 0.18%). This elevated ratio was retained after 24 h incubation of neutrophils in the growth medium (32.4 ± 7.41 vs. 7.65 ± 1.32%). Correspondingly, the mRNA level for caspase-3 was also significantly increased under these conditions. In response...

  18. Neutrophilic dermatosis resembling pyoderma gangrenosum in a dog with polyarthritis.

    Science.gov (United States)

    Bardagí, M; Lloret, A; Fondati, A; Ferrer, L

    2007-04-01

    This report describes a case of neutrophilic dermatosis in a dog, with a number of clinical and pathological similarities to human pyoderma gangrenosum. A seven-year-old, female German shepherd dog with a history of non-erosive idiopathic polyarthritis was presented with severe facial swelling, bilateral erosivoulcerative lesions on the muzzle and multiple, eroded, dermal-subcutaneous nodules on the cranial trunk. Histopathological examination of skin biopsies revealed a necrotising neutrophilic dermatitis. No infectious agents could be detected using specific stains, immunohistochemistry, serology and bacterial aerobic, anaerobic or fungal cultures. A sterile neutrophilic dermatosis resembling human pyoderma gangrenosum was presumptively diagnosed, and the patient showed an excellent response to treatment with prednisone and ciclosporin.

  19. Localized Subcutaneous Acute Febrile Neutrophilic Dermatosis in a Dog

    Directory of Open Access Journals (Sweden)

    Karolin Schoellhorn

    2012-01-01

    Full Text Available A two-year-old spayed female mixed-breed dog was presented with a five-day history of hemorrhagic gastroenteritis and fever. On physical examination, the dog was lethargic and clinically dehydrated. The skin of the entire ventral abdomen extending to both flanks was erythematous, swollen and painful on palpation. Histopathological examination of skin biopsies revealed a severe diffuse neutrophilic dermatitis and panniculitis, resembling the subcutaneous form of Sweet’s syndrome in humans. A large part of the skin lesion developed full-thickness necrosis. After intensive care, three surgical wound debridements and wound adaptations, the wound healed by secondary intention within ten weeks. In the absence of infection of the skin or neoplasia, a diagnosis of neutrophilic dermatosis and panniculitis, resembling the subcutaneous form of acute febrile neutrophilic dermatosis, was made.

  20. Interleukin-8: an expanding universe beyond neutrophil chemotaxis and activation.

    Science.gov (United States)

    Mukaida, N

    2000-12-01

    Since the discovery 13 years ago of interleukin (IL)-8 as a potent neutrophil chemotactic factor, accumulating evidence has established it as a crucial mediator in neutrophil-dependent acute inflammation. Numerous observations have demonstrated that various types of cells can produce a large amount of IL-8, either in response to various stimuli or constitutively, after malignant transformation. Recent studies of IL-8-mediated signaling have revealed that IL-8 activates a wide range of signaling molecules in a coordinate manner. IL-8 has been proven to have diverse actions on various types of leukocytic and nonleukocytic cells besides neutrophils. The author reviews recent progress in IL-8 signal transduction and biological actions on nonneutrophilic leukocytes, including T lymphocytes, monocytes, and hematopoietic progenitor cells. Potential involvement of IL-8 in viral infections and tumor progression is also discussed.

  1. Reversibly tethering growth factors to surfaces : guiding cell function at the cell-material interface

    NARCIS (Netherlands)

    Cabanas Danés, Jordi

    2013-01-01

    Development of novel methodologies for tethering growth factors (GFs) to materials is highly desired for the generation of biomaterials with improved tissue repair properties. Progress in the development of biomaterials that incorporate GFs and the in vivo performance of such biomaterials in tissue

  2. Tethered cord in patients affected by anorectal malformations: a survey from the ARM-Net Consortium

    NARCIS (Netherlands)

    Fanjul, M.; Samuk, I.; Bagolan, P.; Leva, E.; Sloots, C.; Gine, C.; Aminoff, D.; Midrio, P.; Blaauw, I. de; Marcelis, C.L.M.; Rooij, I.A.L.M. van; Wester, T.; Zwink, N.

    2017-01-01

    PURPOSE: The goal of this study was to determine the degree of consensus in the management of spinal cord tethering (TC) in patients with anorectal malformation (ARM) in a large cohort of European pediatric centers. METHODS: A survey was sent to pediatric surgeons (one per center) members of the

  3. Titanium-tethered vancomycin prevents resistance to rifampicin in Staphylococcus aureus in vitro.

    Directory of Open Access Journals (Sweden)

    Martin Rottman

    Full Text Available Rifampicin is currently recognized as the most potent drug against Gram positive implant related infections. The use of rifampicin is limited by the emergence of bacterial resistance, which is often managed by coadministration of a second antibiotic. The purpose of this study was to determine the effectiveness of soluble rifampicin in combination with vancomycin tethered to titanium metal as a means to control bacterial growth and resistance in vitro. Bacterial growth was inhibited when the vancomycin-tethered titanium discs were treated with Staphylococcus aureus inocula of ≤2×10⁶ CFU, however inocula greater than 2×10⁶ CFU/disc adhered and survived. The combination of surface-tethered vancomycin with soluble rifampicin enhanced the inhibitory effect of rifampicin for an inoculum of 10⁶ CFU/cm² by one dilution (combination MIC of 0.008 mg/L versus 0.015 mg/L for rifampicin alone. Moreover, surface tethered vancomycin prevented the emergence of a rifampicin resistant population in an inoculum of 2×10⁸ CFU.

  4. On the escape transition of a tethered Gaussian chain; exact results in two conjugate ensembles

    NARCIS (Netherlands)

    Skvortsov, A.M.; Klushin, L.I.; Leermakers, F.A.M.

