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Sample records for platelet pg synthetase

  1. [Platelet cytochrome c-oxidase and glutamine synthetase-like protein in patients with mild cognitive impairment].

    Science.gov (United States)

    Burbaeva, G Sh; Boksha, I S; Savushkina, O K; Turishcheva, M S; Tereshkina, E B; Starodubtseva, L I; Gavrilova, S I; Fedorova, Ia B; Zhuravin, I A

    2012-01-01

    The study aimed to develop pre-clinical diagnosis of Alzheimer's disease (AD) and - in future - preventive therapy in patients with mild cognitive impairment (MCI). The MCI group (n=44) and AD group (n=42, including 18 patients with soft dementia and 24 patients with mild dementia) were studied. The groups were matched for age (median 70 and 69 years for MCI and AD groups, respectively). The control group comprised 24 mentally healthy relatives of the patients. Correlations between the activity/amounts of platelet enzymes: cytochrome c-oxidase (COX), glutamine synthetase-like protein (GSLP) and the extent of cognitive impairment were studied. The COX activity in MCI and AD groups was significantly lower than in the control group (Kruskal-Wallis test p=0.0001, χ²=11.6, p=0.003). These tests showed significant differences in GSLP amount between three groups (p=0.04 and χ²=9.38, p=0.01, respectively). Significant reverse correlation (Spearman R= -0.43, p=0.007) was found between GSLP amount and MMSE scores for MCI+AD group, i.e., the lower MMSE scores, the higher platelet GSLP level. Platelet COX and GSLP may be considered as early markers of cognitive impairment.

  2. Platelets

    Science.gov (United States)

    ... tiny fraction of the blood volume. The principal function of platelets is to prevent bleeding. Red blood cells are ... forming a long string. This illustrates the basic function of platelets, to stick to any foreign surface and then ...

  3. Potential Participation of calpain in platelet activation studied by use of a cell penetrating calpain inhibitor (Calpeptin)

    Energy Technology Data Exchange (ETDEWEB)

    Tsujinaka, Toshimasa; Ariyoshi, Hideo; Uemura, Yoshio; Sakon, Masato; Kambayashi, Junichi; Mori, Takesada (Osaka Univ. Medical School, Fukushima (Japan))

    1990-01-01

    Employing a cell penetrating calpain inhibitor (calpeptin), the role of calpain in platelet activation was examined. In washed platelets (WPs) both thrombin and collagen-induced platelet aggregation were dose-dependently inhibited by calpeptin. The addition of plasma to WPs interfered with the action of calpeptin, however more than 3 min preincubation of calpeptin with WPs completely abolished the influence of plasma. In thrombin-activated WPs with calcium, the increase of intracellular calcium concentration, (Ca{sup 2+})i, and the production of inositol triphosphate (IP{sub 3}) were dose-dependently inhibited by calpeptin. The generation of thromboxane B{sub 2} (TxB{sub 2}) was inhibited by calpeptin in collagen and thrombin-activated WPs. In ({sub 3}H)-arachidonic acid (AA)-labelled platelets, calpeptin increased the amount of ({sup 3}H)-AA liberated by inhibiting ({sup 3}H)-AA degradation after collagen or thrombin stimulation. When ({sup 14}C)-AA degradation by the platelet suspension was observed, calpeptin inhibited TxB{sub 2} and hydroxyheptadecatrienoic acid (HHT) generation but increased prostaglandin (PG) E{sub 1}, E{sub 2}, 12-hydroxyeicosatetraenoic acid (12HETE) and AA. Based on these findings, calpain may be involved in the activation phospholipase C and thromboxane synthetase.

  4. [Anti-synthetase syndrome].

    Science.gov (United States)

    Novak, Srdan

    2012-01-01

    Antysynthetase syndrome is considered as a group ofidiopathic inflammatory myositis with charcteristic serologic hallmark--antibodies which recognise the aminoacyl-tRNA synthetasses (ARS). Clinical picture of those patients contains myositis and/or intersticial lung disease (ILD) and/or arthritis and/or fever and/or Raynaud phenomenon and sometimes characteristic look of mechanic's hands. Myositis can be overt, sometimes even absent, while IBP is major cause of morbidity and determines the outcome of the disease. Untill now eight different any-synthetase autoantibodies are recognised, and most frequent are findings of anti-histidyl-tRNa synthetase antibodies. Patients with other ARS autoantibodies usually have severe ILD. Drug of choice are steroids in dosage of 1 mg/kg with immunosupresive agent (azatioprin or methotrexate) while in severe IBP cyclophosphamide is needed. Recently succsesful treatment with rituximab in combination with cyclophosphamide is reported.

  5. Genetics Home Reference: glutathione synthetase deficiency

    Science.gov (United States)

    ... Facebook Twitter Home Health Conditions glutathione synthetase deficiency glutathione synthetase deficiency Enable Javascript to view the expand/ ... boxes. Download PDF Open All Close All Description Glutathione synthetase deficiency is a disorder that prevents the ...

  6. 前列腺素E2(PG-E2)、白三烯B4(LT-B4)、血小板活化因子(PAF)及血管内皮生长因子(VEGF)在溃疡性结肠炎中的意义%Prostaglandin E2 (PG - E2), leukotriene B4 (LT - B4), platelet activating factor (PAF) and vascular endothelial growth factor (VEGF) in ulcerative colitis

    Institute of Scientific and Technical Information of China (English)

    何山; 刘梅; 赵亚玲; 熊晶晶; 丁臻博; 黄永坤

    2014-01-01

    the pathogenesis of ulcerative colitis is not clear so far, the diagnosis and treatment of ulcerative colitis, both at home and abroad ,are mainly concentrated in the immune, environmental, genetic, infection and so on many aspects, especially in immune factors, is a research focus.But because in the process of the pathogenesis of ulcerative colitis, inflammatory factors involved in more, so what inflammatory factor plays a key role, there is still no conclusion.According to a series of studies about Ulcerative colitis(Uc) at home and abroad in recent years, selecting high expressed in Uc which closely associated with Uc pathogenesis and disease severity, but the research still is not perfected of four kinds of inflammatory mediators: prostaglandin e2 (PG - e2), leukotriene B4 (lt - B4), platelet activating factor (Paf) and vascular endothelial growth factor (VeGf) were summarized.%溃疡性结肠炎的发病机理,迄今为止尚不清楚,国内外目前对溃疡性结肠炎的诊治,主要集中在免疫、环境、遗传、感染等诸多方面,尤其在免疫因素方面。然而由于在溃疡性结肠炎的发病过程中,参与的炎性因子较多,故究竟哪些炎性因子起到较为关键的作用,目前仍没有定论。本文主要针对近年来,溃疡性结肠炎的国内外研究,选取在Uc 中表达较高,与 Uc 发病及病情严重程度密切相关,但研究尚不完善的四种炎性介质:前列腺素 e2(PG-e2)、白三烯 B4(lt-B4)、血小板活化因子(Paf)及血管内皮生长因子(VeGf)进行综述。

  7. Preparation of Conductive Polymer Graphite (PG) Composites

    Science.gov (United States)

    Munirah Abdullah, Nur; Saddam Kamarudin, M.; Rus, Anika Zafiah M.; Abdullah, M. F. L.

    2017-08-01

    The preparation of conductive polymer graphite (PG) composites thin film is described. The thickness of the PG composites due to slip casting method was set approximately ~0.1 mm. The optical microscope (OM) and fourier transform infra-red spectroscopy (FTIR) has been operated to distinguish the structure-property relationships scheme of PG composites. It shows that the graphite is homogenously dispersed in polymer matrix composites. The electrical characteristics of the PG composite were measured at room temperature and the electrical conductivity (σ) was discovered with respect of its resistivity (Ω). By achieving conductivity of 103 S/m, it is proven that at certain graphite weight loading (PG20, PG25 and PG30) attributes to electron pathway in PG composites.

  8. Interaction of platelets with collagen substrate: role of platelet prostaglandin endoperoxides and thromboxane A/sub 2/

    Energy Technology Data Exchange (ETDEWEB)

    Mazurov, A.B.; Leitin, V.L.; Repin, V.S.

    1985-04-01

    In this investigation, the role of PG-endoperoxides and TA/sub 2/ in interaction of platelets and a collagen-coated surface was studied. For this purpose, the effects of exogenous AA, of U46619, a stable analog of PG endoperoxides, which simulates the action of PG endoperoxides and TA/sub 2/ on platelets at the receptor level, and of aspirin, a cyclooxygenase inhibitor, on platelet-surface interaction were investigated. The quantity of TA/sub 2/ synthesized in the platelets was determined by measuring accumulation of its stable product TB/sub 2/. After adhesion of the platelets the incubation medium was removed, nonadherent platelets were destroyed by freezing and thawing, and TB/sub 2/ was determined by radioimmunoassay.

  9. Platelet mimicry

    DEFF Research Database (Denmark)

    Moghimi, Seyed Moein; Hunter, Alan Christy; Peer, Dan

    2016-01-01

    Here we critically examine whether coating of nanoparticles with platelet membranes can truly disguise them against recognition by elements of the innate immune system. We further assess whether the "cloaking technology" can sufficiently equip nanoparticles with platelet-mimicking functionalities...

  10. Platelet Count

    Science.gov (United States)

    ... their spleen removed surgically Use of birth control pills (oral contraceptives) Some conditions may cause a temporary (transitory) increased ... increased platelet counts include estrogen and birth control pills (oral contraceptives). Mildly decreased platelet counts may be seen in ...

  11. Platelet activation patterns in platelet size sub-populations: differential responses to aspirin in vitro.

    Science.gov (United States)

    Mangalpally, Kiran Kumar R; Siqueiros-Garcia, Alan; Vaduganathan, Muthiah; Dong, Jing-Fei; Kleiman, Neal S; Guthikonda, Sasidhar

    2010-10-01

    Circulating platelets are heterogeneous in size and structure. Whether this translates into differences in platelet function and efficacy of antiplatelet therapy is unclear. Hence, we decided to investigate the activation patterns among different platelet populations differentiated by size, and to compare the inhibitory effects of aspirin in these populations. Circulating platelets from 9 healthy volunteers were separated by size and stratified into the largest and smallest quintiles. Platelets were stimulated with 75 μM arachidonic acid (AA), 10 μM ADP or 25 μM TRAP. Alpha-granule protein secretion and expression (P-selectin, VWF, fibrinogen), surface-protein activation (activated integrin αIIbβ3) were assessed. Platelet thromboxane B(2) (TxB(2)) synthesis following AA stimulation was measured in vitro before and after incubation with 265 μM aspirin. Reticulated (juvenile) platelets were assessed using thiazole orange staining. A greater number of large platelets in the largest quintile were reticulated compared with the smallest quintile (6.1 ± 2.8% vs. 1.2 ± 1.5% respectively, p aspirin (1029 ± 190 pg/mL vs. 851 ± 159 pg/mL, respectively, p = 0.03). After stimulation with each agonist, a greater proportion of large platelets bound fibrinogen, VWF, P-selectin and activated integrin αIIbβ3 than small platelets both in the presence and in the absence of in vitro aspirin. In an in vitro setting, large platelets appear to be more active than small platelets and continue to be more active even after in vitro aspirin. Platelets exhibit heterogeneity in size and structure. Whether this translates into platelet function and efficacy of antiplatelet therapy is unclear. We evaluated platelet functional properties and the effects of aspirin on separated platelet subpopulations in an in vitro setting. Platelets were sorted into the largest and smallest size quintiles using flow cytometry forward scatter. Alpha-granule protein release, dense granule content

  12. Platelet proteomics.

    Science.gov (United States)

    Zufferey, Anne; Fontana, Pierre; Reny, Jean-Luc; Nolli, Severine; Sanchez, Jean-Charles

    2012-01-01

    Platelets are small cell fragments, produced by megakaryocytes, in the bone marrow. They play an important role in hemostasis and diverse thrombotic disorders. They are therefore primary targets of antithrombotic therapies. They are implicated in several pathophysiological pathways, such as inflammation or wound repair. In blood circulation, platelets are activated by several pathways including subendothelial matrix and thrombin, triggering the formation of the platelet plug. Studying their proteome is a powerful approach to understand their biology and function. However, particular attention must be paid to different experimental parameters, such as platelet quality and purity. Several technologies are involved during the platelet proteome processing, yielding information on protein identification, characterization, localization, and quantification. Recent technical improvements in proteomics combined with inter-disciplinary strategies, such as metabolomic, transcriptomics, and bioinformatics, will help to understand platelets biological mechanisms. Therefore, a comprehensive analysis of the platelet proteome under different environmental conditions may contribute to elucidate complex processes relevant to platelet function regarding bleeding disorders or platelet hyperreactivity and identify new targets for antiplatelet therapy.

  13. Platelet lipidomic.

    Science.gov (United States)

    Dolegowska, B; Lubkowska, A; De Girolamo, L

    2012-01-01

    Lipids account for 16-19 percent dry platelet matter and includes 65 percent phospholipids, 25 percent neutral lipids and about 8 percent glycosphingolipids. The cell membrane that surrounds platelets is a bilayer that contains different types phospholipids symmetrically distributed in resting platelets, such as phosphatidylserine (PS), phosphatidylethanolamine (PE), phosphatidylcholine, and sphingomyelin. The collapse of lipid asymmetry is exposure of phosphatidylserine in the external leaflet of the plasma bilayer, where it is known to serve at least two major functions: providing a platform for development of the blood coagulation cascade and presenting the signal that induces phagocytosis of apoptotic cells. During activation, this asymmetrical distribution becomes disrupted, and PS and PE become exposed on the cell surface. The transbilayer movement of phosphatidylserine is responsible for the platelet procoagulant activity. Exposure of phosphatidylserine is a flag for macrophage recognition and clearance from the circulation. Platelets, stored at room temperature for transfusion for more than 5 days, undergo changes collectively known as platelet storage lesions. Thus, the platelet lipid composition and its possible modifications over time are crucial for efficacy of platelet rich plasma therapy. Moreover, a number of substances derived from lipids are contained into platelets. Eicosanoids are lipid signaling mediators generated by the action of lipoxygenase and include prostaglandins, thromboxane A2, 12-hydroxyeicosatetraenoic acid. Isoprostanes have a chemical structure similar to this of prostanoids, but are differently produced into the particle, and are ligands for prostaglandins receptors, exhibiting biological activity like thromboxane A2. Endocannabinoids are derivatives from arachidonic acid which could reduce local pain. Phospholipids growth factors (sphingolipids, lysophosphatidic acid, platelet-activating factor) are involved in tissue

  14. Discovery of Iron in PG1159 Stars

    CERN Document Server

    Werner, K; Kruk, J W

    2010-01-01

    The lack of FeVII lines in PG1159 stars had led to the conclusion that in some objects iron must be strongly depleted. We have now detected FeX lines in FUSE spectra of the very hottest PG1159 stars Teff=150,000 - 200,000 K; RXJ2117.1+3412, K1-16, NGC 246, Longmore 4). Surprisingly, we derive a solar iron abundance. It is conspicuous that they are among the most massive PG1159 stars (0.71-0.82 Msun), in contrast to those objects for which strongest Fe-deficiency was claimed (0.53-0.56 Msun). Based on new FeVIII line identifications in SOHO/SUMER UV spectra of the Sun, we were able to detect these lines in FUSE spectra of several "cooler" (Teff<150,000 K) objects, among them is the prototype PG1159-035. An abundance analysis is in progress.

  15. Acquired platelet function defect

    Science.gov (United States)

    Acquired qualitative platelet disorders; Acquired disorders of platelet function ... blood clotting. Disorders that can cause problems in platelet function include: Idiopathic thrombocytopenic purpura Chronic myelogenous leukemia Multiple ...

  16. Platelet Donation

    Science.gov (United States)

    ... of gratitude that washed over me when I saw those platelets going into my husband’s body. I ... Needles LGBTQ+ Donors Blood Donor Community SleevesUp Games Facebook Avatars and Badges Banners eCards Red Cross Information ...

  17. Distribution of glutamine synthetase and carbamoyl-phosphate synthetase I in vertebrate liver.

    OpenAIRE

    Smith, D. D.; Campbell, J. W.

    1988-01-01

    Mitochondrial glutamine synthetase (EC 6.3.1.2) is the primary ammonia-detoxifying enzyme in avian liver and is therefore analogous in function to carbamoyl-phosphate synthetase I (ammonia) (EC 6.3.4.16) in mammalian liver. In mammalian liver, glutamine synthetase is cytosolic and its distribution is restricted to a few hepatocytes around the terminal venules. These cells do not express carbamoyl-phosphate synthetase I. Using immunocytochemistry, we show here that there is little or no zonati...

  18. 46 CFR 52.01-140 - Certification by stamping (modifies PG-104 through PG-113).

    Science.gov (United States)

    2010-10-01

    ... appropriate ASME Code symbol as required by PG-104 through PG-113 of section I of the ASME Boiler and Pressure... and serial number; (ii) ASME Code Symbol; (iii) Coast Guard symbol, which is affixed only by marine... boilers which are built to section I of section I of the ASME Boiler and Pressure Vessel...

  19. 46 CFR 52.01-90 - Materials (modifies PG-5 through PG-13).

    Science.gov (United States)

    2010-10-01

    ... PG-13 of section I of the ASME Boiler and Pressure Vessel Code (incorporated by reference; see 46 CFR 52.01-1) except as noted otherwise in this section. (b) Material not fully identified with an ASME... requirements providing it satisfies the conditions indicated in paragraph PG-10 of section I of the ASME...

  20. P.G. Lindhardt 1910-2010

    DEFF Research Database (Denmark)

    Bach-Nielsen, Carsten

    Om kirkehistorikeren P.G. Lindhardt (1910-1989), der var blandt de tidligst ansatte professorer i teologi i ved Aarhus Universitet. Her ansattes han i 1942. Bogen rummer bidrag om Lindhardt so kirkehistoriker, debattør og prædikant....

  1. Platelet gel for healing cutaneous chronic wounds.

    Science.gov (United States)

    Crovetti, Giovanni; Martinelli, Giovanna; Issi, Marwan; Barone, Marilde; Guizzardi, Marco; Campanati, Barbara; Moroni, Marco; Carabelli, Angelo

    2004-04-01

    Wound healing is a specific host immune response for restoration of tissue integrity. Experimental studies demonstrated an alteration of growth factors activity due to their reduced synthesis, increased degradation and inactivation. In wound healing platelets play an essential role since they are rich of alpha-granules growth factors (platelet derived growth factor--PDGF; transforming growth factor-beta--TGF-beta; vascular endothelial growth factor--VEGF). Topical use of platelet gel (PG), hemocomponent obtained from mix of activated platelets and cryoprecipitate, gives the exogenous and in situ adding of growth factors (GF). The hemocomponents are of autologous or homologous origin. We performed a technique based on: multicomponent apheretic procedure to obtain plasma rich platelet and cryoprecipitate; manual processing in an open system, in sterile environment, for gel activation. Every step of the gel synthesis was checked by a quality control programme. The therapeutic protocol consists of the once-weekly application of PG. Progressive reduction of the wound size, granulation tissue forming, wound bed detersion, regression and absence of infective processes were considered for evaluating clinical response to hemotherapy. 24 patients were enrolled. They had single or multiple cutaneous ulcers with different ethiopathogenesis. Only 3 patients could perform autologous withdrawal; in the others homologous hemocomponent were used, always considering suitability and traceability criteria for transfusional use of blood. Complete response was observed in 9 patients, 2 were subjected to cutaneous graft, 4 stopped treatment, 9 had partial response and are still receiving the treatment. In each case granulation tissue forming increased following to the first PG applications, while complete re-epithelization was obtained later. Pain was reduced in every treated patient. Topical haemotherapy with PG may be considered as an adjuvant treatment of a multidisciplinary process

  2. Streptomyces hygroscopicus Has Two Glutamine Synthetase Genes

    NARCIS (Netherlands)

    Kumada, Y.; Takano, E.; Nagaoka, Kozo; Thompson, C.J.

    1990-01-01

    Streptomyces hygroscopicus, which produces the glutamine synthetase inhibitor phosphinothricin, possesses at least two genes (glnA and glnB) encoding distinct glutamine synthetase isoforms (GSI and GSII). The glnB gene was cloned from S. hygroscopicus DNA by complementation in an Escherichia coli gl

  3. Treatment of chronic venous leg ulcers by platelet gel.

    Science.gov (United States)

    Ficarelli, Elena; Bernuzzi, Gino; Tognetti, Elena; Bussolati, Ovidio; Zucchi, Alfredo; Adorni, Daniela; De Panfilis, Giuseppe

    2008-07-01

    Chronic venous leg ulcers (CVLU) are chronic wounds, associated with long-standing venous hypertension, which have a poor prognosis for healing. In the process of wound healing the first step is represented by platelet aggregation and subsequent release of growth factors and other mediators, which play a key role in the repair response. Platelet gel (PG), a hemocomponent obtained by mixing platelets, thrombin, and calcium, is able, when applied topically, to release platelet mediators that likely favor CVLU healing. However, unstandardized protocols have been described in studies utilizing PG for the regeneration of a number of tissues, including CVLU; the relative clinical outcomes were hence highly variable. In our experience the topical use of PG, together with the strict adherence to the principles of good wound care, quickly promoted increased granulation tissue, followed by a complete CVLU epithelization. Although further studies and trials are needed to establish the major outcome affecting rules for optimal indications, preparation, and use of PG for CVLU treatment, PG can be undoubtedly considered a useful tool, able to improve the management of CVLU.

  4. Expression of Angiogenesis Regulatory Proteins and Epithelial-Mesenchymal Transition Factors in Platelets of the Breast Cancer Patients

    Directory of Open Access Journals (Sweden)

    Hui Han

    2014-01-01

    Full Text Available Platelets play a role in tumor angiogenesis and growth and are the main transporters of several angiogenesis regulators. Here, we aimed to determine the levels of angiogenesis regulators and epithelial-mesenchymal transition factors sequestered by circulating platelets in breast cancer patients and age-matched healthy controls. Platelet pellets (PP and platelet-poor plasma (PPP were collected by routine protocols. Vascular endothelial growth factor (VEGF, platelet-derived growth factor BB (PDGF-BB, thrombospondin-1 (TSP-1, platelet factor 4 (PF4, and transforming growth factor-β1 (TGF-β1 were measured by enzyme-linked immunosorbent assay. Angiogenesis-associated expression of VEGF (2.1 pg/106 platelets versus 0.9 pg/106 platelets, P < 0.001, PF4 (21.2 ng/106 platelets versus 10.2 ng/106 platelets, P < 0.001, PDGF-BB (42.9 pg/106 platelets versus 19.1 pg/106 platelets, P < 0.001, and TGF-β1 (15.3 ng/106 platelets versus 4.3 ng/106 platelets, P < 0.001 differed in the PP samples of cancer and control subjects. In addition, protein concentrations were associated with clinical characteristics (P<0.05. Circulating platelets in breast cancer sequester higher levels of PF4, VEGF, PDGF-BB, and TGF-β1, suggesting a possible target for early diagnosis. VEGF, PDGF, and TGF-β1 concentrations in platelets may be associated with prognosis.

  5. PG 1325+101 and PG 2303+019: Two new large amplitude subdwarf B pulsators

    Science.gov (United States)

    Silvotti, R.; Østensen, R.; Heber, U.; Solheim, J.-E.; Dreizler, S.; Altmann, M.

    2002-01-01

    We report the detection of short period oscillations in the sdB stars PG 1325+101 (B=13.8) and PG 2303+019 (alias HS 2303+0152, B=16.0) from time-series photometry made at the Nordic Optical Telescope of a sample of 21 candidates. Both stars are multi-mode pulsators with at least three distinct periods in the range 100-140 s, and relatively large amplitudes up to 2.6 and 1.6% respectively. Moreover PG 1325+101 shows the shortest pulsation period ever registered among sdBV stars, 68.9 s, which corresponds to the first harmonic of the main signal. Following previous temperature and gravity determinations for PG 1325+101 (Teff = 34 500 K, log g=6.1) and our NLTE model atmosphere analysis for PG 2303+019 (Teff = 35 200 K, log g=5.7), both stars are well inside the theoretical sdBV instability strip. Based on observations obtained at the Nordic Optical Telescope, operated on the island of La Palma jointly by Denmark, Finland, Iceland, Norway, and Sweden, in the Spanish Observatorio del Roque de los Muchachos of the Instituto de Astrofisica de Canarias; and at the German-Spanish Astronomical Center, Calar Alto, operated by the Max-Plank-Institute für Astronomie Heidelberg jointly with the Spanish National Commission for Astronomy.

  6. Cytosolic glutamine synthetase in barley

    DEFF Research Database (Denmark)

    Thomsen, Hanne Cecilie

    Improving crop nitrogen (N) utilization efficiency (NUE) is of major importance in modern agriculture in order to reduce the amount of N fertilizer used for crop production. There is a high demand for development of crops which are able to produce high yields but with a concomitantly lower N...... fertilizer requirement. The enzyme glutamine synthetase (GS) has been a major topic in plant nitrogen research for decades due to its central role in plant N metabolism. The cytosolic version of this enzyme (GS1) plays an important role in relation to primary N assimilation as well as in relation to N...... and wildtype control. However, when grown to maturity the differences between transgenic lines and wildtype were highly dependent on the growth conditions applied. The transgenic lines had a higher N utilization efficiency (NUtE) than wildtype control, but only when exposed to a mild N stress following...

  7. Platelet Function Tests

    Science.gov (United States)

    ... be limited. Home Visit Global Sites Search Help? Platelet Function Tests Share this page: Was this page helpful? ... their patients by ordering one or more platelet function tests. Platelet function testing may include one or more of ...

  8. Congenital platelet function defects

    Science.gov (United States)

    ... storage pool disorder; Glanzmann's thrombasthenia; Bernard-Soulier syndrome; Platelet function defects - congenital ... Congenital platelet function defects are bleeding disorders that ... function, even though there are normal platelet numbers. Most ...

  9. Seismological constraints on the high-gravity DOV stars PG2131+066 and PG 1707+427

    CERN Document Server

    Córsico, A H; Bertolami, M M Miller; Garc'\\ia--Berro, E

    2009-01-01

    A seismological study of the pulsating PG1159 stars PG2131+066 and PG 1707+427 is presented. We perform extensive adiabatic computations of g-mode pulsation periods of PG1159 evolutionary models with stellar masses ranging from 0.530 to 0.741 Msun. We constrain the stellar mass of PG2131+066 and PG 1707+427 by comparing the observed period spacing of each star with the theoretical asymptotic period spacings and with the average of the computed period spacings. We also employ the individual observed periods to find representative seismological models for both stars.

  10. Genetics Home Reference: phosphoribosylpyrophosphate synthetase superactivity

    Science.gov (United States)

    ... synthetase superactivity ( PRS superactivity ) is characterized by the overproduction and accumulation of uric acid (a waste product ... chemical processes) in the blood and urine. The overproduction of uric acid can lead to gout, which ...

  11. Iron Abundance in the Prototype PG 1159 Star, GW Vir Pulsator PG 1159-035, and Related Objects

    Science.gov (United States)

    Werner, K.; Rauch, T.; Kruk, J. W.; Kurucz, R. L.

    2011-01-01

    We performed an iron abundance determination of the hot, hydrogen deficient post-AGB star PG 1159-035. which is the prototype of the PG 1159 spectral class and the GW Vir pulsators, and of two related objects (PG 1520+525, PG 1144+005), based on the first detection of Fe VIII lines in stellar photospheres. In another PG 1159 star. PG 1424+535. we detect Fe VII lines. In all four stars, each within T(sub eff) = 110,000-150,000 K, we find a solar iron abundance. This result agrees with our recent abundance analysis of the hottest PG 1159 stars (T(sub eff) = 150,000-200,000 K) that exhibit Fe x lines. On the whole, we find that the PG 1159 stars are not significantly iron deficient, in contrast to previous notions.

  12. Iron abundance in the prototype PG1159 star, GW Vir pulsator PG1159-035, and related objects

    CERN Document Server

    Werner, Klaus; Kruk, Jeff W; Kurucz, Robert L

    2011-01-01

    We performed an iron abundance determination of the hot, hydrogen deficient post-AGB star PG1159-035, which is the prototype of the PG1159 spectral class and the GW Vir pulsators, and of two related objects (PG1520+525, PG1144+005), based on the first detection of Fe VIII lines in stellar photospheres. In another PG1159 star, PG1424+535, we detect Fe VII lines. In all four stars, each within Teff = 110,000 - 150,000 K, we find a solar iron abundance. This result agrees with our recent abundance analysis of the hottest PG1159 stars (Teff = 150,000 - 200,000 K) that exhibit Fe X lines. On the whole, we find that the PG1159 stars are not significantly iron deficient, in contrast to previous notions.

  13. A Characterisation of Tangent Subplanes of PG(2,q^3)

    CERN Document Server

    Barwick, S G

    2012-01-01

    In: S.G. Barwick and W.A. Jackson. Sublines and subplanes of PG(2,q^3) in the Bruck--Bose representation in PG(6,q). Finite Fields Th. App. 18 (2012) 93--107., the authors determine the representation of order-q-subplanes and order-q-sublines of PG(2,q^3) in the Bruck-Bose representation in PG(6,q). In particular, they showed that an order-q-subplane of PG(2,q^3) corresponds to a certain ruled surface in PG(6,q). In this article we show that the converse holds, namely that any ruled surface satisfying the required properties corresponds to a tangent order-q-subplane of PG(2,q^3).

  14. Time-resolved FUSE Photometric and Spectroscopic Observations: PG1219+534, PG1605+072, and PG1613+426

    CERN Document Server

    Kuassivi; Ferlet, R

    2005-01-01

    We report on the detection of pulsations in the far ultraviolet (hereafter FUV) light curves of PG1219+534, PG1605+072, and PG1613+426 obtained with the Far Ultraviolet Spectroscopic Explorer (FUSE) in time-tagged mode (TTAG). Exposures of the order of a few Ksecs were sufficient to observe the main frequencies of PG1219+534 and PG1605+072 and confirm the detection of a pulsation mode at the surface of PG1613+426 as reported from ground. For the first time we derive time-resolved spectroscopic FUSE data of a sdB pulsator (PG1605+072) and comment its line profile variation diagram (hereafter lpv diagram). We observe the phase shift between the maximum luminosity and the maximum radius to be consistent with the model of an adiabatic pulsator. We also present evidence that the line broadening previously reported is not caused by rotation but is rather an observational bias due to the rapid Doppler shift of the lines with 17 km.s-1 amplitude. Thus our observations do not support the previous claim that PG1605+072...

  15. Platelet matching for alloimmunized patients

    Institute of Scientific and Technical Information of China (English)

    S H.Hsu

    2010-01-01

    @@ Platelets play an essential role in blood coagulation,hemostasis and maintenance of vascular integrity.Platelets are utilized primarily to prevent or treat bleeding in thrombocytopenic patients and patients with impaired platelet production in the bone marrow and/or with dysfunctional platelets.In current practice,platelet transfusion begins with randomly selected platelet products:either pooled platelets prepared from whole blood derived platelets; or single donor platelets prepared by apheresis procedures.

  16. Reverberation mapping of PG 0934+013

    Science.gov (United States)

    Park, Songyoun; Woo, Jong-Hak; Romero-colmenero, Encarni; Crawford, Steve; Jeon, Yiseul

    2017-01-01

    We present the variability and time lag measurements of PG 0934+013 based on the photometric and spectroscopic monitoring campaign. We obtained 46 epochs of data from the spectroscopic campaign, which was carried out using the Southern African Large Telescope with ˜1 week cadence over two sets of 4 month-long observing period. We also obtained 80 epochs of B-band imaging data using the 2-m Faulkes Telescope North and South of the Las Cumbres Observatory Global Telescope Network and the 1-m telescope at the Mt. Lemon Optical Astronomy Observatory. Due to the seven month gap between the two periods, we separately measured the time lag of the Hβ emission line by comparing the emission line light curve with the B-band continuum light curve using the cross-correlation function techniques. We determined the time lag of 8.5 ± 2.0 days for Year 2, while the time lag for Year 1 was not constrained. We discuss the estimated black hole mass and the kinematics of broad line region gas based on velocity resolved measurements.

  17. The antiplatelet activity of Geiji-Bokryung-Hwan, Korean traditional formulation, is mediated through inhibition of phospholipase C and inhibition of TxB(2) synthetase activity.

    Science.gov (United States)

    Park, Won-Hwan; Kim, Kyoung-Sook; Kim, Kyung-Ho; Kim, Dong-Soo; Kim, Cheorl-Ho

    2003-07-01

    Geiji-Bokryung-Hwan (GBH), consisting of herbes of Cinnamomi ramulus (Geiji), Poria cocos (Bokryun), Mountan cortex radicis (Mokdanpi), Paeoniae radix (Jakyak), and Persicae semen (Doin), on antiplatelet activity in human platelet suspensions was studied. The mechanism involved in the antiplatelet activity of GBH in human platelet suspensions was investigated. GBH did not significantly affect the thromboxane synthetase activity of aspirin-treated platelet microsomes and GBH (15 and 30 microg/ml) significantly inhibited [3H]arachidonic acid released in collagen-activated platelets but not in unactivated-platelets. Nitric oxide (NO) production in human platelets was measured by a chemiluminesence detection method in this study. GBH did not significantly affect nitrate production in collagen (10 microg/ml)-induced human platelet aggregation. Various concentrations of GBH (0, 5, 10, 15, and 30 microg/ml) dose-dependently inhibited [3H]inositol monophosphate formation stimulated by collagen (10 microg/ml) in [3H]myoinositol-loaded platelets at different incubation times (1, 2, 3, and 5 min). These results indicated that the antiplatelet activity of GBH may possibly be due to the inhibition of phospholipase C (PLC) activity, leading to reduce phosphoinositide breakdown, followed by the inhibition of thromboxane A(2) formation, and then inhibition of [Ca(2+)](i) mobilization of platelet aggregation stimulated by agonists. In conclusion, GBH suppressed PLC in a dose-dependent manner, and may have pharmaceutical applications. These data suggest that GBH extracts merit investigation as a potential anti-atherosclerogenic agent in humans.

  18. Substrate specificity of hybrid modules from peptide synthetases

    NARCIS (Netherlands)

    Elsner, A; Engert, H; Saenger, W; Hamoen, L; Venema, G; Bernhard, F

    1997-01-01

    Homologous modules from two different peptide synthetases were analyzed for functionally equivalent regions. Hybrids between the coding regions of the phenylalanine-activating module of tyrocidine synthetase and the valine activating module of surfactin synthetase were constructed by combining the t

  19. Policies, standards and managements associated with PG utilization

    Science.gov (United States)

    Chuan, L. M.; Zheng, H. G.; Zhao, J. J.; Wang, A. L.; Sun, S. F.

    2017-08-01

    With rapid growth in the production of high concentration phosphate and compound fertilizers in China, PG production is increasing every year. However, its utilization is not increasing at the same pace. Phosphogypsum is usually stored in such a way that not only it occupies lot of land, but also leads to minimal environmental pollution. This paper summarized the policies, standards and managements issues associated with PG utilization, and in order to help the PG utilization and management effectively.

  20. Deicing/Propylene Glycol (PG) Microbial Remediation Technology

    Science.gov (United States)

    2011-05-01

    Deicing /Propylene Glycol (PG) Microbial Remediation Technology Environment, Energy Security, & Sustainability (E2S2) Symposium & Exhibition Ernest N...DATES COVERED 00-00-2011 to 00-00-2011 4. TITLE AND SUBTITLE Deicing /Propylene Glycol (PG) Microbial Remediation Technology 5a. CONTRACT...Issues C. PG Remediation Project D. Summary E. Questions 2 3 Background • Aircraft deicing fluids (ADF) work planes fly in the winter o Military

  1. Clinical application of radiolabelled platelets

    Energy Technology Data Exchange (ETDEWEB)

    Kessler, C. (Medical Univ. Lubeck, Lubeck (DE))

    1990-01-01

    This book presents papers on the clinical applications of radiolabelled platelets. The papers are grouped into six sections on platelet labelling techniques, radiolabelled platelets in cardiology, monitoring of antiplatelet therapy, platelet scintigraphy in stroke patients, platelet scintigraphy in angiology, and platelet scintigraphy in hematology and other clinical applications, including renal transplant rejection.

  2. Search For Iron, Nickel, and Fluorine in PG1159 Stars

    CERN Document Server

    Reiff, E; Werner, K; Kruk, J W; Koesterke, L

    2008-01-01

    A possible origin of the iron-deficiency in PG1159 stars could be neutron captures on Fe nuclei. A nickel overabundance would corroborate this idea. Consequently we are looking for nickel lines in PG1159 stars. Prime targets are relatively cool objects, because Ni VI is the dominant ionisation stage and the spectral lines of this ion are accessible with UV observations. We do not find such lines in the coolest PG1159 star observed by FUSE (PG1707+427, Teff = 85,000 K) and conclude that the nickel abundance is not enhanced. Hence, the Fe-deficiency in PG1159 stars remains unexplained. In addition, we present results of a wind analysis of the hybrid-PG1159 star NGC 7094 and the [WC]-PG1159 transition-type object Abell 78 in order to derive F abundances from the F VI 1139.5 Angstrom line. In both cases, we find F overabundances, in agreement with results of photospheric analyses of many PG1159 stars. Surprisingly, we find indications for a very low O abundance in NGC 7094.

  3. Platelets and hemostasis

    Directory of Open Access Journals (Sweden)

    M. A. Panteleev

    2014-09-01

    Full Text Available Platelets are anuclear cell fragments playing important role in hemostasis, termination of bleeding after damage, as well as in pathological thrombus formation. The main action of platelets is the formation of aggregates, overlapping the injury. They obtained the ability to aggregate by the transition process called activation. Despite the relatively simple and definite function platelet structure is very difficult: they have almost a full set of organelles, including the endoplasmic reticulum, mitochondria and other entities. When activated platelets secrete various granules interact with plasma proteins and red blood cells and other tissues. Their activation is controlled by multiple receptors and complex signaling cascades. In this review platelet structure, mechanisms of its functioning in health and disease, diagnostic methods of platelet function and approaches to their correction were considered. Particular attention will be given to those areas of the science of platelets, which still lay hidden mysteries.

  4. Dexamethasone regulates glutamine synthetase expression in rat skeletal muscles

    Science.gov (United States)

    Max, Stephen R.; Konagaya, Masaaki; Konagaya, Yoko; Thomas, John W.; Banner, Carl; Vitkovic, Ljubisa

    1986-01-01

    The regulation of glutamine synthetase by glucocorticoids in rat skeletal muscles was studied. Administration of dexamethasone strikingly enhanced glutamine synthetase activity in plantaris and soleus muscles. The dexamethasone-mediated induction of glutamine synthetase activity was blocked to a significant extent by orally administered RU38486, a glucocorticoid antagonist, indicating the involvement of intracellular glucocorticoid receptors in the induction. Northern blot analysis revealed that dexamethasone-mediated enhancement of glutamine synthetase activity involves dramatically increased levels of glutamine synthetase mRNA. The induction of glutamine synthetase was selective in that glutaminase activity of soleus and plantaris muscles was not increased by dexamethasone. Furthermore, dexamethasone treatment resulted in only a small increase in glutamine synthetase activity in the heart. Accordingly, there was only a slight change in glutamine synthetase mRNA level in this tissue. Thus, glucocorticoids regulate glutamine synthetase gene expression in rat muscles at the transcriptional level via interaction with intracellular glutamine production by muscle and to mechanisms underlying glucocorticoid-induced muscle atrophy.

  5. No positive effect of autologous platelet gel after total knee arthroplasty A double-blind randomized controlled trial: 102 patients with a 3-month follow-up

    NARCIS (Netherlands)

    Peerbooms, J.C.; de Wolf, G.S.; Colaris, J.W.; Bruijn, D.J.; Verhaar, J.A.N.

    2009-01-01

    Background and purpose Activated platelets release a cocktail of growth factors, some of which are thought to stimulate repair. We investigated whether the use of autologous platelet gel (PG) in total knee arthroplasty (TKA) would improve wound healing and knee function, and reduce blood loss and th

  6. No positive effect of autologous platelet gel after total knee arthroplasty: A double-blind randomized controlled trial: 102 patients with a 3-month follow-up

    NARCIS (Netherlands)

    J.C. Peerbooms (Joost); G.S. de Wolf (Gideon); J.W. Colaris (Joost); D.J. Bruijn (Danil); J.A.N. Verhaar (Jan)

    2009-01-01

    textabstractBackground and purpose Activated platelets release a cocktail of growth factors, some of which are thought to stimulate repair. We investigated whether the use of autologous platelet gel (PG) in total knee arthroplasty (TKA) would improve wound healing and knee function, and reduce blood

  7. Platelet alloimmunization after transfusion

    DEFF Research Database (Denmark)

    Taaning, E; Simonsen, A C; Hjelms, E;

    1997-01-01

    BACKGROUND AND OBJECTIVES: The frequency of platelet-specific antibodies after one series of blood transfusions has not been reported, and in multiply transfused patients is controversial. MATERIALS AND METHODS: We studied the frequency of alloimmunization against platelet antigens in 117 patient...