    2006-01-01

    Upon compression between two pistons an end-tethered polymer chain undergoes an abrupt transition from a confined coil state to an inhomogeneous flower-like conformation that is partially escaped from the gap. In the thermodynamic limit the system demonstrates a first-order phase transition. A

  5. The ATPases of cohesin interface with regulators to modulate cohesin-mediated DNA tethering

    Science.gov (United States)

    Çamdere, Gamze; Guacci, Vincent; Stricklin, Jeremiah; Koshland, Douglas

    2015-01-01

    Cohesin tethers together regions of DNA, thereby mediating higher order chromatin organization that is critical for sister chromatid cohesion, DNA repair and transcriptional regulation. Cohesin contains a heterodimeric ATP-binding Cassette (ABC) ATPase comprised of Smc1 and Smc3 ATPase active sites. These ATPases are required for cohesin to bind DNA. Cohesin’s DNA binding activity is also promoted by the Eco1 acetyltransferase and inhibited by Wpl1. Recently we showed that after cohesin stably binds DNA, a second step is required for DNA tethering. This second step is also controlled by Eco1 acetylation. Here, we use genetic and biochemical analyses to show that this second DNA tethering step is regulated by cohesin ATPase. Furthermore, our results also suggest that Eco1 promotes cohesion by modulating the ATPase cycle of DNA-bound cohesin in a state that is permissive for DNA tethering and refractory to Wpl1 inhibition. DOI: http://dx.doi.org/10.7554/eLife.11315.001 PMID:26583750

  6. Endogenous opioids are involved in abnormal stereotyped behaviour of tethered sows

    NARCIS (Netherlands)

    Cronin, G.M.; Wiepkema, P.R.; Ree, van J.M.

    1985-01-01

    Tethered sows continuously performed stereotypies during a substantial part of the day time. A single subcutaneous injection with naloxone significantly decreased the profound stereotypies, while explorative behaviours of pigs were not affected by naloxone. In addition a long-term effect of naloxone

  7. Endogenous opioids are involved in abnormal stereotyped behaviours of tethered sows

    NARCIS (Netherlands)

    Cronin, G.M.; Wiepkema, P.R.; Ree, J.M. van

    1985-01-01

    Tethered sows continuously performed stereotypies during a substantial part of the day time. A single subcutaneous injection with naloxone significantly decreased the profound stereotypies, while explorative behaviours of pigs were not affected by naloxone. In addition a long-term effect of naloxone

  8. Folding of multidomain proteins: biophysical consequences of tethering even in apparently independent folding.

    Science.gov (United States)

    Arviv, Oshrit; Levy, Yaakov

    2012-12-01

    Most eukaryotic and a substantial fraction of prokaryotic proteins are composed of more than one domain. The tethering of these evolutionary, structural, and functional units raises, among others, questions regarding the folding process of conjugated domains. Studying the folding of multidomain proteins in silico enables one to identify and isolate the tethering-induced biophysical determinants that govern crosstalks generated between neighboring domains. For this purpose, we carried out coarse-grained and atomistic molecular dynamics simulations of two two-domain constructs from the immunoglobulin-like β-sandwich fold. Each of these was experimentally shown to behave as the "sum of its parts," that is, the thermodynamic and kinetic folding behavior of the constituent domains of these constructs seems to occur independently, with the folding of each domain uncoupled from the folding of its partner in the two-domain construct. We show that the properties of the individual domains can be significantly affected by conjugation to another domain. The tethering may be accompanied by stabilizing as well as destabilizing factors whose magnitude depends on the size of the interface, the length, and the flexibility of the linker, and the relative stability of the domains. Accordingly, the folding of a multidomain protein should not be viewed as the sum of the folding patterns of each of its parts, but rather, it involves abrogating several effects that lead to this outcome. An imbalance between these effects may result in either stabilization or destabilization owing to the tethering. Copyright © 2012 Wiley Periodicals, Inc.

  9. TETHERED BALLOON MEASUREMENTS OF BIOGENIC VOCS IN THE ATMOSPHERIC BOUNDARY LAYER

    Science.gov (United States)

    Measurements of biogenic volatile organic compounds (BVOCs) have been made on a tethered balloon platform in eleven field deployments between 1985 and 1996. A series of balloon sampling packages have been developed for these campaigns and they have been used to describe boundary ...

  10. Technical and economical assessment on tethered wind-energy systems (TWES)

    Energy Technology Data Exchange (ETDEWEB)

    Furuya, O.; Maekawa, S.

    1982-06-01

    The objective of the work reported was to establish the potential of tethered wind energy systems for energy conversion in the upper atmosphere. Of the concepts investigated, the Vertical Takeoff and Landing (VTOL) lift generation concept had the highest potential as compared to balloon, wind and hybrid concepts.

  11. Organic fouling behavior of superhydrophilic polyvinylidene fluoride (PVDF) ultrafiltration membranes functionalized with surface-tailored nanoparticles: Implications for organic fouling in membrane bioreactors

    KAUST Repository

    Liang, Shuai

    2014-08-01

    This study systematically investigates the organic fouling behavior of a superhydrophilic polyvinylidene fluoride (PVDF) ultrafiltration membrane functionalized via post-fabrication tethering of surface-tailored silica nanoparticles to poly(methacrylic acid)-grafted PVDF membrane surface. Sodium alginate (SA), Suwannee River natural organic matter (SRNOM), and bovine serum albumin (BSA) were used as model organic foulants to investigate the antifouling behavior of the superhydrophilic membrane with combined-fouling (mixture of foulants) and individual-fouling (single foulant) tests. A membrane bioreactor (MBR) plant supernatant was also used to verify the organic antifouling property of the superhydrophilic membrane under realistic conditions. Foulant size distributions and foulant-membrane interfacial forces were measured to interpret the observed membrane fouling behavior. Molecular weight cutoff measurements confirmed that membrane functionalization did not adversely affect the intrinsic membrane selectivity. Both filtration tests with the synthetic foulant-mixture solution (containing SA, SRNOM, and BSA) and MBR plant supernatant demonstrated the reliability and durability of the antifouling property of the superhydrophilic membrane. The conspicuous reduction in foulant-membrane interfacial forces for the functionalized membrane further verified the antifouling properties of the superhydrophilic membrane, suggesting great potential for applications in wastewater treatment. © 2014 Elsevier B.V.

  12. Electrodynamic Tethers and E-Sails as Active Experiment Testbeds and Technologies in Space

    Science.gov (United States)

    Gilchrist, B. E.; Wiegmann, B.; Johnson, L.; Bilen, S. G.; Habash Krause, L.; Miars, G.; Leon, O.

    2017-12-01

    The use of small-to-large flexible structures in space such as tethers continues to be studied for scientific and technology applications. Here we will consider tether electrodynamic and electrostatic interactions with magneto-plasmas in ionospheres, magnetospheres, and interplanetary space. These systems are enabling fundamental studies of basic plasma physics phenomena, allowing direct studies of the space environment, and generating technological applications beneficial for science missions. Electrodynamic tethers can drive current through the tether based on the Lorenz force adding or extracting energy from its orbit allowing for the study of charged bodies or plasma plumes moving through meso-sonic magnetoplasmas [1]. Technologically, this also generates propulsive forces requiring no propellant and little or no consumables in any planetary system with a magnetic field and ionosphere, e.g., Jupiter [2]. Further, so called electric sails (E-sails) are being studied to provide thrust through momentum exchange with the hypersonic solar wind. The E-sail uses multiple, very long (10s of km) charged, mostly bare rotating conducting tethers to deflect solar wind protons. It is estimated that a spacecraft could achieve a velocity over 100 km/s with time [3,4]. 1. Banks, P.M., "Review of electrodynamic tethers for space plasma science," J. Spacecraft and Rockets, vol. 26, no. 4, pp. 234-239, 1989. 2. Talley, C., J. Moore, D. Gallagher, and L. Johnson, "Propulsion and power from a rotating electrodynamic tether at Jupiter," 38th AIAA Aerospace Sciences Meeting and Exhibit, January 2000. 3. Janhunen, P., "The electric sail—A new propulsion method which may enable fast missions to the outer solar system," J. British Interpl. Soc., vol. 61, no. 8, pp. 322-325, 2008. 4. Wiegman, B., T. Scheider, A. Heaton, J. Vaughn, N. Stone, and K. Wright, "The Heliopause Electrostatic Rapid Transit System (HERTS)—Design, trades, and analyses performed in a two-year NASA investigation

  13. Spontaneous neutrophil activation in HTLV-1 infected patients

    Directory of Open Access Journals (Sweden)

    Jaqueline B. Guerreiro

    Full Text Available Human T cell lymphotropic Virus type-1 (HTLV-1 induces lymphocyte activation and proliferation, but little is known about the innate immune response due to HTLV-1 infection. We evaluated the percentage of neutrophils that metabolize Nitroblue tetrazolium (NBT to formazan in HTLV-1 infected subjects and the association between neutrophil activation and IFN-gamma and TNF-alpha levels. Blood was collected from 35 HTLV-1 carriers, from 8 patients with HAM/TSP (HTLV-1- associated myelopathy; 22 healthy individuals were evaluated for spontaneous and lipopolysaccharide (LPS-stimulated neutrophil activity (reduction of NBT to formazan. The production of IFN-gamma and TNF-alpha by unstimulated mononuclear cells was determined by ELISA. Spontaneous NBT levels, as well as spontaneous IFN-gamma and TNF-alpha production, were significantly higher (p<0.001 in HTLV-1 infected subjects than in healthy individuals. A trend towards a positive correlation was noted, with increasing percentage of NBT positive neutrophils and levels of IFN-gamma. The high IFN-gamma producing HTLV-1 patient group had significantly greater NBT than healthy controls, 43±24% and 17±4.8% respectively (p< 0.001, while no significant difference was observed between healthy controls and the low IFN-gamma-producing HTLV-1 patient group (30±20%. Spontaneous neutrophil activation is another marker of immune perturbation resulting from HTLV-1 infection. In vivo activation of neutrophils observed in HTLV-1 infected subjects is likely to be the same process that causes spontaneous IFN-gamma production, or it may partially result from direct IFN-gamma stimulation.

  14. A Neutrophil Phenotype Model for Extracorporeal Treatment of Sepsis.

    Directory of Open Access Journals (Sweden)

    Alexander D Malkin

    2015-10-01

    Full Text Available Neutrophils play a central role in eliminating bacterial pathogens, but may also contribute to end-organ damage in sepsis. Interleukin-8 (IL-8, a key modulator of neutrophil function, signals through neutrophil specific surface receptors CXCR-1 and CXCR-2. In this study a mechanistic computational model was used to evaluate and deploy an extracorporeal sepsis treatment which modulates CXCR-1/2 levels. First, a simplified mechanistic computational model of IL-8 mediated activation of CXCR-1/2 receptors was developed, containing 16 ODEs and 43 parameters. Receptor level dynamics and systemic parameters were coupled with multiple neutrophil phenotypes to generate dynamic populations of activated neutrophils which reduce pathogen load, and/or primed neutrophils which cause adverse tissue damage when misdirected. The mathematical model was calibrated using experimental data from baboons administered a two-hour infusion of E coli and followed for a maximum of 28 days. Ensembles of parameters were generated using a Bayesian parallel tempering approach to produce model fits that could recreate experimental outcomes. Stepwise logistic regression identified seven model parameters as key determinants of mortality. Sensitivity analysis showed that parameters controlling the level of killer cell neutrophils affected the overall systemic damage of individuals. To evaluate rescue strategies and provide probabilistic predictions of their impact on mortality, time of onset, duration, and capture efficacy of an extracorporeal device that modulated neutrophil phenotype were explored. Our findings suggest that interventions aiming to modulate phenotypic composition are time sensitive. When introduced between 3-6 hours of infection for a 72 hour duration, the survivor population increased from 31% to 40-80%. Treatment efficacy quickly diminishes if not introduced within 15 hours of infection. Significant harm is possible with treatment durations ranging from 5

  15. Tethered by Self-Generated Flow: Mucus String Augmented Feeding Current Generation in Larval Oysters

    Science.gov (United States)

    Jiang, H.; Wheeler, J.; Anderson, E.