  8. Flavanols and Platelet Reactivity

    Directory of Open Access Journals (Sweden)

    Debra A. Pearson

    2005-01-01

    Full Text Available Platelet activity and platelet-endothelial cell interactions are important in the acute development of thrombosis, as well as in the pathogenesis of cardiovascular disease. An increasing number of foods have been reported to have platelet-inhibitory actions, and research with a number of flavanol-rich foods, including, grape juice, cocoa and chocolate, suggests that these foods may provide some protection against thrombosis. In the present report, we review a series of in vivo studies on the effects of flavanol-rich cocoa and chocolate on platelet activation and platelet-dependent primary hemostasis. Consumption of flavanol-rich cocoa inhibited several measures of platelet activity including, epinephrine- and ADP-induced glycoprotein (GP IIb/IIIa and P-Selectin expression, platelet microparticle formation, and epinephrine-collagen and ADP-collagen induced primary hemostasis. The epinephrine-induced inhibitory effects on GP IIb/IIIa and primary hemostasis were similar to, though less robust than those associated with the use of low dose (81 mg aspirin. These data, coupled with information from other studies, support the concept that flavanols present in cocoa and chocolate can modulate platelet function through a multitude of pathways.

  9. Platelet activation and aggregation

    DEFF Research Database (Denmark)

    Jensen, Maria Sander; Larsen, O H; Christiansen, Kirsten

    2013-01-01

    This study introduces a new laboratory model of whole blood platelet aggregation stimulated by endogenously generated thrombin, and explores this aspect in haemophilia A in which impaired thrombin generation is a major hallmark. The method was established to measure platelet aggregation initiated...

  10. Gasotransmitters and platelets.

    Science.gov (United States)

    Truss, Nicola J; Warner, Timothy D

    2011-11-01

    Platelets are essential to prevent blood loss and promote wound healing. Their activation comprises of several complex steps which are regulated by a range of mediators. Over the last few decades there has been intense interest in a group of gaseous mediators known as gasotransmitters; currently comprising nitric oxide (NO), carbon monoxide (CO) and hydrogen sulphide (H(2)S). Here we consider the action of gasotransmitters on platelet activity. NO is a well established platelet inhibitor which mediates its effects predominantly through activation of soluble guanylyl cyclase leading to a decrease in intraplatelet calcium. More recently CO has been identified as a gasotransmitter with inhibitory actions on platelets; CO acts through the same mechanism as NO but is less potent. The in vivo and platelet functions of the most recently identified gasotransmitter, H(2)S, are still the subject of investigations, but they appear generally inhibitory. Whilst there is evidence for the individual action of these mediators, it is also likely that combinations of these mediators are more relevant regulators of platelets. Furthermore, current evidence suggests that these mediators in combination alter the production of each other, and so modify the circulating levels of gasotransmitters. The use of gasotransmitters as therapeutic agents is also being explored for a range of indications. In conclusion, the importance of NO in the regulation of vascular tone and platelet activity has long been understood. Other gasotransmitters are now establishing themselves as mediators of vascular tone, and recent evidence suggests that these other gasotransmitters may also modulate platelet function.

  11. In vivo modification of Azotobacter chroococcum glutamine synthetase.

    Science.gov (United States)

    Muñoz-Centeno, M C; Cejudo, F J; Paneque, A

    1994-03-15

    A monospecific anti-(glutamine synthetase) antibody raised against glutamine synthetase of the unicellular cyanobacterium Synechocystis sp. strain PCC 6803 immunoreacted with glutamine synthetase from the N2-fixing heterotrophic bacterium Azotobacter chroococcum. In Western-blotting experiments this antibody recognized a single protein of a molecular mass of 59 kDa corresponding to glutamine synthetase subunit. This protein was in vivo-labelled in response to addition of ammonium, both [3H]adenine and H(3)32PO4 preincubation of the cells being equally effective. Nevertheless, the amount of glutamine synthetase present in A. chroococcum was independent of the available nitrogen source. Modified, inactive glutamine synthetase was re-activated by treatment with snake-venom phosphodiesterase but not by alkaline phosphatase. L-Methionine-DL-sulphoximine, an inhibitor of glutamine synthetase, prevented the enzyme from being covalently modified. We conclude that, in A. chroococcum, glutamine synthetase is adenylylated in response to ammonium and that for the modification to take place ammonium must be metabolized.

  12. Alloimmune refractoriness to platelet transfusions.

    Science.gov (United States)

    Sandler, S G

    1997-11-01

    Patients who are transfused on multiple occasions with red cells or platelets may develop platelet-reactive alloantibodies and experience decreased clinical responsiveness to platelet transfusion. This situation, conventionally described as "refractoriness to platelet transfusions," is defined by an unsatisfactory low post-transfusion platelet count increment. If antibodies to HLAs are detected, improved clinical outcomes may result from transfusions of HLA-matched or donor-recipient cross-matched platelets. Because refractoriness is an expected, frequently occurring phenomenon, prevention of HLA alloimmunization is an important management strategy. Prevention strategies include efforts to decrease the number of transfusions, filtration of cellular components to reduce the number of HLA-bearing leukocytes, or pretransfusion ultraviolet B irradiation of cellular components to decrease their immunogenicity. Other investigational approaches include reducing the expression of HLAs on transfused platelets, inducing a transient reticuloendothelial system blockade by infusions of specialized immunoglobulin products, or transfusing semisynthetic platelet substitutes (thromboerythrocytes, thrombospheres) or modified platelets (infusible platelet membranes, lyophilized platelets).

  13. Retinal Vasculitis in Anti-Synthetase Syndrome.

    Science.gov (United States)

    Donovan, Christopher P; Pecen, Paula E; Baynes, Kimberly; Ehlers, Justis P; Srivastava, Sunil K

    2016-09-01

    A 31-year-old woman with a history of anti-synthetase syndrome-related myositis and interstitial lung disease presented with acute-onset blurry vision and rash on her hands and feet. Visual acuity was hand motion in her right eye and 20/40 in her left eye. Dilated fundus exam showed extensive retinal vasculitis, diffuse intraretinal hemorrhages, and subretinal fluid. Optical coherence tomography revealed significant macular thickening, and fluorescein angiography revealed vascular leakage with peripheral nonperfusion. Aggressive systemic immunosuppression was initiated, with gradual resolution of her disease during 8 months of follow-up. [Ophthalmic Surg Lasers Imaging Retina. 2016;47:874-879.]. Copyright 2016, SLACK Incorporated.

  14. Dissecting and Exploiting Nonribosomal Peptide Synthetases

    Institute of Scientific and Technical Information of China (English)

    Qing-Tao SHEN; Xiu-Lan CHEN; Cai-Yun SUN; Yu-Zhong ZHANG

    2004-01-01

    A large number of therapeutically useful cyclic and linear peptides of bacteria or fungal origin are synthesized via a template-directed, nucleic-acid-independent nonribosomal mechanism. This process is carried out by mega-enzymes called nonribosomal peptide synthetases (NRPSs). NRPSs contain repeated coordinated groups of active sites called modules, and each module is composed of several domains with different catalytic activities. The familiarity to these domains lays base for the future genetic engineering of NRPSs to generate entirely "unnature" Products. The details about NRPSs domain structures and the exploitation of NRPSs are described in this review.

  15. Platelet function in dogs

    DEFF Research Database (Denmark)

    Nielsen, Line A.; Zois, Nora Elisabeth; Pedersen, Henrik D.

    2007-01-01

    Cairn Terriers, 10 Boxers, and 11 Labrador Retrievers) were included in the study. Platelet function was assessed by whole-blood aggregation with ADP (1, 5, 10, and 20 µM) as agonist and by PFA-100 using collagen and epinephrine (Col + Epi) and Cpæ + ADP as agonists. Plasma thromboxane B2 concentration......Background: Clinical studies investigating platelet function in dogs have had conflicting results that may be caused by normal physiologic variation in platelet response to agonists. Objectives: The objective of this study was to investigate platelet function in clinically healthy dogs of 4...... different breeds by whole-blood aggregometry and with a point-of-care platelet function analyzer (PFA-100), and to evaluate the effect of acetylsalicylic acid (ASA) administration on the results from both methods. Methods: Forty-five clinically healthy dogs (12 Cavalier King Charles Spaniels [CKCS], 12...

  16. Cisplatin triggers platelet activation.

    Science.gov (United States)

    Togna, G I; Togna, A R; Franconi, M; Caprino, L

    2000-09-01

    Clinical observations suggest that anticancer drugs could contribute to the thrombotic complications of malignancy in treated patients. Thrombotic microangiopathy, myocardial infarction, and cerebrovascular thrombotic events have been reported for cisplatin, a drug widely used in the treatment of many solid tumours. The aim of this study is to explore in vitro cisplatin effect on human platelet reactivity in order to define the potentially active role of platelets in the pathogenesis of cisplatin-induced thrombotic complications. Our results demonstrate that cisplatin increases human platelet reactivity (onset of platelet aggregation wave and thromboxane production) to non-aggregating concentrations of the agonists involving arachidonic acid metabolism. Direct or indirect activation of platelet phospholipase A(2) appears to be implicated. This finding contributes to a better understanding of the pathogenesis of thrombotic complications occurring during cisplatin-based chemotherapy.

  17. Platelet function in dogs

    DEFF Research Database (Denmark)

    Nielsen, Line A.; Zois, Nora Elisabeth; Pedersen, Henrik D.

    2007-01-01

    Background: Clinical studies investigating platelet function in dogs have had conflicting results that may be caused by normal physiologic variation in platelet response to agonists. Objectives: The objective of this study was to investigate platelet function in clinically healthy dogs of 4...... different breeds by whole-blood aggregometry and with a point-of-care platelet function analyzer (PFA-100), and to evaluate the effect of acetylsalicylic acid (ASA) administration on the results from both methods. Methods: Forty-five clinically healthy dogs (12 Cavalier King Charles Spaniels [CKCS], 12...... applied. However, the importance of these breed differences remains to be investigated. The PFA-100 method with Col + Epi as agonists, and ADP-induced platelet aggregation appear to be sensitive to ASA in dogs....

  18. Discovery of a new PG 1159 (GW Vir) pulsator

    Science.gov (United States)

    Kepler, S. O.; Fraga, Luciano; Winget, Don Earl; Bell, Keaton; Córsico, Alejandro H.; Werner, Klaus

    2014-08-01

    We report the discovery of pulsations in the spectroscopic PG 1159 type pre-white dwarf SDSS J075415.12 + 085232.18. Analysis of the spectrum by Werner et al. indicated Teff = 120 000 ± 10 000 K, log g = 7.0 ± 0.3, mass {M}=0.52 ± 0.02 M_{⊙}, C/He = 0.33 by number. We obtained time series images with the SOAR 4.1 m telescope and 2.1 m Otto Struve telescope at McDonald Observatory and show the star is also a variable PG 1159 type star, with dominant period of 525 s.

  19. Discovery of a new PG1159 (GW Vir) Pulsator

    CERN Document Server

    Kepler, S O; Winget, Don Earl; Bell, Keaton; Corsico, Alejandro H; Werner, Klaus

    2014-01-01

    We report the discovery of pulsations in the spectroscopic PG 1159 type pre-white dwarf SDSS J075415.12+085232.18. Analysis of the spectrum by Werner, Rauch and Kepler (2014) indicated Teff=120 000+/-10 000 K, log g=7.0+/-0.3, mass M=0.52+/-0.02 Msun, C/He=0.33 by number. We obtained time-series images with the SOAR 4.1 m telescope and 2.1 m Otto Struve telescope at McDonald Observatory and show the star is also a variable PG 1159 type star, with dominant period of 525 s.

  20. PG&E WaveConnect Program Final Report

    Energy Technology Data Exchange (ETDEWEB)

    Brendan P. Dooher; Edward Cheslak; Robert Booth; Doug Davy; Annette Faraglia; Ian Caliendo; Gina Morimoto; Douglas Herman

    2011-12-01

    The PG&E WaveConnect project was intended to demonstrate the technical and economic viability of wave power in the open ocean adjacent to PG&E's service territory. WaveConnect was conceived as a multi-stage development process leading to long-term megawatt-scale wave power production. The first-stage tasks consisted of site selection, permitting, pilot plant design, and assessment of technology and commercial readiness. The second stage would have included development of infrastructure, undersea cabling, and deployment of wave energy conversion devices (WECs). In the third stage, the most promising WEC devices would have been deployed in larger quantities and connected to the grid. This report documents the findings of Stage One. Site Selection: After studying the wave energy potential, grid interconnection and other project infrastructure along the California coast, PG&E selected two sites: one near Eureka, called the Humboldt WaveConnect (HWC) project, and another near Vandenberg Air Force Base, called the Central Coast WaveConnect project (CCWC). Permitting: FERC issued PG&E preliminary permits for HWC in 2008 and for CCWC in 2010. PG&E chose to use FERC's Pilot Project Licensing Process, which was intended to streamline licensing to allow relatively quick and easy installation, operation, and environmental testing for pilot projects. Permitting, however, proved to be complicated, time-consuming and expensive, mainly because of the uncertain impacts of WEC devices. PG&E learned that even under the PPLP the project would still require a full analysis under CEQA, including an EIR, as well as Monitoring and Adaptive Management Programs and other requirements that had significant cost and scheduling implications. A majority of efforts were expended on permitting activities. Pilot Plant Design: PG&E prepared a conceptual design for a 5-MW pilot test facility at the Humboldt site, which consisted of an off-shore deployment area where WECs of different

  1. Cluster analysis of the hot subdwarfs in the PG survey

    Science.gov (United States)

    Thejll, Peter; Charache, Darryl; Shipman, Harry L.

    1989-01-01

    Application of cluster analysis to the hot subdwarfs in the Palomar Green (PG) survey of faint blue high-Galactic-latitude objects is assessed, with emphasis on data noise and the number of clusters to subdivide the data into. The data used in the study are presented, and cluster analysis, using the CLUSTAN program, is applied to it. Distances are calculated using the Euclidean formula, and clustering is done by Ward's method. The results are discussed, and five groups representing natural divisions of the subdwarfs in the PG survey are presented.

  2. Characterization of cereulide synthetase, a toxin-producing macromolecular machine.

    Directory of Open Access Journals (Sweden)

    Diego A Alonzo

    Full Text Available Cereulide synthetase is a two-protein nonribosomal peptide synthetase system that produces a potent emetic toxin in virulent strains of Bacillus cereus. The toxin cereulide is a depsipeptide, as it consists of alternating aminoacyl and hydroxyacyl residues. The hydroxyacyl residues are derived from keto acid substrates, which cereulide synthetase selects and stereospecifically reduces with imbedded ketoreductase domains before incorporating them into the growing depsipeptide chain. We present an in vitro biochemical characterization of cereulide synthetase. We investigate the kinetics and side chain specificity of α-keto acid selection, evaluate the requirement of an MbtH-like protein for adenylation domain activity, assay the effectiveness of vinylsulfonamide inhibitors on ester-adding modules, perform NADPH turnover experiments and evaluate in vitro depsipeptide biosynthesis. This work also provides biochemical insight into depsipeptide-synthesizing nonribosomal peptide synthetases responsible for other bioactive molecules such as valinomycin, antimycin and kutzneride.

  3. Measurement of platelet aggregation, independently of patient platelet count

    DEFF Research Database (Denmark)

    Vinholt, P. J.; Frederiksen, H.; Hvas, A.M.

    2017-01-01

    platelet aggregation ruled out bleeding tendency in thrombocytopenic patients. Summary: Background: Methods for testing platelet aggregation in thrombocytopenia are lacking. Objective: To establish a flow-cytometric test of in vitro platelet aggregation independently of the patient's platelet count......, and examine the association of aggregation with a bleeding history in thrombocytopenic patients. Patients/methods: We established a flow-cytometric assay of platelet aggregation, and measured samples from healthy individuals preincubated with antiplatelet drugs, and samples from two patients with inherited...... platelets at platelet counts of > 10 × 109 L-1; otherwise, platelet isolation was required. The platelet aggregation percentage decreased with increasing antiplatelet drug concentration. Platelet aggregation in patients was reduced as compared with healthy individuals: 42% (interquartile range [IQR] 27...

  4. Platelet-collagen adhesion enhances platelet aggregation induced by binding of VWF to platelets

    Energy Technology Data Exchange (ETDEWEB)

    Laduca, F.M.; Bell, W.R.; Bettigole, R.E. (Johns Hopkins Univ. School of Medicine, Baltimore, MD (USA) State Univ. of New York, Buffalo (USA))

    1987-11-01

    Ristocetin-induced platelet aggregation (RIPA) was evaluated in the presence of platelet-collagen adhesion. RIPA of normal donor platelet-rich plasma (PRP) demonstrated a primary wave of aggregation mediated by the binding of von Willebrand factor (VWF) to platelets and a secondary aggregation wave, due to a platelet-release reaction, initiated by VWF-platelet binding and inhibitable by acetylsalicylic acid (ASA). An enhanced RIPA was observed in PRP samples to which collagen had been previously added. These subthreshold concentrations of collagen, which by themselves were insufficient to induce aggregation, caused measurable platelet-collagen adhesion. Subthreshold collagen did not cause microplatelet aggregation, platelet release of ({sup 3}H)serotonin, or alter the dose-responsive binding of {sup 125}I-labeled VWF to platelets, which occurred with increasing ristocetin concentrations. However, ASA inhibition of the platelet release reaction prevented collagen-enhanced RIPA. These results demonstrate that platelet-collagen adhesion altered the platelet-release reaction induced by the binding of VWF to platelets causing a platelet-release reaction at a level of VWF-platelet binding not normally initiating a secondary aggregation. These findings suggest that platelet-collagen adhesion enhances platelet function mediated by VWF.

  5. The microsomal dicarboxylyl-CoA synthetase.

    Science.gov (United States)

    Vamecq, J; de Hoffmann, E; Van Hoof, F

    1985-09-15

    Dicarboxylic acids are products of the omega-oxidation of monocarboxylic acids. We demonstrate that in rat liver dicarboxylic acids (C5-C16) can be converted into their CoA esters by a dicarboxylyl-CoA synthetase. During this activation ATP, which cannot be replaced by GTP, is converted into AMP and PPi, both acting as feedback inhibitors of the reaction. Thermolabile at 37 degrees C, and optimally active at pH 6.5, dicarboxylyl-CoA synthetase displays the highest activity on dodecanedioic acid (2 micromol/min per g of liver). Cell-fractionation studies indicate that this enzyme belongs to the hepatic microsomal fraction. Investigations about the fate of dicarboxylyl-CoA esters disclosed the existence of an oxidase, which could be measured by monitoring the production of H2O2. In our assay conditions this H2O2 production is dependent on and closely follows the CoA consumption. It appears that the chain-length specificity of the handling of dicarboxylic acids by this catabolic pathway (activation to acyl-CoA and oxidation with H2O2 production) parallels the pattern of the degradation of exogenous dicarboxylic acids in vivo.

  6. Aminoacyl-tRNA synthetases database.

    Science.gov (United States)

    Szymanski, M; Deniziak, M A; Barciszewski, J

    2001-01-01

    Aminoacyl-tRNA synthetases (AARSs) are at the center of the question of the origin of life. They constitute a family of enzymes integrating the two levels of cellular organization: nucleic acids and proteins. AARSs arose early in evolution and are believed to be a group of ancient proteins. They are responsible for attaching amino acid residues to their cognate tRNA molecules, which is the first step in the protein synthesis. The role they play in a living cell is essential for the precise deciphering of the genetic code. The analysis of AARSs evolutionary history was not possible for a long time due to a lack of a sufficiently large number of their amino acid sequences. The emerging picture of synthetases' evolution is a result of recent achievements in genomics [Woese,C., Olsen,G.J., Ibba,M. and Söll,D. (2000) Microbiol. Mol. Biol. Rev., 64, 202-236]. In this paper we present a short introduction to the AARSs database. The updated database contains 1047 AARS primary structures from archaebacteria, eubacteria, mitochondria, chloroplasts and eukaryotic cells. It is the compilation of amino acid sequences of all AARSs known to date, which are available as separate entries via the WWW at http://biobases.ibch.poznan.pl/aars/.

  7. The far-ultraviolet spectra of "cool" PG1159 stars

    CERN Document Server

    Werner, K; Kruk, J W

    2015-01-01

    We present a comprehensive study of Far Ultraviolet Spectroscopic Explorer (FUSE) spectra (912-1190 A) of two members of the PG1159 spectral class, which consists of hydrogen-deficient (pre-) white dwarfs with effective temperatures in the range Teff = 75,000-200,000 K. As two representatives of the cooler objects, we have selected PG1707+427 (Teff = 85,000 K) and PG1424+535 (Teff = 110,000 K), complementing a previous study of the hotter prototype PG1159-035 (Teff = 140,000 K). The helium-dominated atmospheres are strongly enriched in carbon and oxygen, therefore, their spectra are dominated by lines from C III-IV and O III-VI, many of which were never observed before in hot stars. In addition, lines of many other metals (N, F, Ne, Si, P, S, Ar, Fe) are detectable, demonstrating that observations in this spectral region are most rewarding when compared to the near-ultraviolet and optical wavelength bands. We perform abundance analyses of these species and derive upper limits for several undetected light and ...

  8. Extracellular Membrane Vesicles and Phytopathogenicity of Acholeplasma laidlawii PG8

    Directory of Open Access Journals (Sweden)

    Vladislav M. Chernov

    2012-01-01

    Full Text Available For the first time, the phytopathogenicity of extracellular vesicles of Acholeplasma laidlawii PG8 (a ubiquitous mycoplasma that is one of the five common species of cell culture contaminants and is a causative agent for phytomycoplasmoses in Oryza sativa L. plants was studied. Data on the ability of extracellular vesicles of Acholeplasma laidlawii PG8 to penetrate from the nutrient medium into overground parts of Oryza sativa L. through the root system and to cause alterations in ultrastructural organization of the plants were presented. As a result of the analysis of ultrathin leaf sections of plants grown in medium with A. laidlawii PG8 vesicles, we detected significant changes in tissue ultrastructure characteristic to oxidative stress in plants as well as their cultivation along with bacterial cells. The presence of nucleotide sequences of some mycoplasma genes within extracellular vesicles of Acholeplasma laidlawii PG8 allowed a possibility to use PCR (with the following sequencing to perform differential detection of cells and bacterial vesicles in samples under study. The obtained data may suggest the ability of extracellular vesicles of the mycoplasma to display in plants the features of infection from the viewpoint of virulence criteria—invasivity, infectivity—and toxigenicity—and to favor to bacterial phytopathogenicity.

  9. Tetrads of lines spanning PG(7,2)

    CERN Document Server

    Shaw, Ron; Havlicek, Hans

    2012-01-01

    Our starting point is a very simple one, namely that of a set L_4 of four mutually skew lines in PG(7,2): Under the natural action of the stabilizer group G(L_4) < GL(8,2) the 255 points of PG(7,2) fall into four orbits omega_1, omega_2, omega_3 omega_4; of respective lengths 12, 54, 108, 81: We show that the 135 points in omega_2 \\cup omega_4 are the internal points of a hyperbolic quadric H_7 determined by L_4; and that the 81-set omega_4 (which is shown to have a sextic equation) is an orbit of a normal subgroup G_81 isomorphic to (Z_3)^4 of G(L_4): There are 40 subgroups (isomorphic to (Z_3)^3) of G_81; and each such subgroup H < G_81 gives rise to a decomposition of omega_4 into a triplet of 27-sets. We show in particular that the constituents of precisely 8 of these 40 triplets are Segre varieties S_3(2) in PG(7,2): This ties in with the recent finding that each Segre S = S_3(2) in PG(7,2) determines a distinguished Z_3 subgroup of GL(8,2) which generates two sibling copies S'; S" of S.

  10. The far-ultraviolet spectra of "cool" PG 1159 stars

    Science.gov (United States)

    Werner, K.; Rauch, T.; Kruk, J. W.

    2015-10-01

    We present a comprehensive study of Far Ultraviolet Spectroscopic Explorer (FUSE) spectra (912-1190 Å) of two members of the PG 1159 spectral class, which consists of hydrogen-deficient (pre-) white dwarfs with effective temperatures in the range Teff = 75 000-200 000 K. As two representatives of the cooler objects, we have selected PG 1707+427 (Teff = 85 000 K) and PG 1424+535 (Teff = 110 000 K), complementing a previous study of the hotter prototype PG 1159-035 (Teff = 140 000 K). The helium-dominated atmospheres are strongly enriched in carbon and oxygen, therefore, their spectra are dominated by lines from C iii-iv and O iii-vi, many of which were never observed before in hot stars. In addition, lines of many other metals (N, F, Ne, Si, P, S, Ar, Fe) are detectable, demonstrating that observations in this spectral region are most rewarding when compared to the near-ultraviolet and optical wavelength bands. We perform abundance analyses of these species and derive upper limits for several undetected light and heavy metals including iron-group and trans-iron elements. The results are compared to predictions of stellar evolution models for neutron-capture nucleosynthesis and good agreement is found. Appendix A is available in electronic form at http://www.aanda.org

  11. Defining Platelet Function During Polytrauma

    Science.gov (United States)

    2013-02-01

    using calibrated automated thrombography ( CAT ). 3. Platelet-induced clot contraction and using viscoelastic measures such as TEG with Platelet Mapping...using calibrated automated thrombography ( CAT ) in platelet-rich plasma. 3. Platelet-induced clot contraction and effect on clot structure by platelet...if injury with stable vital signs on initial evaluation.  Pregnancy (confirmed with urine pregnancy testing)  Documented do not resuscitate order

  12. PG&E WaveConnect Program Final Report

    Energy Technology Data Exchange (ETDEWEB)

    Brendan P. Dooher; Edward Cheslak; Robert Booth; Doug Davy; Annette Faraglia; Ian Caliendo; Gina Morimoto; Douglas Herman

    2011-12-01

    The PG&E WaveConnect project was intended to demonstrate the technical and economic viability of wave power in the open ocean adjacent to PG&E's service territory. WaveConnect was conceived as a multi-stage development process leading to long-term megawatt-scale wave power production. The first-stage tasks consisted of site selection, permitting, pilot plant design, and assessment of technology and commercial readiness. The second stage would have included development of infrastructure, undersea cabling, and deployment of wave energy conversion devices (WECs). In the third stage, the most promising WEC devices would have been deployed in larger quantities and connected to the grid. This report documents the findings of Stage One. Site Selection: After studying the wave energy potential, grid interconnection and other project infrastructure along the California coast, PG&E selected two sites: one near Eureka, called the Humboldt WaveConnect (HWC) project, and another near Vandenberg Air Force Base, called the Central Coast WaveConnect project (CCWC). Permitting: FERC issued PG&E preliminary permits for HWC in 2008 and for CCWC in 2010. PG&E chose to use FERC's Pilot Project Licensing Process, which was intended to streamline licensing to allow relatively quick and easy installation, operation, and environmental testing for pilot projects. Permitting, however, proved to be complicated, time-consuming and expensive, mainly because of the uncertain impacts of WEC devices. PG&E learned that even under the PPLP the project would still require a full analysis under CEQA, including an EIR, as well as Monitoring and Adaptive Management Programs and other requirements that had significant cost and scheduling implications. A majority of efforts were expended on permitting activities. Pilot Plant Design: PG&E prepared a conceptual design for a 5-MW pilot test facility at the Humboldt site, which consisted of an off-shore deployment area where WECs of different

  13. Skin regeneration stimulation: the role of PCL-platelet gel nanofibrous scaffold.

    Science.gov (United States)

    Ranjbarvan, Parviz; Soleimani, Masoud; Samadi Kuchaksaraei, Ali; Ai, Jafar; Faridi Majidi, Reza; Verdi, Javad

    2017-05-01

    Skin is the largest organ of the human body. Thus far, tissue engineering of skin has developed rapidly and has used many types of growth factors and nanofibrous scaffolds. In this study, we differentiated neonate keratinocytes for epithelialization on the polycaprolactone-Platelet gel (PCL-PG) scaffold. Fabricated PCL nanofibers prepared by electrospinning technology and coated by platelet gel. Subsequently, the structure of the scaffold was evaluated by SEM, FTIR-ATR, contact angle and tensile test assays. After seeding the neonate keratinocytes on neat PCL and PCL-PG scaffolds, the epidermal maturation was tested by detecting cytokeratin 10 and loricrin determinants by immunocytochemistry; moreover, keratinocyte genes such as keratin 14, keratin 10, and Involucrin were investigated by real-time PCR. The results of MTT assay indicated an increase in cell viability and cell proliferation of neonate keratinocytes on PCL-PG nanofiber scaffolds compared with PCL. RT-PCR and immunocytochemical analysis showed better cell differentiation on the PCL-PG scaffolds than neat PCL. Furthermore, SEM microscopy images demonstrated that neo-keratinocytes enhance adhesion and proliferation on PCL-PG nanofiber scaffolds. We found that PG increases biocompatibility and wettability of scaffold, cell adhesion, and expression of keratinocyte markers. Overall, this procedure is recommended to be employed in skin tissue engineering and wounds healing. © 2016 Wiley Periodicals, Inc.

  14. Uptake and release of arachidonic acid by platelets and cultured cells

    Energy Technology Data Exchange (ETDEWEB)

    Neufeld, E.J.

    1985-01-01

    The release by thrombin of arachidonic acid, and the accompanying phospholipid metabolism, were studied in human platelets. At 23/sup 0/C, arachidonate release was half-maximal by 10-30 sec after stimulation, and preceded substantial increase in phosphatidic acid (PA) mass. (/sup 3/H)-glycerol-labeled platelets synthesized phospholipids from (/sup 3/H) PA at a rate of 0.08-0.3 nmol/min/10/sup 9/ cells at 37/sup 0/C. This rate of PA turnover was not enhanced by thrombin stimulation. Thus, an increase in PA mass is not a necessary event in the pathway loading to arachidonate release, and the release of several nmol of arachidonate from PI in the first minute after thrombin stimulation could not have arisen via PA as an intermediate. Biological function of arachidonate-specific acyl-CoA synthetase was examined in platelets and in HSDM/sub 1/C/sub 1/ murine fibrosarcoma cells. Washed platelets were found to take up and esterify into cellular phospholipids eicosanoid precursor fatty acids present at concentrations of 5-500 nM. The uptake process was saturable with respect to fatty acid concentration, with apparent K/sub m/ less than or equal to 85 nM. Stearate, oleate and linoleate were taken up less rapidly, and with higher apparent K/sub m/'s (greater than or equal to 170 nM). High affinity uptake was also found in HSDM/sub 1/C/sub 1/ cells. The fatty acid structural requirements of arachidonoyl-CoA synthetase were examined. Among common mammalian fatty acids, only eicosanoid precursors and docosahexaenoate could serve as substrates. These studies strongly suggest that the synthetase is required for normal eicosanoid homeostasis.

  15. Glutamine Synthetase: Role in Neurological Disorders.

    Science.gov (United States)

    Jayakumar, Arumugam R; Norenberg, Michael D

    2016-01-01

    Glutamine synthetase (GS) is an ATP-dependent enzyme found in most species that synthesizes glutamine from glutamate and ammonia. In brain, GS is exclusively located in astrocytes where it serves to maintain the glutamate-glutamine cycle, as well as nitrogen metabolism. Changes in the activity of GS, as well as its gene expression, along with excitotoxicity, have been identified in a number of neurological conditions. The literature describing alterations in the activation and gene expression of GS, as well as its involvement in different neurological disorders, however, is incomplete. This review summarizes changes in GS gene expression/activity and its potential contribution to the pathogenesis of several neurological disorders, including hepatic encephalopathy, ischemia, epilepsy, Alzheimer's disease, amyotrophic lateral sclerosis, traumatic brain injury, Parkinson's disease, and astroglial neoplasms. This review also explores the possibility of targeting GS in the therapy of these conditions.

  16. Mechanistic issues in asparagine synthetase catalysis.

    Science.gov (United States)

    Richards, N G; Schuster, S M

    1998-01-01

    The enzymatic synthesis of asparagine is an ATP-dependent process that utilizes the nitrogen atom derived from either glutamine or ammonia. Despite a long history of kinetic and mechanistic investigation, there is no universally accepted catalytic mechanism for this seemingly straightforward carboxyl group activating enzyme, especially as regards those steps immediately preceding amide bond formation. This chapter considers four issues dealing with the mechanism: (a) the structural organization of the active site(s) partaking in glutamine utilization and aspartate activation; (b) the relationship of asparagine synthetase to other amidotransferases; (c) the way in which ATP is used to activate the beta-carboxyl group; and (d) the detailed mechanism by which nitrogen is transferred.

  17. Clinical application of radiolabelled platelets

    Energy Technology Data Exchange (ETDEWEB)

    Kessler, C. (Medical University Luebeck (Federal Republic of Germany). Department of Neurology); Hardeman, M.R. (Amsterdam Univ. (Netherlands). Academisch Ziekenhuis); Henningsen, H. (Heidelberg Univ. (Germany, F.R.). Neurologische Klinik); Petrovici, J.-N. (Cologne-Merheim Hospital (Federal Republic of Germany). Department of Neurology) (eds.)

    1990-01-01

    The increasing number of therapeutic modalities available for the management of patients with thromboembolic complications, such as fibrinolytic treatment or vascular surgery, require the development of new imaging techniques to provide more information on the xtent, age and activity of the thromboembolic material causing clinical symptoms. Since the introduction of radiolabelling of platelets with indium-111, platelet scintigraphy (PSC) has been used as a tool in the diagnosis of various thromboembolic diseases. During the International Symposium on Radiolabelled Platelets scientists from a variety of medical backgrounds presented their results on the clinical applictions of radiolabelled platelets. The papers presented there have been updated to take account of the latest results before publication in this volume. The papers are grouped into six sections on platelet labelling techniques, radiolabelled platelets in cardiology, monitoring of antiplatelet therapy, platelet scintigraphy in stroke patients, platelet scintigraphy in angiology, and platelet scintigraphy in hematology and other clinical applications, including renal transplant rejection. refs.; figs.; tabs.

  18. Platelet preservation: agitation and containers.

    Science.gov (United States)

    van der Meer, Pieter F; de Korte, Dirk

    2011-06-01

    For platelets to maintain their in vitro quality and in vivo effectiveness, they need to be stored at room temperature with gentle agitation in gas-permeable containers. The mode of agitation affects the quality of the platelets, and a gentle method of agitation, either a circular or a flat bed movement, provides the best results. Tumblers or elliptical agitators induce platelet activation and subsequent damage. As long as the platelets remain in suspension, the agitation speed is not important. Agitation of the platelet concentrates ensures that the platelets are continuously oxygenated, that sufficient oxygen can enter the storage container and that excess carbon dioxide can be expelled. During transportation of platelet concentrates, nowadays over long distances where they are held without controlled agitation, platelets may tolerate a certain period without agitation. However, evidence is accumulating that during the time without agitation, local hypoxia surrounding the platelets may induce irreversible harm to the platelets. Over the decades, more gas-permeable plastics have been used to manufacture platelet containers. The use of different plastics and their influence on the platelet quality both in vitro and in vivo is discussed. The improved gas-permeability has allowed the extension of platelet storage from 3 days in the early 1980s, to currently at least 7 days. In the light of new developments, particularly the introduction of pathogen reduction techniques, the use of platelet additive solutions and the availability of improved automated separators, further (renewed) research in this area is warranted.

  19. Mermin's Pentagram as an Ovoid of PG(3,2)

    CERN Document Server

    Saniga, Metod

    2011-01-01

    Mermin's pentagram, a specific set of ten three-qubit observables arranged in quadruples of pairwise commuting ones into five edges of a pentagram and used to provide a very simple proof of the Kochen-Specker theorem, is shown to be isomorphic to an ovoid (elliptic quadric) of the three-dimensional projective space of order two, PG(3,2). This demonstration employs properties of the real three-qubit Pauli group embodied in the geometry of the symplectic polar space W(5,2) and rests on the facts that: 1) the four observables/operators on any of the five edges of the pentagram can be viewed as points of an affine plane of order two, 2) all the ten observables lie on a hyperbolic quadric of the five-dimensional projective space of order two, PG(5,2), and 3) that the points of this quadric are in a well-known bijective correspondence with the lines of PG(3,2).

  20. Time delays in PG1115+080: new estimates

    CERN Document Server

    Vakulik, V G; Schild, R E; Tsvetkova, V S; Dudinov, V N; Minakov, A A; Nuritdinov, S N; Artamonov, B P; Kochetov, A Ye; Smirnov, G V; Sergeyev, A A; Konichek, V V; Sinelnikov, I Ye; Bruevich, V V; Akhunov, T; Burkhonov, O

    2009-01-01

    We report new estimates of the time delays in the quadruple gravitationally lensed quasar PG1115+080, obtained from the monitoring data in filter R with the 1.5-m telescope at the Maidanak Mountain (Uzbekistan, Central Asia) in 2004-2006. The time delays are 16.4 days between images C and B, and 12 days between C and A1+A2, with image C being leading for both pairs. The only known estimates of the time delays in PG1115 are those based on observations by Schechter et al. (1997) -- 23.7 and 9.4 days between images C and B, C and A1+A2, respectively, as calculated by Schechter et al., and 25 and 13.3 days as revised by Barkana (1997) for the same image components with the use of another method. The new values of time delays in PG 1115+080 may be expected to provide larger estimates of the Hubble constant thus decreasing a diversity between the H_0 estimates taken from gravitationally lensed quasars and with other methods.

  1. Platelets and cardiac arrhythmia

    Directory of Open Access Journals (Sweden)

    Jonas S De Jong

    2010-12-01

    Full Text Available Sudden cardiac death remains one of the most prevalent modes of death in industrialized countries, and myocardial ischemia due to thrombotic coronary occlusion is its primary cause. The role of platelets in the occurrence of SCD extends beyond coronary flow impairment by clot formation. Here we review the substances released by platelets during clot formation and their arrhythmic properties. Platelet products are released from three types of platelet granules: dense core granules, alpha-granules, and platelet lysosomes. The physiologic properties of dense granule products are of special interest as a potential source of arrhythmic substances. They are released readily upon activation and contain high concentrations of serotonin, histamine, purines, pyrimidines, and ions such as calcium and magnesium. Potential arrhythmic mechanisms of these substances, e.g. serotonin and high energy phosphates, include induction of coronary constriction, calcium overloading, and induction of delayed after-depolarizations. Alpha-granules produce thromboxanes and other arachidonic acid products with many potential arrhythmic effects mediated by interference with cardiac sodium, calcium and potassium channels. Alpha-granules also contain hundreds of proteins that could potentially serve as ligands to receptors on cardiomyocytes. Lysosomal products probably do not have an important arrhythmic effect. Platelet products and ischemia can induce coronary permeability, thereby enhancing interaction with surrounding cardiomyocytes. Antiplatelet therapy is known to improve survival after myocardial infarction. Although an important part of this effect results from prevention of coronary clot formation, there is evidence to suggest that antiplatelet therapy also induces anti-arrhythmic effects during ischemia by preventing the release of platelet activation products.

  2. Turnover of bacterial glutamine synthetase: oxidative inactivation precedes proteolysis.

    OpenAIRE

    Levine, R L; Oliver, C N; Fulks, R M; Stadtman, E R

    1981-01-01

    We partially purified a preparation from Escherichia coli that proteolytically degrades the enzyme glutamine synthetase [L-glutamate:ammonia ligase (ADP-forming), EC 6.3.1.2]. The degradation is at least a two-step process. First, the glutamine synthetase undergoes an oxidative modification. This modification leads to loss of catalytic activity and also renders the protein susceptible to proteolytic attack in the second step. The oxidative step displays characteristics of a mixed-function oxi...

  3. Release of transforming growth factor beta 1 and platelet derived growth factor type AB from canine platelet gels obtained by the tube method and activated with calcium salts

    OpenAIRE

    RF Silva; GC Santana; FOP Leme; JU Carmona; CMF Rezende

    2013-01-01

    The objectives of this study were: 1) to measure the concentrations of transforming growth factor beta 1 (TGF-β1) and platelet-derived growth factor type AB (PDGF-AB) in plasma and platelet gel (PG) activated with calcium salts (gluconate or chloride) in dogs, and 2) to determine correlations between cell results and growth factors (GF) concentrations. Blood samples were collected from fourteen Brazilian Fila dogs. EDTA was used to obtain whole blood and plasma while ACD-A solution was used t...