    2016-02-01

    Marine zooplankton live in a nutritionally dilute environment. To survive, they must process an enormous volume of water relative to their own body volume for food. To achieve this, many zooplankters including copepods, invertebrate larvae, and protists create a feeding current to concentrate and transport food items to their food gathering structures. To enhance the efficiency of the feeding current, these zooplankters often rely on certain "tethering" mechanisms to retard their translational motion for producing a strong feeding current. The tethering force may include excess weight due to gravity, force from attachment to solid surfaces, and drag experienced by strategically placed morphological structures. Larval oysters are known from previous studies to release mucus strings during feeding, presumably for supplying a tethering force to enhance their feeding-current efficiency. But the underlying mechanism is unclear. In this study, we used a high-speed microscale imaging system (HSMIS) to observe the behavior of freely swimming and feeding larval oysters. We also used HSMIS to measure larval imposed feeding currents via a micro-particle image velocimetry (µPIV) technique. HSMIS allows observations along a vertically oriented focal plane in a relatively large water vessel with unprecedented spatial and temporal resolutions. Our high-speed videos show that a feeding larval oyster continuously released a long mucus string into its feeding current that flows downward; the feeding current subsequently dragged the mucus string downward. Analysis of our µPIV data combined with a hydrodynamic model further suggests that the drag force experienced by the mucus string in the feeding current contributes significantly to the tethering force required to generate the feeding current. Thus, mucus strings in larval oysters act as "anchors" in larval self-generated flow to actively tether the feeding larvae.

  16. Type 1 Diabetes Prone NOD Mice Have Diminished Cxcr1 mRNA Expression in Polymorphonuclear Neutrophils and CD4+ T Lymphocytes.

    Directory of Open Access Journals (Sweden)

    Karine Haurogné

    Full Text Available In humans, CXCR1 and CXCR2 are two homologous proteins that bind ELR+ chemokines. Both receptors play fundamental roles in neutrophil functions such as migration and reactive oxygen species production. Mouse Cxcr1 and Cxcr2 genes are located in an insulin-dependent diabetes genetic susceptibility locus. The non obese diabetic (NOD mouse is a spontaneous well-described animal model for insulin-dependent type 1 diabetes. In this disease, insulin deficiency results from the destruction of insulin-producing beta cells by autoreactive T lymphocytes. This slow-progressing disease is dependent on both environmental and genetic factors. Here, we report descriptive data about the Cxcr1 gene in NOD mice. We demonstrate decreased expression of mRNA for Cxcr1 in neutrophils and CD4+ lymphocytes isolated from NOD mice compared to other strains, related to reduced NOD Cxcr1 gene promoter activity. Looking for Cxcr1 protein, we next analyze the membrane proteome of murine neutrophils by mass spectrometry. Although Cxcr2 protein is clearly found in murine neutrophils, we did not find evidence of Cxcr1 peptides using this method. Nevertheless, in view of recently-published experimental data obtained in NOD mice, we argue for possible Cxcr1 involvement in type 1 diabetes pathogenesis.

  17. The emerging role of neutrophils in thrombosis – The journey of TF through NETs

    Directory of Open Access Journals (Sweden)

    Konstantinos eKambas

    2012-12-01

    Full Text Available The production of TF by neutrophils and their contribution in thrombosis was until recently a matter of scientific debate. Experimental data suggested the de novo TF production by neutrophils under inflammatory stimuli, while others proposed that these cells acquired microparticle-derived TF. Recent experimental evidence revealed the critical role of neutrophils in thrombotic events. Neutrophil derived TF has been implicated in this process in several human and animal models. Additionally, neutrophil extracellular trap (NET release has emerged as a major contributor in neutrophil-driven thrombogenicity in disease models including sepsis, deep venous thrombosis and malignancy. It is suggested that NETs provide the scaffold for fibrin deposition and platelet entrapment and subsequent activation. The recently reported autophagy-dependent extracellular delivery of TF in NETs further supports the involvement of neutrophils in thrombosis. Herein, we seek to review novel data regarding the role of neutrophils in thrombosis, emphasizing the implication of TF and NETs.

  18. CXCR2 mediates NADPH oxidase-independent neutrophil extracellular trap formation in cystic fibrosis airway inflammation

    NARCIS (Netherlands)

    Marcos, Veronica; Zhou, Zhe; Yildirim, Ali Onder; Bohla, Alexander; Hector, Andreas; Vitkov, Ljubomir; Wiedenbauer, Eva-Maria; Krautgartner, Wolf Dietrich; Stoiber, Walter; Belohradsky, Bernd H.; Rieber, Nikolaus; Kormann, Michael; Koller, Barbara; Roscher, Adelbert; Roos, Dirk; Griese, Matthias; Eickelberg, Oliver; Döring, Gerd; Mall, Marcus A.; Hartl, Dominik

    2010-01-01

    Upon activation, neutrophils release DNA fibers decorated with antimicrobial proteins, forming neutrophil extracellular traps (NETs). Although NETs are bactericidal and contribute to innate host defense, excessive NET formation has been linked to the pathogenesis of autoinflammatory diseases.

  19. Presence of intratumoral neutrophils is an independent prognostic factor in localized renal cell carcinoma

    DEFF Research Database (Denmark)

    Jensen, Hanne Krogh; Donskov, Frede; Marcussen, Niels

    2009-01-01

    : The intratumoral neutrophils ranged from zero to 289 cells/mm(2) tumor tissue. The presence of intratumoral neutrophils was statistically significantly associated with increasing tumor size, low hemoglobin, high creatinine, and CA IX

  20. Functional characterization of mitochondria in neutrophils: a role restricted to apoptosis

    NARCIS (Netherlands)

    Maianski, N. A.; Geissler, J.; Srinivasula, S. M.; Alnemri, E. S.; Roos, D.; Kuijpers, T. W.