  4. The Platelet and Platelet Function Testing in Liver Disease

    NARCIS (Netherlands)

    Hugenholtz, Greg G. C.; Porte, Robert J.; Lisman, Ton

    2009-01-01

    Patients who have liver disease commonly present with alterations in platelet number and function. Recent data have questioned the contribution of these changes to bleeding complications in these patients. Modern tests of platelet function revealed compensatory mechanisms for the decreased platelet

  5. Investigation of platelet function and platelet disorders using flow cytometry.

    Science.gov (United States)

    Rubak, Peter; Nissen, Peter H; Kristensen, Steen D; Hvas, Anne-Mette

    2016-01-01

    Patients with thrombocytopenia or platelet disorders are at risk of severe bleeding. We report the development and validation of flow cytometry assays to diagnose platelet disorders and to assess platelet function independently of platelet count. The assays were developed to measure glycoprotein levels (panel 1) and platelet function (panel 2) in sodium citrated blood. Twenty healthy volunteers and five patients diagnosed with different platelet disorders were included. Glycoprotein expression levels of the receptors Ia, Ib, IIb, IIIa and IX were measured and normalised with forward scatter (FS) as a measurement of platelet size. Platelet function was assessed by CD63, P-selectin and bound fibrinogen in response to arachidonic acid, adenosine diphosphate (ADP), collagen-related peptide, ristocetin and thrombin receptor-activation peptide-6. All patients except one with suspected δ-granule defect showed aberrant levels of glycoproteins in panel 1. Glanzmann's thrombasthenia and genetically verified Bernard-Soulier syndrome could be diagnosed using panel 1. All patients showed reduced platelet function according to at least one agonist. Using panel 2 it was possible to diagnose Bernard-Soulier syndrome, δ-granule defect and GPVI disorder. By combining the two assays, we were able to diagnose different platelet disorders and investigate platelet function independent of platelet count.

  6. Reproducibility of Manual Platelet Estimation Following Automated Low Platelet Counts

    Directory of Open Access Journals (Sweden)

    Zainab S Al-Hosni

    2016-11-01

    Full Text Available Objectives: Manual platelet estimation is one of the methods used when automated platelet estimates are very low. However, the reproducibility of manual platelet estimation has not been adequately studied. We sought to assess the reproducibility of manual platelet estimation following automated low platelet counts and to evaluate the impact of the level of experience of the person counting on the reproducibility of manual platelet estimates. Methods: In this cross-sectional study, peripheral blood films of patients with platelet counts less than 100 × 109/L were retrieved and given to four raters to perform manual platelet estimation independently using a predefined method (average of platelet counts in 10 fields using 100× objective multiplied by 20. Data were analyzed using intraclass correlation coefficient (ICC as a method of reproducibility assessment. Results: The ICC across the four raters was 0.840, indicating excellent agreement. The median difference of the two most experienced raters was 0 (range: -64 to 78. The level of platelet estimate by the least-experienced rater predicted the disagreement (p = 0.037. When assessing the difference between pairs of raters, there was no significant difference in the ICC (p = 0.420. Conclusions: The agreement between different raters using manual platelet estimation was excellent. Further confirmation is necessary, with a prospective study using a gold standard method of platelet counts.

  7. Multiple blocking sets in PG(n,q), n>=3

    DEFF Research Database (Denmark)

    Barat, Janos

    2004-01-01

    This article discusses minimal s-fold blocking sets B in PG (n, q), q = ph, p prime, q > 661, n > 3, of size |B| > sq + cp q2/3 - (s - 1) (s - 2)/2 (s > min (cp q1/6, q1/4/2)). It is shown that these s-fold blocking sets contain the disjoint union of a collection of s lines and/or Baer subplanes...... of Hamada and Helleseth on codes meeting the Griesmer bound....

  8. Microfocusing at the PG1 beamline at FLASH

    Energy Technology Data Exchange (ETDEWEB)

    Dziarzhytski, Siarhei, E-mail: siarhei.dziarzhytski@desy.de [DESY, Notkestrasse 85, 22067 Hamburg (Germany); Gerasimova, Natalia [European XFEL GmbH, Albert-Einstein-Ring 19, 22761 Hamburg (Germany); Goderich, Rene [University of South Florida (United States); Mey, Tobias [Laser Laboratorium Göttingen eV, Hans-Adolf-Krebs-Weg 1, 37077 Göttingen (Germany); Reininger, Ruben [Advanced Photon Source, Argonne National Laboratory, Argonne, IL 60439 (United States); Rübhausen, Michael [University of Hamburg and Center for Free-Electron Laser Science, Notkestrasse 85, 22607 Hamburg (Germany); Siewert, Frank [Institute for Nanometre Optics and Technology at Helmholtz Zentrum Berlin/BESSY II, Albert-Einstein-Strasse 15, 12489 Berlin (Germany); Weigelt, Holger; Brenner, Günter [DESY, Notkestrasse 85, 22067 Hamburg (Germany)

    2016-01-01

    The Kirkpatrick–Baez (KB) refocusing mirrors unit at the PG1 beamline at FLASH has been newly designed, developed and fully commissioned. The vertical focal size of the KB optics is measured to be 5.8 ± 1 µm FWHM and the horizontal 6 ± 2 µm FWHM; astigmatism has been minimized to below 1 mm between waist positions. Such a tight focus is essential for the VUV double Raman spectrometer as it serves as an entrance slit for the first monochromator and defines its resolution to a very large extent. The Raman spectrometer is a permanent end-station at the PG1 beamline, dedicated to inelastic soft X-ray scattering experiments. The Kirkpatrick–Baez (KB) refocusing mirror system installed at the PG1 branch of the plane-grating monochromator beamline at the soft X-ray/XUV free-electron laser in Hamburg (FLASH) is designed to provide tight aberration-free focusing down to 4 µm × 6 µm full width at half-maximum (FWHM) on the sample. Such a focal spot size is mandatory to achieve ultimate resolution and to guarantee best performance of the vacuum-ultraviolet (VUV) off-axis parabolic double-monochromator Raman spectrometer permanently installed at the PG1 beamline as an experimental end-station. The vertical beam size on the sample of the Raman spectrometer, which operates without entrance slit, defines and limits the energy resolution of the instrument which has an unprecedented design value of 2 meV for photon energies below 70 eV and about 15 meV for higher energies up to 200 eV. In order to reach the designed focal spot size of 4 µm FWHM (vertically) and to hold the highest spectrometer resolution, special fully motorized in-vacuum manipulators for the KB mirror holders have been developed and the optics have been aligned employing wavefront-sensing techniques as well as ablative imprints analysis. Aberrations like astigmatism were minimized. In this article the design and layout of the KB mirror manipulators, the alignment procedure as well as microfocus

  9. Glucocorticoid receptor-mediated induction of glutamine synthetase in skeletal muscle cells in vitro

    Science.gov (United States)

    Max, Stephen R.; Thomas, John W.; Banner, Carl; Vitkovic, Ljubisa; Konagaya, Masaaki

    1987-01-01

    The regulation by glucocorticoids of glutamine synthetase in L6 muscle cells in culture is studied. Glutamine synthetase activity was strikingly enhanced by dexamethasone. The dexamethasone-mediated induction of glutamine synthetase activity was blocked by RU38486, a glucocorticoid antagonist, indicating the involvement of intracellular glucocorticoid receptors in the induction process. RU38486 alone was without effect. Northern blot analysis revealed that dexamethasone-mediated enhancement of glutamine synthetase activity involves increased levels of glutamine synthetase mRNA. Glucocorticoids regulate the expression of glutamine synthetase mRNA in cultured muscle cells via interaction with intracellular receptors. Such regulation may be relevant to control of glutamine production by muscle.

  10. Mean platelet volume and mean platelet volume/platelet count ratio ...

    African Journals Online (AJOL)

    Amira M. Elsayed

    2016-03-30

    Mar 30, 2016 ... Abstract The mean platelet volume (MPV) is a laboratory marker associated with platelet func- tion and activity. .... the first 24 h of presentation to the emergency department. Severity of ..... J Neurol Neurosurg Psychiatry.

  11. Glutamine synthetase induced spinal seizures in rats.

    Science.gov (United States)

    Shin, Dong Won; Yoon, Young Sul; Matsumoto, Masato; Huang, Wencheng; Ceraulo, Phil; Young, Wise

    2003-02-01

    Glutamine synthetase (GS) is a key enzyme in the regulation of glutamate neurotransmission in the central nervous system. It is responsible for converting glutamate to glutamine, consuming one ATP and NH3 in the process. Glutamate is neurotoxic when it accumulates in extracellular fluids. We investigated the effects of GS in both a spinal cord injury (SCI) model and normal rats. 0.1-ml of low (2- micro M) and high (55- micro M) concentrations of GS were applied, intrathecally, to the spinal cord of rats under pentobarbital anesthesia. Immediately after an intrathecal injection into the L1-L3 space, the rats developed convulsive movements. These movements initially consisted of myoclonic twitches of the paravertebral muscles close to the injection site, repeated tonic and clonic contractions and extensions of the hind limbs (hind limb seizures) that spread to the fore limbs, and finally rotational axial movements of the body. An EMG of the paravertebral muscles, fore and hind limbs, showed the extent of the muscle activities. GS (2- micro M) caused spinal seizures in the rats after the SCI, and GS (6- micro M) produced seizures in the uninjured anesthetized rats. Denatured GS (70 degrees C, 1 hour) also produced spinal seizures, although higher concentrations were required. We suggest that GS may be directly blocking the release of GABA, or the receptors, in the spinal cord.

  12. PG 1553+113: five years of observations with MAGIC

    CERN Document Server

    Aleksić, : J; Antonelli, L A; Antoranz, P; Asensio, M; Backes, M; Barrio, J A; Bastieri, D; González, J Becerra; Bednarek, W; Berdyugin, A; Berger, K; Bernardini, E; Biland, A; Blanch, O; Bock, R K; Boller, A; Bonnoli, G; Tridon, D Borla; Braun, I; Bretz, T; Cañellas, A; Carmona, E; Carosi, A; Colin, P; Colombo, E; Contreras, J L; Cortina, J; Cossio, L; Covino, S; Dazzi, F; De Angelis, A; De Caneva, G; del Pozo, E De Cea; De Lotto, B; Mendez, C Delgado; Ortega, A Diago; Doert, M; Domínguez, A; Prester, D Dominis; Dorner, D; Doro, M; Elsaesser, D; Ferenc, D; Fonseca, M V; Font, L; Fruck, C; López, R J García; Garczarczyk, M; Garrido, D; Giavitto, G; Godinović, N; Hadasch, D; Häfner, D; Herrero, A; Hildebrand, D; Höhne-Mönch, D; Hose, J; Hrupec, D; Huber, B; Jogler, T; Kellermann, H; Klepser, S; Krähenbühl, T; Krause, J; La Barbera, A; Lelas, D; Leonardo, E; Lindfors, E; Lombardi, S; López, M; López-Oramas, A; Lorenz, E; Makariev, M; Maneva, G; Mankuzhiyil, N; Mannheim, K; Maraschi, L; Mariotti, M; Martínez, M; Mazin, D; Meucci, M; Miranda, J M; Mirzoyan, R; Miyamoto, H; Moldón, J; Moralejo, A; Munar-Adrover, P; Nieto, D; Nilsson, K; Orito, R; Oya, I; Paneque, D; Paoletti, R; Pardo, S; Paredes, J M; Partini, S; Pasanen, M; Pauss, F; Perez-Torres, M A; Persic, M; Peruzzo, L; Pilia, M; Pochon, J; Prada, F; Moroni, P G Prada; Prandini, E; Puljak, I; Reichardt, I; Reinthal, R; Rhode, W; Ribó, M; Rico, J; Rügamer, S; Saggion, A; Saito, K; Saito, T Y; Salvati, M; Satalecka, K; Scalzotto, V; Scapin, V; Schultz, C; Schweizer, T; Shayduk, M; Shore, S N; Sillanpää, A; Sitarek, J; Sobczynska, D; Spanier, F; Spiro, S; Stamatescu, V; Stamerra, A; Steinke, B; Storz, J; Strah, N; Surić, T; Takalo, L; Takami, H; Tavecchio, F; Temnikov, P; Terzić, T; Tescaro, D; Teshima, M; Tibolla, O; Torres, D F; Treves, A; Uellenbeck, M; Vankov, H; Vogler, P; Wagner, R M; Weitzel, Q; Zabalza, V; Zandanel, F; Zanin, R; Buson, S; Horan, D; Larsson, S

    2011-01-01

    We present the results of five years (2005-2009) of MAGIC observations of the BL Lac object PG 1553+113 at very high energies (VHEs, E > 100 GeV). Power law fits of the individual years are compatible with a steady mean photon index $\\Gamma$ = 4.27 \\pm 0.14. In the last three years of data, the flux level above 150 GeV shows a clear variability (probability of constant flux < 0.001%). The flux variations are modest, lying in the range from 4% to 11% of the Crab Nebula flux. Simultaneous optical data also show only modest variability that seems to be correlated with VHE gamma ray variability. We also performed a temporal analysis of (all available) simultaneous Fermi/LAT data of PG 1553+113 above 1 GeV, which reveals hints of variability in the 2008-2009 sample. Finally, we present a combination of the mean spectrum measured at very high energies with archival data available for other wavelengths. The mean spectral energy distribution can be modeled with a one-zone Synchrotron Self Compton (SSC) model, whic...

  13. K-Pg Wildfires: modeling, experiments and observations

    Science.gov (United States)

    Morgan, J.; Artemieva, N.; Belcher, C.; Hadden, R.; Rein, G.; Goldin, T.

    2013-09-01

    The discovery of soot in K-Pg boundary clays [1] started a long debate about whether the asteroid impact ignited global wildfires. The K-Pg layer is formed from material ejected from the Chicxulub site, which travelled at hypervelocities around the world. When such ejecta re-enters the Earth's atmosphere it decelerates and heats up, and delivers a pulse of radiation to the Earth's surface. Recent estimates of the radiation associated with ejecta re-entry [2] are argued to be large enough to have ignited fires globally [3]. Here, we present new 3D models of the thermal pulse that takes in to account the asymmetric distribution of ejecta, which depends on the angle and direction of the Chicxulub impact [4]. We have replicated some of the modeled thermal pulses with a Fire propagation Apparatus (FPA), to investigate their effect on both dry and living plant matter. The models, experiments and observational data are consistent with some wildfires being ignited as a direct result of the impact, but the mass flux of ejecta at sites uprange of Chicxulub is too low to ignite even the most susceptible of plant matter.

  14. PG 1553+113: Five Years of Observations with MAGIC

    Science.gov (United States)

    Aleksić, J.; Alvarez, E. A.; Antonelli, L. A.; Antoranz, P.; Asensio, M.; Backes, M.; Barrio, J. A.; Bastieri, D.; Becerra González, J.; Bednarek, W.; Berdyugin, A.; Berger, K.; Bernardini, E.; Biland, A.; Blanch, O.; Bock, R. K.; Boller, A.; Bonnoli, G.; Borla Tridon, D.; Braun, I.; Bretz, T.; Cañellas, A.; Carmona, E.; Carosi, A.; Colin, P.; Colombo, E.; Contreras, J. L.; Cortina, J.; Cossio, L.; Covino, S.; Dazzi, F.; De Angelis, A.; De Caneva, G.; De Cea del Pozo, E.; De Lotto, B.; Delgado Mendez, C.; Diago Ortega, A.; Doert, M.; Domínguez, A.; Dominis Prester, D.; Dorner, D.; Doro, M.; Elsaesser, D.; Ferenc, D.; Fonseca, M. V.; Font, L.; Fruck, C.; García López, R. J.; Garczarczyk, M.; Garrido, D.; Giavitto, G.; Godinović, N.; Hadasch, D.; Häfner, D.; Herrero, A.; Hildebrand, D.; Höhne-Mönch, D.; Hose, J.; Hrupec, D.; Huber, B.; Jogler, T.; Kellermann, H.; Klepser, S.; Krähenbühl, T.; Krause, J.; La Barbera, A.; Lelas, D.; Leonardo, E.; Lindfors, E.; Lombardi, S.; López, M.; López-Oramas, A.; Lorenz, E.; Makariev, M.; Maneva, G.; Mankuzhiyil, N.; Mannheim, K.; Maraschi, L.; Mariotti, M.; Martínez, M.; Mazin, D.; Meucci, M.; Miranda, J. M.; Mirzoyan, R.; Miyamoto, H.; Moldón, J.; Moralejo, A.; Munar-Adrover, P.; Nieto, D.; Nilsson, K.; Orito, R.; Oya, I.; Paneque, D.; Paoletti, R.; Pardo, S.; Paredes, J. M.; Partini, S.; Pasanen, M.; Pauss, F.; Perez-Torres, M. A.; Persic, M.; Peruzzo, L.; Pilia, M.; Pochon, J.; Prada, F.; Prada Moroni, P. G.; Prandini, E.; Puljak, I.; Reichardt, I.; Reinthal, R.; Rhode, W.; Ribó, M.; Rico, J.; Rügamer, S.; Saggion, A.; Saito, K.; Saito, T. Y.; Salvati, M.; Satalecka, K.; Scalzotto, V.; Scapin, V.; Schultz, C.; Schweizer, T.; Shayduk, M.; Shore, S. N.; Sillanpää, A.; Sitarek, J.; Sobczynska, D.; Spanier, F.; Spiro, S.; Stamatescu, V.; Stamerra, A.; Steinke, B.; Storz, J.; Strah, N.; Surić, T.; Takalo, L.; Takami, H.; Tavecchio, F.; Temnikov, P.; Terzić, T.; Tescaro, D.; Teshima, M.; Tibolla, O.; Torres, D. F.; Treves, A.; Uellenbeck, M.; Vankov, H.; Vogler, P.; Wagner, R. M.; Weitzel, Q.; Zabalza, V.; Zandanel, F.; Zanin, R.; Buson, S.; Horan, D.; Larsson, S.; D'Ammando, F.

    2012-03-01

    We present the results of five years (2005-2009) of MAGIC observations of the BL Lac object PG 1553+113 at very high energies (VHEs; E > 100 GeV). Power-law fits of the individual years are compatible with a steady mean photon index Γ = 4.27 ± 0.14. In the last three years of data, the flux level above 150 GeV shows a clear variability (probability of constant flux < 0.001%). The flux variations are modest, lying in the range from 4% to 11% of the Crab Nebula flux. Simultaneous optical data also show only modest variability that seems to be correlated with VHE gamma-ray variability. We also performed a temporal analysis of (all available) simultaneous Fermi/Large Area Telescope data of PG 1553+113 above 1 GeV, which reveals hints of variability in the 2008-2009 sample. Finally, we present a combination of the mean spectrum measured at VHEs with archival data available for other wavelengths. The mean spectral energy distribution can be modeled with a one-zone synchrotron self-Compton model, which gives the main physical parameters governing the VHE emission in the blazar jet.

  15. SCREENING OF ANTIMICROBIAL ACTIVITY AND GENES CODING POLYKETIDE SYNTHETASE AND NONRIBOSOMAL PEPTIDE SYNTHETASE OF ACTINOMYCETE ISOLATES

    Directory of Open Access Journals (Sweden)

    Silvia Kovácsová

    2013-12-01

    Full Text Available The aim of this study was to observe antimicrobial activity using agar plate diffusion method and screening genes coding polyketide synthetase (PKS-I and nonribosomal peptide synthetase (NRPS from actinomycetes. A total of 105 actinomycete strains were isolated from arable soil. Antimicrobial activity was demonstrated at 54 strains against at least 1 of total 12 indicator organisms. Antifungal properties were recorded more often than antibacterial properties. The presence of PKS-I and NRPS genes were founded at 61 of total 105 strains. The number of strains with mentioned biosynthetic enzyme gene fragments matching the anticipated length were 19 (18% and 50 (47% respectively. Overall, five actinomycete strains carried all the biosynthetical genes, yet no antimicrobial activity was found against any of tested pathogens. On the other hand, twenty-one strains showed antimicrobial activity even though we were not able to amplify any of the PKS or NRPS genes from them. Combination of the two methods showed broad-spectrum antimicrobial activity of actinomycetes isolated from arable soil, which indicate that actinomycetes are valuable reservoirs of novel bioactive compounds.

  16. Kinetics profiling of gramicidin S synthetase A, a member of nonribosomal peptide synthetases.

    Science.gov (United States)

    Sun, Xun; Li, Hao; Alfermann, Jonas; Mootz, Henning D; Yang, Haw

    2014-12-23

    Nonribosomal peptide synthetases (NRPS) incorporate assorted amino acid substrates into complex natural products. The substrate is activated via the formation of a reactive aminoacyl adenylate and is subsequently attached to the protein template via a thioester bond. The reactive nature of such intermediates, however, leads to side reactions that also break down the high-energy anhydride bond. The off-pathway kinetics or their relative weights compared to that of the on-pathway counterpart remains generally elusive. Here, we introduce multiplatform kinetics profiling to quantify the relative weights of on- and off-pathway reactions. Using the well-defined stoichiometry of thioester formation, we integrate a mass spectrometry (MS) kinetics assay, a high-performance liquid chromatography (HPLC) assay, and an ATP-pyrophosphate (PPi) exchange assay to map out a highly efficient on-pathway kinetics profile of the substrate activation and intermediate uploading (>98% relative weight) for wide-type gramicidin S synthetase A (GrsA) and a 87% rate profile for a cysteine-free GrsA mutant. Our kinetics profiling approach complements the existing enzyme-coupled byproduct-release assays, unraveling new mechanistic insights of substrate activation/channeling in NRPS enzymes.

  17. Prophylactic platelets in dengue

    DEFF Research Database (Denmark)

    Whitehorn, James; Rodriguez Roche, Rosmari; Guzman, Maria G

    2012-01-01

    of platelets in dengue. Respondents were all physicians involved with the treatment of patients with dengue. Respondents were asked that their answers reflected what they would do if they were the treating physician. We received responses from 306 physicians from 20 different countries. The heterogeneity...

  18. Rho GTPases in platelet function.

    Science.gov (United States)

    Aslan, J E; McCarty, O J T

    2013-01-01

    The Rho family of GTP binding proteins, also commonly referred to as the Rho GTPases, are master regulators of the platelet cytoskeleton and platelet function. These low-molecular-weight or 'small' GTPases act as signaling switches in the spatial and temporal transduction, and amplification of signals from platelet cell surface receptors to the intracellular signaling pathways that drive platelet function. The Rho GTPase family members RhoA, Cdc42 and Rac1 have emerged as key regulators in the dynamics of the actin cytoskeleton in platelets and play key roles in platelet aggregation, secretion, spreading and thrombus formation. Rho GTPase regulators, including GEFs and GAPs and downstream effectors, such as the WASPs, formins and PAKs, may also regulate platelet activation and function. In this review, we provide an overview of Rho GTPase signaling in platelet physiology. Previous studies of Rho GTPases and platelets have had a shared history, as platelets have served as an ideal, non-transformed cellular model to characterize Rho function. Likewise, recent studies of the cell biology of Rho GTPase family members have helped to build an understanding of the molecular regulation of platelet function and will continue to do so through the further characterization of Rho GTPases as well as Rho GAPs, GEFs, RhoGDIs and Rho effectors in actin reorganization and other Rho-driven cellular processes. © 2012 International Society on Thrombosis and Haemostasis.

  19. Evolution of echinoderms may not have required modification of the ancestral deuterostome HOX gene cluster: first report of PG4 and PG5 Hox orthologues in echinoderms.

    Science.gov (United States)

    Long, Suzanne; Martinez, Pedro; Chen, Wei-Chung; Thorndyke, Michael; Byrne, Maria

    2003-11-01

    Is the extreme derivation of the echinoderm body plan reflected in a derived echinoderm Hox genotype? Building on previous work, we exploited the sequence conservation of the homeobox to isolate putative orthologues of several Hox genes from two asteroid echinoderms. The 5-peptide motif (LPNTK) diagnostic of PG4 Hox genes was identified immediately downstream of one of the partial homeodomains from Patiriella exigua. This constitutes the first unequivocal report of a PG4 Hox gene orthologue from an echinoderm. Subsequent screenings identified genes of both PG4 and PG4/5 in Asterias rubens. Although in echinoids only a single gene (PG4/5) occupies these two contiguous cluster positions, we conclude that the ancestral echinoderm must have had the complete deuterostome suite of medial Hox genes, including orthologues of both PG4 and PG4/5 (=PG5). The reported absence of PG4 in the HOX cluster of echinoids is therefore a derived state, and the ancestral echinoderm probably had a HOX cluster not dissimilar to that of other deuterostomes. Modification of the ancestral deuterostome Hox genotype may not have been required for evolution of the highly derived echinoderm body plan.

  20. The glutamine synthetase gene family in Populus

    Directory of Open Access Journals (Sweden)

    Cánovas Francisco M

    2011-08-01

    Full Text Available Abstract Background Glutamine synthetase (GS; EC: 6.3.1.2, L-glutamate: ammonia ligase ADP-forming is a key enzyme in ammonium assimilation and metabolism of higher plants. The current work was undertaken to develop a more comprehensive understanding of molecular and biochemical features of GS gene family in poplar, and to characterize the developmental regulation of GS expression in various tissues and at various times during the poplar perennial growth. Results The GS gene family consists of 8 different genes exhibiting all structural and regulatory elements consistent with their roles as functional genes. Our results indicate that the family members are organized in 4 groups of duplicated genes, 3 of which code for cytosolic GS isoforms (GS1 and 1 which codes for the choroplastic GS isoform (GS2. Our analysis shows that Populus trichocarpa is the first plant species in which it was observed the complete GS family duplicated. Detailed expression analyses have revealed specific spatial and seasonal patterns of GS expression in poplar. These data provide insights into the metabolic function of GS isoforms in poplar and pave the way for future functional studies. Conclusions Our data suggest that GS duplicates could have been retained in order to increase the amount of enzyme in a particular cell type. This possibility could contribute to the homeostasis of nitrogen metabolism in functions associated to changes in glutamine-derived metabolic products. The presence of duplicated GS genes in poplar could also contribute to diversification of the enzymatic properties for a particular GS isoform through the assembly of GS polypeptides into homo oligomeric and/or hetero oligomeric holoenzymes in specific cell types.

  1. Evolutionary divergence of chloroplast FAD synthetase proteins

    Directory of Open Access Journals (Sweden)

    Arilla-Luna Sonia

    2010-10-01

    Full Text Available Abstract Background Flavin adenine dinucleotide synthetases (FADSs - a group of bifunctional enzymes that carry out the dual functions of riboflavin phosphorylation to produce flavin mononucleotide (FMN and its subsequent adenylation to generate FAD in most prokaryotes - were studied in plants in terms of sequence, structure and evolutionary history. Results Using a variety of bioinformatics methods we have found that FADS enzymes localized to the chloroplasts, which we term as plant-like FADS proteins, are distributed across a variety of green plant lineages and constitute a divergent protein family clearly of cyanobacterial origin. The C-terminal module of these enzymes does not contain the typical riboflavin kinase active site sequence, while the N-terminal module is broadly conserved. These results agree with a previous work reported by Sandoval et al. in 2008. Furthermore, our observations and preliminary experimental results indicate that the C-terminus of plant-like FADS proteins may contain a catalytic activity, but different to that of their prokaryotic counterparts. In fact, homology models predict that plant-specific conserved residues constitute a distinct active site in the C-terminus. Conclusions A structure-based sequence alignment and an in-depth evolutionary survey of FADS proteins, thought to be crucial in plant metabolism, are reported, which will be essential for the correct annotation of plant genomes and further structural and functional studies. This work is a contribution to our understanding of the evolutionary history of plant-like FADS enzymes, which constitute a new family of FADS proteins whose C-terminal module might be involved in a distinct catalytic activity.

  2. Changes in the activity levels of glutamine synthetase, glutaminase and glycogen synthetase in rats subjected to hypoxic stress

    Science.gov (United States)

    Vats, P.; Mukherjee, A. K.; Kumria, M. M. L.; Singh, S. N.; Patil, S. K. B.; Rangnathan, S.; Sridharan, K.

    Exposure to high altitude causes loss of body mass and alterations in metabolic processes, especially carbohydrate and protein metabolism. The present study was conducted to elucidate the role of glutamine synthetase, glutaminase and glycogen synthetase under conditions of chronic intermittent hypoxia. Four groups, each consisting of 12 male albino rats (Wistar strain), were exposed to a simulated altitude of 7620 m in a hypobaric chamber for 6 h per day for 1, 7, 14 and 21 days, respectively. Blood haemoglobin, blood glucose, protein levels in the liver, muscle and plasma, glycogen content, and glutaminase, glutamine synthetase and glycogen synthetase activities in liver and muscle were determined in all groups of exposed and in a group of unexposed animals. Food intake and changes in body mass were also monitored. There was a significant reduction in body mass (28-30%) in hypoxia-exposed groups as compared to controls, with a corresponding decrease in food intake. There was rise in blood haemoglobin and plasma protein in response to acclimatisation. Over a three-fold increase in liver glycogen content was observed following 1 day of hypoxic exposure (4.76+/-0.78 mg.g-1 wet tissue in normal unexposed rats; 15.82+/-2.30 mg.g-1 wet tissue in rats exposed to hypoxia for 1 day). This returned to normal in later stages of exposure. However, there was no change in glycogen synthetase activity except for a decrease in the 21-days hypoxia-exposed group. There was a slight increase in muscle glycogen content in the 1-day exposed group which declined significantly by 56.5, 50.6 and 42% following 7, 14, and 21 days of exposure, respectively. Muscle glycogen synthetase activity was also decreased following 21 days of exposure. There was an increase in glutaminase activity in the liver and muscle in the 7-, 14- and 21-day exposed groups. Glutamine synthetase activity was higher in the liver in 7- and 14-day exposed groups; this returned to normal following 21 days of exposure

  3. PG 1411 + 442 - The nearest broad absorption line quasar

    Science.gov (United States)

    Malkan, Matthew A.; Green, Richard F.; Hutchings, John B.

    1987-01-01

    IUE observations reveal strong, moderately broad absorption troughs in the blue wings of the C IV and N V emission lines of the quasar PG 1411 + 442. No absorption from weakly ionized gas is detected. The emission-line strengths and overall shape of the ultraviolet/optical/near-infrared/far-infrared continuum of the new broad absorption line quasar are within the range normally measured in quasars. Its redshift is low enough to allow the morphology of the host galaxy to be studied in deep broad-band and intermediate-band CCD images. The galaxy appears to be a large spiral with a very long arm or tail. The inclination angle is 57 deg, which rules out the possibility that the line of sight to the nucleus intersects a large path length in a galactic disk.

  4. Revisiting wildfires at the K-Pg boundary

    Science.gov (United States)

    Morgan, Joanna; Artemieva, Natalia; Goldin, Tamara

    2013-12-01

    discovery of large amounts of soot in clays deposited at the Cretaceous-Paleogene (K-Pg) boundary and linked to the ~65 Ma Chicxulub impact crater led to the hypothesis that major wildfires were a consequence of the asteroid impact. Subsequently, several lines of evidence, including the lack of charcoal in North American sites, were used to argue against global wildfires. Close to the impact site fires are likely to be directly ignited by the impact fireball, whereas globally they could be ignited by radiation from the reentry of hypervelocity ejecta. To-date, models of the latter have yet to take into account that ejection—and thus the emission of thermal radiation—is asymmetric and dependent on impact angle. Here, we model: (1) the impact and ejection of material, (2) the ballistic continuation of ejecta around a spherical Earth, and (3) the thermal pulse delivered to the Earth's surface when ejecta reenters the atmosphere. We find that thermal pulses in the downrange direction are sufficient to ignite flora several thousand kilometers from Chicxulub, whereas pulses at most sites in the uprange direction are too low to ignite even the most susceptible plant matter. Our analyses and models suggest some fires were ignited by the impact fireball and ejecta reentry, but that the nonuniform distribution of thermal radiation across the surface of the Earth is inconsistent with the ignition of fires globally as a direct and immediate result of the Chicxulub impact. Instead, we propose that the desiccation of flora by ejecta reentry, as well as the effects of postimpact global cooling/darkness, left much of the terrestrial flora prone to fires, and that the volume of soot in the global K-Pg layer is explained by a combination of syn- and postimpact wildfires.

  5. Crystal Structure of PG16 and Chimeric Dissection with Somatically Related PG9: Structure-Function Analysis of Two Quaternary-Specific Antibodies That Effectively Neutralize HIV-1

    Energy Technology Data Exchange (ETDEWEB)

    Pancera, Marie; McLellan, Jason S.; Wu, Xueling; Zhu, Jiang; Changela, Anita; Schmidt, Stephen D.; Yang, Yongping; Zhou, Tongqing; Phogat, Sanjay; Mascola, John R.; Kwong, Peter D. (NIH); (Aids Vaccine)

    2010-11-03

    HIV-1 resists neutralization by most antibodies. Two somatically related human antibodies, PG9 and PG16, however, each neutralize 70 to 80% of circulating HIV-1 isolates. Here we present the structure of the antigen-binding fragment of PG16 in monoclinic and orthorhombic lattices at 2.4 and 4.0 {angstrom}, respectively, and use a combination of structural analysis, paratope dissection, and neutralization assessment to determine the functional relevance of three unusual PG9/PG16 features: N-linked glycosylation, extensive affinity maturation, and a heavy chain-third complementarity-determining region (CDR H3) that is one of the longest observed in human antibodies. Glycosylation extended off the side of the light chain variable domain and was not required for neutralization. The CDR H3 formed an axe-shaped subdomain, which comprised 42% of the CDR surface, with the axe head looming {approx}20 {angstrom} above the other combining loops. Comprehensive sets of chimeric swaps between PG9 and PG16 of light chain, heavy chain, and CDR H3 were employed to decipher structure-function relationships. Chimeric swaps generally complemented functionally, with differences in PG9/PG16 neutralization related primarily to residue differences in CDR H3. Meanwhile, chimeric reversions to genomic V genes showed isolate-dependent effects, with affinity maturation playing a significant role in augmenting neutralization breadth (P = 0.036) and potency (P < 0.0001). The structural and functional details of extraordinary CDR H3 and extensive affinity maturation provide insights into the neutralization mechanism of and the elicitation pathway for broadly neutralizing antibodies like PG9 and PG16.

  6. Characterization of a Salmonella typhimurium mutant defective in phosphoribosylpyrophosphate synthetase

    DEFF Research Database (Denmark)

    Jochimsen, Bjarne; Hove-Jensen, Bjarne; Garber, Bruce B.;

    1985-01-01

    This study describes the isolation and characterization of a mutant (strain GP122) of Salmonella typhimurium with a partial deficiency of phosphoribosylpyrophosphate (PRPP) synthetase activity. This strain was isolated in a purE deoD gpt purine auxotroph by a procedure designed to select guanosine......-utilizing mutants. Strain GP122 had roughly 15% of the PRPP synthetase activity and 25% of the PRPP pool of its parent strain. The mutant exhibited many of the predicted consequences of a decreased PRPP pool and a defective PRPP synthetase enzyme, including: poor growth on purine bases; decreased accumulation of 5...... phosphoribosyltransferase, enzymes involved in the pyrimidine de novo biosynthetic pathway; growth stimulation by PRPP-sparing compounds (e.g. guanosine, histidine); poor growth in low phosphate medium; and increased heat lability of the defective enzyme. This mutant strain also had increased levels of guanosine 5...

  7. Expansion of the neonatal platelet mass is achieved via an extension of platelet lifespan

    OpenAIRE

    Liu, Zhi-Jian; Hoffmeister, Karin M.; Hu, Zhongbo; Mager, Donald E.; Ait-Oudhia, Sihem; Debrincat, Marlyse A.; Pleines, Irina; Josefsson, Emma C.; Benjamin T Kile; Italiano, Joseph; Ramsey, Haley; Grozovsky, Renata; Veng-Pedersen, Peter; Chavda, Chaitanya; Sola-Visner, Martha

    2014-01-01

    Rapid growth and rising platelet counts result in a significant expansion of platelet mass during neonatal life.The rise in platelet counts is mediated by a prolongation in the neonatal platelet lifespan.

  8. Recurrent Isolated Neonatal Hemolytic Anemia: Think About Glutathione Synthetase Deficiency.

    Science.gov (United States)

    Signolet, Isabelle; Chenouard, Rachel; Oca, Florine; Barth, Magalie; Reynier, Pascal; Denis, Marie-Christine; Simard, Gilles

    2016-09-01

    Hemolytic anemia (HA) of the newborn should be considered in cases of rapidly developing, severe, or persistent hyperbilirubinemia. Several causes of corpuscular hemolysis have been described, among which red blood cell enzyme defects are of particular concern. We report a rare case of red blood cell enzyme defect in a male infant, who presented during his first months of life with recurrent and isolated neonatal hemolysis. All main causes were ruled out. At 6.5 months of age, the patient presented with gastroenteritis requiring hospitalization; fortuitously, urine organic acid chromatography revealed a large peak of 5-oxoproline. Before the association between HA and 5-oxoprolinuria was noted, glutathione synthetase deficiency was suspected and confirmed by a low glutathione synthetase concentration and a collapse of glutathione synthetase activity in erythrocytes. Moreover, molecular diagnosis revealed 2 mutations in the glutathione synthetase gene: a previously reported missense mutation (c.[656A>G]; p.[Asp219Gly]) and a mutation not yet described in the binding site of the enzyme (c.[902T>C]; p.[Leu301Pro]). However, 15 days later, a control sample revealed no signs of 5-oxoprolinuria and the clinical history discovered administration of acetaminophen in the 48 hours before hospitalization. Thus, in this patient, acetaminophen exposure allowed the diagnosis of a mild form of glutathione synthetase deficiency, characterized by isolated HA. Early diagnosis is important because treatment with bicarbonate, vitamins C and E, and elimination of trigger factors are recommended to improve long-term outcomes. Glutathione synthetase deficiency should be screened for in cases of unexplained newborn HA. Copyright © 2016 by the American Academy of Pediatrics.

  9. PREGNANCY WITH PLATELET FUNCTION DISORDER

    Directory of Open Access Journals (Sweden)

    Sheila K

    2014-01-01

    Full Text Available latelets play a vital role in haemostasis . Antenatal patients with platelet function disorders should be managed in tertiary care centres that are well equipped to tackle any obstetric haemorrhage that can ensue during labour and delivery . Primi gravida was admitted for safe confinement . She had been evaluated earlier for complaints of multiple episodes of mucosal bleeding . On evaluation she had nor mal platelet counts and coagulation factor assay was normal . Platelet aggregometry revealed mild disorder of platelet aggregation . She was planned for induction of labour after arranging enough blood and blood products . She got into active labour and was p ut on syntocinon augmentation . She had emergency Caesarean section for foetal distress . Oxytocics were given proactively . Intraoperatively platelet transfusions and tranexamic acid infusion were given . Complete haemostasis was achieved . She had an uneventf ul postoperative period . Patients with functional platelet disorders can be successfully managed with local application of antifibrinolytic agents like tranexamic acid , in case of minor bleeds . Platelet transfusions are very effective in tackling major ble eds , especially during surgeries and for obstetric indications . If a patient has the history of clinically significant bleeding suggestive of platelet dysfunction , appropriate platelet function tests should be obtained so that the risk of bleeding can be adequately assessed and therapy chosen more rationally . . In obstetric practice the response of such patients to platelet transfusions has been excellent

  10. Effects of hormones on platelet aggregation.

    Science.gov (United States)

    Farré, Antonio López; Modrego, Javier; Zamorano-León, José J

    2014-04-01

    Platelets and their activation/inhibition mechanisms play a central role in haemostasis. It is well known agonists and antagonists of platelet activation; however, during the last years novel evidences of hormone effects on platelet activation have been reported. Platelet functionality may be modulated by the interaction between different hormones and their platelet receptors, contributing to sex differences in platelet function and even in platelet-mediated vascular damage. It has suggested aspects that apparently are well established should be reviewed. Hormones effects on platelet activity are included among them. This article tries to review knowledge about the involvement of hormones in platelet biology and activity.

  11. 手性两亲超支化嵌段共聚物PG-b-PBTQMO-b-PG的合成%Synthesis of chiral amphiphilic hyperbranched block copolymer PG-b-PBTQMO-b-PG

    Institute of Scientific and Technical Information of China (English)

    蒋伟伟; 李胜夏; 郭素珍; 胡志国

    2013-01-01

    以叠氮基修饰的超支化共聚物PG-b-PBAMO-b-PG和10,11-二氢化奎宁为原料,通过“click”化学反应合成了一种新型侧链含有奎宁的光学活性两亲超支化嵌段共聚物PG-b-PBTQMO-b-PG.用傅里叶转变红外光谱(FT-IR)和核磁共振氢谱(1HNMR)对产物结构和组成进行了表征,并利用圆二色谱法研究了手性共聚物的光学活性.%A new optically active amphiphilic hyperbranehed block copolymer bearing quinine pendants pol-yglyeerol-b-poly [3,3-bis(triazolyl-L-quinine) methyl oxetane]-b-polyglycerol (PG-b-PBTQMO-b-PG) was synthesized by" click" reaction of azido-modified polyglycerol-b-poly(3,3-bis(azidomethyl) oxetane)-b-polyglycerol (PG-b-PBAMO-b-PG) hyperbranched eopolymer and 10,11-didehydro quinine.The Fourier transform infrared spectrum(FT-IR) and 1H nuclear magnetic resonance spectroscopy(1HNMR)were used to confirm its structure and composition.Additionally,the solution properties of this chiral copolymer were stu-died by circular dichroism(CD) spectroscopy.

  12. Platelet aggregation following trauma

    DEFF Research Database (Denmark)

    Windeløv, Nis A; Sørensen, Anne M; Perner, Anders

    2014-01-01

    We aimed to elucidate platelet function in trauma patients, as it is pivotal for hemostasis yet remains scarcely investigated in this population. We conducted a prospective observational study of platelet aggregation capacity in 213 adult trauma patients on admission to an emergency department (ED......). Inclusion criteria were trauma team activation and arterial cannula insertion on arrival. Blood samples were analyzed by multiple electrode aggregometry initiated by thrombin receptor agonist peptide 6 (TRAP) or collagen using a Multiplate device. Blood was sampled median 65 min after injury; median injury...... severity score (ISS) was 17; 14 (7%) patients received 10 or more units of red blood cells in the ED (massive transfusion); 24 (11%) patients died within 28 days of trauma: 17 due to cerebral injuries, four due to exsanguination, and three from other causes. No significant association was found between...

  13. Platelets in inflammation and immunity.

    Science.gov (United States)

    Herter, J M; Rossaint, J; Zarbock, A

    2014-11-01

    The paradigm of platelets as mere mediators of hemostasis has long since been replaced by a dual role: hemostasis and inflammation. Now recognized as key players in innate and adaptive immune responses, platelets have the capacity to interact with almost all known immune cells. These platelet-immune cell interactions represent a hallmark of immunity, as they can potently enhance immune cell functions and, in some cases, even constitute a prerequisite for host defense mechanisms such as NETosis. In addition, recent studies have revealed a new role for platelets in immunity: They are ubiquitous sentinels and rapid first-line immune responders, as platelet-pathogen interactions within the vasculature appear to precede all other host defense mechanisms. Here, we discuss recent advances in our understanding of platelets as inflammatory cells, and provide an exemplary review of their role in acute inflammation.

  14. Estrogen, inflammation, and platelet phenotype.

    Science.gov (United States)

    Miller, Virginia M; Jayachandran, Muthuvel; Hashimoto, Kazumori; Heit, John A; Owen, Whyte G

    2008-01-01

    Although exogenous estrogenic therapies increase the risk of thrombosis, the effects of estrogen on formed elements of blood are uncertain. This article examines the genomic and nongenomic actions of estrogen on platelet phenotype that may contribute to increased thrombotic risk. To determine aggregation, secretion, protein expression, and thrombin generation, platelets were collected from experimental animals of varying hormonal status and from women enrolled in the Kronos Early Estrogen Prevention Study. Estrogen receptor beta predominates in circulating platelets. Estrogenic treatment in ovariectomized animals decreased platelet aggregation and adenosine triphosphate (ATP) secretion. However, acute exposure to 17beta-estradiol did not reverse decreases in platelet ATP secretion invoked by lipopolysaccharide. Thrombin generation was positively correlated to the number of circulating microvesicles expressing phosphatidylserine. Assessing the effect of estrogen treatments on blood platelets may lead to new ways of identifying women at risk for adverse thrombotic events with such therapies.

  15. Complement Activation Alters Platelet Function

    Science.gov (United States)

    2015-12-01

    Award Number: W81XWH-12-1-0523 TITLE: Complement Activation Alters Platelet Function PRINCIPAL INVESTIGATOR: George Tsokos, M.D. CONTRACTING...Activation Alters Platelet Function 5a. CONTRACT NUMBER 5b. GRANT NUMBER W81XWH-12-1-0523 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) George Tsokos, M.D...a decreased level of disease. Further studies will expand upon these observations better outlining the function of platelets in the injury associated

  16. Platelet effects on ovarian cancer

    Science.gov (United States)

    Davis, Ashley; Afshar-Kharghan, Vahid; Sood, Anil K.

    2014-01-01

    Growing understanding of the role of thrombocytosis, high platelet turnover, and the presence of activated platelets in the circulation in cancer progression and metastasis has brought megakaryocytes into focus. Platelet biology is essential to hemostasis, vascular integrity, angiogenesis, inflammation, innate immunity, wound healing, and cancer biology. However, before megakaryocyte/platelet-directed therapies can be considered for clinical use, understanding of the mechanism and biology of paraneoplastic thrombocytosis in malignancy is required. Here, we provide an overview of the clinical implications, biological significance, and mechanisms of paraneoplastic thrombocytosis in the context of ovarian cancer. PMID:25023353

  17. Novel aspects of platelet aggregation

    Directory of Open Access Journals (Sweden)

    Roka-Moya Y. M.

    2014-01-01

    Full Text Available The platelet aggregation is an important process, which is critical for the hemostatic plug formation and thrombosis. Recent studies have shown that the platelet aggregation is more complex and dynamic than it was previously thought. There are several mechanisms that can initiate the platelet aggregation and each of them operates under specific conditions in vivo. At the same time, the influence of certain plasma proteins on this process should be considered. This review intends to summarize the recent data concerning the adhesive molecules and their receptors, which provide the platelet aggregation under different conditions.

  18. Overview of platelet physiology and laboratory evaluation of platelet function.

    Science.gov (United States)

    Rodgers, G M

    1999-06-01

    Appropriate laboratory testing for the platelet-type bleeding disorders hinges on an adequate assessment in the history and physical examination. Patients with histories and screening laboratory results consistent with coagulation disorders (hemophilia, disseminated intravascular coagulation) are not appropriate candidates for platelet function testing. In contrast, patients with a lifelong history of platelet-type bleeding symptoms and perhaps a positive family history of bleeding would be appropriate for testing. Figure 6 depicts one strategy to evaluate these patients. Platelet morphology can easily be evaluated to screen for two uncommon qualitative platelet disorders: Bernard-Soulier syndrome (associated with giant platelets) and gray platelet syndrome, a subtype of storage pool disorder in which platelet granulation is morphologically abnormal by light microscopy. If the bleeding disorder occurred later in life (no bleeding with surgery or trauma early in life), the focus should be on acquired disorders of platelet function. For those patients thought to have an inherited disorder, testing for vWD should be done initially because approximately 1% of the population has vWD. The complete vWD panel (factor VIII coagulant activity, vWf antigen, ristocetin cofactor activity) should be performed because many patients will have abnormalities of only one particular panel component. Patients diagnosed with vWD should be classified using multimeric analysis to identify the type 1 vWD patients likely to respond to DDAVP. If vWD studies are normal, platelet aggregation testing should be performed, ensuring that no antiplatelet medications have been ingested at least 1 week before testing. If platelet aggregation tests are normal and if suspicion for an inherited disorder remains high, vWD testing should be repeated. The evaluation of thrombocytopenia may require bone marrow examination to exclude primary hematologic disorders. If future studies with thrombopoietin assays

  19. Binding of divalent magnesium by Escherichia coli phosphoribosyl diphosphate synthetase

    DEFF Research Database (Denmark)

    Willemoës, Martin; Hove-Jensen, Bjarne

    1997-01-01

    The mechanism of binding of the substrates Mg x ATP and ribose 5-phosphate as well as Mg2+ to the enzyme 5-phospho-D-ribosyl (alpha-1-diphosphate synthetase from Escherichia coli has been analyzed. By use of the competive inhibitors of ATP and ribose 5-phosphate binding, alpha,beta-methylene ATP ...

  20. Glutamine Synthetase Deficiency in Murine Astrocytes Results in Neonatal Death

    NARCIS (Netherlands)

    Y. He; T.B.M. Hakvoort; J.L.M. Vermeulen; W.T. Labruyere; D.R. de Waart; W.S. van der Hel; J.M. Ruijter; H.B.M. Uylings; W.H. Lamers

    2010-01-01

    Glutamine synthetase (GS) is a key enzyme in the "glutamine-glutamate cycle" between astrocytes and neurons, but its function in vivo was thus far tested only pharmacologically. Crossing GS(fl/lacZ) or GS(fl/f)l mice with hGFAP-Cre mice resulted in prenatal excision of the GS(fl) allele in astrocyte

  1. Polyspecific pyrrolysyl-tRNA synthetases from directed evolution.

    Science.gov (United States)

    Guo, Li-Tao; Wang, Yane-Shih; Nakamura, Akiyoshi; Eiler, Daniel; Kavran, Jennifer M; Wong, Margaret; Kiessling, Laura L; Steitz, Thomas A; O'Donoghue, Patrick; Söll, Dieter

    2014-11-25

    Pyrrolysyl-tRNA synthetase (PylRS) and its cognate tRNA(Pyl) have emerged as ideal translation components for genetic code innovation. Variants of the enzyme facilitate the incorporation >100 noncanonical amino acids (ncAAs) into proteins. PylRS variants were previously selected to acylate N(ε)-acetyl-Lys (AcK) onto tRNA(Pyl). Here, we examine an N(ε)-acetyl-lysyl-tRNA synthetase (AcKRS), which is polyspecific (i.e., active with a broad range of ncAAs) and 30-fold more efficient with Phe derivatives than it is with AcK. Structural and biochemical data reveal the molecular basis of polyspecificity in AcKRS and in a PylRS variant [iodo-phenylalanyl-tRNA synthetase (IFRS)] that displays both enhanced activity and substrate promiscuity over a chemical library of 313 ncAAs. IFRS, a product of directed evolution, has distinct binding modes for different ncAAs. These data indicate that in vivo selections do not produce optimally specific tRNA synthetases and suggest that translation fidelity will become an increasingly dominant factor in expanding the genetic code far beyond 20 amino acids.

  2. Polyspecific pyrrolysyl-tRNA synthetases from directed evolution

    Science.gov (United States)

    Guo, Li-Tao; Wang, Yane-Shih; Nakamura, Akiyoshi; Eiler, Daniel; Kavran, Jennifer M.; Wong, Margaret; Kiessling, Laura L.; Steitz, Thomas A.; O’Donoghue, Patrick; Söll, Dieter

    2014-01-01

    Pyrrolysyl-tRNA synthetase (PylRS) and its cognate tRNAPyl have emerged as ideal translation components for genetic code innovation. Variants of the enzyme facilitate the incorporation >100 noncanonical amino acids (ncAAs) into proteins. PylRS variants were previously selected to acylate Nε-acetyl-Lys (AcK) onto tRNAPyl. Here, we examine an Nε-acetyl-lysyl-tRNA synthetase (AcKRS), which is polyspecific (i.e., active with a broad range of ncAAs) and 30-fold more efficient with Phe derivatives than it is with AcK. Structural and biochemical data reveal the molecular basis of polyspecificity in AcKRS and in a PylRS variant [iodo-phenylalanyl-tRNA synthetase (IFRS)] that displays both enhanced activity and substrate promiscuity over a chemical library of 313 ncAAs. IFRS, a product of directed evolution, has distinct binding modes for different ncAAs. These data indicate that in vivo selections do not produce optimally specific tRNA synthetases and suggest that translation fidelity will become an increasingly dominant factor in expanding the genetic code far beyond 20 amino acids. PMID:25385624

  3. Increased hepatic glycogen synthetase and decreased phosphorylase in trained rats

    DEFF Research Database (Denmark)

    Galbo, H; Saugmann, P; Richter, Erik

    1979-01-01

    Rats were either physically trained by a 12 wk swimming program or were freely eating or weight matched, sedentary controls. Trained rats had a higher relative liver weight and total hepatic glycogen synthetase (EC 2.4.1.11) activity and a lower phosphorylase (EC 2.4.1.1) activity than the other...

  4. The rotating wind of the quasar PG 1700+518.

    Science.gov (United States)

    Young, S; Axon, D J; Robinson, A; Hough, J H; Smith, J E

    2007-11-01

    It is now widely accepted that most galaxies undergo an active phase, during which a central super-massive black hole generates vast radiant luminosities through the gravitational accretion of gas. Winds launched from a rotating accretion disk surrounding the black hole are thought to play a critical role, allowing the disk to shed angular momentum that would otherwise inhibit accretion. Such winds are capable of depositing large amounts of mechanical energy in the host galaxy and its environs, profoundly affecting its formation and evolution, and perhaps regulating the formation of large-scale cosmological structures in the early Universe. Although there are good theoretical grounds for believing that outflows from active galactic nuclei originate as disk winds, observational verification has proven elusive. Here we show that structures observed in polarized light across the broad Halpha emission line in the quasar PG 1700+518 originate close to the accretion disk in an electron scattering wind. The wind has large rotational motions (approximately 4,000 km s(-1)), providing direct observational evidence that outflows from active galactic nuclei are launched from the disks. Moreover, the wind rises nearly vertically from the disk, favouring launch mechanisms that impart an initial acceleration perpendicular to the disk plane.

  5. Increased platelet reactivity in Klinefelter men: something new to consider.

    Science.gov (United States)

    Di Minno, M N D; Esposito, D; Di Minno, A; Accardo, G; Lupoli, G; Cittadini, A; Giugliano, D; Pasquali, D

    2015-09-01

    Patients with Klinefelter syndrome (KS) exhibit an increased cardiovascular risk, but underlying mechanisms are largely unknown. The present cross-sectional study has been conducted to evaluate platelet reactivity and the expression of platelet activation markers (8-iso-prostaglandin F2α[8-iso-PGF2α] and 11-dehydro-thromboxane-B₂[11-dehydro-TXB2]) in KS patients and healthy controls. Twenty-three consecutive KS patients under testosterone replacement therapy have been included as case group and 46 age-matched healthy males recruited among hospital staff served as controls. Light transmission aggregometry was performed in both cases and controls and maximal platelet aggregation (max-A%) was defined as maximal light transmittance reached within 5 min after the addition of 0.2 or 0.4 mm arachidonic acid (AA). A ≥ 50% irreversible light transmittance (LT-50%) following platelet stimulation defined an adequate platelet aggregation and AC-50% was defined as the minimal agonist concentration needed to achieve LT-50%. The AC-50% was 0.26 mm AA for KS and 0.36 mm for controls (p < 0.001). Whereas AA (0.2 mm) induced LT-50% in 69.6% of KS and in 15.2% of controls (p < 0.001), the stimulation with AA (0.4 mm) determined LT-50% in all cases and controls. However, max-A% was higher in KS than in controls both after AA (0.2 mm) (65.61% vs. 46.30%, p = 0.002,) and after AA (0.4 mm) (96.43% vs. 81.04%, p < 0.001). 8-iso-PGF2α and 11-dehydro-TXB2 were higher in KS than in controls (446.54 pg/mg creatinine vs. 230.00 pg/mg creatinine, p < 0.001 and 1278.36 pg/mg creatinine vs. 595.08 pg/mg creatinine, p = 0.001, respectively) and AC-50% inversely correlated with 8-iso-PGF2α (ρ = -0.548, p < 0.001) and with 11-dehydro-TXB2 (ρ = -0.523, p < 0.001). In a linear regression model, KS independently predicted a lower AC-50% (β = -0.597, p < 0.001) and higher levels of 8-iso-PGF2α (β = 0.709, p < 0.001) and 11-dehydro-TXB2 (β = 0

  6. The relationship between change of serum G-17,PG-Ⅰ,PG-Ⅱ and Helicobacter pylori infection%血清 G-17 PG-Ⅰ PG-Ⅱ水平与幽门螺杆菌感染的相关性分析

    Institute of Scientific and Technical Information of China (English)

    谢曙文; 李树锦; 胡召锁

    2015-01-01

    Objective To detect the levels of gastrin-17(G-17),pepsinogen I(PG-Ⅰ)and pepsinogen Ⅱ(PG-Ⅱ)in serum of patients with Helicobacter pylori infection,and to evaluate the relationship between the occurrence of Helicobacter pylori infection and serum levels. Methods Serum was collected from cases of 41 male and 44 female with positive Helicobacter pylori,and 44 male and 41 female with negative Helicobacter pylori. Serum levels of G-17,PG-Ⅰ and PG-Ⅱ were quantitatively detected by ELISA. Results The serum lev-els of G-17,PG-Ⅱ and PG-Ⅰ/ PG-Ⅱ in Hp positive group were higher than those in Hp negative group,with significant differences in con-tent in serum of two groups(P ﹤ 0. 05);in each group of PG- I there was no significant statistically significant difference(P ﹥ 0. 05). Con-clusion Serum levels of G-17 and PG-Ⅱ levels are associated with Helicobacter pylori infection,which can be used as the relevant factors to provide reference basis for diagnosis of Helicobacter pylori infection or previous infection.%目的:检测幽门螺杆菌(HP)感染患者血清中胃泌素-17(G-17)、胃蛋白酶原Ⅰ(PG-Ⅰ)和胃蛋白酶原Ⅱ(PG-Ⅱ)的含量,探讨其与 HP 感染发生的相关性。方法用 ELISA 法分别定量检测 HP 感染阳性组和 HP 感染阴性组患者血清中 G-17、PG-Ⅰ和 PG-Ⅱ的含量。结果 HP 感染阳性组患者 G-17、PG-Ⅱ和 PG-Ⅰ/ PG-Ⅱ的阳性检出量明显高于阴性组,差异有统计学意义(P ﹤0.05),PG-Ⅰ在该两组之间的差异无统计学意义(P ﹥0.05)。结论 G-17和 PG-Ⅱ水平与 HP 感染有关联,可为 HP 感染或既往感染的诊断提供参考依据。

  7. The importance of cytosolic glutamine synthetase in nitrogen assimilation and recycling

    Energy Technology Data Exchange (ETDEWEB)

    Bernard, S.M.; Habash, D.Z.

    2009-07-02

    Glutamine synthetase assimilates ammonium into amino acids, thus it is a key enzyme for nitrogen metabolism. The cytosolic isoenzymes of glutamine synthetase assimilate ammonium derived from primary nitrogen uptake and from various internal nitrogen recycling pathways. In this way, cytosolic glutamine synthetase is crucial for the remobilization of protein-derived nitrogen. Cytosolic glutamine synthetase is encoded by a small family of genes that are well conserved across plant species. Members of the cytosolic glutamine synthetase gene family are regulated in response to plant nitrogen status, as well as to environmental cues, such as nitrogen availability and biotic/abiotic stresses. The complex regulation of cytosolic glutamine synthetase at the transcriptional to post-translational levels is key to the establishment of a specific physiological role for each isoenzyme. The diverse physiological roles of cytosolic glutamine synthetase isoenzymes are important in relation to current agricultural and ecological issues.

  8. The importance of cytosolic glutamine synthetase in nitrogen assimilation and recycling.

    Science.gov (United States)

    Bernard, Stéphanie M; Habash, Dimah Z

    2009-01-01

    Glutamine synthetase assimilates ammonium into amino acids, thus it is a key enzyme for nitrogen metabolism. The cytosolic isoenzymes of glutamine synthetase assimilate ammonium derived from primary nitrogen uptake and from various internal nitrogen recycling pathways. In this way, cytosolic glutamine synthetase is crucial for the remobilization of protein-derived nitrogen. Cytosolic glutamine synthetase is encoded by a small family of genes that are well conserved across plant species. Members of the cytosolic glutamine synthetase gene family are regulated in response to plant nitrogen status, as well as to environmental cues, such as nitrogen availability and biotic/abiotic stresses. The complex regulation of cytosolic glutamine synthetase at the transcriptional to post-translational levels is key to the establishment of a specific physiological role for each isoenzyme. The diverse physiological roles of cytosolic glutamine synthetase isoenzymes are important in relation to current agricultural and ecological issues.

  9. Platelet Concentrates: Past, Present and Future

    OpenAIRE

    2011-01-01

    Platelets play a crucial role in hemostasis and wound healing, platelet growth factors are well known source of healing cytokines. Numerous techniques of autologous platelet concentrates have been developed and applied in oral and maxillofacial surgery. This review describes the evolution of the first and second generation of platelet concentrates (platelet rich plasma and platelet rich fibrin respectively) from their fore runner-fibrin sealants.

  10. Studies on megakaryopoiesis and platelet function

    OpenAIRE

    Meinders, M.

    2015-01-01

    Platelets are blood circulating specialized subcellular fragments, which are produced by megakaryocytes. Platelets are essential for hemostasis and wound healing but also play a role in non-hemostatic processes such as the immune response or cancer metastasis. Considering the immediate precursors of platelets, normal megakaryocyte development is essential for normal platelet function. Although much is known about platelet development, some aspects of platelet production remain poorly understo...

  11. [STRUCTURAL CHARACTERIZATION OF PLATELETS AND PLATELET-DERIVED MICROVESICLES].

    Science.gov (United States)

    Ponomareva, A A; Nevzorova, T A; Mordakhanova, E R; Andrianova, I A; Litvinov, R I

    2016-01-01

    Platelets are the anucleated blood cells, wich together with the fibrin stop bleeding (hemostasis). Cellular microvesicles are membrane-surrounded microparticles released into extracellular space upon activation and/or apoptosis of various cells. Platelet-derived macrovesicles from the major population of circulating blood microparticles that play an important role in hemostasis and thrombosis. Despite numerous studies on the pathophysiology of platelet-derived macrovesicles, mechanisms of their formation and structural details remain poorly understood. Here we investigated the ultrastructure of parental platelets and platelet-derived microvesicles formed in vitro by quiescent cells as well as by cells stimulated with one of the following activators: arachidonic acid, ADP, thrombin, calcium ionophore A23187. Using transmission electron microscopy of human platelets and isolated microvesicles, we analyzed the intracellular origin, steps of formation, structural diversity, and size distributions of the subcellular particles. We have revealed that thrombin, unlike other stimuli, not only induced vesiculation of the plasma membrane but also caused break-up of the cells followed by formation of microparticles that are comparable with microvesicles by size. A fraction of these microparticles contained cellular organelles surrounded by a thin membrane. The size of platelet-derived macrovesicles varied from 30 nm to 500 nm, however, the size distributions depended on the nature of a cell-activating stimulus. The results obtained provide new information about the formation of platelet-derived macrovesicles and their structural diversity, wich is important to understand their multiple functions in normal and disease states.

  12. Perbedaan Kadar Platelet Activating Factor Plasma antara Penderita Demam Berdarah Dengue dan Demam Dengue

    Directory of Open Access Journals (Sweden)

    Djatnika Setiabudi

    2013-12-01

    Full Text Available Dengue virus infection can manifest as dengue fever and, more severely, as dengue hemorrhagic fever. Their pathogenesis until now is not fully understood. One of the most favorable theories stated the presence of increasing titer of pro-inflammatory mediator in severe dengue. The aim of this study was to determine the difference of plasma platelet activating factor titer between dengue hemorrhagic fever and dengue fever patients. This observational study with cross sectional design was conducted during January–February 2013. Subjects were dengue patients, 1 to 14 years old, hospitalized at Dr. Hasan Sadikin General Hospital, Bandung District Hospital (Ujungberung, and Cimahi District Hospital (Cibabat. Dengue cases were confirmed based on nonstructural-1 antigen and/or immunoglobulin M and G rapid test. Blood samples from febrile, critical and recovery phase were drawn for the examination of platelet activating factor titer using the enzyme-linked immunosorbent assay method. There were 26 dengue cases (14 as dengue fever and 12 as dengue hemorrhagic fever. Plasma platelet activating factor titer at the critical phase was significantly higher in dengue hemorrhagic fever patients [541.45 (239.30–2,449.00] pg/mL compared to dengue fever patients [289.55 (149.50–961.50] pg/mL; p=0.007. In conclusion, plasma platelet activating factor titer at the critical phase is higher in dengue hemorrhagic fever patients than in dengue fever patients.

  13. Vascular endothelial growth factor corrected for platelet count and hematocrit is associated with the clinical course of aplastic anemia in children.

    Science.gov (United States)

    Kodama, Yuichi; Okamoto, Yasuhiro; Hashiguchi, Teruto; Shinkoda, Yuichi; Nishikawa, Takuro; Tanabe, Takayuki; Kawano, Yoshifumi

    2012-05-01

    The wide variety of clinical courses that lead to the development of severe aplastic anemia (AA) makes it difficult to speculate whether treatment for AA is required in the early phase. The objective of this study was to identify a method for predicting the clinical course of AA at the onset of the disease. First, in healthy adults, vascular endothelial growth factor (VEGF) released per platelet was measured by the activation of platelet-rich plasma (PRP) and platelet-poor plasma (PPP). Serum concentration of VEGF, serum concentration of VEGF corrected for platelet count, and serum concentration of VEGF corrected for both platelet count and hematocrit (corrected VEGF) were then compared to VEGF released per platelet. Corrected VEGF showed the best correlation with VEGF released per platelet by the activation of PRP in healthy subjects (R (2) = in a single 0.806, p = 0.001). Next, corrected VEGF was assayed in 11 pediatric patients with AA at the time of diagnosis. Corrected VEGF in AA patients was significantly greater than that in age-matched control subjects [1.32 × 10(-6) pg (range 0.36-1.85) vs. 0.18 × 10(-6) pg (range 0.12-0.94)] (p = 0.002). Moreover, corrected VEGF in AA patients who did not require treatment for more than 2 years was significantly greater than that in AA patients who required earlier treatment [1.67 × 10(-6) pg (range 1.32-1.85) vs. 0.87 × 10(-6) pg (0.36-1.34)] (p = 0.011). These data indicate that a compensatory mechanism for increasing VEGF and preventing disease progression might play a role in AA. Corrected VEGF may be useful for predicting the clinical course of AA.

  14. Platelets, inflammation and tissue regeneration.

    Science.gov (United States)

    Nurden, Alan T

    2011-05-01

    Blood platelets have long been recognised to bring about primary haemostasis with deficiencies in platelet production and function manifesting in bleeding while upregulated function favourises arterial thrombosis. Yet increasing evidence indicates that platelets fulfil a much wider role in health and disease. First, they store and release a wide range of biologically active substances including the panoply of growth factors, chemokines and cytokines released from a-granules. Membrane budding gives rise to microparticles (MPs), another active participant within the blood stream. Platelets are essential for the innate immune response and combat infection (viruses, bacteria, micro-organisms). They help maintain and modulate inflammation and are a major source of pro-inflammatory molecules (e.g. P-selectin, tissue factor, CD40L, metalloproteinases). As well as promoting coagulation, they are active in fibrinolysis; wound healing, angiogenesis and bone formation as well as in maternal tissue and foetal vascular remodelling. Activated platelets and MPs intervene in the propagation of major diseases. They are major players in atherosclerosis and related diseases, pathologies of the central nervous system (Alzheimers disease, multiple sclerosis), cancer and tumour growth. They participate in other tissue-related acquired pathologies such as skin diseases and allergy, rheumatoid arthritis, liver disease; while, paradoxically, autologous platelet-rich plasma and platelet releasate are being used as an aid to promote tissue repair and cellular growth. The above mentioned roles of platelets are now discussed.

  15. Clone and functional analysis of Seryl-tRNA synthetase and Tyrosyl-tRNA synthetase from silkworm, Bombyx mori

    Science.gov (United States)

    Hu, Jingsheng; Tian, Jianghai; Li, Fanchi; Xue, Bin; Hu, Jiahuan; Cheng, Xiaoyu; Li, Jinxin; Shen, Weide; Li, Bing

    2017-01-01

    Aminoacyl-tRNA synthetases are the key enzymes for protein synthesis. Glycine, alanine, serine and tyrosine are the major amino acids composing fibroin of silkworm. Among them, the genes of alanyl-tRNA synthetase (AlaRS) and glycyl-tRNA synthetase (GlyRS) have been cloned. In this study, the seryl-tRNA synthetase (SerRS) and tyrosyl-tRNA synthetase (TyrRS) genes from silkworm were cloned. Their full length are 1709 bp and 1868 bp and contain open reading frame (ORF) of 1485 bp and 1575 bp, respectively. RT-PCR examination showed that the transcription levels of SerRS, TyrRS, AlaRS and GlyRS are significantly higher in silk gland than in other tissues. In addition, their transcription levels are much higher in middle and posterior silk gland than in anterior silk gland. Moreover, treatment of silkworms with phoxim, an inhibitor of silk protein synthesis, but not TiO2 NP, an enhancer of silk protein synthesis, significantly reduced the transcription levels of aaRS and content of free amino acids in posterior silk gland, therefore affecting silk protein synthesis, which may be the mechanism of phoxim-silking disorders. Furthermore, low concentration of TiO2 NPs showed no effect on the transcription of aaRS and content of free amino acids, suggesting that TiO2 NPs promotes silk protein synthesis possibly by increasing the activity of fibroin synthase in silkworm. PMID:28134300

  16. Analyzing the platelet proteome.

    Science.gov (United States)

    García, Angel; Zitzmann, Nicole; Watson, Steve P

    2004-08-01

    During the last 10 years, mass spectrometry (MS) has become a key tool for protein analysis and has underpinned the emerging field of proteomics. Using high-throughput tandem MS/MS following protein separation, it is potentially possible to analyze hundreds to thousands of proteins in a sample at a time. This technology can be used to analyze the protein content (i.e., the proteome) of any cell or tissue and complements the powerful field of genomics. The technology is particularly suitable for platelets because of the absence of a nucleus. Cellular proteins can be separated by either gel-based methods such as two-dimensional gel electrophoresis or one-dimensional sodium dodecyl sulfate polyacrylamide gel electrophoresis followed by liquid chromatography (LC) -MS/MS or by multidimensional LC-MS/MS. Prefractionation techniques, such as subcellular fractionations or immunoprecipitations, can be used to improve the analysis. Each method has particular advantages and disadvantages. Proteomics can be used to compare the proteome of basal and diseased platelets, helping to reveal information on the molecular basis of the disease.

  17. Platelets in inflammation and infection.

    Science.gov (United States)

    Jenne, Craig N; Kubes, Paul

    2015-01-01

    Although platelets are traditionally recognized for their central role in hemostasis, many lines of research clearly demonstrate these rather ubiquitous blood components are potent immune modulators and effectors. Platelets have been shown to directly recognize, sequester and kill pathogens, to activated and recruit leukocytes to sites of infection and inflammation, and to modulate leukocyte behavior, enhancing their ability to phagocytose and kill pathogens and inducing unique effector functions, such as the production of Neutrophil Extracellular Traps (NETs). This multifaceted response to infection and inflammation is due, in part, to the huge array of soluble mediators and cell surface molecules expressed by platelets. From their earliest origins as primordial hemocytes in invertebrates to their current form as megakaryocyte-derived cytoplasts, platelets have evolved to be one of the key regulators of host intravascular immunity and inflammation. In this review, we present the diverse roles platelets play in immunity and inflammation associated with autoimmune diseases and infection. Additionally, we highlight recent advances in our understanding of platelet behavior made possible through the use of advanced imaging techniques that allow us to visualize platelets and their interactions, in real-time, within the intact blood vessels of a living host.

  18. [Murine models of platelet diseases].

    Science.gov (United States)

    Lanza, F

    2007-05-01

    Platelet-related diseases correspond to functional defects or abnormal production (thrombopoiesis) of hereditary and immunological origins. Recent progress in the manipulation of the mouse genome (transgenesis, gene inactivation or insertion) has resulted in the generation of numerous strains exhibiting defective platelet function or production. Some strains reproduce known hereditary diseases affecting haemostasis (Glanzmann thrombasthenia, Bernard-Soulier syndrome (BSS) or thrombopoiesis (Wiscott-Aldrich or May-Hegglin syndrome). More often the mutated strains have no human equivalent and represent useful models to study: (i) the role of adhesive or signalling receptors or of signalling proteins in platelet-dependent haemostasis and thrombosis or; (ii) to study the poorly characterized mechanisms of thrombopoiesis, which implicate transcription factors (GATA, Fli1), growth factors and receptors (TPO, cMPL), and cytoskeletal or contractile proteins (tubulin, myosin). Additional mouse strains result from the selection of spontaneous mutants many of which affect intracellular platelet granules, representing models of storage pool diseases (SPD) such as the Gray platelet syndrome (alphaSPD) or Hermansky-Pudlack syndrome (deltaSPD). More recently, a systematic chemical mutagenesis approach has also identified genes involved in thrombopoiesis and platelet survival. Finally, mouse models of auto- or allo-immune thrombocytopenia have been developed to study the mechanisms of platelet destruction or removal.

  19. Platelet scintigraphy in atherothrombotic disease

    Energy Technology Data Exchange (ETDEWEB)

    Isaka, Yoshinari (Osaka National Hospital (Japan))

    1993-01-01

    Indium-111 platelet scintigraphy for the measurement of in vivo thrombogenicity is a useful noninvasive technique with a number of applications. From 1982 to 1989, we explored clinical relevance of this method for 576 consecutive patients with atherothrombotic disease. There was a disease-related difference in the percentage of positive platelet accumulation; 85% in patients with Dacron bifurcation graft, 75% in abdominal or thoracic aneurysm, 40% in intra-cardiac thrombi, 33% in arteriosclerosis obliterans and 25% in ischemic cerebrovascular disease. Labelled platelets accumulated frequently in the lesion with severe arteriographic abnormality. Aspirin clearly inhibited platelet accumulation on carotid atheroma but the effect of ticlopidine has been less conclusive. Short-term orally active PGI[sub 2] analogue had inhibitory effects on platelet accumulation in carotid atheroma and platelet aggregability, but did not cause significant reduction in plaque size. The results suggest the usefulness of platelet scintigraphy for monitoring the thrombogenicity in various atherothrombotic diseases. It will be necessary, however, to simplify the labelling procedures and to develop a new [sup 99m]Tc-labelled thrombus imaging agent, if thrombus imaging is to be considered for more generall use for patients with atherosclerosis. (author).

  20. Cyclosporine A enhances platelet aggregation.

    Science.gov (United States)

    Grace, A A; Barradas, M A; Mikhailidis, D P; Jeremy, J Y; Moorhead, J F; Sweny, P; Dandona, P

    1987-12-01

    In view of the reported increase in thromboembolic episodes following cyclosporine A (CyA) therapy, the effect of this drug on platelet aggregation and thromboxane A2 release was investigated. The addition of CyA, at therapeutic concentrations to platelet rich plasma from normal subjects in vitro was found to increase aggregation in response to adrenaline, collagen and ADP. Ingestion of CyA by healthy volunteers was also associated with enhanced platelet aggregation. The CyA-mediated enhancement of aggregation was further enhanced by the addition in vitro of therapeutic concentrations of heparin. Platelets from renal allograft recipients treated with CyA also showed hyperaggregability and increased thromboxane A2 release, which were most marked at "peak" plasma CyA concentration and less so at "trough" concentrations. Platelet hyperaggregability in renal allograft patients on long-term CyA therapy tended to revert towards normal following the replacement of CyA with azathioprine. Hypertensive patients with renal allografts on nifedipine therapy had normal platelet function and thromboxane release in spite of CyA therapy. These observations suggest that CyA-mediated platelet activation may contribute to the pathogenesis of the thromboembolic phenomena associated with the use of this drug. The increased release of thromboxane A2 (a vasoconstrictor) may also play a role in mediating CyA-related nephrotoxicity.

  1. Aminoacyl-tRNA Synthetase Complexes in Evolution

    Directory of Open Access Journals (Sweden)

    Svitlana Havrylenko

    2015-03-01

    Full Text Available Aminoacyl-tRNA synthetases are essential enzymes for interpreting the genetic code. They are responsible for the proper pairing of codons on mRNA with amino acids. In addition to this canonical, translational function, they are also involved in the control of many cellular pathways essential for the maintenance of cellular homeostasis. Association of several of these enzymes within supramolecular assemblies is a key feature of organization of the translation apparatus in eukaryotes. It could be a means to control their oscillation between translational functions, when associated within a multi-aminoacyl-tRNA synthetase complex (MARS, and nontranslational functions, after dissociation from the MARS and association with other partners. In this review, we summarize the composition of the different MARS described from archaea to mammals, the mode of assembly of these complexes, and their roles in maintenance of cellular homeostasis.

  2. Glutathione production by recombinant Escherichia coli expressing bifunctional glutathione synthetase.

    Science.gov (United States)

    Wang, Dezheng; Wang, Cheng; Wu, Hui; Li, Zhimin; Ye, Qin

    2016-01-01

    Glutathione (GSH) is an important bioactive substance applied widely in pharmaceutical and food industries. Due to the strong product inhibition in the GSH biosynthetic pathway, high levels of intracellular content, yield and productivity of GSH are difficult to achieve. Recently, a novel bifunctional GSH synthetase was identified to be less sensitive to GSH. A recombinant Escherichia coli strain expressing gshF encoding the bifunctional glutathione synthetase of Streptococcus thermophilus was constructed for GSH production. In this study, efficient GSH production using this engineered strain was investigated. The cultivation process was optimized by controlling dissolved oxygen (DO), amino acid addition and glucose feeding. 36.8 mM (11.3 g/L) GSH were formed at a productivity of 2.06 mM/h when the amino acid precursors (75 mM each) were added and glucose was supplied as the sole carbon and energy source.

  3. Phosphoribosylpyrophosphate synthetase of Escherichia coli, Identification of a mutant enzyme

    DEFF Research Database (Denmark)

    Hove-Jensen, Bjarne; Nygaard, Per

    1982-01-01

    , stimulated the mutant enzyme. The activity of PRib-PP synthetase in crude extract was higher in the mutant than in the parent. When starved for purines an accumulation of PRib-PP was observed in the parent strain, while the pool decreased in the mutant. During pyrimidine starvation derepression of PRib....... Kinetic analysis of the mutant PRib-PP synthetase revealed an apparent Km for ATP and ribose 5-phosphate of 1.0 mM and 240 μM respectively, compared to 60 μM and 45 μM respectively for the wild-type enzyme. ADP, which inhibits the wild-type enzyme at a concentration of 0.5 mM ribose 5-phosphate...

  4. Hemolytic anemia and metabolic acidosis: think about glutathione synthetase deficiency.

    Science.gov (United States)

    Ben Ameur, Salma; Aloulou, Hajer; Nasrallah, Fehmi; Kamoun, Thouraya; Kaabachi, Naziha; Hachicha, Mongia

    2015-02-01

    Glutathione synthetase deficiency (GSSD) is a rare disorder of glutathione metabolism with varying clinical severity. Patients may present with hemolytic anemia alone or together with acidosis and central nervous system impairment. Diagnosis is made by clinical presentation and detection of elevated concentrations of 5-oxoproline in urine and low glutathione synthetase activity in erythrocytes or cultured skin fibroblasts. The prognosis seems to depend on early diagnosis and treatment. We report a 4 months old Tunisian male infant who presented with severe metabolic acidosis with high anion gap and hemolytic anemia. High level of 5-oxoproline was detected in her urine and diagnosis of GSSD was made. Treatment consists of the correction of acidosis, blood transfusion, and supplementation with antioxidants. He died of severe metabolic acidosis and sepsis at the age of 15 months.

  5. Phosphoribosylpyrophosphate synthetase of Escherichia coli, Identification of a mutant enzyme

    DEFF Research Database (Denmark)

    Hove-Jensen, Bjarne; Nygaard, Per

    1982-01-01

    . Kinetic analysis of the mutant PRib-PP synthetase revealed an apparent Km for ATP and ribose 5-phosphate of 1.0 mM and 240 μM respectively, compared to 60 μM and 45 μM respectively for the wild-type enzyme. ADP, which inhibits the wild-type enzyme at a concentration of 0.5 mM ribose 5-phosphate......, stimulated the mutant enzyme. The activity of PRib-PP synthetase in crude extract was higher in the mutant than in the parent. When starved for purines an accumulation of PRib-PP was observed in the parent strain, while the pool decreased in the mutant. During pyrimidine starvation derepression of PRib...