    2004-01-01

    Mitochondria are known to combine life-supporting functions with participation in apoptosis by controlling caspase activity. Here, we report that in human blood neutrophils the mitochondria are different, because they preserve mainly death-mediating abilities. Neutrophil mitochondria hardly

  1. Increased neutrophil priming and sensitization before commencing cardiopulmonary bypass in cardiac surgical patients

    NARCIS (Netherlands)

    Gu, YJ; Schoen, P; Tigchelaar, [No Value; Loef, BG; Ebels, T; Rankin, AJ; van Oeveren, W

    2002-01-01

    Background. Neutrophil activation is implicated in postoperative complications in patients having cardiac surgery with cardiopulmonary bypass (CPB). This study was designed to determine the temporal fluctuations in the primability of neutrophils in the preoperative, intraoperative, and postoperative

  2. Membrane paradigm

    International Nuclear Information System (INIS)

    Price, R.H.; Thorne, K.S.

    1986-01-01

    The membrane paradigm is a modified frozen star approach to modeling black holes, with particles and fields assuming a complex, static, boundary-layer type structure (membrane) near the event horizon. The membrane has no effects on the present or future evolution of particles and fields above itself. The mathematical representation is a combination of a formalism containing terms for the shear and bulk viscosity, surface pressure, momentum, temperature, entropy, etc., of the horizon and the 3+1 formalism. The latter model considers a family of three-dimensional spacelike hypersurfaces in one-dimensional time. The membrane model considers a magnetic field threading the hole and undergoing torque from the hole rotation. The field is cleaned by the horizon and distributed over the horizon so that ohmic dissipation is minimized. The membrane paradigm is invalid inside the horizon, but is useful for theoretically probing the properties of slowly evolving black holes

  3. Membrane processes

    Science.gov (United States)

    Staszak, Katarzyna

    2017-11-01

    The membrane processes have played important role in the industrial separation process. These technologies can be found in all industrial areas such as food, beverages, metallurgy, pulp and paper, textile, pharmaceutical, automotive, biotechnology and chemical industry, as well as in water treatment for domestic and industrial application. Although these processes are known since twentieth century, there are still many studies that focus on the testing of new membranes' materials and determining of conditions for optimal selectivity, i. e. the optimum transmembrane pressure (TMP) or permeate flux to minimize fouling. Moreover the researchers proposed some calculation methods to predict the membrane processes properties. In this article, the laboratory scale experiments of membrane separation techniques, as well their validation by calculation methods are presented. Because membrane is the "heart" of the process, experimental and computational methods for its characterization are also described.

  4. Soluble CD40 ligand stimulates CD40-dependent activation of the β2 integrin Mac-1 and protein kinase C zeda (PKCζ in neutrophils: implications for neutrophil-platelet interactions and neutrophil oxidative burst.

    Directory of Open Access Journals (Sweden)

    Rong Jin

    Full Text Available Recent work has revealed an essential involvement of soluble CD40L (sCD40L in inflammation and vascular disease. Activated platelets are the major source of sCD40L, which has been implicated in platelet and leukocyte activation, although its exact functional impact on leukocyte-platelet interactions and the underlying mechanisms remain undefined. We aimed to determine the impact and the mechanisms of sCD40L on neutrophils. We studied neutrophil interactions with activated, surface-adherent platelets as a model for leukocyte recruitment to the sites of injury. Our data show that CD40L contributes to neutrophil firm adhesion to and transmigration across activated surface-adherent platelets, possibly through two potential mechanisms. One involves the direct interaction of ligand-receptor (CD40L-CD40, i.e., platelet surface CD40L interaction with neutrophil CD40; another involves an indirect mechanism, i.e. soluble CD40L stimulates activation of the leukocyte-specific β2 integrin Mac-1 in neutrophils and thereby further promotes neutrophil adhesion and migration. Activation of the integrin Mac-1 is known to be critical for mediating neutrophil adhesion and migration. sCD40L activated Mac-1 in neutrophils and enhanced neutrophil-platelet interactions in wild-type neutrophils, but failed to elicit such responses in CD40-deficient neutrophils. Furthermore, our data show that the protein kinase C zeta (PKCζ is critically required for sCD40L-induced Mac-1 activation and neutrophil adhesive function. sCD40L strongly stimulated the focal clustering of Mac-1 (CD11b and the colocalization of Mac-1 with PKCζ in wild-type neutrophils, but had minimal effect in CD40-deficient neutrophils. Blocking PKCζ completely inhibited sCD40L-induced neutrophil firm adhesion. Moreover, sCD40L strongly stimulates neutrophil oxidative burst via CD40-dependent activation of PI3K/NF-KB, but independent of Mac-1 and PKCζ. These findings may contribute to a better

  5. File list: His.Bld.10.AllAg.Neutrophils [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available His.Bld.10.AllAg.Neutrophils hg19 Histone Blood Neutrophils SRX956551,SRX956548,SRX...956545,SRX956544,SRX956550,SRX956547 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/His.Bld.10.AllAg.Neutrophils.bed ...

  6. File list: His.Bld.50.AllAg.Neutrophils [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available His.Bld.50.AllAg.Neutrophils hg19 Histone Blood Neutrophils SRX956551,SRX956548,SRX...956545,SRX956544,SRX956547,SRX956550 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/His.Bld.50.AllAg.Neutrophils.bed ...

  7. File list: His.Bld.50.AllAg.Neutrophils [Chip-atlas[Archive

    Lifescience Database Archive (English)

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    Lifescience Database Archive (English)

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  18. Neutrophil CD64 has a high negative predictive value for exclusion ...

    African Journals Online (AJOL)

    [13] Multiple studies agree that neutrophil CD64 has high diagnostic speci city and sensitivity.[13,18-20] In the light of the above information, we prospectively evaluated the usefulness of neutrophil CD64 expression in diagnosing neonatal infection. e main objective of the study was quantitation of neutrophil. CD64 by ow ...

  19. Evidence for a self-enforcing inflammation in neutrophil-mediated chronic diseases

    NARCIS (Netherlands)

    Overbeek, S.A.

    2011-01-01

    In summary, this thesis provides evidence for the self-sustaining role of neutrophils in the inflammatory state in the pathogenesis of COPD and CD. In active disease, neutrophils release proteolytic enzymes that breakdown collagen. One of the collagen fragments can be neutrophilic chemoattractant

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    Lifescience Database Archive (English)

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  1. Neutrophil extracellular traps in the host defense against sepsis induced by Burkholderia pseudomallei (melioidosis)

    NARCIS (Netherlands)

    de Jong, Hanna K.; Koh, Gavin C. K. W.; Achouiti, Ahmed; van der Meer, Anne J.; Bulder, Ingrid; Stephan, Femke; Roelofs, Joris J. T. H.; Day, Nick P. J.; Peacock, Sharon J.; Zeerleder, Sacha; Wiersinga, W. Joost

    2014-01-01

    Neutrophil extracellular traps (NETs) are a central player in the host response to bacteria: neutrophils release extracellular DNA (nucleosomes) and neutrophil elastase to entrap and kill bacteria. We studied the role of NETs in Burkholderia pseudomallei infection (melioidosis), an important cause

  2. On the pharmacology of oxidative burst of neutrophils

    Czech Academy of Sciences Publication Activity Database

    Nosáľ, R.; Drábiková, K.; Harmatha, Juraj; Jančinová, V.; Mačičková, T.; Pečivová, J.; Perečko, T.

    2011-01-01

    Roč. 4, č. 2 (2011), A51-A51 ISSN 1337-6853. [TOXCON 2011. Interdisciplinary Toxicology Conference /16./. 17.05.2011-20.05.2011, Praha] Institutional research plan: CEZ:AV0Z40550506 Keywords : N-feruloyl- serotonin * oxidative burst * inhibition of neutrophil activation Subject RIV: CC - Organic Chemistry

  3. Flavonoids inhibit the respiratory burst of neutrophils in mammals

    Czech Academy of Sciences Publication Activity Database

    Číž, Milan; Denev, P.; Kratchanova, M.; Vašíček, Ondřej; Ambrožová, Gabriela; Lojek, Antonín

    2012-01-01

    Roč. 2012, č. 2012 (2012), ID 181295 ISSN 1942-0900 R&D Projects: GA ČR(CZ) GA524/08/1753 Institutional research plan: CEZ:AV0Z50040702 Keywords : flavonoids * neutrophils * respiratory burst Subject RIV: BO - Biophysics Impact factor: 3.393, year: 2012

  4. Activity of neutrophil elastase reflects the progression of acute pancreatitis

    DEFF Research Database (Denmark)

    Novovic, Srdan; Andersen, Anders M; Nord, Magnus

    2013-01-01

    Abstract Objective. Neutrophil elastase (NE) concentration is associated with progression of acute pancreatitis (AP), but measuring total NE concentration includes biologically inactive NE. This study aims to investigate the relationship between NE activity and the aetiology and severity of AP...... was associated with predicted severity of AP and AP-associated respiratory failure. Specific NE inhibitors may have therapeutic potential in acute pancreatitis....

  5. Neutrophil superoxide-anion generating capacity in chronic smoking ...

    Indian Academy of Sciences (India)

    We investigated whether long-term -tocopherol therapy in chronic smoking affects superoxide generating capacity of neutrophils ex vivo. To this purpose, we randomly assigned 128 male chronic smokers (37 ± 21 pack years of smoking) to treatment with placebo ( = 64) or -tocopherol (400 IU dL--tocopherol daily, ...

  6. Platelet indices and neutrophil to lymphocyte ratio in adults with ...

    African Journals Online (AJOL)

    Background: A study was performed in adults with acute appendicitis and matched controls to assess the utility of the platelet indices and neutrophil to lymphocyte ratio, as a diagnostic adjunct. Methods: Data were retrospectively collected from a complete blood count test of 155 adult patients (72 men and 83 women) with ...

  7. Enhancement by platelets of oxygen radical responses of human neutrophils

    Energy Technology Data Exchange (ETDEWEB)

    McCulloch, K.K.; Powell, J.; Johnson, K.J.; Ward, P.A.

    1986-03-01

    When human blood neutrophils were incubated with immune complexes (consisting of IgG antibody) in the presence of platelets, there was a 2 to 10 fold enhancement in the generation of O-/sub 2/ and H/sub 2/O/sub 2/. This enhancement phenomenon was proportional to the dose of immune complex added and the number of platelets present. The response was not agonist specific since similar enhancement also occurred with the following agonists: phorbol myristate acetate, opsonized zymosan particles and the chemotactic peptide N-formyl-met-leu-phe. The platelet related phenomenon of enhanced O-/sub 2/ generation could not be reproduced by the addition of serotonin, histamine or platelet-derived growth factor and was not affected by prior treatment of platelets with cyclooxygenase inhibitors (indomethacin, piroxicam) or lipoxygenase inhibitors (nafazatrom, BW755C or nordihydroguaiaretic acid). However, activation of platelets by thrombin caused release into the platelet supernatant fluid of a factor that, only in the presence of immune complexes, caused enhanced O-/sub 2/ responses to neutrophils. These data indicate that platelets potentiate oxygen radical responses of human neutrophils and suggest a mechanisms by which platelets may participate in tissue injury which is mediated by oxygen radical products from activated neutrophils.