  6. Glutamine synthetase gene evolution: A good molecular clock

    Energy Technology Data Exchange (ETDEWEB)

    Pesole, G.; Lanvave, C.; Saccone, C. (Consiglio Nazionale delle Richerche, Bari (Italy)); Bozzetti, M.P. (Univ. di Bari (Italy)); Preparata, G. (Univ. di Milano (Italy))

    1991-01-15

    Glutamine synthetase gene evolution in various animals, plants, and bacteria was evaluated by a general stationary Markov model. The evolutionary process proved to be unexpectedly regular even for a time span as long as that between the divergence of prokaryotes from eukaryotes. This enabled us to draw phylogenetic trees for species whose phylogeny cannot be easily reconstructed from the fossil record. The calculation of the times of divergence of the various organelle-specific enzymes led us to hypothesize that the pea and bean chloroplast genes for these enzymes originated from the duplication of nuclear genes as a result of the different metabolic needs of the various species. The data indicate that the duplication of plastid glutamine synthetase genes occurred long after the endosymbiotic events that produced the organelles themselves.

  7. Platelet enzyme abnormalities in leukemias

    Directory of Open Access Journals (Sweden)

    S Sharma

    2011-01-01

    Full Text Available Aim of the Study: The aim of this study was to evaluate platelet enzyme activity in cases of leukemia. Materials and Methods: Platelet enzymes glucose-6-phosphate dehydrogenase (G6PD, pyruvate kinase (PK and hexokinase (HK were studied in 47 patients of acute and chronic leukemia patients, 16 patients with acute myeloid leukemia (AML(13 relapse, three in remission, 12 patients with acute lymphocytic leukemia (ALL (five in relapse, seven in remission, 19 patients with chronic myeloid leukemia (CML. Results: The platelet G6PD activity was significantly low in cases of AML, ALL and also in CML. G6PD activity was normalized during AML remission. G6PD activity, although persistently low during ALL remission, increased significantly to near-normal during remission (P < 0.05 as compared with relapse (P < 0.01. Platelet PK activity was high during AML relapse (P < 0.05, which was normalized during remission. Platelet HK however was found to be decreased during all remission (P < 0.05. There was a significant positive correlation between G6PD and PK in cases of AML (P < 0.001 but not in ALL and CML. G6PD activity did not correlate with HK activity in any of the leukemic groups. A significant positive correlation was however seen between PK and HK activity in cases of ALL remission (P < 0.01 and CML (P < 0.05. Conclusions: Both red cell and platelet enzymes were studied in 36 leukemic patients and there was no statistically significant correlation between red cell and platelet enzymes. Platelet enzyme defect in leukemias suggests the inherent abnormality in megakaryopoiesis and would explain the functional platelet defects in leukemias.

  8. Platelet surface glutathione reductase-like activity.

    Science.gov (United States)

    Essex, David W; Li, Mengru; Feinman, Richard D; Miller, Anna

    2004-09-01

    We previously found that reduced glutathione (GSH) or a mixture of GSH/glutathione disulfide (GSSG) potentiated platelet aggregation. We here report that GSSG, when added to platelets alone, also potentiates platelet aggregation. Most of the GSSG was converted to GSH by a flavoprotein-dependent platelet surface mechanism. This provided an appropriate redox potential for platelet activation. The addition of GSSG to platelets generated sulfhydryls in the beta subunit of the alpha(IIb)beta(3) fibrinogen receptor, suggesting a mechanism for facilitation of agonist-induced platelet activation.

  9. Recurrent adenylation domain replacement in the microcystin synthetase gene cluster

    Directory of Open Access Journals (Sweden)

    Laakso Kati

    2007-10-01

    Full Text Available Abstract Background Microcystins are small cyclic heptapeptide toxins produced by a range of distantly related cyanobacteria. Microcystins are synthesized on large NRPS-PKS enzyme complexes. Many structural variants of microcystins are produced simulatenously. A recombination event between the first module of mcyB (mcyB1 and mcyC in the microcystin synthetase gene cluster is linked to the simultaneous production of microcystin variants in strains of the genus Microcystis. Results Here we undertook a phylogenetic study to investigate the order and timing of recombination between the mcyB1 and mcyC genes in a diverse selection of microcystin producing cyanobacteria. Our results provide support for complex evolutionary processes taking place at the mcyB1 and mcyC adenylation domains which recognize and activate the amino acids found at X and Z positions. We find evidence for recent recombination between mcyB1 and mcyC in strains of the genera Anabaena, Microcystis, and Hapalosiphon. We also find clear evidence for independent adenylation domain conversion of mcyB1 by unrelated peptide synthetase modules in strains of the genera Nostoc and Microcystis. The recombination events replace only the adenylation domain in each case and the condensation domains of mcyB1 and mcyC are not transferred together with the adenylation domain. Our findings demonstrate that the mcyB1 and mcyC adenylation domains are recombination hotspots in the microcystin synthetase gene cluster. Conclusion Recombination is thought to be one of the main mechanisms driving the diversification of NRPSs. However, there is very little information on how recombination takes place in nature. This study demonstrates that functional peptide synthetases are created in nature through transfer of adenylation domains without the concomitant transfer of condensation domains.

  10. Glutamine synthetase localization in cortisol-induced chick embryo retinas

    OpenAIRE

    1980-01-01

    We report here for the first time, in chick retina, Muller cell localization of glutamine synthetase (GS) activity by an immunohistochemical technique, in agreement with previous reports of glial localization of this enzyme in rat brain and retina. Age- dependent changes in the endogenous enzyme activity as well as cortisol- induced changes in GS activity, both in ovo and in vitro, measured biochemically, reflect the changes observed by staining.

  11. Glutamine synthetase activity in the ruminal bacterium Succinivibrio dextrinosolvens.

    OpenAIRE

    Patterson, J A; Hespell, R B

    1985-01-01

    Succinivibrio dextrinosolvens C18 was found to possess glutamine synthetase (GS), urease, glutamate dehydrogenase, and several other nitrogen assimilation enzymes. When grown in continuous culture under ammonia limitation, both GS and urease activities were high and glutamate dehydrogenase activity was low, but the opposite activity pattern was observed for growth in the presence of ample ammonia. The addition of high-level (15 mM) ammonium chloride to ammonia-limited cultures resulted in a r...

  12. Data of evolutionary structure change: 1ACMB-1PG5B [Confc[Archive

    Lifescience Database Archive (English)

    Full Text Available 1ACMB-1PG5B 1ACM 1PG5 B B GVEAIKRGTVIDHIPAQIGFKLLSLFKLTETDQRITIGL...nfEVID> 0 1ACM B 1ACM...n> 1ACM B 1ACMB FKLT...Chain> 1ACM B 1ACMB ...PHE CA 192 ARG CA 220 ILE CA 292 ALA CA 295

  13. Agreement between PG-SGA Short Form, MUST and SNAQ in hospital patients

    NARCIS (Netherlands)

    Angerman, Kim; Boer, Baukje de; Ottery, Faith D.; Bielderman, Annemiek; Roodenburg, Jan L.N.; Krijnen, Wim P.; Laan, Bernhard F.A.M. van der; Jutte, Paul; Jager-Wittenaar, Harriët

    2015-01-01

    Rationale: The Patient-Generated Subjective Global Assessment (PG-SGA) is a validated instrument to assess malnutrition and its risk factors in clinical populations. Its patient component, PG-SGA Short Form (SF), can be used as screening instrument. In this cross-sectional study we aimed to assess a

  14. Study of thymidylate synthetase-function by laser Raman spectroscopy.

    Science.gov (United States)

    Sharma, R K; Kisliuk, R L; Verma, S P; Wallach, D F

    1975-05-23

    The Laser-Raman spectra of thymidylate synthetase have been obtained with 488 nm excitation from an argon ion laser. Raman bands observed in the range 600-800 cm-minus-1 have been assigned to functional groups of constituent amino acids. The band positions and intensities in the Amide I (1600-1700 cm-minus-1) and Amide III (1200-1300 cm-minus-1) regions, suggest that the enzyme is a mixture of alpha-helical and unordered conformations. Low levels of beta-structure cannot be excluded. The spectra of the ternary complex formed by reacting thymidylate synthetase with (+)-L-methylenetetrahydrofolate and fluorodeoxyuridylate reveals a new band at 1618 cm-minus-1 assigned to the C=N stretching vibration. This band may be due to formation of dihydrofolate or an iminium ion. The overall secondary structure of thymidylate synthetase does not change on formation of the ternary complex. However, the spectrum of the complex indicates local changes in groups such as ionized carboxyl (1400 cm-minus-1), tryptophan (1003 cm-minus-1) and CH-3, CH-2 deformation modes (1440-1470 cm-minus-1).

  15. Mitochondrial aminoacyl-tRNA synthetases in human disease.

    Science.gov (United States)

    Konovalova, Svetlana; Tyynismaa, Henna

    2013-04-01

    Mitochondrial aminoacyl-tRNA synthetases (mtARSs) are essential in the process of transferring genetic information from mitochondrial DNA to the complexes of the oxidative phosphorylation system. These synthetases perform an integral step in the initiation of mitochondrial protein synthesis by charging tRNAs with their cognate amino acids. All mtARSs are encoded by nuclear genes, nine of which have recently been described as disease genes for mitochondrial disorders. Unexpectedly, the clinical presentations of these diseases are highly specific to the affected synthetase. Encephalopathy is the most common manifestation but again with gene-specific outcomes. Other clinical presentations include myopathy with anemia, cardiomyopathy, tubulopathy and hearing loss with female ovarian dysgenesis. Here we review the described mutation types and the associated patient phenotypes. The identified mutation spectrum suggests that only mutation types that allow some residual tRNA-charging activity can result in the described mtARS diseases but the molecular mechanisms behind the selective tissue involvement are not currently understood.

  16. Turnover of bacterial glutamine synthetase: oxidative inactivation precedes proteolysis.

    Science.gov (United States)

    Levine, R L; Oliver, C N; Fulks, R M; Stadtman, E R

    1981-04-01

    We partially purified a preparation from Escherichia coli that proteolytically degrades the enzyme glutamine synthetase [L-glutamate:ammonia ligase (ADP-forming), EC 6.3.1.2]. The degradation is at least a two-step process. First, the glutamine synthetase undergoes an oxidative modification. This modification leads to loss of catalytic activity and also renders the protein susceptible to proteolytic attack in the second step. The oxidative step displays characteristics of a mixed-function oxidation, requiring both molecular oxygen and a reduced nucleotide. This step can also be catalyzed by a purified, mammalian cytochrome P-450 system, as well as by a model system consisting of ascorbic acid and oxygen. Catalase blocks this oxidative modification step. Thus, the overall process of proteolytic degradation can be observed only if care is taken to remove catalase activity from the extracts. The inactivation reaction is dependent on the state of adenylylation of the glutamine synthetase, suggesting that this a physiologically important reaction. If so, then mixed-function oxidases are now implicated in the process of intracellular protein turnover.

  17. Identification of the glutamine synthetase adenylyltransferase of Azospirillum brasilense.

    Science.gov (United States)

    Van Dommelen, Anne; Spaepen, Stijn; Vanderleyden, Jozef

    2009-04-01

    Glutamine synthetase, a key enzyme in nitrogen metabolism of both prokaryotes and eukaryotes, is strictly regulated. One means of regulation is the modulation of activity through adenylylation catalyzed by adenylyltransferases. Using PCR primers based on conserved sequences in glutamine synthetase adenylyltransferases, we amplified part of the glnE gene of Azospirillum brasilense Sp7. The complete glnE sequence of A. brasilense Sp245 was retrieved from the draft genome sequence of this organism (http://genomics.ornl.gov/research/azo/). Adenylyltransferase is a bifunctional enzyme consisting of an N-terminal domain responsible for deadenylylation activity and a C-terminal domain responsible for adenylylation activity. Both domains are partially homologous to each other. Residues important for catalytic activity were present in the deduced amino acid sequence of the A. brasilense Sp245 glnE sequence. A glnE mutant was constructed in A. brasilense Sp7 by inserting a kanamycin resistance cassette between the two active domains of the enzyme. The resulting mutant was unable to adenylylate the glutamine synthetase enzyme and was impaired in growth when shifted from nitrogen-poor to nitrogen-rich medium.

  18. Mechanisms of platelet-mediated liver regeneration.

    Science.gov (United States)

    Lisman, Ton; Porte, Robert J

    2016-08-04

    Platelets have multiple functions beyond their roles in thrombosis and hemostasis. Platelets support liver regeneration, which is required after partial hepatectomy and acute or chronic liver injury. Although it is widely assumed that platelets stimulate liver regeneration by local excretion of mitogens stored within platelet granules, definitive evidence for this is lacking, and alternative mechanisms deserve consideration. In-depth knowledge of mechanisms of platelet-mediated liver regeneration may lead to new therapeutic strategies to treat patients with failing regenerative responses.

  19. Platelets as delivery systems for disease treatments

    OpenAIRE

    Shi, Qizhen; Montgomery, Robert R.

    2010-01-01

    Platelets are small, anucleate, discoid shaped blood cells that play a fundamental role in hemostasis. Platelets contain a large number of biologically active molecules within cytoplasmic granules that are critical to normal platelet function. Because platelets circulate in blood through out the body, release biological molecules and mediators on demand, and participate in hemostasis as well as many other pathophysiologic processes, targeting expression of proteins of interest to platelets an...

  20. Crystal structures of trypanosomal histidyl-tRNA synthetase illuminate differences between eukaryotic and prokaryotic homologs

    OpenAIRE

    Merritt, Ethan A.; Arakaki, Tracy L; Gillespie, J Robert; Larson, Eric T.; Kelley, Angela; Mueller, Natascha; Napuli, Alberto J.; Kim, Jessica; Li ZHANG; Verlinde, Christophe L M J; Fan, Erkang; Zucker, Frank; Buckner, Frederick S.; Van Voorhis, Wesley C.; Hol, Wim G. J.

    2010-01-01

    Crystal structures of histidyl-tRNA synthetase from the eukaryotic parasites Trypanosoma brucei and Trypanosoma cruzi provide a first structural view of a eukaryotic form of this enzyme, and reveal differences from bacterial homologs. Histidyl-tRNA synthetases in general contain an extra domain inserted between conserved motifs 2 and 3 of the Class II aminoacyl-tRNA synthetase catalytic core. The current structures show that the three dimensional topology of this domain is very different in b...

  1. Expression of glutamine synthetase in balloon cells: a basis of their antiepileptic role?

    Science.gov (United States)

    Buccoliero, Anna Maria; Barba, Carmen; Giordano, Flavio; Baroni, Gianna; Genitori, Lorenzo; Guerrini, Renzo; Taddei, Gian Luigi

    2015-01-01

    Glutamine synthetase is an enzyme involved in the clearance of glutamate, the most potent excitatory neurotransmitter. We studied the immunohistochemical expression of glutamine synthetase in neocortical samples from 5 children who underwent surgery for pharmacoresistant epilepsy and a histological diagnosis of focal cortical dysplasia IIb. In all cases, balloon cells, but not dysmorphic neurons, were immunopositive for glutamine synthetase. This finding suggests that balloon cells can be involved in the neutralization of glutamate and play a protective anti-seizure role.

  2. [Protein kinase C activation induces platelet apoptosis].

    Science.gov (United States)

    Zhao, Li-Li; Chen, Meng-Xing; Zhang, Ming-Yi; Dai, Ke-Sheng

    2013-10-01

    Platelet apoptosis elucidated by either physical or chemical compound or platelet storage occurs wildly, which might play important roles in controlling the numbers and functions of circulated platelets, or in the development of some platelet-related diseases. However, up to now, a little is known about the regulatory mechanisms of platelet apoptosis. Protein kinase C (PKC) is highly expressed in platelets and plays central roles in regulating platelet functions. Although there is evidence indicating that PKC is involved in the regulation of apoptosis of nucleated cells, it is still unclear whether PKC plays a role in platelet apoptosis. The aim of this study was to investigate the role of PKC in platelet apoptosis. The effects of PKC on mitochondrial membrane potential (ΔΨm), phosphatidylserine (PS) exposure, and caspase-3 activation of platelets were analyzed by flow cytometry and Western blot. The results showed that the ΔΨm depolarization in platelets was induced by PKC activator in time-dependent manner, and the caspase-3 activation in platelets was induced by PKC in concentration-dependent manner. However, the platelets incubated with PKC inhibitor did not results in ΔΨm depolarization and PS exposure. It is concluded that the PKC activation induces platelet apoptosis through influencing the mitochondrial functions and activating caspase 3. The finds suggest a novel mechanism for PKC in regulating platelet numbers and functions, which has important pathophysiological implications for thrombosis and hemostasis.

  3. Inherited platelet disorders and oral health.

    Science.gov (United States)

    Valera, Marie-Cécile; Kemoun, Philippe; Cousty, Sarah; Sie, Pierre; Payrastre, Bernard

    2013-02-01

    Platelets play a key role in thrombosis and hemostasis. Accumulation of platelets at the site of vascular injury is the first step in the formation of hemostatic plugs, which play a pivotal role in preventing blood loss after injury. Platelet adhesion at sites of injury results in spreading, secretion, recruitment of additional platelets, and formation of platelet aggregates. Inherited platelet disorders are rare causes of bleeding syndromes, ranging from mild bruising to severe hemorrhage. The defects can reflect deficiency or dysfunction of platelet surface glycoproteins, granule contents, cytoskeletal proteins, platelet pro-coagulant function, and signaling pathways. For instance, Bernard-Soulier syndrome and Glanzmann thrombasthenia are attributed to deficiencies of glycoprotein Ib/IX/V and GPIIb/IIIa, respectively, and are rare but severe platelet disorders. Inherited defects that impair platelet secretion and/or signal transduction are among the most common forms of mild platelet disorders and include gray platelet syndrome, Hermansky-Pudlak syndrome, and Chediak-Higashi syndrome. When necessary, desmopressin, antifibrinolytic agents, and transfusion of platelets remain the most common treatment of inherited platelet disorders. Alternative therapies such as recombinant activated factor VII are also available for a limited number of situations. In this review, we will discuss the management of patients with inherited platelet disorders in various clinical situations related to dental cares, including surgical intervention. © 2012 John Wiley & Sons A/S.

  4. Platelet-rich plasma as treatment for persistent ocular epithelial defects.

    Science.gov (United States)

    Ronci, Corrado; Ferraro, Angelo Salvatore; Lanti, Alessandro; Missiroli, Filippo; Sinopoli, Silvia; Del Proposto, Gianpaolo; Cipriani, Chiara; De Felici, Cecilia; Ricci, Federico; Ciotti, Marco; Cudillo, Laura; Arcese, William; Adorno, Gaspare

    2015-06-01

    Platelet- rich plasma (PRP) exhibits regenerative proprieties in wound healing but the biochemical mechanisms are unclear. In this study, autologous PRP with a mean value of 338 × 10(3) platelets/µL was used to treat corneal lesions of different aetiology, while homologous PRP with 1 × 10(6) platelets/µL was used to treat cornel lesions induced by a graft versus host disease. The impact of platelet count on the levels of PDGF AA and BB, VEGF, and EGF in the two PRPs was evaluated after a cycle of freezing/thawing. Treated corneal lesions healed or improved. The levels of PDGF AA and BB, VEGF, and EGF in the autologous PRP raised from 296 ± 61; 201.8 ± 24; 53 ± 14 and 8.9 ± 2 to 1017 ± 253; 924.7 ± 222; 101 ± 46.5 and 174 ± 15.5 pg/mL, while in the homologous PRP were 3.4, 4.5, 3.2 and 2 folds higher, respectively. High level of platelet counts seems not required to treat corneal lesions.

  5. Platelet-rich fibrin (PRF): a second-generation platelet concentrate. Part II: platelet-related biologic features.

    Science.gov (United States)

    Dohan, David M; Choukroun, Joseph; Diss, Antoine; Dohan, Steve L; Dohan, Anthony J J; Mouhyi, Jaafar; Gogly, Bruno

    2006-03-01

    Platelet-rich fibrin (PRF) belongs to a new generation of platelet concentrates, with simplified processing and without biochemical blood handling. In this second article, we investigate the platelet-associated features of this biomaterial. During PRF processing by centrifugation, platelets are activated and their massive degranulation implies a very significant cytokine release. Concentrated platelet-rich plasma platelet cytokines have already been quantified in many technologic configurations. To carry out a comparative study, we therefore undertook to quantify PDGF-BB, TGFbeta-1, and IGF-I within PPP (platelet-poor plasma) supernatant and PRF clot exudate serum. These initial analyses revealed that slow fibrin polymerization during PRF processing leads to the intrinsic incorporation of platelet cytokines and glycanic chains in the fibrin meshes. This result would imply that PRF, unlike the other platelet concentrates, would be able to progressively release cytokines during fibrin matrix remodeling; such a mechanism might explain the clinically observed healing properties of PRF.

  6. Platelet-containing tantalum powders

    Energy Technology Data Exchange (ETDEWEB)

    Schiele, E.K.

    1988-04-26

    A method of forming platelet tantalum powders is described comprising the steps of: (a) providing an ingot-derived precursor tantalum powder, and (b) ball-milling the precursor powder for a time sufficient to form a platelet powder having an average FSSS of less than about 2 micrometers, a Scott density not greater than about 30 g/in/sup 3/ and a BET surface area of at least about 0.7 in/sup 2//g.

  7. In vitro function of random donor platelets stored for 7 days in composol platelet additive solution

    Directory of Open Access Journals (Sweden)

    Gupta Ashish

    2011-01-01

    Full Text Available Background and Aim: Platelets are routinely isolated from whole blood and stored in plasma for 5 days. The present study was done to assess the in vitro function of random donor platelets stored for 7 days in composol platelet additive solution at 22°C. Materials and Methods: The study sample included 30 blood donors of both sex in State Blood Bank, CSM Medical University, Lucknow. Random donor platelets were prepared by platelet rich plasma method. Whole blood (350 ml was collected in anticoagulant Citrate Phosphate Dextrose Adenine triple blood bags. Random donor platelets were stored for 7 days at 22°C in platelet incubators and agitators, with and without additive solution. Results: Platelet swirling was present in all the units at 22°C on day 7, with no evidence of bacterial contamination. Comparison of the mean values of platelet count, platelet factor 3, lactate dehydrogenase, pH, glucose and platelet aggregation showed no significant difference in additive solution, whereas platelet factor 3, glucose and platelet aggregation showed significant difference (P < 0.001 on day 7 without additive solution at 22°C. Conclusion: Our study infers that platelet viability and aggregation were best maintained within normal levels on day 7 of storage in platelet additive solution at 22°C. Thus, we may conclude that in vitro storage of random donor platelets with an extended shelf life of 7 days using platelet additive solution may be advocated to improve the inventory of platelets.

  8. Evidence of platelet activation in multiple sclerosis

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    Alexander J Steven

    2008-06-01

    Full Text Available Abstract Objective A fatality in one multiple sclerosis (MS patient due to acute idiopathic thrombocytopenic purpura (ITP and a near fatality in another stimulated our interest in platelet function abnormalities in MS. Previously, we presented evidence of platelet activation in a small cohort of treatment-naive MS patients. Methods In this report, 92 normal controls and 33 stable, untreated MS patients were studied. Platelet counts, measures of platelet activation [plasma platelet microparticles (PMP, P-selectin expression (CD62p, circulating platelet microaggragtes (PAg], as well as platelet-associated IgG/IgM, were carried out. In addition, plasma protein S activity was measured. Results Compared to controls, PMP were significantly elevated in MS (p Conclusion Platelets are significantly activated in MS patients. The mechanisms underlying this activation and its significance to MS are unknown. Additional study of platelet activation and function in MS patients is warranted.

  9. Regulation of glutamine synthetase, aspartokinase, and total protein turnover in Klebsiella aerogenes.

    Science.gov (United States)

    Fulks, R M; Stadtman, E R

    1985-12-13

    When suspensions of Klebsiella aerogenes are incubated in a nitrogen-free medium there is a gradual decrease in the levels of acid-precipitable protein and of aspartokinase III (lysine-sensitive) and aspartokinase I (threonine-sensitive) activities. In contrast, the level of glutamine synthetase increases slightly and then remains constant. Under these conditions, the glutamine synthetase and other proteins continue to be synthesized as judged by the incorporation of [14C]leucine into the acid-precipitable protein fraction and into protein precipitated by anti-glutamine synthetase antibodies, by the fact that growth-inhibiting concentrations of chloramphenicol also inhibit the incorporation of [14C]leucine into protein and into protein precipitated by anti-glutamine synthetase antibody, and by the fact that chloramphenicol leads to acceleration in the loss of aspartokinases I and III and promotes a net decrease in the level of glutamine synthetase and its cross-reactive protein. The loss of aspartokinases I and III in cell suspensions is stimulated by glucose and is inhibited by 2,4-dinitrophenol. Glucose also stimulates the loss of aspartokinases and glutamine synthetase in the presence of chloramphenicol. Cell-free extracts of K. aerogenes catalyze rapid inactivation of endogenous glutamine synthetase as well as exogenously added pure glutamine synthetase. This loss of glutamine synthetase is not associated with a loss of protein that cross-reacts with anti-glutamine synthetase antibodies. The inactivation of glutamine synthetase in extracts is not due to adenylylation. It is partially prevented by sulfhydryl reagents, Mn2+, antimycin A, 2,4-dinitrophenol, EDTA, anaerobiosis and by dialysis. Following 18 h dialysis, the capacity of extracts to catalyze inactivation of glutamine synthetase is lost but can be restored by the addition of Fe2+ (or Ni2+) together with ATP (or other nucleoside di- and triphosphates. After 40-60 h dialysis Fe3+ together with NADH (but

  10. Effectiveness of tissue engineered chitosan-gelatin composite scaffold loaded with human platelet gel in regeneration of critical sized radial bone defect in rat.

    Science.gov (United States)

    Oryan, Ahmad; Alidadi, Soodeh; Bigham-Sadegh, Amin; Moshiri, Ali; Kamali, Amir

    2017-03-29

    Although many strategies have been utilized to accelerate bone regeneration, an appropriate treatment strategy to regenerate a new bone with optimum morphology and mechanical properties has not been invented as yet. This study investigated the healing potential of a composite scaffold consisting of chitosan (CS), gelatin (Gel) and platelet gel (PG), named CS-Gel-PG, on a bilateral critical sized radial bone defect in rat. Eighty radial bone defects were bilaterally created in 40 Sprague-Dawley rats and were randomly divided into eight groups including untreated, autograft, CS, Gel, CS-PG, Gel-PG, CS-Gel, and CS-Gel-PG treated defects. The bone defects were evaluated clinically and radiologically during the study and their bone samples were assessed by gross and histopathology, histomorphometry, CT-scan, scanning electron microscopy, and biomechanical testing after 8weeks of bone injury. The autograft and CS-Gel-PG groups showed significantly higher new bone formation, density of osseous and cartilaginous tissues, bone volume, and mechanical performance than the defect, CS and Gel-PG groups (P˂0.05). In addition, bone volume, density of osseous and cartilaginous tissues, and numbers of osteons in the CS-Gel-PG group were significantly superior to the CS-PG, CS-Gel and Gel groups (P˂0.05). Increased mRNA levels of alkaline phosphatase, runt-related transcription factor 2, osteocalcin, collagen type 1 and CD31, vascular endothelial growth factor as osteogenic and angiogenic differentiation markers were found with the CS-Gel-PG scaffold by quantitative real-time PCR in vitro after 30days of culturing on bone marrow-derived mesenchymal stem cells. In conclusion, the healing potential of CS-Gel scaffold embedded with PG was comparable to autografting and therefore, it can be offered as an appropriate scaffold in bone tissue engineering and regenerative applications.

  11. Unusual domain architecture of aminoacyl tRNA synthetases and their paralogs from Leishmania major

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    Gowri V S

    2012-11-01

    Full Text Available Abstract Background Leishmania major, a protozoan parasite, is the causative agent of cutaneous leishmaniasis. Due to the development of resistance against the currently available anti-leishmanial drugs, there is a growing need for specific inhibitors and novel drug targets. In this regards, aminoacyl tRNA synthetases, the linchpins of protein synthesis, have received recent attention among the kinetoplastid research community. This is the first comprehensive survey of the aminoacyl tRNA synthetases, their paralogs and other associated proteins from L. major. Results A total of 26 aminoacyl tRNA synthetases were identified using various computational and bioinformatics tools. Phylogenetic analysis and domain architectures of the L. major aminoacyl tRNA synthetases suggest a probable archaeal/eukaryotic origin. Presence of additional domains or N- or C-terminal extensions in 11 aminoacyl tRNA synthetases from L. major suggests possibilities such as additional tRNA binding or oligomerization or editing activity. Five freestanding editing domains were identified in L. major. Domain assignment revealed a novel asparagine tRNA synthetase paralog, asparagine synthetase A which has been so far reported from prokaryotes and archaea. Conclusions A comprehensive bioinformatic analysis revealed 26 aminoacyl tRNA synthetases and five freestanding editing domains in L. major. Identification of two EMAP (endothelial monocyte-activating polypeptide II-like proteins similar to human EMAP II-like proteins suggests their participation in multisynthetase complex formation. While the phylogeny of tRNA synthetases suggests a probable archaeal/eukaryotic origin, phylogeny of asparagine synthetase A strongly suggests a bacterial origin. The unique features identified in this work provide rationale for designing inhibitors against parasite aminoacyl tRNA synthetases and their paralogs.

  12. ADAPTATION TO UNFAVORABLE CONDITIONS OF GROWTH: PATHOGENICITY OF ACHOLEPLASMA LAIDLAWII PG8

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    Maxim V. Trushin

    2006-11-01

    Full Text Available ABSTRACT:As a result of cultivation of A. laidlawii PG8 cells on the deficient medium during 480 days, the mycoplasma culture adapted in vitro to unfavorable growth conditions was obtained. The culture consisted of cells with sizes less than 0.2 µm and features of A. laidlawii PG8 ultramicroforms, nanocells. A. laidlawii PG8 culture adapted in vitro to unfavorable growth conditions shows more evident phytopathogenicity than the unadapted one. Infecting plants V. minor L. by A. laidlawii PG8 culture adapted in vitro to UGC resulted in the appearance of chloroses in 75%, necrosis – 50%, leaves marcescence – 50% and abnormalities of bine development in 30% of plants through 12 days, while infecting plants by A. laidlawii PG8 culture unadapted to UGC led to respective signs in 40%, 25%, 25% and 0% of samples, respectively, through 30 days. The ability of A. laidlawii PG8 to form UMF resistant to stress factors in UGC with high phytopathogenic potential seems to demand a new approach to investigate the precise mechanisms of interacting the mycoplasma with host organisms.RESUMENComo resultado del cultivo de células de A. laidlawii PG8 en medio deficiente durante 480 días, fue obtenido un cultivo de mycoplasma adaptado in vitro a las condiciones desfavorables del crecimiento. El cultivo consistió en células con tamaño menor de 0.2 µm y características PG8 ultramicroformas de A. laidlawii nanocélulas. El cultivo de A. laidlawii PG8 adaptado in vitro a condiciones desfavorables del crecimiento muestra más evidente fitopatogenicidad que el inadaptado. Plantas infectadas V. minor L. por el cultivo del A. laidlawii PG8 adaptado in vitro a UGC dio como resultado la aparición de clorosis en el 75%, necrosis en el 50%, marcescencia de las hojas en el 50% y anormalidades del desarrollo del bine en el 30% de plantas a los 12 días, mientras que las plantas infectadas por el cultivo del A. laidlawii PG8 inadaptado a UGC, condujo a dichos signos en

  13. Impact of reticulated platelets on antiplatelet response to thienopyridines is independent of platelet turnover.

    Science.gov (United States)

    Stratz, Christian; Nührenberg, Thomas; Amann, Michael; Cederqvist, Marco; Kleiner, Pascal; Valina, Christian M; Trenk, Dietmar; Neumann, Franz-Josef; Hochholzer, Willibald

    2016-10-28

    Reticulated platelets are associated with impaired antiplatelet response to thienopyridines. It is uncertain whether this interaction is caused by a decreased drug exposure due to high platelet turnover reflected by elevated levels of reticulated platelets or by intrinsic properties of reticulated platelets. This study sought to investigate if the impact of reticulated platelets on early antiplatelet response to thienopyridines is mainly caused by platelet turnover as previously suggested. Elective patients undergoing coronary intervention were randomised to loading with clopidogrel 600 mg or prasugrel 60 mg (n=200). Adenosine diphosphate (ADP)-induced platelet reactivity was determined by impedance aggregometry before, at 30, 60, 90, and 120 minutes and at day 1 after loading. Immature platelet count was assessed as marker of reticulated platelets by flow cytometry. Platelet reactivity increased with rising levels of immature platelet count in both groups. This effect was more distinctive in patients on clopidogrel as compared to patients on prasugrel. Overall, immature platelet count correlated well with on-treatment platelet reactivity at all time-points (p < 0.001). These correlations did not change over time in the entire cohort as well as in patients treated with clopidogrel or prasugrel indicating an effect independent of platelet turnover (comparison of correlations 120 minutes/day 1: p = 0.64). In conclusion, the association of immature platelet count with impaired antiplatelet response to thienopyridines is similar early and late after loading. This finding suggests as main underlying mechanism another effect of reticulated platelets on thienopyridines than platelet turnover.

  14. Platelets and infection — an emerging role of platelets in viral infection

    Directory of Open Access Journals (Sweden)

    Alice eAssinger

    2014-12-01

    Full Text Available Platelets are anucleate blood cells that play a crucial role in the maintenance of hemostasis. While platelet activation and elevated platelet counts (thrombocytosis are associated with increased risk of thrombotic complications, low platelet counts (thrombocytopenia and several platelet function disorders increase the risk of bleeding. Over the last years more and more evidence has emerged that platelets and their activation state can also modulate innate and adaptive immune responses and low platelet counts have been identified as a surrogate marker for poor prognosis in septic patients.Viral infections often coincide with platelet activation. Host inflammatory responses result in the release of platelet activating mediators and a pro-oxidative and pro-coagulant environment, which favours platelet activation. However, viruses can also directly interact with platelets and megakaryocytes and modulate their function. Furthermore, platelets can be activated by viral antigen-antibody complexes and in response to some viruses B-lymphocytes also generate anti-platelet antibodies.All these processes contributing to platelet activation result in increased platelet consumption and removal and often lead to thrombocytopenia, which is frequently observed during viral infection. However, virus-induced platelet activation does not only modulate platelet count, but also shapes immune responses. Platelets and their released products have been reported to directly and indirectly suppress infection and to support virus persistence in response to certain viruses, making platelets a double-edged sword during viral infections. This review aims to summarize the current knowledge on platelet interaction with different types of viruses, the viral impact on platelet activation and platelet-mediated modulations of innate and adaptive immune responses.

  15. Platelets and infection - an emerging role of platelets in viral infection.

    Science.gov (United States)

    Assinger, Alice

    2014-01-01

    Platelets are anucleate blood cells that play a crucial role in the maintenance of hemostasis. While platelet activation and elevated platelet counts (thrombocytosis) are associated with increased risk of thrombotic complications, low platelet counts (thrombocytopenia) and several platelet function disorders increase the risk of bleeding. Over the last years, more and more evidence has emerged that platelets and their activation state can also modulate innate and adaptive immune responses and low platelet counts have been identified as a surrogate marker for poor prognosis in septic patients. Viral infections often coincide with platelet activation. Host inflammatory responses result in the release of platelet activating mediators and a pro-oxidative and pro-coagulant environment, which favors platelet activation. However, viruses can also directly interact with platelets and megakaryocytes and modulate their function. Furthermore, platelets can be activated by viral antigen-antibody complexes and in response to some viruses B-lymphocytes also generate anti-platelet antibodies. All these processes contributing to platelet activation result in increased platelet consumption and removal and often lead to thrombocytopenia, which is frequently observed during viral infection. However, virus-induced platelet activation does not only modulate platelet count but also shape immune responses. Platelets and their released products have been reported to directly and indirectly suppress infection and to support virus persistence in response to certain viruses, making platelets a double-edged sword during viral infections. This review aims to summarize the current knowledge on platelet interaction with different types of viruses, the viral impact on platelet activation, and platelet-mediated modulations of innate and adaptive immune responses.

  16. Response of transgenic poplar overexpressing cytosolic glutamine synthetase to phosphinothricin.

    Science.gov (United States)

    Pascual, María Belén; Jing, Zhong Ping; Kirby, Edward G; Cánovas, Francisco M; Gallardo, Fernando

    2008-01-01

    Glutamine synthetase (GS) is the main enzyme involved in ammonia assimilation in plants and is the target of phosphinothricin (PPT), an herbicide commonly used for weed control in agriculture. As a result of the inhibition of GS, PPT also blocks photorespiration, resulting in the depletion of leaf amino acid pools leading to the plant death. Hybrid transgenic poplar (Populus tremula x P. alba INRA clone 7171-B4) overexpressing cytosolic GS is characterized by enhanced vegetative growth [Gallardo, F., Fu, J., Cantón, F.R., García-Gutiérrez, A., Cánovas, F.M., Kirby, E.G., 1999. Expression of a conifer glutamine synthetase gene in transgenic poplar. Planta 210, 19-26; Fu, J., Sampalo, R., Gallardo, F., Cánovas, F.M., Kirby, E.G., 2003. Assembly of a cytosolic pine glutamine synthetase holoenzyme in leaves of transgenic poplar leads to enhanced vegetative growth in young plants. Plant Cell Environ. 26, 411-418; Jing, Z.P., Gallardo, F., Pascual, M.B., Sampalo, R., Romero, J., Torres de Navarra, A., Cánovas, F.M., 2004. Improved growth in a field trial of transgenic hybrid poplar overexpressing glutamine synthetase. New Phytol. 164, 137-145], increased photosynthetic and photorespiratory capacities [El-Khatib, R.T., Hamerlynck, E.P., Gallardo, F., Kirby, E.G., 2004. Transgenic poplar characterized by ectopic expression of a pine cytosolic glutamine synthetase gene exhibits enhanced tolerance to water stress. Tree Physiol. 24, 729-736], enhanced tolerance to water stress (El-Khatib et al., 2004), and enhanced nitrogen use efficiency [Man, H.-M., Boriel, R., El-Khatib, R.T., Kirby, E.G., 2005. Characterization of transgenic poplar with ectopic expression of pine cytosolic glutamine synthetase under conditions of varying nitrogen availability. New Phytol. 167, 31-39]. In vitro plantlets of GS transgenic poplar exhibited enhanced resistance to PPT when compared with non-transgenic controls. After 30 days exposure to PPT at an equivalent dose of 275 g ha(-1), growth

  17. Glutamine versus ammonia utilization in the NAD synthetase family.

    Directory of Open Access Journals (Sweden)

    Jessica De Ingeniis

    Full Text Available NAD is a ubiquitous and essential metabolic redox cofactor which also functions as a substrate in certain regulatory pathways. The last step of NAD synthesis is the ATP-dependent amidation of deamido-NAD by NAD synthetase (NADS. Members of the NADS family are present in nearly all species across the three kingdoms of Life. In eukaryotic NADS, the core synthetase domain is fused with a nitrilase-like glutaminase domain supplying ammonia for the reaction. This two-domain NADS arrangement enabling the utilization of glutamine as nitrogen donor is also present in various bacterial lineages. However, many other bacterial members of NADS family do not contain a glutaminase domain, and they can utilize only ammonia (but not glutamine in vitro. A single-domain NADS is also characteristic for nearly all Archaea, and its dependence on ammonia was demonstrated here for the representative enzyme from Methanocaldococcus jannaschi. However, a question about the actual in vivo nitrogen donor for single-domain members of the NADS family remained open: Is it glutamine hydrolyzed by a committed (but yet unknown glutaminase subunit, as in most ATP-dependent amidotransferases, or free ammonia as in glutamine synthetase? Here we addressed this dilemma by combining evolutionary analysis of the NADS family with experimental characterization of two representative bacterial systems: a two-subunit NADS from Thermus thermophilus and a single-domain NADS from Salmonella typhimurium providing evidence that ammonia (and not glutamine is the physiological substrate of a typical single-domain NADS. The latter represents the most likely ancestral form of NADS. The ability to utilize glutamine appears to have evolved via recruitment of a glutaminase subunit followed by domain fusion in an early branch of Bacteria. Further evolution of the NADS family included lineage-specific loss of one of the two alternative forms and horizontal gene transfer events. Lastly, we identified NADS

  18. Inactivation of Glutamine Synthetase by Ammonia Shock in the Gram-Positive Bacterium Streptomyces cattleya.

    Science.gov (United States)

    Wax, R; Synder, L; Kaplan, L

    1982-10-01

    In cultures of the gram-positive bacterium Streptomyces cattleya, a rapid inactivation of glutamine synthetase was seen after ammonia shock. pH activity curves for ammonia-shocked and control cultures are shown. A peak of glutamine synthetase activity was seen during fermentation for production of the antibiotic thienamycin.

  19. Inactivation of Glutamine Synthetase by Ammonia Shock in the Gram-Positive Bacterium Streptomyces cattleya

    OpenAIRE

    Wax, Richard; Synder, Linda; Kaplan, Louis

    1982-01-01

    In cultures of the gram-positive bacterium Streptomyces cattleya, a rapid inactivation of glutamine synthetase was seen after ammonia shock. pH activity curves for ammonia-shocked and control cultures are shown. A peak of glutamine synthetase activity was seen during fermentation for production of the antibiotic thienamycin.

  20. Roles of Long-chain Acyl Coenzyme A Synthetase in Absorption and Transport of Fatty Acid

    Institute of Scientific and Technical Information of China (English)

    Fan Gao; Xue-feng Yang; Nian Fu; Yang Hu; Yan Ouyang; Kai Qing

    2016-01-01

    Abstract Long-chain acyl coenzyme A synthetase (ACSL) is a member of the synthetase family encoded by a multigene family; it plays an important role in the absorption and transport of fatty acid. Here we review the roles of ACSL in the regulating absorption and transport of fatty acid, as well as the connection between ACSL and some metabolic diseases.

  1. Primer Dependent and Independent Forms of Soluble Starch Synthetase from Developing Barley Endosperms

    DEFF Research Database (Denmark)

    Kreis, M.

    1980-01-01

    The activity of soluble starch synthetase (ADP-glucose: agr-1,4-glucan agr-4-glucosyltransferase) in the non-purified extract from 16 day-old Bomi barley endosperms (Hordeum vulgare L.) was low and the reaction was non-linear when plotted against protein concentration. Starch synthetase was purif...

  2. [The anti-synthetase syndrome: muscle disease and multisystem disorder at the same time

    NARCIS (Netherlands)

    Hengstman, G.J.D.; Venrooij, W.J.W. van; Hoogen, F.H.J. van den; Engelen, B.G.M. van

    2003-01-01

    In three women, aged 60, 45 and 38 years, who presented with exertional dyspnoea (due to lung fibrosis) and Raynaud's phenomenon, dermatomyopathy and Raynaud's phenomenon, and symmetrical arthralgia and myalgia, respectively, the anti-synthetase syndrome was diagnosed. The anti-synthetase syndrome c

  3. Human platelet/erythroleukemia cell prostaglandin G/H synthase: cDNA cloning, expression, and gene chromosomal assignment

    Energy Technology Data Exchange (ETDEWEB)

    Funk, C.D.; Funk, L.B.; Kennedy, M.E.; Pong, A.S.; Fitzgerald, G.A. (Vanderbilt Univ., Nashville, TN (United States))

    1991-06-01

    Platelets metabolize arachidonic acid to thromboxane A{sub 2}, a potent platelet aggregator and vasoconstrictor compound. The first step of this transformation is catalyzed by prostaglandin (PG) G/H synthase, a target site for nonsteroidal antiinflammatory drugs. We have isolated the cDNA for both human platelet and human erythroleukemia cell PGG/H synthase using the polymerase chain reaction and conventional screening procedures. The cDNA encoding the full-length protein was expressed in COS-M6 cells. Microsomal fractions from transfected cells produced prostaglandin endoperoxide derived products which were inhibited by indomethacin and aspirin. Mutagenesis of the serine residue at position 529, the putative aspirin acetylation site, to an asparagine reduced cyclooxygenase activity to barely detectable levels, an effect observed previously with the expressed sheep vesicular gland enzyme. Platelet-derived growth factor and phorbol ester differentially regulated the expression of PGG/H synthase mRNA levels in the megakaryocytic/platelet-like HEL cell line. The PGG/H synthase gene was assigned to chromosome 9 by analysis of a human-hamster somatic hybrid DNA panel. The availability of platelet PGG/H synthase cDNA should enhance our understanding of the important structure/function domains of this protein and it gene regulation.

  4. A polygalacturonase-inhibiting protein from grapevine reduces the symptoms of the endopolygalacturonase BcPG2 from Botrytis cinerea in Nicotiana benthamiana leaves without any evidence for in vitro interaction

    NARCIS (Netherlands)

    Joubert, D.A.; Kars, I.; Wagemakers, L.; Bergmann, C.; Kemp, G.; Vivier, M.A.; Kan, van J.A.L.

    2007-01-01

    Six endopolygalacturonases from Botrytis cinerea (BcPG1 to BcPG6) as well as mutated forms of BcPG1 and BcPG2 were expressed transiently in leaves of Nicotiana benthamiana using agroinfiltration. Expression of BcPG1, BcPG2, BcPG4, BcPG5, and mutant BcPG1-D203A caused symptoms, whereas BcPG3, BcPG6,

  5. The Mitochondrial Aminoacyl tRNA Synthetases: Genes and Syndromes.

    Science.gov (United States)

    Diodato, Daria; Ghezzi, Daniele; Tiranti, Valeria

    2014-01-01

    Mitochondrial respiratory chain (RC) disorders are a group of genetically and clinically heterogeneous diseases. This is because protein components of the RC are encoded by both mitochondrial and nuclear genomes and are essential in all cells. In addition, the biogenesis and maintenance of mitochondria, including mitochondrial DNA (mtDNA) replication, transcription, and translation, require nuclear-encoded genes. In the past decade, a growing number of syndromes associated with dysfunction of mtDNA translation have been reported. This paper reviews the current knowledge of mutations affecting mitochondrial aminoacyl tRNAs synthetases and their role in the pathogenic mechanisms underlying the different clinical presentations.

  6. The Mitochondrial Aminoacyl tRNA Synthetases: Genes and Syndromes

    Directory of Open Access Journals (Sweden)

    Daria Diodato

    2014-01-01

    Full Text Available Mitochondrial respiratory chain (RC disorders are a group of genetically and clinically heterogeneous diseases. This is because protein components of the RC are encoded by both mitochondrial and nuclear genomes and are essential in all cells. In addition, the biogenesis and maintenance of mitochondria, including mitochondrial DNA (mtDNA replication, transcription, and translation, require nuclear-encoded genes. In the past decade, a growing number of syndromes associated with dysfunction of mtDNA translation have been reported. This paper reviews the current knowledge of mutations affecting mitochondrial aminoacyl tRNAs synthetases and their role in the pathogenic mechanisms underlying the different clinical presentations.

  7. Phosphorylation and Acetylation of Acyl-CoA Synthetase- I

    DEFF Research Database (Denmark)

    Frahm, Jennifer L; Li, Lei O; Grevengoed, Trisha J

    2011-01-01

    Long chain acyl-CoA synthetase 1 (ACSL1) contributes 50 to 90% of total ACSL activity in liver, adipose tissue, and heart and appears to direct the use of long chain fatty acids for energy. Although the functional importance of ACSL1 is becoming clear, little is understood about its post...... and acetylated amino acids by mass spectrometry. We then compared these results to the post-translational modifications observed in vivo in liver and brown adipose tissue after mice were fasted or exposed to a cold environment. We identified universal N-terminal acetylation, 15 acetylated lysines, and 25...

  8. The K-Pg Event-Bed at ODP 207 Reloaded: Search for the Meteoritic Component

    Science.gov (United States)

    Deutsch, A.; Vollmer, C.; Tagle, R.; Salge, T.; Hansen, B.; Ott, U.; Hoppe, P.; Berndt, J.

    2013-09-01

    We report on the search for traces of the Chicxulub bolide in the K-Pg bed drilled in the western tropical Atlantic, using advanced separation techniques and microanalytical tools with high spatial resolution.

  9. Classification of minimal 1-saturating sets in $PG(2,q)$, $q\\leq 23$

    CERN Document Server

    Bartoli, Daniele; Pambianco, Fernanda

    2012-01-01

    Minimal 1-saturating sets in the projective plane $PG(2,q)$ are considered. They correspond to covering codes which can be applied to many branches of combinatorics and information theory, as data compression, compression with distortion, broadcasting in interconnection network, write-once memory or steganography (see \\cite{Coh} and \\cite{BF2008}). The full classification of all the minimal 1-saturating sets in PG(2,9) and PG(2,11) and the classification of minimal 1-saturating sets of smallest size in PG(2,q), $16\\leq q\\leq 23$ are given. These results have been found using a computer-based exhaustive search that exploits projective equivalence properties.

  10. Understanding the spectrum of the very hot DA white dwarf PG0948+534

    CERN Document Server

    Preval, S P

    2016-01-01

    PG0948+534 is currently one of the hottest DA white dwarf stars, and is also one of the most mysterious. Attempts to model the sharp, deep absorption features of this star have been unsuccessful. In these proceedings we describe our analysis of PG0948+534. We perform a line survey of the UV spectrum of PG0948+534, making detections of 300+ absorption features, and identifying four distinct velocity regimes. We find evidence of circumstellar absorption in the profiles of C {\\sc iv} and Si {\\sc iv}. Using non-local thermodynamic equilibrium model atmospheres, we are able to correctly model the absorption features of the star, providing abundance measurements for C, N, O, and Si for PG0948+534 for the first time. We also revise the effective temperature and gravity for this star using models including these new abundances.

  11. Increasing effect of a high dose of PG-1 peptide on the infectivity of Chlamydophila abortus.

    Science.gov (United States)

    Donati, Manuela; Di Francesco, Antonietta; Gennaro, Renato; Benincasa, Monica; Di Paolo, Maria; Shurdhi, Alisa; Ostanello, Fabio; Baldelli, Raffaella; Cevenini, Roberto

    2010-07-01

    Cathelicidins are antimicrobial peptides, stored by mammalian leukocytes, showing an antimicrobial activity against bacteria, fungi, protozoa and enveloped viruses. In accordance with other authors, we reported in a previous study that the protegrin-1 (PG-1), at 80 microg mL(-1), inhibited the in vitro growth of Chlamydia trachomatis serovars D, H and L2; however, we observed an increased infectivity of some animal chlamydial species after their treatment with the same PG-1 concentration. In this study, the treatment of LLC-MK2 cells with PG-1 before chlamydial infection resulted in an increased infectivity of Chlamydophila abortus probably due to their easier entry into the host cells, whereas no increase in S26/3 infectivity was detected in LLC-MK2 cells treated with PG-1 postchlamydial infection.

  12. Platelet satellitism in infectious disease?

    Science.gov (United States)

    Laskaj, Renata; Sikiric, Dubravka; Skerk, Visnja

    2015-01-01

    Background Platelet satellitism is a phenomenon of unknown etiology of aggregating platelets around polymorphonuclear neutrophils and other blood cells which causes pseudothrombocytopenia, visible by microscopic examination of blood smears. It has been observed so far in about a hundred cases in the world. Case subject and methods Our case involves a 73-year-old female patient with a urinary infection. Biochemical serum analysis (CRP, glucose, AST, ALT, ALP, GGT, bilirubin, sodium, potassium, chloride, urea, creatinine) and blood cell count were performed with standard methods on autoanalyzers. Serum protein fractions were examined by electrophoresis and urinalysis with standard methods on autoanalyzer together with microscopic examination of urine sediment. Erythrocyte sedimentation rate, blood culture and urine culture tests were performed with standard methods. Results Due to typical pathological values for bacterial urinary infection, the patient was admitted to the hospital. Blood smear examination revealed phenomenon, which has persisted for three weeks after the disease has been cured. Blood smears with EDTA as an anticoagulant had platelet satellitism whereas the phenomenon was not observed in tubes with different anticoagulants (Na, Li-heparin) and capillary blood. Discussion We hypothesize that satellitism was induced by some immunological mechanism through formation of antibodies which have mediated platelets binding to neutrophil membranes and vice versa. Unfortunately we were unable to determine the putative trigger for this phenomenon. To our knowledge this is the second case of platelet satellitism ever described in Croatia. PMID:26110042

  13. Evaluation of platelet aggregation in platelet concentrates: storage implications

    Directory of Open Access Journals (Sweden)

    Neiva Teresinha J.C.

    2003-01-01

    Full Text Available The use of hemo-derivatives is nowadays a fundamentally important therapeutic modality in the exercise of medicine. Among the various hemo-components employed, we have the platelet concentrate (PC, indicated in cases of hemorrhagic disturbances. We previously showed that platelet function in blood donors is reduced in their screening phase and after the separation process of PCs. Currently, we are providing evidence for the existence of biochemical and functional changes in PC preparations stored for three days at temperatures of 20 ± 2 ºC. Platelet concentrates from 40 healthy donors, collected in CPD anticoagulant and PL-146 polyvinylchloride containers, were examined in order to determine the pH value, pCO2 ,pO2 and lactate concentrations. In addition, the aggregation of platelets with thrombin and collagen were examined to evaluate platelet function. A pH increase from 7.07 ± 0.04 to 7.36 ± 0.07 (p < 0.01 was observed. The pCO2 concentration decreased progressively from 69.2 ± 7.7 mmHg to 28.8 ± 6.2 mmHg (p < 0.001 during the storage period. In contrast, pO2 value increase from 103.4 ± 30.6 to 152.3 ± 24.6 mmHg (p < 0.001 was evidenced during the 48 hours of storage. The lactate concentration increased from 17.97 ± 5.2 to 57.21 ± 5.7 mg/dl (p < 0.001. Platelet aggregation using 0.25 U/ml-thrombin and 2.0 µg/ml-collagen showed significant hypofunction from 61.8 ± 2.7% to 24.8 ± 9.8% and 62.7±5.0 to 33.4± 6.2 (p < 0.001, respectively. We concluded that the evaluated biochemical parameters and the platelet function changed significantly when the platelets were kept under routine storage conditions.

  14. Radioimmunoassay of a human serum growth factor for Balb/c-3T3 cells: derivation from platelets.

    Science.gov (United States)

    Antoniades, H N; Scher, C D

    1977-05-01

    A radioimmunoassay has been developed for the detection and quantification of a human serum polypeptide that has growth-promoting activity for confluent Balb/c-3T3 cells. Antiserum to this growth factor does not recognize antigens in mouse, guinea pig, or bovine serum but does detect some crossreacting antigen in the serum of the New World monkey Cebus albifrons and more in the serum of the Old World rhesus monkeys Macaca mulatta and M. fascicularis, demonstrating that the antigenic determinants of the growth factor have a degree of species specificity. Serum derived from whole human blood contains approximately 770 pg of the growth factor per mg of protein; serum derived from platelet-poor blood contains about 112 pg of the growth factor per mg of protein. As much as 1 microng of the growth factor per mg of protein has been recovered from human platelets by heating them at 100 degrees for 2 min. Approximately 1-2 ng of the growth factor, in either whole serum or platelets, stimulates 5 to 10 X 10(3) confluent Balb/c-3T3 cells to replicate. The heat treatment of platelets allows the purification and quantitative recovery of the growth factor from blood.

  15. Circumstantial evidence for a role of glutamine-synthetase in suicide.

    Science.gov (United States)

    Kalkman, Hans O

    2011-06-01

    Suicide occurs during depression, schizophrenia, diabetes and epilepsy. A common denominator of these disorders is the presence of inflammation. Inflammatory cytokines affect function and expression of the glial enzyme glutamine synthetase and post mortem studies indicate that brain glutamine synthetase function is suppressed in mood disorders and epilepsy. In a study of schizophrenia brains, the expression of glutamine synthetase was reduced in those cases where the cause of death was suicide. The glycogen synthase kinase 3 (GSK3) inhibitor, lithium, which has a proven efficacy against suicide, increased in an animal experiment the expression of glutamine synthetase. Based on these data one could reason that suicide may be prevented by centrally acting GSK3 inhibitors. However, since inhibition of glutamine synthetase may lead to a deficit in glutamine and as consequence a GABA and glutamate deficit, even simple food supplementation with glutamine might help to reduce suicide.

  16. CD8+ T cells induce platelet clearance in the liver via platelet desialylation in immune thrombocytopenia

    Science.gov (United States)

    Qiu, Jihua; Liu, Xuena; Li, Xiaoqing; Zhang, Xu; Han, Panpan; Zhou, Hai; Shao, Linlin; Hou, Yu; Min, Yanan; Kong, Zhangyuan; Wang, Yawen; Wei, Yu; Liu, Xinguang; Ni, Heyu; Peng, Jun; Hou, Ming

    2016-01-01

    In addition to antiplatelet autoantibodies, CD8+ cytotoxic T lymphocytes (CTLs) play an important role in the increased platelet destruction in immune thrombocytopenia (ITP). Recent studies have highlighted that platelet desialylation leads to platelet clearance via hepatocyte asialoglycoprotein receptors (ASGPRs). Whether CD8+ T cells induce platelet desialylation in ITP remains unclear. Here, we investigated the cytotoxicity of CD8+ T cells towards platelets and platelet desialylation in ITP. We found that the desialylation of fresh platelets was significantly higher in ITP patients with positive cytotoxicity of CD8+ T cells than those without cytotoxicity and controls. In vitro, CD8+ T cells from ITP patients with positive cytotoxicity induced significant platelet desialylation, neuraminidase-1 expression on the platelet surface, and platelet phagocytosis by hepatocytes. To study platelet survival and clearance in vivo, CD61 knockout mice were immunized and their CD8+ splenocytes were used. Platelets co-cultured with these CD8+ splenocytes demonstrated decreased survival in the circulation and increased phagocytosis in the liver. Both neuraminidase inhibitor and ASGPRs competitor significantly improved platelet survival and abrogated platelet clearance caused by CD8+ splenocytes. These findings suggest that CD8+ T cells induce platelet desialylation and platelet clearance in the liver in ITP, which may be a novel mechanism of ITP. PMID:27321376

  17. An overview of platelet indices and methods for evaluating platelet function in thrombocytopenic patients

    DEFF Research Database (Denmark)

    Vinholt, Pernille Just; Hvas, Anne-Mette; Nybo, Mads

    2014-01-01

    in thrombocytopenia. Flow cytometry, platelet aggregometry and platelet secretion tests are used to diagnose specific platelet function defects. The flow cytometric activation marker P-selectin and surface coverage by the Cone and Plate[let] analyser™ predict bleeding in selected thrombocytopenic populations...

  18. Platelet antigens and antibodies. Literature review

    Directory of Open Access Journals (Sweden)

    N. V. Mineeva

    2013-01-01

    Full Text Available Platelet antigens structure, role of platelet antibodies in the pathogenesis of various clinical conditions, characteristic of modern antibodies detection methods are presented in this article.

  19. Platelet antigens and antibodies. Literature review

    Directory of Open Access Journals (Sweden)

    N. V. Mineeva

    2014-07-01

    Full Text Available Platelet antigens structure, role of platelet antibodies in the pathogenesis of various clinical conditions, characteristic of modern antibodies detection methods are presented in this article.

  20. Effect of photodynamic therapy on mouse platelets

    Science.gov (United States)

    Zhou, Chuannong; Chi, Shunji; Deng, Jinsheng; Zhang, Hua; Liang, Junlin; Ha, Xian-wen

    1993-06-01

    Normal mice received hematoporphyrin derivative (HpD) i.v. prior to red light irradiation and the platelet-rich plasma was prepared and irradiated by red light. The platelets were processed for EM examination and stereological analysis. It was shown the 16 hrs after irradiation almost all platelets were necrotized; 8 hours after irradiation about one fourth of the platelets were necrotized and the remaining were considerably damaged. Immediately after irradiation a small number of platelets became necrotic and most other platelets were swollen and deformated, showing significantly increased mean area, perimeter and short axis, and mean cell volume and cell surface area. The findings indicate that platelets are highly sensitive to PDT action and can be directly and rapidly damaged by PDT even in the absence of vascular endothelial cells. The early platelet photoactivation may play an important role in the initiation of early vascular damage and microcirculatory alterations induced by PDT in vivo.

  1. Platelet Disorders: MedlinePlus Health Topic

    Science.gov (United States)

    ... Article: Erythropoietin and thrombopoietin mimetics: Natural alternatives to erythrocyte and platelet... Article: Detection of CALR Mutation in Clonal and Nonclonal Hematologic Diseases... Platelet Disorders -- see more articles Thrombocytopenias -- see more ...

  2. Effect of platelet age on adhesiveness to collagen and platelet surface charge

    Energy Technology Data Exchange (ETDEWEB)

    Castellan, R.M.; Steiner, M.

    1976-11-30

    Adhesion to collagen was investigated as a function of platelet age in rat platelets. Platelet adherence was measured using EDTA-containing platelet- rich plasma which was added to preparations of collagen fibers clamped between magnetic stirrers by recording changes in light transmission. The plot of light transmission versus logarithm of time was linear and allowed calculation of a slope factor which related to the rate of adherence. Neither the amount of collagen nor the platelet count were limiting in the test. Young platelet populations (less than or equal to 1 day old) were obtained during the recovery phase from immune induced thrombocytopenia. Old platelet populations were prepared by blocking thrombopoiesis with cyclophosphamide. Young platelets did not differ significantly from randomly aged platelets in this function. The electrophoretic mobility of platelets was not affected by their age.

  3. Portability of oxidase domains in nonribosomal peptide synthetase modules.

    Science.gov (United States)

    Schneider, Tanya L; Walsh, Christopher T

    2004-12-21

    Oxazole and thiazole rings are present in numerous nonribosomal peptide natural products. Oxidase domains are responsible for catalyzing the oxidation of thiazolines and oxazolines to yield fully aromatic heterocycles. Unlike most domains, the placement of oxidase domains within assembly line modules varies. Noting this tolerance, we investigated the portability of an oxidase domain to a heterologous assembly line. The epimerase domain of PchE, involved in pyochelin biosynthesis, was replaced with the oxidase domain from MtaD, involved in myxothiazol biosynthesis. The chimeric module was expressed in soluble form as a flavin mononucleotide-containing flavoprotein. The functionality of the inserted oxidase domain was assayed within PchE and in transfer of the growing siderophore acyl chain from PchE to the next downstream module. While pyochelin-like product release was not observed downstream, the robust activity of the transplanted oxidase domain and the ability of the chimeric module to produce an advanced intermediate bound to the synthetase underscore the possibility of future engineering within nonribosomal peptide synthetase pathways using oxidase domains.

  4. Holocarboxylase synthetase deficiency pre and post newborn screening

    Directory of Open Access Journals (Sweden)

    Taraka R. Donti

    2016-06-01

    Full Text Available Holocarboxylase synthetase deficiency is an autosomal recessive disorder of biotin metabolism resulting in multiple carboxylase deficiency. The typical presentation described in the medical literature is of neonatal onset within hours to weeks of birth with emesis, hypotonia, lethargy, seizures, metabolic ketolactic acidosis, hyperammonemia, developmental delay, skin rash and alopecia. The condition is screened for by newborn screening (NBS tandem mass spectroscopy by elevated hydroxypentanoylcarnitine on dried blood spots. Urine organic acid profile may demonstrate elevated lactic, 3-OH isovaleric, 3-OH propionic, 3-MCC, methylcitric acids, and tiglylglycine consistent with loss of function of the above carboxylases. Here we describe a cohort of patients, 2 diagnosed pre-NBS and 3 post-NBS with broad differences in initial presentation and phenotype. In addition, prior to the advent of NBS, there are isolated reports of late-onset holocarboxylase synthetase deficiency in the medical literature, which describe patients diagnosed between 1 and 8 years of life, however to our knowledge there are no reports of late-onset HCLS being missed by NBS. Also we report two cases, each with novel pathogenic variants HCLS, diagnosed at age 3 years and 21 months respectively. The first patient had a normal newborn screen whilst the second had an abnormal newborn screen but was misdiagnosed as 3-methylcrotonylcarboxylase (3-MCC deficiency and subsequently lost to follow-up until they presented again with severe metabolic acidosis.

  5. Dengue platelets meet Sir Arthur Conan Doyle.

    Science.gov (United States)

    Bray, Paul F

    2013-11-14

    In this issue of Blood, Hottz et al provide compelling evidence that dengue virus (DV) induces (1) platelet synthesis of interleukin-1b (IL-1b); (2) platelet-derived IL-1b–containing microvesicles (MVs) that increase vascular permeability; and (3) DV-triggered inflammasome activation in platelets.

  6. Molecular Basis Linking Platelet to Inflammation

    Institute of Scientific and Technical Information of China (English)

    马丽萍

    2010-01-01

    @@ Introduction Blood platelets not only play an important role in hemostasis and thrombosis,but increasing evidence show that they participate in the induction of inflammation.Firstly,platelets contain and release cytokines and immune mediators.And platelets are able to modulate and regulate the function of surrounding cells by adhesion molecules or by the release of various factors.

  7. Platelets Inhibit Migration of Canine Osteosarcoma Cells.

    Science.gov (United States)

    Bulla, S C; Badial, P R; Silva, R C; Lunsford, K; Bulla, C

    2017-01-01

    The interaction between platelets and tumour cells is important for tumour growth and metastasis. Thrombocytopenia or antiplatelet treatment negatively impact on cancer metastasis, demonstrating potentially important roles for platelets in tumour progression. To our knowledge, there is no information regarding the role of platelets in cancer progression in dogs. This study was designed to test whether canine platelets affected the migratory behaviour of three canine osteosarcoma cell lines and to give insights of molecular mechanisms. Intact platelets, platelet lysate and platelet releasate inhibited the migration of canine osteosarcoma cell lines. Addition of blood leucocytes to the platelet samples did not alter the inhibitory effect on migration. Platelet treatment also significantly downregulated the transcriptional levels of SNAI2 and TWIST1 genes. The interaction between canine platelets or molecules released during platelet activation and these tumour cell lines inhibits their migration, which suggests that canine platelets might antagonize metastasis of canine osteosarcoma. This effect is probably due to, at least in part, downregulation of genes related to epithelial-mesenchymal transition. Copyright © 2016. Published by Elsevier Ltd.

  8. Platelet regulating properties of insulin revisited

    NARCIS (Netherlands)

    Andrade Ferreira, I. (Irlando)

    2005-01-01

    Disturbances in platelet responsiveness in diabetes mellitus (DM) lead to platelet-dependent complications in the vasculature. Our studies showed that insulin inhibits platelet activation by inhibiting ADP- and thrombin-induced Ca2+ levels. Ca2+ is under control of cAMP that is a potent endogenous p

  9. Image analysis of blood platelets adhesion.

    Science.gov (United States)

    Krízová, P; Rysavá, J; Vanícková, M; Cieslar, P; Dyr, J E

    2003-01-01

    Adhesion of blood platelets is one of the major events in haemostatic and thrombotic processes. We studied adhesion of blood platelets on fibrinogen and fibrin dimer sorbed on solid support material (glass, polystyrene). Adhesion was carried on under static and dynamic conditions and measured as percentage of the surface covered with platelets. Within a range of platelet counts in normal and in thrombocytopenic blood we observed a very significant decrease in platelet adhesion on fibrin dimer with bounded active thrombin with decreasing platelet count. Our results show the imperative use of platelet poor blood preparations as control samples in experiments with thrombocytopenic blood. Experiments carried on adhesive surfaces sorbed on polystyrene showed lower relative inaccuracy than on glass. Markedly different behaviour of platelets adhered on the same adhesive surface, which differed only in support material (glass or polystyrene) suggest that adhesion and mainly spreading of platelets depends on physical quality of the surface. While on polystyrene there were no significant differences between fibrin dimer and fibrinogen, adhesion measured on glass support material markedly differed between fibrin dimer and fibrinogen. We compared two methods of thresholding in image analysis of adhered platelets. Results obtained by image analysis of spreaded platelets showed higher relative inaccuracy than results obtained by image analysis of platelets centres and aggregates.

  10. Human platelet antigen genotyping of platelet donors in southern Brazil.

    Science.gov (United States)

    Merzoni, J; Fagundes, I S; Lunardi, L W; Lindenau, J D-R; Gil, B C; Jobim, M; Dias, V G; Merzoni, L; Sekine, L; Onsten, T G H; Jobim, L F

    2015-10-01

    Human platelet antigens (HPA) are immunogenic structures that result from single nucleotide polymorphisms (SNPs) leading to single amino acid substitutions. This study sought to determine the allele and genotype frequencies of HPA-1, HPA-2, HPA-3, HPA-4, HPA-5 and HPA-15 in platelet donors from the state of Rio Grande do Sul (RS), Brazil, and compare their allele frequencies to those observed in other populations. HPA genotyping was performed by PCR-SSP method. The study sample comprised 201 platelet donors (167 Caucasians and 34 non-Caucasians). Allele 'a' was that most commonly found for HPA-1 to 5 in both groups. The HPA-15ab genotype predominated over homozygous genotypes of this system. Fisher's exact test revealed statistically significant differences for the HPA-5 system, with a greater prevalence of the HPA-5b allele in non-Caucasians. The neighbour-joining method and principal components analysis revealed genetic proximity between our Caucasian group and European populations. We conclude that the allele frequencies of HPA-1 to 5 and HPA-15 found in our Caucasian sample are similar to those reported for European populations. These findings corroborate the ethnic makeup of the population of RS. The higher frequency of the HPA-5b allele found in the non-Caucasian group of our sample suggests the possibility of allosensitization in patients who receive platelet transfusions from genetically incompatible donors.

  11. Platelet count and platelet indices in women with preeclampsia

    Directory of Open Access Journals (Sweden)

    AlSheeha MA

    2016-11-01

    Full Text Available Muneera A AlSheeha,1 Rafi S Alaboudi,1 Mohammad A Alghasham,1 Javed Iqbal,2 Ishag Adam1 1Department of Obstetrics and Gynaecology, College of Medicine, Qassim University, Buriadah, 2Department of Obstetrics and Gynecology, Maternity and Children’s Hospital, Qassim, Kingdom of Saudi Arabia Background: Although the exact pathophysiology of preeclampsia is not completely understood, the utility of different platelets indices can be utilized to predict preeclampsia.Objective: To compare platelet indices, namely platelet count (PC, mean platelet volume (MPV, platelet distribution width (PDW, and PC to MPV ratio in women with preeclampsia compared with healthy controls.Setting: Qassim Hospital, Kingdom of Saudi Arabia.Design: A case–control study. Sixty preeclamptic women were the cases and an equal number of healthy pregnant women were the controls.Results: There was no significant difference in age, parity, and body mass index between the study groups. Sixteen and 44 of the cases were severe and mild preeclampsia, respectively. There was no significant difference in PDW and MPV between the preeclamptic and control women. Both PC and PC to MPV ratios were significantly lower in the women with preeclampsia compared with the controls. There was no significant difference in the PC, PDW, MPV, and PC to MPV ratio when women with mild and severe preeclampsia were compared. Using receiver operating characteristic (ROC curves, the PC cutoff was 248.0×103/µL for diagnosis of preeclampsia (P=0.019; the area under the ROC curve was 62.4%. Binary regression suggests that women with PC <248.010×103/µL were at higher risk of preeclampsia (odds ratio =2.2, 95% confidence interval =1.08–4.6, P=0.03. The PC/MPV cutoff was 31.2 for diagnosis of preeclampsia (P=0.035, the area under the ROC curve was 62.2%.Conclusion: PC <248.010×103/µL and PC to MPV ratio 31.2 are valid predictors of preeclampsia. Keywords: preeclampsia, platelets, PDW, mean platelet

  12. Elevated thrombopoietin and platelet indices confirm active thrombopoiesis but fail to predict clinical severity of puumala hantavirus infection

    Science.gov (United States)

    Laine, Outi; Joutsi-Korhonen, Lotta; Lassila, Riitta; Huhtala, Heini; Vaheri, Antti; Mäkelä, Satu; Mustonen, Jukka

    2016-01-01

    Abstract We evaluated the mechanisms of thrombocytopenia and procoagulant changes in relation with clinical variables in a cohort of patients with acute hantavirus disease. Blood samples of 33 prospectively recruited, consecutive, hospitalized patients with acute Puumala virus–induced hemorrhagic fever with renal syndrome (HFRS) were collected acutely and at the recovery visit (control). Serum thrombopoietin (TPO) and activity of plasma microparticles (MPs) from various cell sources were measured with enzyme-linked immunosorbent assay-based methods. The results were related to data on platelet indices and functions, coagulation variables, and clinical disease. Serum TPO was nearly 4-fold higher acutely compared with the control (median 207 pg/mL, range 56–1258 pg/mL vs. median 58 pg/mL, range 11–241 pg/mL, P < 0.001) and coincided with high mean platelet volume (MPV) and immature platelet fraction (IPF%). Prothrombin fragments and D-dimer were high acutely compared with the control (F1 + 2 median 704 pmol/L, range 284–1875 pmol/L vs. median 249 pmol/L, range 118–556 pmol/L, P < 0.001; d-dimer median 2.8 mg/L, range 0.6–34.0 mg/L vs. median 0.4 mg/L, range 0.2–1.1 mg/L, P < 0.001), and associated with low platelet count and severe acute kidney injury (AKI). MPs’ procoagulant activity was high acutely only among patients with mild AKI (plasma creatinine below the median at the time of the measurement). Upregulated TPO together with high MPV and IPF% confirm active thrombopoiesis, but do not predict severity of HFRS. Simultaneously, elevated prothrombin fragments and d-dimer suggest increased consumption of platelets in patients with severe AKI. Activity of platelet-derived MPs in HFRS should be studied with flow cytometry in a larger cohort of patients. PMID:28033261

  13. Platelet count and platelet indices in women with preeclampsia.

    Science.gov (United States)

    AlSheeha, Muneera A; Alaboudi, Rafi S; Alghasham, Mohammad A; Iqbal, Javed; Adam, Ishag

    2016-01-01

    Although the exact pathophysiology of preeclampsia is not completely understood, the utility of different platelets indices can be utilized to predict preeclampsia. To compare platelet indices, namely platelet count (PC), mean platelet volume (MPV), platelet distribution width (PDW), and PC to MPV ratio in women with preeclampsia compared with healthy controls. Qassim Hospital, Kingdom of Saudi Arabia. A case-control study. Sixty preeclamptic women were the cases and an equal number of healthy pregnant women were the controls. There was no significant difference in age, parity, and body mass index between the study groups. Sixteen and 44 of the cases were severe and mild preeclampsia, respectively. There was no significant difference in PDW and MPV between the preeclamptic and control women. Both PC and PC to MPV ratios were significantly lower in the women with preeclampsia compared with the controls. There was no significant difference in the PC, PDW, MPV, and PC to MPV ratio when women with mild and severe preeclampsia were compared. Using receiver operating characteristic (ROC) curves, the PC cutoff was 248.0×10(3)/µL for diagnosis of pre-eclampsia (P=0.019; the area under the ROC curve was 62.4%). Binary regression suggests that women with PC preeclampsia (odds ratio =2.2, 95% confidence interval =1.08-4.6, P=0.03). The PC/MPV cutoff was 31.2 for diagnosis of preeclampsia (P=0.035, the area under the ROC curve was 62.2%). PC preeclampsia.

  14. Pooled platelet concentrates: an alternative to single donor apheresis platelets?

    Science.gov (United States)

    Pietersz, R N I

    2009-10-01

    Three types of platelet concentrates (PC) are compared: PC either processed with the platelet-rich plasma (PRP) or the Buffy coat (BC) method from whole blood units and PC obtained by apheresis. Leuko-reduction (LR) pre-storage is advocated to improve quality of the PC during storage and reduce adverse reactions in recipients. Standardization of methods allow preparation of PC with comparable yields of approximately 400 x 10(9) platelets in pooled non-LR-PRP, approximately 370 x 10(9) in pooled LR-BC-PC and in LR apheresis PC the number of platelets can be targeted on 350 x 10(9) or more with devices of various manufacturers. While viral transmission can be prevented by outstanding laboratory tests, the risk of bacterial contamination should be reduced by improved arm disinfection, deviation of the first 20-30 ml of blood and culture or rapid detection assays of the PC pre-issue. In a large prospective multicenter trial no significant difference was observed between cultures of apheresis PC (n = 15,198): 0.09% confirmed positive units versus 0.06% in pooled BC-PC (n = 37,045), respectively. Though platelet activation as measured by CD62 expression may differ in vitro in PC obtained with various apheresis equipment, and also between PC processed with the two whole blood methods there is scarce literature about the clinical impact of these findings. In conclusion the final products of LR-PC derived from whole blood or obtained by apheresis can be comparable, provided the critical steps of the processing method are identified and covered and the process is in control.

  15. Effect of ionizing radiation on platelet function in vitro

    Energy Technology Data Exchange (ETDEWEB)

    Kalovidouris, A.E.; Papayannis, A.G. (Evangelismos Hospital, Athens (Greece))

    1981-01-01

    The effect of ionizing radiation on platelet function was investigated in vitro. Platelet-rich plasma (300x10/sup 9//l) was irradiated with doses of 1, 4, 10, 20 and 50 Gy. Platelet function tests were performed on both irradiated and control (non-irradiated) platelet samples. The platelet function tests were (1) platelet aggregation by ADP (1, 2, 4 ..mu..mol final concentration), adrenaline and collagen, (2) ADP-release from platelets, (3) clot retraction and (4) platelet factor-3 availability. It was found that roentgen irradiation of platelets in vitro did not affect these platelet function tests.

  16. Molecular Cloning and Expression Analysis of Eight PgWRKY Genes in Panax ginseng Responsive to Salt and Hormones.

    Science.gov (United States)

    Xiu, Hao; Nuruzzaman, Mohammed; Guo, Xiangqian; Cao, Hongzhe; Huang, Jingjia; Chen, Xianghui; Wu, Kunlu; Zhang, Ru; Huang, Yuzhao; Luo, Junli; Luo, Zhiyong

    2016-03-04

    Despite the importance of WRKY genes in plant physiological processes, little is known about their roles in Panax ginseng C.A. Meyer. Forty-eight unigenes on this species were previously reported as WRKY transcripts using the next-generation sequencing (NGS) technology. Subsequently, one gene that encodes PgWRKY1 protein belonging to subgroup II-d was cloned and functionally characterized. In this study, eight WRKY genes from the NGS-based transcriptome sequencing dataset designated as PgWRKY2-9 have been cloned and characterized. The genes encoding WRKY proteins were assigned to WRKY Group II (one subgroup II-c, four subgroup II-d, and three subgroup II-e) based on phylogenetic analysis. The cDNAs of the cloned PgWRKYs encode putative proteins ranging from 194 to 358 amino acid residues, each of which includes one WRKYGQK sequence motif and one C₂H₂-type zinc-finger motif. Quantitative real-time PCR (qRT-PCR) analysis demonstrated that the eight analyzed PgWRKY genes were expressed at different levels in various organs including leaves, roots, adventitious roots, stems, and seeds. Importantly, the transcription responses of these PgWRKYs to methyl jasmonate (MeJA) showed that PgWRKY2, PgWRKY3, PgWRKY4, PgWRKY5, PgWRKY6, and PgWRKY7 were downregulated by MeJA treatment, while PgWRKY8 and PgWRKY9 were upregulated to varying degrees. Moreover, the PgWRKY genes increased or decreased by salicylic acid (SA), abscisic acid (ABA), and NaCl treatments. The results suggest that the PgWRKYs may be multiple stress-inducible genes responding to both salt and hormones.

  17. Molecular Cloning and Expression Analysis of Eight PgWRKY Genes in Panax ginseng Responsive to Salt and Hormones

    Directory of Open Access Journals (Sweden)

    Hao Xiu

    2016-03-01

    Full Text Available Despite the importance of WRKY genes in plant physiological processes, little is known about their roles in Panax ginseng C.A. Meyer. Forty-eight unigenes on this species were previously reported as WRKY transcripts using the next-generation sequencing (NGS technology. Subsequently, one gene that encodes PgWRKY1 protein belonging to subgroup II-d was cloned and functionally characterized. In this study, eight WRKY genes from the NGS-based transcriptome sequencing dataset designated as PgWRKY2-9 have been cloned and characterized. The genes encoding WRKY proteins were assigned to WRKY Group II (one subgroup II-c, four subgroup II-d, and three subgroup II-e based on phylogenetic analysis. The cDNAs of the cloned PgWRKYs encode putative proteins ranging from 194 to 358 amino acid residues, each of which includes one WRKYGQK sequence motif and one C2H2-type zinc-finger motif. Quantitative real-time PCR (qRT-PCR analysis demonstrated that the eight analyzed PgWRKY genes were expressed at different levels in various organs including leaves, roots, adventitious roots, stems, and seeds. Importantly, the transcription responses of these PgWRKYs to methyl jasmonate (MeJA showed that PgWRKY2, PgWRKY3, PgWRKY4, PgWRKY5, PgWRKY6, and PgWRKY7 were downregulated by MeJA treatment, while PgWRKY8 and PgWRKY9 were upregulated to varying degrees. Moreover, the PgWRKY genes increased or decreased by salicylic acid (SA, abscisic acid (ABA, and NaCl treatments. The results suggest that the PgWRKYs may be multiple stress–inducible genes responding to both salt and hormones.