  8. Semi-Automatic Rating Method for Neutrophil Alkaline Phosphatase Activity.

    Science.gov (United States)

    Sugano, Kanae; Hashi, Kotomi; Goto, Misaki; Nishi, Kiyotaka; Maeda, Rie; Kono, Keigo; Yamamoto, Mai; Okada, Kazunori; Kaga, Sanae; Miwa, Keiko; Mikami, Taisei; Masauzi, Nobuo

    2017-01-01

    The neutrophil alkaline phosphatase (NAP) score is a valuable test for the diagnosis of myeloproliferative neoplasms, but it has still manually rated. Therefore, we developed a semi-automatic rating method using Photoshop ® and Image-J, called NAP-PS-IJ. Neutrophil alkaline phosphatase staining was conducted with Tomonaga's method to films of peripheral blood taken from three healthy volunteers. At least 30 neutrophils with NAP scores from 0 to 5+ were observed and taken their images. From which the outer part of neutrophil was removed away with Image-J. These were binarized with two different procedures (P1 and P2) using Photoshop ® . NAP-positive area (NAP-PA) and granule (NAP-PGC) were measured and counted with Image-J. The NAP-PA in images binarized with P1 significantly (P < 0.05) differed between images with NAP scores from 0 to 3+ (group 1) and those from 4+ to 5+ (group 2). The original images in group 1 were binarized with P2. NAP-PGC of them significantly (P < 0.05) differed among all four NAP score groups. The mean NAP-PGC with NAP-PS-IJ indicated a good correlation (r = 0.92, P < 0.001) to results by human examiners. The sensitivity and specificity of NAP-PS-IJ were 60% and 92%, which might be considered as a prototypic method for the full-automatic rating NAP score. © 2016 Wiley Periodicals, Inc.

  9. Yersinia pestis targets neutrophils via complement receptor 3

    Science.gov (United States)

    Merritt, Peter M.; Nero, Thomas; Bohman, Lesley; Felek, Suleyman; Krukonis, Eric S.; Marketon, Melanie M.

    2015-01-01

    Yersinia species display a tropism for lymphoid tissues during infection, and the bacteria select innate immune cells for delivery of cytotoxic effectors by the type III secretion system. Yet the mechanism for target cell selection remains a mystery. Here we investigate the interaction of Yersinia pestis with murine splenocytes to identify factors that participate in the targeting process. We find that interactions with primary immune cells rely on multiple factors. First, the bacterial adhesin Ail is required for efficient targeting of neutrophils in vivo. However, Ail does not appear to directly mediate binding to a specific cell type. Instead, we find that host serum factors direct Y. pestis to specific innate immune cells, particularly neutrophils. Importantly, specificity towards neutrophils was increased in the absence of bacterial adhesins due to reduced targeting of other cell types, but this phenotype was only visible in the presence of mouse serum. Addition of antibodies against complement receptor 3 and CD14 blocked target cell selection, suggesting that a combination of host factors participate in steering bacteria toward neutrophils during plague infection. PMID:25359083

  10. Circulating neutrophil transcriptome may reveal intracranial aneurysm signature.

    Directory of Open Access Journals (Sweden)

    Vincent M Tutino

    Full Text Available Unruptured intracranial aneurysms (IAs are typically asymptomatic and undetected except for incidental discovery on imaging. Blood-based diagnostic biomarkers could lead to improvements in IA management. This exploratory study examined circulating neutrophils to determine whether they carry RNA expression signatures of IAs.Blood samples were collected from patients receiving cerebral angiography. Eleven samples were collected from patients with IAs and 11 from patients without IAs as controls. Samples from the two groups were paired based on demographics and comorbidities. RNA was extracted from isolated neutrophils and subjected to next-generation RNA sequencing to obtain differential expressions for identification of an IA-associated signature. Bioinformatics analyses, including gene set enrichment analysis and Ingenuity Pathway Analysis, were used to investigate the biological function of all differentially expressed transcripts.Transcriptome profiling identified 258 differentially expressed transcripts in patients with and without IAs. Expression differences were consistent with peripheral neutrophil activation. An IA-associated RNA expression signature was identified in 82 transcripts (p<0.05, fold-change ≥2. This signature was able to separate patients with and without IAs on hierarchical clustering. Furthermore, in an independent, unpaired, replication cohort of patients with IAs (n = 5 and controls (n = 5, the 82 transcripts separated 9 of 10 patients into their respective groups.Preliminary findings show that RNA expression from circulating neutrophils carries an IA-associated signature. These findings highlight a potential to use predictive biomarkers from peripheral blood samples to identify patients with IAs.

  11. Enhancement by platelets of oxygen radical responses of human neutrophils

    International Nuclear Information System (INIS)

    McCulloch, K.K.; Powell, J.; Johnson, K.J.; Ward, P.A.

    1986-01-01

    When human blood neutrophils were incubated with immune complexes (consisting of IgG antibody) in the presence of platelets, there was a 2 to 10 fold enhancement in the generation of O- 2 and H 2 O 2 . This enhancement phenomenon was proportional to the dose of immune complex added and the number of platelets present. The response was not agonist specific since similar enhancement also occurred with the following agonists: phorbol myristate acetate, opsonized zymosan particles and the chemotactic peptide N-formyl-met-leu-phe. The platelet related phenomenon of enhanced O- 2 generation could not be reproduced by the addition of serotonin, histamine or platelet-derived growth factor and was not affected by prior treatment of platelets with cyclooxygenase inhibitors (indomethacin, piroxicam) or lipoxygenase inhibitors (nafazatrom, BW755C or nordihydroguaiaretic acid). However, activation of platelets by thrombin caused release into the platelet supernatant fluid of a factor that, only in the presence of immune complexes, caused enhanced O- 2 responses to neutrophils. These data indicate that platelets potentiate oxygen radical responses of human neutrophils and suggest a mechanisms by which platelets may participate in tissue injury which is mediated by oxygen radical products from activated neutrophils

  12. Modulation of neutrophil oxidative burst via histamine receptors

    Czech Academy of Sciences Publication Activity Database

    Číž, Milan; Lojek, Antonín

    2013-01-01

    Roč. 170, č. 1 (2013), s. 17-22 ISSN 0007-1188 R&D Projects: GA MŠk(CZ) LD11010 Institutional support: RVO:68081707 Keywords : neutrophil * oxidative burst * reactive oxygen species Subject RIV: BO - Biophysics Impact factor: 4.990, year: 2013

  13. (neutrophil) Activity, Chronic Gastritis, Gastric Atrophy And Intestinal ...

    African Journals Online (AJOL)

    Incidental (early gastric) cancer was found in 3%, dysplasia in 2% and reactive gastropathy in 7% of the cases. A statistically significant relationship was found between Helicobacter pylori colonization intensity and the degrees of neutrophil activity, chronic inflammation and intestinal metaplasia. Conclusion: We concluded ...

  14. On the Pharmacology of Oxidative Burst of Human Neutrophils

    Czech Academy of Sciences Publication Activity Database

    Nosáľ, R.; Drábiková, K.; Jančinová, V.; Mačičková, T.; Pečivová, J.; Perečko, T.; Harmatha, Juraj; Šmidrkal, J.

    2015-01-01

    Roč. 64, Suppl 4 (2015), S445-S452 ISSN 0862-8408 Institutional support: RVO:61388963 Keywords : human neutrophils * oxidative burst * chemiluminescence * protein kinase C * apoptosis Subject RIV: FR - Pharmacology ; Medidal Chemistry Impact factor: 1.643, year: 2015 http://www.biomed.cas.cz/physiolres/pdf/64/64_S445.pdf

  15. ADAM9 Is a Novel Product of Polymorphonuclear Neutrophils

    DEFF Research Database (Denmark)

    Roychaudhuri, Robin; Hergrueter, Anja H; Polverino, Francesca

    2014-01-01

    A disintegrin and a metalloproteinase domain (ADAM) 9 is known to be expressed by monocytes and macrophages. In this study, we report that ADAM9 is also a product of human and murine polymorphonuclear neutrophils (PMNs). ADAM9 is not synthesized de novo by circulating PMNs. Rather, ADAM9 protein...

  16. Nucleases from Prevotella intermedia can degrade neutrophil extracellular traps.

    Science.gov (United States)

    Doke, M; Fukamachi, H; Morisaki, H; Arimoto, T; Kataoka, H; Kuwata, H

    2017-08-01

    Periodontitis is an inflammatory disease caused by periodontal bacteria in subgingival plaque. These bacteria are able to colonize the periodontal region by evading the host immune response. Neutrophils, the host's first line of defense against infection, use various strategies to kill invading pathogens, including neutrophil extracellular traps (NETs). These are extracellular net-like fibers comprising DNA and antimicrobial components such as histones, LL-37, defensins, myeloperoxidase, and neutrophil elastase from neutrophils that disarm and kill bacteria extracellularly. Bacterial nuclease degrades the NETs to escape NET killing. It has now been shown that extracellular nucleases enable bacteria to evade this host antimicrobial mechanism, leading to increased pathogenicity. Here, we compared the DNA degradation activity of major Gram-negative periodontopathogenic bacteria, Porphyromonas gingivalis, Prevotella intermedia, Fusobacterium nucleatum, and Aggregatibacter actinomycetemcomitans. We found that Pr. intermedia showed the highest DNA degradation activity. A genome search of Pr. intermedia revealed the presence of two genes, nucA and nucD, putatively encoding secreted nucleases, although their enzymatic and biological activities are unknown. We cloned nucA- and nucD-encoding nucleases from Pr. intermedia ATCC 25611 and characterized their gene products. Recombinant NucA and NucD digested DNA and RNA, which required both Mg 2+ and Ca 2+ for optimal activity. In addition, NucA and NucD were able to degrade the DNA matrix comprising NETs. © 2016 The Authors Molecular Oral Microbiology Published by John Wiley & Sons Ltd.

  17. Neutrophil elastase-mediated increase in airway temperature during inflammation

    DEFF Research Database (Denmark)

    Schmidt, Annika; Belaaouaj, Azzaq; Bissinger, Rosi

    2014-01-01

    in the exhaled air of cystic fibrosis (CF) patients. To further test our hypothesis, a pouch inflammatory model using neutrophil elastase-deficient mice was employed. Next, the impact of temperature changes on the dominant CF pathogen Pseudomonas aeruginosa growth was tested by plating method and RNAseq. Results...

  18. Neutrophil extracellular traps in patients with pulmonary tuberculosis

    NARCIS (Netherlands)

    van der Meer, Anne Jan; Zeerleder, Sacha; Blok, Dana C.; Kager, Liesbeth M.; Lede, Ivar O.; Rahman, Wahid; Afroz, Rumana; Ghose, Aniruddha; Visser, Caroline E.; Zahed, Abu Shahed Md; Husain, Md Anwar; Alam, Khan Mashrequl; Barua, Pravat Chandra; Hassan, Mahtabuddin; Tayab, Md Abu; Dondorp, Arjen M.; van der Poll, Tom

    2017-01-01

    Tuberculosis is a devastating infectious disease causing many deaths worldwide. Recent investigations have implicated neutrophil extracellular traps (NETs) in the host response to tuberculosis. The aim of the current study was to obtain evidence for NETs release in the circulation during human

  19. Increased neutrophil expression of pattern recognition receptors during COPD exacerbations

    NARCIS (Netherlands)

    Pouwels, Simon D.; Van Geffen, Wouter H.; Jonker, Marnix R.; Kerstjens, Huib A. M.; Nawijn, Martijn C.; Heijink, Irene H.

    Previously, we observed increased serum levels of damage-associated molecular patterns (DAMPs) during COPD exacerbations. Here, gene expression of DAMP receptors was measured in peripheral blood neutrophils of COPD patients during stable disease and severe acute exacerbation. The expression of

  20. The strength of integrin binding between neutrophils and endothelial cells

    Czech Academy of Sciences Publication Activity Database

    Labrador, V.; Říha, Pavel; Muller, S.; Dumas, D.; Wang, X.; Stoltz, J. F.

    2003-01-01

    Roč. 32, č. 8 (2003), s. 684-688 ISSN 0175-7571 R&D Projects: GA ČR GA305/01/1605 Institutional research plan: CEZ:AV0Z2060917 Keywords : endothelium * integrins * neutrophil adhesion * scanning microscopy Subject RIV: BO - Biophysics Impact factor: 1.769, year: 2003