  18. Platelets: crossroads of immunity and hemostasis.

    Science.gov (United States)

    Jenne, Craig N

    2014-07-31

    In this issue of Blood, Koupenova and colleagues report that platelets express functional TOLL-like receptor 7 (TLR7) and contribute to host survival during viral infection. Through a series of experiments utilizing mice deficient for TLR7 together with adoptive transfer of wild-type platelets, Koupenova et al demonstrate that platelets specifically respond to viral analogs and intact virus, leading to platelet activation and binding to various leukocyte subsets. Perhaps most importantly, this platelet activation appears absolutely essential for host survival during infection with some viral pathogens such as encephalomyocarditis virus (EMCV).

  19. Evidence that platelet buoyant density, but not size, correlates with platelet age in man.

    Science.gov (United States)

    Mezzano, D; Hwang, K; Catalano, P; Aster, R H

    1981-01-01

    Following infusion of 51Cr-labeled autologous platelets into normal subjects, high-density (HD) and low-density (LD) platelet cohorts were isolated by prolonged centrifugation in isosmotic arabino-galactan (Stractan). Specific radio-activity of LD platelets declined rapidly post-infusion (T1/2 = 1.5 days), but specific radioactivity of HD platelets remained constant or increased over a 3--4-day period and gradually declined for 6--7 days thereafter. These differences were exaggerated when platelet cohorts enriched in LD or HD cells by slow centrifugation in high-density albumin were labeled and transfused. Mean survival of a platelet cohort enriched with HD cells was significantly (P less than 0.02) shorter (7.73 days) than that of a cohort enriched with LD cells (9.33) days). In normal subjects treated with aspirin, capacity for thromboxane synthesis was regained more rapidly (P less than 0.05) in LD than in HD platelets. HD and LD platelets differed only slightly in mean volume (HD platelets = 7.57 mu3, LD platelets = 6.87 mu3, 0.05 less than P less than 0.01). We believe the most logical interpretation of these findings is that under normal conditions in man, newly formed platelets are less dense on the average than total platelets and become more dense as they age in the circulation. Thus, specific radioactivity of LD platelets declines rapidly as these platelets move into a more dense compartment and are replaced by newly formed, unlabelled cells; specific radioactivity of HD platelets remains constant or increases as labelled platelets enter this compartment in numbers equal to or greater than the number leaving it at the end of their life span. The similarity in mean volumes of LD and HD platelets suggests that platelet size is unrelated to platelet age under normal conditions.

  20. Evidence that platelet buoyant density, but not size, correlates with platelet age in man

    Energy Technology Data Exchange (ETDEWEB)

    Mezzano, D.; Hwang, K.; Catalano, P.; Aster, R.H.

    1981-01-01

    Following infusion of 51Cr-labeled autologous platelets into normal subjects, high-density (HD) and low-density (LD) platelet cohorts were isolated by prolonged centrifugation in isosmotic arabino-galactan (Stractan). Specific radio-activity of LD platelets declined rapidly post-infusion (T1/2 . 1.5 days), but specific radioactivity of HD platelets remained constant or increased over a 3--4-day period and gradually declined for 6--7 days thereafter. These differences were exaggerated when platelet cohorts enriched in LD or HD cells by slow centrifugation in high-density albumin were labeled and transfused. Mean survival of a platelet cohort enriched with HD cells was significantly (P less than 0.02) shorter (7.73 days) than that of a cohort enriched with LD cells (9.33) days). In normal subjects treated with aspirin, capacity for thromboxane synthesis was regained more rapidly (P less than 0.05) in LD than in HD platelets. HD and LD platelets differed only slightly in mean volume (HD platelets . 7.57 mu3, LD platelets . 6.87 mu3, 0.05 less than P less than 0.01). We believe the most logical interpretation of these findings is that under normal conditions in man, newly formed platelets are less dense on the average than total platelets and become more dense as they age in the circulation. Thus, specific radioactivity of LD platelets declines rapidly as these platelets move into a more dense compartment and are replaced by newly formed, unlabelled cells; specific radioactivity of HD platelets remains constant or increases as labelled platelets enter this compartment in numbers equal to or greater than the number leaving it at the end of their life span. The similarity in mean volumes of LD and HD platelets suggests that platelet size is unrelated to platelet age under normal conditions.

  1. Antenatal and postnatal radiologic diagnosis of holocarboxylase synthetase deficiency: a systematic review

    Energy Technology Data Exchange (ETDEWEB)

    Bandaralage, Sahan P.S. [Gold Coast Hospital and Health Service, Southport, Queensland (Australia); Griffith University, School of Medicine, Southport, Queensland (Australia); Farnaghi, Soheil [Caboolture Hospital, Caboolture, Queensland (Australia); Dulhunty, Joel M.; Kothari, Alka [Redcliffe Hospital, Redcliffe, Queensland (Australia); The University of Queensland, School of Medicine, Herston, Queensland (Australia)

    2016-03-15

    Holocarboxylase synthetase deficiency results in impaired activation of enzymes implicated in glucose, fatty acid and amino acid metabolism. Antenatal imaging and postnatal imaging are useful in making the diagnosis. Untreated holocarboxylase synthetase deficiency is fatal, while antenatal and postnatal biotin supplementation is associated with good clinical outcomes. Although biochemical assays are required for definitive diagnosis, certain radiologic features assist in the diagnosis of holocarboxylase synthetase deficiency. To review evidence regarding radiologic diagnostic features of holocarboxylase synthetase deficiency in the antenatal and postnatal period. A systematic review of all published cases of holocarboxylase synthetase deficiency identified by a search of Pubmed, Scopus and Web of Science. A total of 75 patients with holocarboxylase synthetase deficiency were identified from the systematic review, which screened 687 manuscripts. Most patients with imaging (19/22, 86%) had abnormal findings, the most common being subependymal cysts, ventriculomegaly and intraventricular hemorrhage. Although the radiologic features of subependymal cysts, ventriculomegaly, intraventricular hemorrhage and intrauterine growth restriction may be found in the setting of other pathologies, these findings should prompt consideration of holocarboxylase synthetase deficiency in at-risk children. (orig.)

  2. Effect of Liver Damage and Hyperbaric Oxygenation on Glutamine Synthetase of Hepatocytes.

    Science.gov (United States)

    Savilov, P N; Yakovlev, V N

    2016-01-01

    Activity of glutamine synthetase in the hepatocytes of healthy animals and animals with chronic CCl4-induced hepatitis was studied on white mature female rats after liver resection (15-20% of organ weight) and hyperbaric oxygenation (3 atm, 50 min, 3 times). Surgically operated left and non-operated middle lobes of the liver were analyzed on day 3 after liver resection and exposure to hyperbaric oxygenation. On day 65 of CCl4 poisoning, activity of glutamine synthetase decreased in both lobes and did not recover on day 3 after toxin cessation. Liver resection under conditions of CCl4-induced hepatitis restored reduced activity of glutamine synthetase in both liver lobes to the normal level. In healthy rats, the increase in glutamine synthetase activity after liver resection was found only in the middle lobe of the liver. Hyperbaric oxygenation enhanced the stimulatory effect of liver resection on glutamine synthetase activity in hepatocytes during chronic CCl4-induced hepatitis. In healthy animals with liver resection, activity of glutamine synthetase did not change after hyperbaric oxygenation, while normally oxygenation inhibited glutamine synthetase activity.

  3. Encapsulation of glutamine synthetase in mouse erythrocytes: a new procedure for ammonia detoxification.

    Science.gov (United States)

    Kosenko, Elena A; Venediktova, Natalia I; Kudryavtsev, Andrey A; Ataullakhanov, Fazoil I; Kaminsky, Yury G; Felipo, Vicente; Montoliu, Carmina

    2008-12-01

    There are a number of pathological situations in which ammonia levels increase leading to hyperammonemia, which may cause neurological alterations and can lead to coma and death. Currently, there are no efficient treatments allowing rapid and sustained decrease of ammonia levels in these situations. A way to increase ammonia detoxification would be to increase its incorporation in glutamine by glutamine synthetase. The aim of this work was to develop a procedure to encapsulate glutamine synthetase in mouse erythrocytes and to assess whether administration of these erythrocytes containing glutamine synthetase (GS) reduce ammonia levels in hyperammonemic mice. The procedure developed allowed the encapsulation of 3 +/- 0.25 IU of GS / mL of erythrocytes with a 70% cell recovery. Most metabolites, including ATP, remained unaltered in glutamine synthetase-loaded erythrocytes (named ammocytes by us) compared with native erythrocytes. The glutamine synthetase-loaded ammocytes injected in mice survived and retained essentially all of their glutamine synthetase activity for at least 48 h in vivo. Injection of these ammocytes into hyperammonemic mice reduced ammonia levels in the blood by about 50%. The results reported indicate that ammocytes are able to keep their integrity, normal energy metabolism, the inserted glutamine synthetase activity, and can be useful to reduce ammonia levels in hyperammonemic situations.

  4. Solubilization, partial purification, and immunodetection of squalene synthetase from tobacco cell suspension cultures.

    Science.gov (United States)

    Hanley, K; Chappell, J

    1992-01-01

    Squalene synthetase, an integral membrane protein and the first committed enzyme for sterol biosynthesis, was solubilized and partially purified from tobacco (Nicotiana tabacum) cell suspension cultures. Tobacco microsomes were prepared and the enzyme was solubilized from the lipid bilayer using a two-step procedure. Microsomes were initially treated with concentrations of octyl-beta-d-thioglucopyranoside and glycodeoxycholate below their critical micelle concentration, 4.5 and 1.1 millimolar, respectively, to remove loosely associated proteins. Complete solubilization of the squalene synthetase enzyme activity was achieved after a second treatment at detergent concentrations above or at their critical micelle concentration, 18 and 2.2 millimolar, respectively. The detergent-solubilized enzyme was further purified by a combination of ultrafiltration, gel permeation, and Fast Protein Liquid Chromatography anion exchange. A 60-fold purification and 20% recovery of the enzyme activity was achieved. The partially purified squalene synthetase protein was used to generate polyclonal antibodies from mice that efficiently inhibited synthetase activity in an in vitro assay. The apparent molecular mass of the squalene synthetase protein as determined by immunoblot analysis of the partially purified squalene synthetase protein separated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis was 47 kilodaltons. The partially purified squalene synthetase activity was optimal at pH 6.0, exhibited a K(m) for farnesyl diphosphate of 9.5 micromolar, and preferred NADPH as a reductant rather than NADH.

  5. Platelets: bridging hemostasis, inflammation, and immunity.

    Science.gov (United States)

    Jenne, C N; Urrutia, R; Kubes, P

    2013-06-01

    Although the function of platelets in the maintenance of hemostasis has been studied in great detail, more recent evidence has highlighted a central role for platelets in the host inflammatory and immune responses. Platelets by virtue of their large numbers and their ability to rapidly release a broad spectrum of immunomodulatory cytokines, chemokines, and other mediators act as circulating sentinels. Upon detection of a pathogen, platelets quickly activate and begin to drive the ensuing inflammatory response. Platelets have the ability to directly modulate the activity of neutrophils (phagocytosis, oxidative burst), endothelium (adhesion molecule and chemokine expression), and lymphocytes. Due to their diverse array of adhesion molecules and preformed chemokines, platelets are able to adhere to leukocytes and facilitate their recruitment to sites of tissue damage or infection. Furthermore, platelets directly participate in the capture and sequestration of pathogens within the vasculature. Platelet-neutrophil interactions are known to induce the release of neutrophil extracellular traps (NETs) in response to either bacterial or viral infection, and platelets have been shown to internalize pathogens, sequestering them in engulfment vacuoles. Finally, emerging data indicate that platelets also participate in the host immune response by directly killing infected cells. This review will highlight the central role platelets play in the initiation and modulation of the host inflammatory and immune responses.

  6. Calpain Activator Dibucaine Induces Platelet Apoptosis

    Directory of Open Access Journals (Sweden)

    Jun Liu

    2011-03-01

    Full Text Available Calcium-dependent calpains are a family of cysteine proteases that have been demonstrated to play key roles in both platelet glycoprotein Ibα shedding and platelet activation and altered calpain activity is associated with thrombotic thrombocytopenic purpura. Calpain activators induce apoptosis in several types of nucleated cells. However, it is not clear whether calpain activators induce platelet apoptosis. Here we show that the calpain activator dibucaine induced several platelet apoptotic events including depolarization of the mitochondrial inner transmembrane potential, up-regulation of Bax and Bak, down-regulation of Bcl-2 and Bcl-XL, caspase-3 activation and phosphatidylserine exposure. Platelet apoptosis elicited by dibucaine was not affected by the broad spectrum metalloproteinase inhibitor GM6001. Furthermore, dibucaine did not induce platelet activation as detected by P-selectin expression and PAC-1 binding. However, platelet aggregation induced by ristocetin or α-thrombin, platelet adhesion and spreading on von Willebrand factor were significantly inhibited in platelets treated with dibucaine. Taken together, these data indicate that dibucaine induces platelet apoptosis and platelet dysfunction.

  7. Dynamics of Antagonistic Potency of Rhodobacter capsulatus PG Lipopolysaccharide against Endotoxin-Induced Effects.

    Science.gov (United States)

    Kabanov, D S; Serov, D A; Zubova, S V; Grachev, S V; Prokhorenko, I R

    2016-03-01

    The dynamics of antagonistic potency of lipopolysaccharide (LPS) isolated from Rhodobacter capsulatus PG on the synthesis of proinflammatory (TNF-α, IL-1β, IL-8, IL-6, IFN-γ) and antiinflammatory (IL-10, IL-1Ra) cytokines induced by highly stimulatory endotoxins from Escherichia coli or Salmonella enterica have been studied. Using human whole blood, we have shown that R. capsulatus PG LPS inhibited most pronouncedly the endotoxin-induced synthesis of TNF-α, IL-1β, IL-8, and IL-6 during the first 6 h after endotoxin challenge. Similarly, the endotoxin-induced release of IFN-γ was abolished by R. capsulatus PG LPS as well (24 h). In contrast to the above-mentioned cytokines, the relatively weak antagonistic activity of R. capsulatus PG LPS against endotoxin-triggered production of IL-6 and IL-8 was revealed. Since R. capsulatus PG LPS displays more potent antagonistic activity against deleterious effects of S. enterica LPS than those of E. coli LPS in the cases of such cytokines as IL-1β (6 and 24 h), IL-6 and IL-8 (4 h), we conclude that the effectiveness of protective action of antagonist is mostly determined by the primary lipid A structure of the employed agonist.

  8. Efficient statistical analysis method of power/ground (P/G) network

    Institute of Scientific and Technical Information of China (English)

    Zuying Luo; Sheldon X.D. Tan

    2008-01-01

    In this paper, we propose an incremental statistical analysis method with complexity reduction as a pre-process for on-chip power/ground (P/G) networks. The new method exploits locality of P/G network analyses and aims at P/G networks with a large number of strongly connected subcircuits (called strong connects) such as trees and chains. The method consists of three steps. First it compresses P/G circuits by removing strong connects. As a result, current variations (CVs) of nodes in strong connects are transferred to some remain-ing nodes. Then based on the locality of power grid voltage responses to its current inputs, it efficiently calculates the correlative resistor (CR) matrix in a local way to directly compute the voltage variations by using small parts of the remaining circuit. Last it statistically recovers voltage variations of the suppressed nodes inside strong connects. This new method for statistically compressing and expanding strong connects in terms of current or voltage variations in a closed form is very efficient owning to its property of incremental analysis. Experimental results demonstrate that the method can efficiently compute low-bounds of voltage variations for P/G networks and it has two or three orders of magnitudes speedup over the traditional Monte-Carlo-based simulation method, with only 2.0% accuracy loss.

  9. Relationship Between Ca2+-CaM and Ethylene-Induced PG Activity in Tomato Fruit

    Institute of Scientific and Technical Information of China (English)

    GU Cai-qin; XI Yu-fang; GUAN Jun-feng; LI Guang-min

    2003-01-01

    Polygalacturonase (PG) was studied during ripening and senescence of postharvest tomatofruit at pink stage at low and normal temperature. The results showed that the PG activity increased, thendecreased during ripening and senescence of tomato. Low temperature inhibited but ethylene enhanced PGactivity. Ethylene also enhanced caimodulin content, which was dependent on Ca2+ concentration in cell.When EGTA(Ca2+ chelator), verapamil (Vp) and LaCl3 (Ca2+ channel blockers), trifluoperazine and chloro-promaize (two CaM antagonisms) were used to treat tomato fruit at green mature stage with ethylene, theycould reverse ethylene-induced increase in PG activity, but Vp, chloropromaize (CPZ), trifluoperazine(TFP) could not directly influence PG activity, which indirectly indicated that influx of Ca2+ from the ex-tracellular space including the cell wall via the Ca2+ channel localized in plasma membrane and CaM were re-quired for ethylene-induced PG activity increase and that ethylene signal transduction may be related to Ca2+- CaM messenger system.

  10. High-resolution ultraviolet spectroscopy of PG1159-035 with HST and FUSE

    CERN Document Server

    Jahn, D; Reiff, E; Werner, K; Kruk, J W; Herwig, F

    2006-01-01

    PG1159-035 is the prototype of the PG1159 spectral class which consists of extremely hot hydrogen-deficient (pre-) white dwarfs. It is also the prototype of the GW Vir variables, which are non-radial g-mode pulsators. The study of PG1159 stars reveals insight into stellar evolution and nucleosynthesis during AGB and post-AGB phases. We perform a quantitative spectral analysis of PG1159-035 focusing on the abundance determination of trace elements. We have taken high-resolution ultraviolet spectra of PG1159-035 with the Hubble Space Telescope and the Far Ultraviolet Spectroscopic Explorer. They are analysed with non-LTE line blanketed model atmospheres. We confirm the high effective temperature with high precision (Teff=140,000+/-5000 K) and the surface gravity of logg=7. For the first time we assess the abundances of silicon, phosphorus, sulfur, and iron. Silicon is about solar. For phosphorus we find an upper limit of solar abundance. A surprisingly strong depletion of sulfur (2% solar) is discovered. Iron i...

  11. The pulsation modes of the pre-white dwarf PG 1159-035

    CERN Document Server

    Costa, J E S; Winget, D E; O'Brien, M S; Kawaler, S D; Costa, A F M; Giovannini, O; Kanaan, A; Mukadam, A S; Mullally, F; Nitta, A; Provençal, J L; Shipman, H; Wood, M A; Ahrens, T J; Grauer, A; Kilic, M; Bradley, P A; Sekiguchi, K; Crowe, R; Jiang, X J; Sullivan, D; Sullivan, T; Rosen, R; Clemens, J C; Janulis, R; O'Donoghue, D; Ogloza, W; Baran, A; Silvotti, R; Marinoni, S; Vauclair, G; Dolez, N; Chevreton, M; Dreizler, S; Schuh, S; Deetjen, J; Nagel, T; Solheim, J -E; Perez, J M Gonzalez; Ulla, A; Barstow, Martin; Burleigh, M; Good, S; Metcalfe, T S; Kim, S -L; Lee, H; Sergeev, A; Akan, M C; Çakirli, Ö; Paparo, M; Viraghalmy, G; Ashoka, B N; Handler, G; Hürkal, Özlem; Johannessen, F; Kleinman, S J; Kalytis, R; Krzesínski, J; Klumpe, E; Larrison, J; Lawrence, T; Mestas, E; Martínez, P; Nather, R E; Fu, J -N; Pakstien, E; Rosen, R; Romero-Colmenero, E; Riddle, R; Seetha, S; Silvestri, N M; Vuckovic, M; Warner, B; Zola, S; Althaus, L G; Córsico, A H; Montgomery, M H

    2007-01-01

    PG 1159-035, a pre-white dwarf with T_eff=140,000 K, is the prototype of both two classes: the PG1159 spectroscopic class and the DOV pulsating class. Previous studies of PG 1159-035 photometric data obtained with the Whole Earth Telescope (WET) showed a rich frequency spectrum allowing the identification of 122 pulsation modes. In this work, we used all available WET photometric data from 1983, 1985, 1989, 1993 and 2002 to identify the pulsation periods and identified 76 additional pulsation modes, increasing to 198 the number of known pulsation modes in PG 1159-035, the largest number of modes detected in any star besides the Sun. From the period spacing we estimated a mass M = 0.59 +/- 0.02 solar masses for PG 1159-035, with the uncertainty dominated by the models, not the observation. Deviations in the regular period spacing suggest that some of the pulsation modes are trapped, even though the star is a pre-white dwarf and the gravitational settling is ongoing. The position of the transition zone that cau...

  12. Seryl-tRNA Synthetases in Translation and Beyond

    Directory of Open Access Journals (Sweden)

    Marko Močibob

    2016-06-01

    Full Text Available For a long time seryl-tRNA synthetases (SerRSs stood as an archetypal, canonical aminoacyl-tRNA synthetases (aaRS, exhibiting only basic tRNA aminoacylation activity and with no moonlighting functions beyond protein biosynthesis. The picture has changed substantially in recent years after the discovery that SerRSs play an important role in antibiotic production and resistance and act as a regulatory factor in vascular development, as well as after the discovery of mitochondrial morphogenesis factor homologous to SerRS in insects. In this review we summarize the recent research results from our laboratory, which advance the understanding of seryl-tRNA synthetases and further paint the dynamic picture of unexpected SerRS activities. SerRS from archaeon Methanothermobacter thermautotrophicus was shown to interact with the large ribosomal subunit and it was postulated to contribute to a more efficient translation by the"tRNA channeling" hypothesis. Discovery of the atypical SerRS in a small number of methanogenic archaea led to the discovery of a new family of enzymes in numerous bacteria - amino acid:[carrier protein] ligases (aa:CP ligases. These SerRS homologues resigned tRNA aminoacylation activity, and instead adopted carrier proteins as the acceptors of activated amino acids. The crystal structure of the aa:CP ligase complex with the carrier protein revealed that the interactions between two macromolecules are incomparable to tRNA binding by the aaRS and consequently represent a true evolutionary invention. Kinetic investigations of SerRSs and the accuracy of amino acid selection revealed that SerRSs possess pre-transfer proofreading activity, challenging the widely accepted presumption that hydrolytic proofreading activity must reside in an additional, separate editing domain, not present in SerRSs. Finally, the plant tRNA serylation system is discussed, which is particularly interesting due to the fact that protein biosynthesis takes place

  13. Platelet-mediated cytotoxicity and its enhancement by platelet activating factor.

    Science.gov (United States)

    Bykovskaya, S N; Bolvacheva, A V; Kiselevsky, M V; Khaylenko, V A; Bykovsky, A F

    1991-01-01

    Platelet cytotoxicity was assessed in 70 cancer patients with various tumor localizations and in 30 normal donors. The data presented reveal that the ACL cell line displays the highest sensitivity to platelet cytotoxicity. Using the ACL cells, we discovered that platelets from oncological patients and normal donors display comparable cytotoxicity. The level of platelet lytic activity is irrelevant to tumor localisation; however, it appears to be dependent on the stage of tumor growth. Incubation of platelets, both from donors and patients, with PAF (concentration range 10 pM to 10 nM) results in a significant rise of the killing activity of platelets. PAF induces greater cytotoxicity enhancement for platelets with lower initial activity, this pattern appearing to be the specific feature of the PAF mediated effect. Hence, platelets can be considered as effector cells relevant to antitumor immunity; PAF-mediated enhancement of platelet cytotoxicity can appear to be useful in the search for new immunotherapeutic drugs.

  14. Platelet function tests: a comparative review

    Directory of Open Access Journals (Sweden)

    Paniccia R

    2015-02-01

    Full Text Available Rita Paniccia,1,2 Raffaella Priora,1,2 Agatina Alessandrello Liotta,2 Rosanna Abbate1,2 1Department of Experimental and Clinical Medicine, Thrombosis Center, University of Florence, Florence, Italy; 2Department of Heart and Vessels, Azienda Ospedaliero-Universitaria Careggi, Florence, Italy Abstract: In physiological hemostasis a prompt recruitment of platelets on the vessel damage prevents the bleeding by the rapid formation of a platelet plug. Qualitative and/or quantitative platelet defects promote bleeding, whereas the high residual reactivity of platelets in patients on antiplatelet therapies moves forward thromboembolic complications. The biochemical mechanisms of the different phases of platelet activation – adhesion, shape change, release reaction, and aggregation – have been well delineated, whereas their complete translation into laboratory assays has not been so fulfilled. Laboratory tests of platelet function, such as bleeding time, light transmission platelet aggregation, lumiaggregometry, impedance aggregometry on whole blood, and platelet activation investigated by flow cytometry, are traditionally utilized for diagnosing hemostatic disorders and managing patients with platelet and hemostatic defects, but their use is still limited to specialized laboratories. To date, a point-of-care testing (POCT dedicated to platelet function, using pertinent devices much simpler to use, has now become available (ie, PFA-100, VerifyNow System, Multiplate Electrode Aggregometry [MEA]. POCT includes new methodologies which may be used in critical clinical settings and also in general laboratories because they are rapid and easy to use, employing whole blood without the necessity of sample processing. Actually, these different platelet methodologies for the evaluation of inherited and acquired bleeding disorders and/or for monitoring antiplatelet therapies are spreading and the study of platelet function is strengthening. In this review, well

  15. Platelet Function Tests in Bleeding Disorders.

    Science.gov (United States)

    Lassila, Riitta

    2016-04-01

    Functional disorders of platelets can involve any aspect of platelet physiology, with many different effects or outcomes. These include platelet numbers (thrombocytosis or thrombocytopenia); changes in platelet production or destruction, or capture to the liver (Ashwell receptor); altered adhesion to vascular injury sites and/or influence on hemostasis and wound healing; and altered activation or receptor functions, shape change, spreading and release reactions, procoagulant and antifibrinolytic activity. Procoagulant membrane alterations, and generation of thrombin and fibrin, also affect platelet aggregation. The above parameters can all be studied, but standardization and quality control of assay methods have been limited despite several efforts. Only after a comprehensive clinical bleeding assessment, including family history, information on drug use affecting platelets, and exclusion of coagulation factor, and tissue deficits, should platelet function testing be undertaken to confirm an abnormality. Current diagnostic tools include blood cell counts, platelet characteristics according to the cell counter parameters, peripheral blood smear, exclusion of pseudothrombocytopenia, whole blood aggregometry (WBA) or light transmission aggregometry (LTA) in platelet-rich plasma, luminescence, platelet function analysis (PFA-100) for platelet adhesion and deposition to collagen cartridges under blood flow, and finally transmission electron microscopy to exclude rare structural defects leading to functional deficits. The most validated test panels are included in WBA, LTA, and PFA. Because platelets are isolated from their natural environment, many simplifications occur, as circulating blood and interaction with vascular wall are omitted in these assays. The target to reach a highly specific platelet disorder diagnosis in routine clinical management can be exhaustive, unless needed for genetic counseling. The elective overall assessment of platelet function disorder

  16. Critical Evaluation of the Changes in Glutamine Synthetase Activity in Models of Cerebral Stroke.

    Science.gov (United States)

    Jeitner, Thomas M; Battaile, Kevin; Cooper, Arthur J L

    2015-12-01

    The following article addresses some seemingly paradoxical observations concerning cerebral glutamine synthetase in ischemia-reperfusion injury. In the brain, this enzyme is predominantly found in astrocytes and catalyzes part of the glutamine-glutamate cycle. Glutamine synthetase is also thought to be especially sensitive to inactivation by the oxygen- and nitrogen-centered radicals generated during strokes. Despite this apparent sensitivity, glutamine synthetase specific activity is elevated in the affected tissues during reperfusion. Given the central role of the glutamine-glutamate cycle in the brain, we sought to resolve these conflicting observations with the view of providing an alternative perspective for therapeutic intervention in stroke.

  17. In vitro function of random donor platelets stored for 7 days in composol platelet additive solution

    Directory of Open Access Journals (Sweden)

    Gupta Ashish

    2011-01-01

    Full Text Available Background and Aim: Platelets are routinely isolated from whole blood and stored in plasma for 5 days. This study was done to assess the in vitro function of random donor platelets stored for 7 days in composol platelet additive solution at 22°C. Materials and Methods: The study sample included 30 blood donors of both sex in State Blood Bank, C S M Medical University, Lucknow. Random donor platelets were prepared by the platelet-rich plasma method. Whole blood (350 ml was collected in anticoagulant Citrate Phosphate Dextrose Adenine triple blood bags. Random donor platelets were stored for 7 days at 22°C in platelet incubators and agitators with and without additive solution. Results: Platelet swirling was present in all the units at 22°C on day 7 with no evidence of bacterial contamination. Comparison of the mean values of platelet count, platelet factor 3, lactate dehydrogenase, pH, glucose and platelet aggregation showed no significant difference in additive solution while platelet factor 3, glucose and platelet aggregation showed significant difference (P < 0.001 on day 7 without additive solution at 22°C. Conclusion: Our study infers that the platelet viability and aggregation were the best maintained within normal levels on day 7 of storage in platelet additive solution at 22°C. Thus, we may conclude that in vitro storage of random donor platelets with an extended shelf life of 7 days using platelet additive solution may be advocated to improve the inventory of platelets.

  18. Are broad optical balmer lines from central accretion disk in PG 1613+658?

    CERN Document Server

    Zhang, XueGuang

    2014-01-01

    In this letter, we report positive correlations between broad line width and broad line flux for the broad balmer lines of the long-term observed AGN PG 1613+658. Rather than the expected negative correlations under the widely accepted virialization assumption for AGN BLRs, the positive correlations indicate much different BLR structures of PG 1613+658 from the commonly considered BLR structures which are dominated by the equilibrium between radiation pressure and gas pressure. Therefore, accretion disk origin is preferred for the observed broad single-peaked optical balmer lines of PG 1613+658, because of the mainly gravity dominated disk-like BLRs with radial structures having few effects from radiation pressure.

  19. Oncogenic Myc Induces Expression of Glutamine Synthetase through Promoter Demethylation.

    Science.gov (United States)

    Bott, Alex J; Peng, I-Chen; Fan, Yongjun; Faubert, Brandon; Zhao, Lu; Li, Jinyu; Neidler, Sarah; Sun, Yu; Jaber, Nadia; Krokowski, Dawid; Lu, Wenyun; Pan, Ji-An; Powers, Scott; Rabinowitz, Joshua; Hatzoglou, Maria; Murphy, Daniel J; Jones, Russell; Wu, Song; Girnun, Geoffrey; Zong, Wei-Xing

    2015-12-01

    c-Myc is known to promote glutamine usage by upregulating glutaminase (GLS), which converts glutamine to glutamate that is catabolized in the TCA cycle. Here we report that in a number of human and murine cells and cancers, Myc induces elevated expression of glutamate-ammonia ligase (GLUL), also termed glutamine synthetase (GS), which catalyzes the de novo synthesis of glutamine from glutamate and ammonia. This is through upregulation of a Myc transcriptional target thymine DNA glycosylase (TDG), which promotes active demethylation of the GS promoter and its increased expression. Elevated expression of GS promotes cell survival under glutamine limitation, while silencing of GS decreases cell proliferation and xenograft tumor growth. Upon GS overexpression, increased glutamine enhances nucleotide synthesis and amino acid transport. These results demonstrate an unexpected role of Myc in inducing glutamine synthesis and suggest a molecular connection between DNA demethylation and glutamine metabolism in Myc-driven cancers.

  20. Astrocyte glutamine synthetase: pivotal in health and disease.

    Science.gov (United States)

    Rose, Christopher F; Verkhratsky, Alexei; Parpura, Vladimir

    2013-12-01

    The multifunctional properties of astrocytes signify their importance in brain physiology and neurological function. In addition to defining the brain architecture, astrocytes are primary elements of brain ion, pH and neurotransmitter homoeostasis. GS (glutamine synthetase), which catalyses the ATP-dependent condensation of ammonia and glutamate to form glutamine, is an enzyme particularly found in astrocytes. GS plays a pivotal role in glutamate and glutamine homoeostasis, orchestrating astrocyte glutamate uptake/release and the glutamate-glutamine cycle. Furthermore, astrocytes bear the brunt of clearing ammonia in the brain, preventing neurotoxicity. The present review depicts the central function of astrocytes, concentrating on the importance of GS in glutamate/glutamine metabolism and ammonia detoxification in health and disease.

  1. Bisphosphonic acids as effective inhibitors of Mycobacterium tuberculosis glutamine synthetase.

    Science.gov (United States)

    Kosikowska, Paulina; Bochno, Marta; Macegoniuk, Katarzyna; Forlani, Giuseppe; Kafarski, Paweł; Berlicki, Łukasz

    2016-12-01

    Inhibition of glutamine synthetase (GS) is one of the most promising strategies for the discovery of novel drugs against tuberculosis. Forty-three bisphosphonic and bis-H-phosphinic acids of various scaffolds, bearing aromatic substituents, were screened against recombinant GS from Mycobacterium tuberculosis. Most of the studied compounds exhibited activities in micromolar range, with N-(3,5-dichlorophenyl)-2-aminoethylidenebisphoshonic acid, N-(3,5-difluorophenyl)-2-aminoethylidene-bisphoshonic acid and N-(3,4-dichlorophenyl)-1-hydroxy-1,1-ethanebisphosphonic acid showing the highest potency with kinetic parameters similar to the reference compound - L-methionine-S-sulfoximine. Moreover, these inhibitors were found to be much more effective against pathogen enzyme than against the human ortholog. Thus, with the bone-targeting properties of the bisphosphonate compounds in mind, this activity/selectivity profile makes these compounds attractive agents for the treatment of bone tuberculosis.

  2. In Silico Discovery of Aminoacyl-tRNA Synthetase Inhibitors

    Directory of Open Access Journals (Sweden)

    Yaxue Zhao

    2014-01-01

    Full Text Available Aminoacyl-tRNA synthetases (aaRSs are enzymes that catalyze the transfer of amino acids to their cognate tRNA. They play a pivotal role in protein synthesis and are essential for cell growth and survival. The aaRSs are one of the leading targets for development of antibiotic agents. In this review, we mainly focused on aaRS inhibitor discovery and development using in silico methods including virtual screening and structure-based drug design. These computational methods are relatively fast and cheap, and are proving to be of great benefit for the rational development of more potent aaRS inhibitors and other pharmaceutical agents that may usher in a much needed generation of new antibiotics.

  3. Phenotypic analysis of individuals with Costello syndrome due to HRAS p.G13C.

    Science.gov (United States)

    Gripp, Karen W; Hopkins, Elizabeth; Sol-Church, Katia; Stabley, Deborah L; Axelrad, Marni E; Doyle, Daniel; Dobyns, William B; Hudson, Cindy; Johnson, John; Tenconi, Romano; Graham, Gail E; Sousa, Ana Berta; Heller, Raoul; Piccione, Maria; Corsello, Giovanni; Herman, Gail E; Tartaglia, Marco; Lin, Angela E

    2011-04-01

    Costello syndrome is characterized by severe failure-to-thrive, short stature, cardiac abnormalities (heart defects, tachyarrhythmia, and hypertrophic cardiomyopathy (HCM)), distinctive facial features, a predisposition to papillomata and malignant tumors, postnatal cerebellar overgrowth resulting in Chiari 1 malformation, and cognitive disabilities. De novo germline mutations in the proto-oncogene HRAS cause Costello syndrome. Most mutations affect the glycine residues in position 12 or 13, and more than 80% of patients share p.G12S. To test the hypothesis that subtle genotype-phenotype differences exist, we report the first cohort comparison between 12 Costello syndrome individuals with p.G13C and individuals with p.G12S. The individuals with p.G13C had many typical findings including polyhydramnios, failure-to-thrive, HCM, macrocephaly with posterior fossa crowding, and developmental delay. Subjectively, their facial features were less coarse. Statistically significant differences included the absence of multifocal atrial tachycardia (P-value = 0.033), ulnar deviation of the wrist (P < 0.001) and papillomata (P = 0.003), and fewer neurosurgical procedures (P = 0.024). Fewer individuals with p.G13C had short stature (height below -2 SD) without use of growth hormone (P < 0.001). The noteworthy absence of malignant tumors did not reach statistical significance. Novel ectodermal findings were noted in individuals with p.G13C, including loose anagen hair resulting in easily pluckable hair with a matted appearance, different from the tight curls typical for most Costello syndrome individuals. Unusually long eye lashes requiring trimming are a novel finding we termed dolichocilia. These distinctive ectodermal findings suggest a cell type specific effect of this particular mutation. Additional patients are needed to validate these findings.

  4. Platelet receptors and patient responses: The contributions of Professor Stan Heptinstall to platelet research.

    Science.gov (United States)

    Clemetson, Kenneth J

    2015-01-01

    Stan Heptinstall's contributions to platelet research covered organising meetings at the national and European level as well as starting and maintaining the journal "Platelets". The major part of his research addressed problems of inhibition of platelet receptors and the effects of this on patient health. In particular, the effects of P2Y12 inhibitors on patients with acute cardiovascular problems were a major focus. Other studies included the effects of feverfew (Tanacetum parthenium) extracts on platelets, of direct anti-IIb/IIIa receptor (αIIbβ3) inhibitors and of prostanoids on platelet function. Recently, methods for assessing the effectiveness of platelet inhibition were investigated.

  5. Transformation of Bacillus Subtilis with cloned thymidylate synthetases

    Energy Technology Data Exchange (ETDEWEB)

    Rubin, Edward M.

    1980-01-01

    Bacillus subtilis carries two genes, thyA and thyB, each encoding different protein products, with thymidylate synthetase (TSase) activity. Either of these genes alone is sufficient for thymidine independence in B. subtilis. In addition there exist two B. subtilis temperate bacteriophages which upon infection of thymine requiring auxotrophs results in conversion of the organism to thymine independence. Chimeric plasmids selected for Thy/sup +/ transforming activity in E. coli were constructed and then used as a source of defined highly enriched DNA with which to transform competent B. subtilis. These plasmids were studied for their: (1) abiility to transform B. subtilis to thymine independence; (2) site of integration within the B. subtilis chromosome upon transformation; (3) phenotype of Thy/sup +/ plasmid generated transformants; and (4) nucleotide sequence homology among the cloned DNA fragments conferring thymine independence. Plasmids containing the two bacteriophage thy genes displayed the phenotype associated with thyA, whereas the plasmids containing the cloned B. subtilis chromosomal genes displayed the phenotype associated with thyB. Utilizing similar technology, the ability of an entirely foreign hybred bacterial plasmiid to transform B. subtilis was examined. In this case the gene from E. coli encoding thymidylate synthetase was cloned in the plasmid pBR322. The resulting chimeric plasmid was effective in transforming both E. coli and B. subtilis to thymine prototrophy. Uncloned linear E. coli chromosomal DNA was unable to transform thymine requiring strains of B. subtilis to thymine independence. Although the Thy/sup +/ transformants of E. coli contained plasmid DNA, the Thy/sup +/ transformants derived from the transformation of B. subtilis did not contain detectable extrachromosomal DNA. Instead the DNA from the chimeric plasmid was integrated into the chromosome of B. subtilis. (ERB)

  6. Common peptides study of aminoacyl-tRNA synthetases.

    Directory of Open Access Journals (Sweden)

    Assaf Gottlieb

    Full Text Available BACKGROUND: Aminoacyl tRNA synthetases (aaRSs constitute an essential enzyme super-family, providing fidelity of the translation process of mRNA to proteins in living cells. They are common to all kingdoms and are of utmost importance to all organisms. It is thus of great interest to understand the evolutionary relationships among them and underline signature motifs defining their common domains. RESULTS: We utilized the Common Peptides (CPs framework, based on extracted deterministic motifs from all aaRSs, to study family-specific properties. We identified novel aaRS-class related signatures that may supplement the current classification methods and provide a basis for identifying functional regions specific to each aaRS class. We exploited the space spanned by the CPs in order to identify similarities between aaRS families that are not observed using sequence alignment methods, identifying different inter-aaRS associations across different kingdom of life. We explored the evolutionary history of the aaRS families and evolutionary origins of the mitochondrial aaRSs. Lastly, we showed that prevalent CPs significantly overlap known catalytic and binding sites, suggesting that they have meaningful functional roles, as well as identifying a motif shared between aaRSs and a the Biotin-[acetyl-CoA carboxylase] synthetase (birA enzyme overlapping binding sites in both families. CONCLUSIONS: The study presents the multitude of ways to exploit the CP framework in order to extract meaningful patterns from the aaRS super-family. Specific CPs, discovered in this study, may play important roles in the functionality of these enzymes. We explored the evolutionary patterns in each aaRS family and tracked remote evolutionary links between these families.

  7. PG1058 Is a Novel Multidomain Protein Component of the Bacterial Type IX Secretion System

    Science.gov (United States)

    Veith, Paul D.; Butler, Catherine A.; Nor Muhammad, Nor A.; Chen, Yu-Yen; Slakeski, Nada; Peng, Benjamin; Zhang, Lianyi; Dashper, Stuart G.; Cross, Keith J.; Cleal, Steven M.; Moore, Caroline; Reynolds, Eric C.

    2016-01-01

    Porphyromonas gingivalis utilises the Bacteroidetes-specific type IX secretion system (T9SS) to export proteins across the outer membrane (OM), including virulence factors such as the gingipains. The secreted proteins have a conserved carboxy-terminal domain essential for type IX secretion that is cleaved upon export. In P. gingivalis the T9SS substrates undergo glycosylation with anionic lipopolysaccharide (A-LPS) and are attached to the OM. In this study, comparative analyses of 24 Bacteroidetes genomes identified ten putative novel components of the T9SS in P. gingivalis, one of which was PG1058. Computer modelling of the PG1058 structure predicted a novel N- to C-terminal architecture comprising a tetratricopeptide repeat (TPR) domain, a β-propeller domain, a carboxypeptidase regulatory domain-like fold (CRD) and an OmpA_C-like putative peptidoglycan binding domain. Inactivation of pg1058 in P. gingivalis resulted in loss of both colonial pigmentation and surface-associated proteolytic activity; a phenotype common to T9SS mutants. Immunoblot and LC-MS/MS analyses of subcellular fractions revealed T9SS substrates accumulated within the pg1058 mutant periplasm whilst whole-cell ELISA showed the Kgp gingipain was absent from the cell surface, confirming perturbed T9SS function. Immunoblot, TEM and whole-cell ELISA analyses indicated A-LPS was produced and present on the pg1058 mutant cell surface although it was not linked to T9SS substrate proteins. This indicated that PG1058 is crucial for export of T9SS substrates but not for the translocation of A-LPS. PG1058 is a predicted lipoprotein and was localised to the periplasmic side of the OM using whole-cell ELISA, immunoblot and LC-MS/MS analyses of subcellular fractions. The structural prediction and localisation of PG1058 suggests that it may have a role as an essential scaffold linking the periplasmic and OM components of the T9SS. PMID:27711252

  8. Platelet count and platelet indices in women with preeclampsia

    OpenAIRE

    AlSheeha MA; Alaboudi RS; Alghasham MA; Iqbal J; Adam I

    2016-01-01

    Muneera A AlSheeha,1 Rafi S Alaboudi,1 Mohammad A Alghasham,1 Javed Iqbal,2 Ishag Adam1 1Department of Obstetrics and Gynaecology, College of Medicine, Qassim University, Buriadah, 2Department of Obstetrics and Gynecology, Maternity and Children’s Hospital, Qassim, Kingdom of Saudi Arabia Background: Although the exact pathophysiology of preeclampsia is not completely understood, the utility of different platelets indices can be utilized to predict preeclampsia.Obj...

  9. Pathogen-Reduced, Platelet Additive Solution, Extended Stored Platelets (PREPS)

    Science.gov (United States)

    2015-10-01

    associated sepsis remains the principal lethal risk associated with platelet transfusion. Cold storage (4°C) is known to reduce post transfusion...and no residual radiation is detectable . *P-selectin samples will be prepped on end of storage day and batch tested. **Bacterial Culture sample...temperature controlled room until such time as they have no detectable residual radiation. This is generally about 3-4 months. At that point they are

  10. Inflammation, oxidative stress and platelet activation in aspirin-treated critical limb ischaemia: beneficial effects of iloprost.

    Science.gov (United States)

    Lessiani, Gianfranco; Vazzana, Natale; Cuccurullo, Chiara; Di Michele, Dario; Laurora, Giuseppe; Sgrò, Giuseppe; Di Ruscio, Paolo; Simeone, Emilio; Di Iorio, Pierangelo; Lattanzio, Stefano; Liani, Rossella; Ferrante, Elisabetta; Davì, Giovanni

    2011-02-01

    Platelets critically contribute to atherothrombosis and worsening ischaemia in patients with peripheral arterial disease (PAD), eventually leading to critical limb ischaemia (CLI). Furthermore, persistent platelet activation despite antiplatelet therapy has been reported in this setting. The prostacyclin analogue iloprost is currently recommended in CLI patients for its effects in relieving symptoms by promoting local perfusion. In this study, we investigated the effects of iloprost infusion on urinary 11-dehydro-TXB₂ and 8-iso-PGF(₂α) excretion rate, as in vivo indexes of thromboxane-dependent platelet activation and lipid peroxidation, respectively, and on platelet-derived proinflammatory sCD40L and nitric oxide bioavailability in 44 patients with CLI while on chronic treatment with low-dose aspirin. Daily iloprost infusion for one-week significantly decreased urinary 11-dehydro-TXB₂ [499 (277-807) vs. 380 (189-560) pg/mg creatinine, p iloprost treatment (Rho = 0.695, p iloprost is able to significantly reduce residual thromboxane biosynthesis, oxidative stress, endothelial dysfunction and platelet-derived inflammation in low-dose aspirin treated patients with CLI.

  11. Detection of microbial contamination in platelets

    Science.gov (United States)

    Berg, Tracy L.; Leparc, German; Huffman, Debra E.; Gennaccaro, Angela L.; Garcia-Lopez, Alicia; Klungness, Greta; Stephans, Christie; Garcia-Rubio, Luis H.

    2005-03-01

    In the United States, approximately 100 patients develop fatal sepsis associated with platelet transfusions every year. Current culture methods take 24-48 hours to acquire results, which in turn decrease the shelf life of platelets. Many of the microorganisms that contaminate platelets can replicate easily at room temperature, which is the necessary storage temperature to keep platelets functional. Therefore, there is a need for in-situ quality control assessment of the platelet quality. For this purpose, a real time spectrophotometric technique has been developed. The Spectral Acquisition Processing Detection (SAPD) method, comprised of a UV-vis spectrophotometer and modeling algorithms, is a rapid method that can be performed prior to platelet transfusion to decrease the risk of bacterial infection to patients. The SAPD method has been used to determine changes in cell suspensions, based on size, shape, chemical composition and internal structure. Changes in these cell characteristics can in turn be used to determine microbial contamination, platelet aging and other physiologic changes. Detection limits of this method for platelet suspensions seeded with bacterial contaminants were identified to be less than 100 cfu/ml of sample. Bacterial counts below 1000 cfu/ml are not considered clinically significant. The SAPD method can provide real-time identification of bacterial contamination of platelets affording patients an increased level of safety without causing undue strain on laboratory budgets or personnel while increasing the time frame that platelets can be used by dramatically shortening contaminant detection time.

  12. Influence of Oxidative Stress on Stored Platelets

    Directory of Open Access Journals (Sweden)

    K. Manasa

    2016-01-01

    Full Text Available Platelet storage and its availability for transfusion are limited to 5-6 days. Oxidative stress (OS is one of the causes for reduced efficacy and shelf-life of platelets. The studies on platelet storage have focused on improving the storage conditions by altering platelet storage solutions, temperature, and materials. Nevertheless, the role of OS on platelet survival during storage is still unclear. Hence, this study was conducted to investigate the influence of storage on platelets. Platelets were stored for 12 days at 22°C. OS markers such as aggregation, superoxides, reactive oxygen species, glucose, pH, lipid peroxidation, protein oxidation, and antioxidant enzymes were assessed. OS increased during storage as indicated by increments in aggregation, superoxides, pH, conjugate dienes, and superoxide dismutase and decrements in glucose and catalase. Thus, platelets could endure OS till 6 days during storage, due to the antioxidant defense system. An evident increase in OS was observed from day 8 of storage, which can diminish the platelet efficacy. The present study provides an insight into the gradual changes occurring during platelet storage. This lays the foundation towards new possibilities of employing various antioxidants as additives in storage solutions.

  13. Effects of Physical (Inactivity on Platelet Function

    Directory of Open Access Journals (Sweden)

    Stefan Heber

    2015-01-01

    Full Text Available As platelet activation is closely related to the liberation of growth factors and inflammatory mediators, platelets play a central role in the development of CVD. Virtually all cardiovascular risk factors favor platelet hyperreactivity and, accordingly, also physical (inactivity affects platelet function. Within this paper, we will summarize and discuss the current knowledge on the impact of acute and habitual exercise on platelet function. Although there are apparent discrepancies regarding the reported effects of acute, strenuous exercise on platelet activation, a deeper analysis of the available literature reveals that the applied exercise intensity and the subjects’ cardiorespiratory fitness represent critical determinants for the observed effects. Consideration of these factors leads to the summary that (i acute, strenuous exercise can lead to platelet activation, (ii regular physical activity and/or physical fitness diminish or prevent platelet activation in response to acute exercise, and (iii habitual physical activity and/or physical fitness also favorably modulate platelet function at physical rest. Notably, these effects of exercise on platelet function show obvious similarities to the well-recognized relation between exercise and the risk for cardiovascular events where vigorous exercise transiently increases the risk for myocardial infarction and a physically active lifestyle dramatically reduces cardiovascular mortality.

  14. Trehalose lyophilized platelets for wound healing.

    Science.gov (United States)

    Pietramaggiori, Giorgio; Kaipainen, Arja; Ho, David; Orser, Cindy; Pebley, Walter; Rudolph, Alan; Orgill, Dennis P

    2007-01-01

    Fresh platelet preparations are utilized to treat a wide variety of wounds, although storage limitations and mixed results have hampered their clinical use. We hypothesized that concentrated lyophilized and reconstituted platelet preparations, preserved with trehalose, maintain and possibly enhance fresh platelets' ability to improve wound healing. We studied the ability of a single dose of trehalose lyophilized and reconstituted platelets to enhance wound healing when topically applied on full-thickness wounds in the genetically diabetic mouse. We compared these results with the application of multiple doses of fresh platelet preparations and trehalose lyophilized and reconstituted platelets as well as multiple doses of vascular endothelial growth factor (VEGF) and wounds left untreated. Trehalose lyophilized and reconstituted platelets, in single and multiple applications, multiple applications of fresh platelets and multiple applications of VEGF increased granulation tissue deposition, vascularity, and proliferation when compared with untreated wounds, as assessed by histology and immunohistochemistry. Wounds treated with multiple doses of VEGF and a single dose of freeze-dried platelets reached 90% closure faster than wounds left untreated. A single administration of trehalose lyophilized and reconstituted platelet preparations enhanced diabetic wound healing, therefore representing a promising strategy for the treatment of nonhealing wounds.

  15. Small RNAs as potential platelet therapeutics.

    Science.gov (United States)

    Edelstein, Leonard C; Bray, Paul F

    2012-01-01

    MicroRNAs (miRNAs) are 21-23 nucleotide RNAs that regulate more than 60% of mammalian protein coding genes. miRNAs play critical roles in hematopoiesis and megakaryocyte function and development. Platelets, in addition to possessing functional miRNA processing machinery, have miRNA levels that have been correlated with platelet reactivity, and these miRNAs have been shown to target mRNAs that encode proteins that alter platelet function. There are potential uses of platelet miRNA as biomarkers and therapeutic agents. Due to the ability of platelets to release miRNA-containing microparticles at sites of activation, including angiogenic regions, tumors, and atherosclerotic plaques, there is the possibility of engineering platelets to deliver miRNA-based therapies to these sites. Cellpreferential expression of miRNAs could be exploited to restrict transgene expression in hematopoietic stem cell gene therapy to the desired lineage, including megakaryocytes and platelets. Finally, manipulation of gene expression in stored platelets may allow more effective platelet storage. Although much work remains to be done, there is great potential in miRNA-based platelet therapies.

  16. Platelet MicroRNAs: An Overview.

    Science.gov (United States)

    Dahiya, Neetu; Sarachana, Tewarit; Vu, Long; Becker, Kevin G; Wood, William H; Zhang, Yongqing; Atreya, Chintamani D

    2015-10-01

    MicroRNAs (miRNAs) are short ~22-nucleotide noncoding RNA that have been found to influence the expression of many genes and cellular processes by either repressing translation or degrading messenger RNA transcripts. Platelet miRNA expression has been shown to be perturbed during ex vivo storage of platelets and in platelet-associated disorders. Although bioinformatics-based miRNA target predictions have been established, direct experimental validation of the role of miRNAs in platelet biology has been rather slow. Target prediction studies are, nonetheless, valuable in directing the design of appropriate experiments to test specific miRNA:messenger RNA interactions relevant to the underlying mechanisms of platelet function in general and in disease as well as in ex vivo storage-associated "storage lesions," a collective term used to include physiologic, biochemical, and morphologic changes that occur in stored platelets. This brief review will focus on emerging human platelet miRNA studies to emphasize their potential role relevant to transfusion medicine field in terms of regulating platelet signaling pathways, markers of platelet associated disorders, and remote impactors of gene expression (intercellular biomodulators) as well as potential platelet quality markers of storage and pathogen reduction treatments.

  17. Understanding platelet function through signal transduction.

    Science.gov (United States)

    Lazarus, Alan H; Song, Seng; Crow, Andrew R

    2003-01-01

    Platelets are activated by a number of stimuli resulting in the expression and/or activation of surface receptors, secretion of vasoactive substances, adhesion, aggregation, and finally thrombus formation. These events are propagated by a process known as transmembrane signaling, which relays the activating signal from the platelet membrane (eg, von Willebrand Factor binding to glycoprotein Ib) to the inside of the platelet which then serves to activate the platelet via a cascade of biochemical interactions. Inhibition of these transmembrane signaling molecules with a variety of available inhibitors or antagonists can in many cases prevent the platelet from becoming activated. An awareness of the mechanisms involved in platelet transmembrane signaling and the recent availability of new reagents to inhibit signaling may provide us with additional means to prevent platelet activation and perhaps even ameliorate the platelet storage lesion. This review will provide an introduction to the field of platelet transmembrane signaling and give an overview of some of the platelet signaling mechanisms that are relevant to transfusion medicine. Copyright 2003, Elsevier Science (USA). All rights reserved.

  18. Platelet destruction in autoimmune thrombocytopenic purpura: kinetics and clearance of indium-111-labeled autologous platelets

    Energy Technology Data Exchange (ETDEWEB)

    Stratton, J.R.; Ballem, P.J.; Gernsheimer, T.; Cerqueira, M.; Slichter, S.J.

    1989-05-01

    Using autologous /sup 111/In-labeled platelets, platelet kinetics and the sites of platelet destruction were assessed in 16 normal subjects (13 with and three without spleens), in 17 studies of patients with primary autoimmune thrombocytopenic purpura (AITP), in six studies of patients with secondary AITP, in ten studies of patients with AITP following splenectomy, and in five thrombocytopenic patients with myelodysplastic syndromes. In normal subjects, the spleen accounted for 24 +/- 4% of platelet destruction and the liver for 15 +/- 2%. Untreated patients with primary AITP had increased splenic destruction (40 +/- 14%, p less than 0.001) but not hepatic destruction (13 +/- 5%). Compared with untreated patients, prednisone treated patients did not have significantly different spleen and liver platelet sequestration. Patients with secondary AITP had similar platelet counts, platelet survivals, and increases in splenic destruction of platelets as did patients with primary AITP. In contrast, patients with myelodysplastic syndromes had a normal pattern of platelet destruction. In AITP patients following splenectomy, the five nonresponders all had a marked increase (greater than 45%) in liver destruction compared to five responders (all less than 40%). Among all patients with primary or secondary AITP, there was an inverse relationship between the percent of platelets destroyed in the liver plus spleen and both the platelet count (r = 0.75, p less than 0.001) and the platelet survival (r = 0.86, p less than 0.001). In a stepwise multiple linear regression analysis, total liver plus spleen platelet destruction, the platelet survival and the platelet turnover were all significant independent predictors of the platelet count. Thus platelet destruction is shifted to the spleen in primary and secondary AITP. Failure of splenectomy is associated with a marked elevation in liver destruction.

  19. High cerebral guanidinoacetate and variable creatine concentrations in argininosuccinate synthetase and lyase deficiency : Implications for treatment?

    NARCIS (Netherlands)

    van Spronsen, F. J.; Reijngoud, D. J.; Verhoeven, N. M.; Soorani-Lunsing, R. J.; Jakobs, C.; Sijens, P. E.

    2006-01-01

    Cerebral creatine and guanidinoacetate and blood and urine metabolites were studied in four patients with argininosuccinate synthetase (ASS) or argininosuccinate lyase (ASL) deficiency receiving large doses of arginine. Urine and blood metabolites varied largely. Cerebral guanidinoacetate was

  20. 3-substituted anilines as scaffolds for the construction of glutamine synthetase and DXP-reductoisomerase inhibitors

    CSIR Research Space (South Africa)

    Mutorwa, M

    2009-01-01

    Full Text Available -1 Synthetic Communications Volume 39, Issue 15, 2009 3-Substituted Anilines as Scaffolds for the Construction of Glutamine Synthetase and DXP-Reductoisomerase Inhibitors Marius Mutorwaa, Sheriff Salisua, Gregory L. Blatchbc, Colin Kenyond & Perry T...

  1. Regulation of active site coupling in glutamine-dependent NAD[superscript +] synthetase

    Energy Technology Data Exchange (ETDEWEB)

    LaRonde-LeBlanc, Nicole; Resto, Melissa; Gerratana, Barbara; (Maryland)

    2009-05-21

    NAD{sup +} is an essential metabolite both as a cofactor in energy metabolism and redox homeostasis and as a regulator of cellular processes. In contrast to humans, Mycobacterium tuberculosis NAD{sup +} biosynthesis is absolutely dependent on the activity of a multifunctional glutamine-dependent NAD{sup +} synthetase, which catalyzes the ATP-dependent formation of NAD{sup +} at the synthetase domain using ammonia derived from L-glutamine in the glutaminase domain. Here we report the kinetics and structural characterization of M. tuberculosis NAD{sup +} synthetase. The kinetics data strongly suggest tightly coupled regulation of the catalytic activities. The structure, the first of a glutamine-dependent NAD{sup +} synthetase, reveals a homooctameric subunit organization suggesting a tight dependence of catalysis on the quaternary structure, a 40-{angstrom} intersubunit ammonia tunnel and structural elements that may be involved in the transfer of information between catalytic sites.

  2. High cerebral guanidinoacetate and variable creatine concentrations in argininosuccinate synthetase and lyase deficiency : Implications for treatment?

    NARCIS (Netherlands)

    van Spronsen, F. J.; Reijngoud, D. J.; Verhoeven, N. M.; Soorani-Lunsing, R. J.; Jakobs, C.; Sijens, P. E.

    2006-01-01

    Cerebral creatine and guanidinoacetate and blood and urine metabolites were studied in four patients with argininosuccinate synthetase (ASS) or argininosuccinate lyase (ASL) deficiency receiving large doses of arginine. Urine and blood metabolites varied largely. Cerebral guanidinoacetate was increa

  3. Diffuse glutamine synthetase overexpression restricted to areas of peliosis in a β-catenin-activated hepatocellular adenoma: a potential pitfall in glutamine synthetase interpretation.

    Science.gov (United States)

    Berry, Ryan S; Gullapalli, Rama R; Wu, Jin; Morris, Katherine; Hanson, Joshua A

    2014-08-01

    Hepatocellular adenomas have recently been classified into four subtypes based on molecular findings: hepatocyte nuclear factor 1α (HNF1α) inactivated, inflammatory/telangiectatic, β-catenin activated, and unclassifiable. β-catenin-activated adenomas have the potential for malignant transformation and are thus important to recognize. Diffuse glutamine synthetase immunohistochemical positivity has been shown to be a reliable surrogate marker for β-catenin activation, though variations in staining patterns may be difficult to interpret. We report a case of a peliotic adenoma that was morphologically consistent with a β-catenin wild-type hepatocellular adenoma but harbored a β-catenin mutation by molecular analysis. The tumor lacked nuclear β-catenin positivity and demonstrated a hitherto undescribed pattern of glutamine synthetase overexpression restricted to areas of peliosis with mostly negative staining in non-peliotic areas. This pattern was initially interpreted as physiologic and may represent a potential pitfall in glutamine synthetase interpretation.

  4. Glutamine synthetase 2 is not essential for biosynthesis of compatible solutes in Halobacillus halophilus

    OpenAIRE

    Anna eShiyan; Melanie eThompson; Saskia eKöcher; Michaela eTausendschön; Helena eSantos; Inga eHänelt; Volker eMüller

    2014-01-01

    Halobacillus halophilus, a moderately halophilic bacterium isolated from salt marshes, produces various compatible solutes to cope with osmotic stress. Glutamate and glutamine are dominant compatible solutes at mild salinities. Glutamine synthetase activity in cell suspensions of Halobacillus halophilus wild type was shown to be salt dependent and chloride modulated. A possible candidate to catalyze glutamine synthesis is glutamine synthetase A2, whose transcription is stimulated by chloride....

  5. The identification of new cytosolic glutamine synthetase and asparagine synthetase genes in barley (Hordeum vulgare L.), and their expression during leaf senescence.

    Science.gov (United States)

    Avila-Ospina, Liliana; Marmagne, Anne; Talbotec, Joël; Krupinska, Karin; Masclaux-Daubresse, Céline

    2015-04-01

    Glutamine synthetase and asparagine synthetase are two master enzymes involved in ammonium assimilation in plants. Their roles in nitrogen remobilization and nitrogen use efficiency have been proposed. In this report, the genes coding for the cytosolic glutamine synthetases (HvGS1) and asparagine synthetases (HvASN) in barley were identified. In addition to the three HvGS1 and two HvASN sequences previously reported, two prokaryotic-like HvGS1 and three HvASN cDNA sequences were identified. Gene structures were then characterized, obtaining full genomic sequences. The response of the five HvGS1 and five HvASN genes to leaf senescence was then studied. Developmental senescence was studied using primary and flag leaves. Dark-exposure or low-nitrate conditions were also used to trigger stress-induced senescence. Well-known senescence markers such as the chlorophyll and Rubisco contents were monitored in order to characterize senescence levels in the different leaves. The three eukaryotic-like HvGS1_1, HvGS1_2, and HvGS1_3 sequences showed the typical senescence-induced reduction in gene expression described in many plant species. By contrast, the two prokaryotic-like HvGS1_4 and HvGS1_5 sequences were repressed by leaf senescence, similar to the HvGS2 gene, which encodes the chloroplast glutamine synthetase isoenzyme. There was a greater contrast in the responses of the five HvASN and this suggested that these genes are needed for N remobilization in senescing leaves only when plants are well fertilized with nitrate. Responses of the HvASN sequences to dark-induced senescence showed that there are two categories of asparagine synthetases, one induced in the dark and the other repressed by the same conditions.

  6. STABILIZATION OF STANDARD PLATELET CONCENTRATES AND MINIMIZATION OF THE PLATELET STORAGE LESION BY A PROSTACYCLIN ANALOG

    NARCIS (Netherlands)

    ELIAS, M; HEETHUIS, A; BOM, [No Value; BLOM, N; MCSHINE, RL; HALIE, MR; SIBINGA, CTS

    Platelet concentrates were pretreated with a stable synthetic prostacyclin analogue (Iloprost) at two different concentrations before the second centrifugation step (pelleting step) of preparation. This resulted in loss. of platelet sensitivity to aggregating agents. To mimic the situation after

  7. P&G saab 57 miljardi dollari eest Gillette'i / Peeter Teder

    Index Scriptorium Estoniae

    Teder, Peeter

    2005-01-01

    Habemeajamistarvete tootjana tuntud ettevõtte Gilette'i võtab üle kaubanduse suurvalitseja Procter & Gamble, mis kujuneb ilmselt selle aasta suurimaiks ülevõtmistehinguks. Diagramm: Gilette'i aktsia aastaga tõusnud kolmandiku võrra. Vt. samas: P&G mõjukas tehing

  8. The curious time lags of PG 1244+026: discovery of the iron K reverberation lag

    NARCIS (Netherlands)

    Kara, E.; Cackett, E.M.; Fabian, A.C.; Reynolds, C.; Uttley, P.

    2014-01-01

    High-frequency iron K reverberation lags, where the red wing of the line responds before the line centroid, are a robust signature of relativistic reflection off the inner accretion disc. In this Letter, we report the discovery of the Fe K lag in PG 1244+026 from ∼120 ks of data (one orbit of the

  9. 82 FR 39535 - Safety Zone: PG&E Evolution, King Salmon, CA

    Science.gov (United States)

    2017-08-21

    ...-AA00 Safety Zone: PG&E Evolution, King Salmon, CA AGENCY: Coast Guard, DHS. ACTION: Temporary final... Humboldt Bay in King Salmon, CA in support of the Pacific Gas and Electric Evolution that will be effective... workers, mariners, and other vessels transiting the area from the dangers associated with this evolution...

  10. Silver Nanoparticles Induce HePG-2 Cells Apoptosis Through ROS-Mediated Signaling Pathways

    Science.gov (United States)

    Zhu, Bing; Li, Yinghua; Lin, Zhengfang; Zhao, Mingqi; Xu, Tiantian; Wang, Changbing; Deng, Ning

    2016-04-01

    Recently, silver nanoparticles (AgNPs) have been shown to provide a novel approach to overcome tumors, especially those of hepatocarcinoma. However, the anticancer mechanism of silver nanoparticles is unclear. Thus, the purpose of this study was to estimate the effect of AgNPs on proliferation and activation of ROS-mediated signaling pathway on human hepatocellular carcinoma HePG-2 cells. A simple chemical method for preparing AgNPs with superior anticancer activity has been showed in this study. AgNPs were detected by transmission electronic microscopy (TEM) and energy dispersive X-ray (EDX). The size distribution and zeta potential of silver nanoparticles were detected by Zetasizer Nano. The average size of AgNPs (2 nm) observably increased the cellular uptake by endocytosis. AgNPs markedly inhibited the proliferation of HePG-2 cells through induction of apoptosis with caspase-3 activation and PARP cleavage. AgNPs with dose-dependent manner significantly increased the apoptotic cell population (sub-G1). Furthermore, AgNP-induced apoptosis was found dependent on the overproduction of reactive oxygen species (ROS) and affecting of MAPKs and AKT signaling and DNA damage-mediated p53 phosphorylation to advance HePG-2 cells apoptosis. Therefore, our results show that the mechanism of ROS-mediated signaling pathways may provide useful information in AgNP-induced HePG-2 cell apoptosis.

  11. Fermi Observations of the Very Hard Gamma-ray Blazar PG 1553+113

    CERN Document Server

    ,

    2009-01-01

    We report the observations of PG 1553+113 during the first ~200 days of Fermi Gamma-ray Space Telescope science operations, from 4 August 2008 to 22 February 2009 (MJD 54682.7-54884.2). This is the first detailed study of PG 1553+113 in the GeV gamma-ray regime and it allows us to fill a gap of three decades in energy in its spectral energy distribution. We find PG 1553+113 to be a steady source with a hard spectrum that is best fit by a simple power-law in the Fermi energy band. We combine the Fermi data with archival radio, optical, X-ray and very high energy (VHE) gamma-ray data to model its broadband spectral energy distribution and find that a simple, one-zone synchrotron self-Compton model provides a reasonable fit. PG 1553+113 has the softest VHE spectrum of all sources detected in that regime and, out of those with significant detections across the Fermi energy bandpass so far, the hardest spectrum in that energy regime. Thus, it has the largest spectral break of any gamma-ray source studied to date, ...

  12. UV and FUV spectroscopy of the hybrid PG 1159-type central star NGC 7094

    CERN Document Server

    Ziegler, M; Reiff, E; Werner, K; Kruk, J W; Oliveira, C M

    2008-01-01

    Previous studies aiming at the iron-abundance determination in three PG 1159 stars (K 1-16, PG 1159-035, NGC 7094) and a [WC]-PG 1159 transition star (Abell 78) have revealed that no object shows any iron line in the UV spectrum. The stars are iron-deficient by at least 1 dex, typically. A possible explanation is that iron nuclei were transformed by neutron captures into heavier elements (s-process), however, the extent of the iron-destruction would be much stronger than predicted by AGB star models. But if n-captures are the right explanation, then we should observe an enrichment of trans-iron elements. In this paper we report on our search for a possible nickel overabundance in one of the four Fe deficient PG 1159 stars, namely the central star NGC 7094. We are unable to identify any nickel line in HST and FUSE spectra and conclude that Ni is not overabundant. It is conceivable that iron was transformed into even heavier elements, but their identification suffers from the lack of atomic data.

  13. Independent adsorption of monovalent cations and cationic polymers at PE/PG lipid membranes

    Science.gov (United States)

    Khomich, Daria A.; Nesterenko, Alexey M.; Kostritskii, Andrei Yu; Kondinskaia, Diana A.; Ermakov, Yuri A.; Gurtovenko, Andrey A.

    2017-01-01

    Synthetic cationic polymers constitute a wide class of polymeric biocides. Commonly their antimicrobial effect is associated to their interaction with bacterial membranes. In the present study we analyze the interaction of various cationic polymers with model bacterial membranes comprised of a mixture of phosphatidylethanolamine (PE) and phosphatidylglycerol (PG). We describe a polymer-membrane interaction as a process of modification of the surface charge. It is well known that small monovalent inorganic cations (Na+, K+) cannot overcharge the surface of a bilayer containing anionic lipids. In contrast, polycations are able to overcharge anionic membranes and demonstrate a very large input to the electric field distribution at the membrane-water interface. We aimed here to study the electrostatic effects associated with the interaction of polycations of different types with a model lipid membrane whose composition closely resembles that of bacterial membranes (PE:PG = 1:4). Four different cationic polymers (polyvinylamine, polyallylamine, poly-L-lysine and polyethylenimine) were adsorbed at a model PE/PG bilayer in MD simulations. Adsorption of sodium cations was inspected separately for PE/PG bilayers of different composition and cation’s binding parameters were determined. From computational experiments and consequent theoretical analysis we concluded that sodium adsorption at anionic binding sites does not depend on the presence of polycations. Therefore, we hypothesize that antimicrobial activity of the studied cationic polymers should depend on the ionic composition of the medium.

  14. Distribuciones de masas de estrellas PG; DO y DB: posibles conexiones evolutivas

    Science.gov (United States)

    Panei, J. A.; Althaus, L. G.; Miller Bertolami, M. M.; García-Berro, E.; Córsico, A. H.; Romero, A. D.; Kepler, S. O.; Rohrmann, R. D.

    A 20 % of white dwarf stars has hydrogen deficient atmospheres, known like no-DA white dwarfs. The results of this work allow for the first time to study a possible evolutionary connection between different low mass and hydrogen deficient post-AGB stars, like DO white dwarfs, PG 1159, O(He), DB and RCrB, among others. FULL TEXT IN SPANISH

  15. Mean platelet volume in acute rheumatic fever.

    Science.gov (United States)

    Sert, Ahmet; Aypar, Ebru; Odabas, Dursun

    2013-01-01

    Acute rheumatic fever (ARF) is still an endemic disease, especially among school-aged children in developing countries. Mean platelet volume (MPV), which is commonly used as a measure of platelet size, indicates the rate of platelet production and platelet activation. We aimed to investigate MPV in children with ARF. The study population consisted of 40 children with ARF (32 patients with carditis and 8 patients without carditis) and 40 healthy control subjects. White blood cell (WBC) and platelet counts were significantly higher and MPV values were significantly lower in patients with ARF during the acute stage when compared to controls. Erythrocyte sedimentation rate (ESR) and C-reactive protein values significantly decreased in patients with ARF after the treatment when compared to baseline, whereas MPV values increased. MPV values were negatively correlated with ESR and WBC, and platelet counts. In conclusion, during the acute stage of ARF, MPV values were lower when compared to controls.

  16. Therapeutic platelet reduction: Use in postsplenectomy thrombocytosis

    Directory of Open Access Journals (Sweden)

    Gita Negi

    2015-01-01

    Full Text Available Therapeutic platelet reduction is an effective modality for the reduction of platelet count in patients with treatment of extreme thrombocytosis resulting from a variety of primary and secondary causes of thrombocytosis, which may be associated with thrombotic or hemorrhagic complications of varying degrees. These cases when symptomatic fall into the ASFA Category II indication for therapeutic platelet apheresis procedure. Here, we report a case of postsplenectomy secondary thrombocytosis presenting with extremely high platelet counts and subsequent thrombosis in the shunt and successful treatment after therapeutic platelet reduction. The case is being presented to bring forth the fact that therapeutic platelet reduction is an easy procedure that gives quick and good results and also to bring to the attention of transfusion specialists an associated but as yet unreported procedural finding.

  17. Laboratory testing for platelet function disorders.

    Science.gov (United States)

    Israels, S J

    2015-05-01

    Platelet function testing is both complex and labor intensive. A stepwise approach to the evaluation of patients with suspected platelet disorders will optimize the use of laboratory resources, beginning with an appropriate clinical evaluation to determine whether the bleeding is consistent with a defect of primary hemostasis. Bleeding assessment tools, evaluation of platelet counts, and review of peripheral blood cell morphology can aid the initial assessment. For patients requiring further laboratory testing, platelet aggregometry, secretion assays, and von Willebrand factor assays are the most useful next steps and will direct further specialized testing including flow cytometry, electron microscopy, and molecular diagnostics. Guidelines and recommendations for standardizing platelet function testing, with a particular focus on light transmission aggregometry, are available and can provide a template for clinical laboratories in establishing procedures that will optimize diagnosis and assure quality results. This review outlines an approach to platelet function testing and reviews testing methods available to clinical laboratories.

  18. Differential effects of platelets and platelet inhibition by ticagrelor on TLR2- and TLR4-mediated inflammatory responses

    NARCIS (Netherlands)

    Tunjungputri, R.N.; Ven, A.J.A.M. van der; Riksen, N.P.; Rongen, G.A.P.J.M.; Tacke, S.; Berg, T.N.A. van den; Fijnheer, R.; Gomes, M.E.; Dinarello, C.A.; Veerdonk, F.L. van de; Gasem, M.H.; Netea, M.G.; Joosten, L.A.B.; Groot, P.G. de; Mast, Q. de

    2015-01-01

    Platelets and platelet-monocyte interaction play an important role in inflammation. Both pro- and anti-inflammatory effects of platelet inhibition have been reported in animal models. This study aimed to investigate the effect of platelets and platelet inhibition by the new P2Y12 receptor antagonist

  19. Effect of heat shock on poly(ADP-ribose) synthetase and DNA repair in Drosophila cells

    Energy Technology Data Exchange (ETDEWEB)

    Nolan, N.L.; Kidwell, W.R.

    1982-04-01

    Poly(ADP-ribose) synthetase, a chromatin-bound enzyme which attaches polyanionic chains of ADP-ribose to nuclear proteins, was found to be temperature sensitive in intact Drosophila melanogaster cells. The synthetase was completely inactivated by heat-shocking the cells at 37/sup 0/C for 5 min, a condition which had no appreciable effect on the subsequent growth of Drosophila cells at their physiological temperature. The heat-shock effect on synthetase was reversible; enzyme activity began to reappear about 2 hr post heat shock. During the 2-hr interval when poly(ADP-ribose) synthetase was absent, the cells were competent in repair of ..gamma..-ray-induced DNA strand breaks as shown by DNA sedimentation studies on alkaline sucrose gradients. It is thus concluded that poly(ADP-ribose) synthesis is unnecessary for repair of DNA strand breaks introduced by irradiation. The same conclusion was reached from the fact that two inhibitors of poly(ADP-ribose) synthetase 3-aminobenzamide and 5-methylnicotinamide, failed to block repair of ..gamma..-ray-induced DNA chain breaks even though both inhibitors reduced the amount of poly(ADP-ribose) synthesized in cells by 50-75%. Although it was found that the repair of DNA strand breaks is independent of poly(ADP-ribose) synthesis, irradiation does activate the synthetase in control cells, as shown by radioimmunoassay of poly(ADP-ribose) levels.

  20. Recurrent seizures and brain pathology after inhibition of glutamine synthetase in the hippocampus in rats.

    Science.gov (United States)

    Eid, Tore; Ghosh, Arko; Wang, Yue; Beckström, Henning; Zaveri, Hitten P; Lee, Tih-Shih W; Lai, James C K; Malthankar-Phatak, Gauri H; de Lanerolle, Nihal C

    2008-08-01

    An excess of extracellular glutamate in the hippocampus has been linked to the generation of recurrent seizures and brain pathology in patients with medically intractable mesial temporal lobe epilepsy (MTLE). However, the mechanism which results in glutamate excess in MTLE remains unknown. We recently reported that the glutamate-metabolizing enzyme glutamine synthetase is deficient in the hippocampus in patients with MTLE, and we postulated that this deficiency is critically involved in the pathophysiology of the disease. To further explore the role of glutamine synthetase in MTLE we created a novel animal model of hippocampal glutamine synthetase deficiency by continuous (approximately 28 days) microinfusion of methionine sulfoximine (MSO: 0.625 to 2.5 microg/h) unilaterally into the hippocampus in rats. This treatment led to a deficiency in hippocampal glutamine synthetase activity by 82-97% versus saline. The majority (>95%) of the MSO-treated animals exhibited recurrent seizures that continued for several weeks. Some of the MSO-treated animals exhibited neuropathological features that were similar to mesial temporal sclerosis, such as hippocampal atrophy and patterned loss of hippocampal neurons. However, many MSO-treated animals displayed only minimal injury to the hippocampus, with no clear evidence of mesial temporal sclerosis. These findings support the hypothesis that a deficiency in hippocampal glutamine synthetase causes recurrent seizures, even in the absence of classical mesial temporal sclerosis, and that restoration of glutamine synthetase may represent a novel approach to therapeutic intervention in this disease.

  1. LDL oxidation by platelets propagates platelet activation via an oxidative stress-mediated mechanism.

    Science.gov (United States)

    Carnevale, Roberto; Bartimoccia, Simona; Nocella, Cristina; Di Santo, Serena; Loffredo, Lorenzo; Illuminati, Giulio; Lombardi, Elisabetta; Boz, Valentina; Del Ben, Maria; De Marco, Luigi; Pignatelli, Pasquale; Violi, Francesco

    2014-11-01

    Platelets generate oxidized LDL (ox-LDL) via NOX2-derived oxidative stress. We investigated if once generated by activated platelets ox-LDL can propagate platelet activation. Experiments were performed in platelets from healthy subjects (HS), hyper-cholesterolemic patients and patients with NOX2 hereditary deficiency. Agonist-stimulated platelets from HS added with LDL were associated with a dose-dependent increase of reactive oxidant species and ox-LDL. Agonist-stimulated platelets from HS added with a fixed dose of LDL (57.14 μmol/L) or added with homogenized human atherosclerotic plaque showed enhanced ox-LDL formation (approximately +50% and +30% respectively), which was lowered by a NOX2 inhibitor (approximately -35% and -25% respectively). Compared to HS, ox-LDL production was more pronounced in agonist-stimulated platelet rich plasma (PRP) from hyper-cholesterolemic patients but was almost absent in PRP from NOX2-deficient patients. Platelet aggregation and 8-iso-PGF2α-ΙΙΙ formation increased in LDL-treated washed platelets (+42% and +53% respectively) and PRP (+31% and +53% respectively). Also, LDL enhanced platelet-dependent thrombosis at arterial shear rate (+33%) but did not affect platelet activation in NOX2-deficient patients. Platelet activation by LDL was significantly inhibited by CD36 or LOX1 blocking peptides, two ox-LDL receptor antagonists, or by a NOX2 inhibitor. LDL-added platelets showed increased p38MAPK (+59%) and PKC (+51%) phosphorylation, p47(phox) translocation to platelet membrane (+34%) and NOX2 activation (+30%), which were inhibited by ox-LDL receptor antagonists. Platelets oxidize LDL, which in turn amplify platelet activation via specific ox-LDL receptors; both effects are mediated by NOX2 activation. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  2. A systems analysis of the chemosensitivity of breast cancer cells to the polyamine analogue PG-11047

    Directory of Open Access Journals (Sweden)

    Feiler Heidi S

    2009-12-01

    Full Text Available Abstract Background Polyamines regulate important cellular functions and polyamine dysregulation frequently occurs in cancer. The objective of this study was to use a systems approach to study the relative effects of PG-11047, a polyamine analogue, across breast cancer cells derived from different patients and to identify genetic markers associated with differential cytotoxicity. Methods A panel of 48 breast cell lines that mirror many transcriptional and genomic features present in primary human breast tumours were used to study the antiproliferative activity of PG-11047. Sensitive cell lines were further examined for cell cycle distribution and apoptotic response. Cell line responses, quantified by the GI50 (dose required for 50% relative growth inhibition were correlated with the omic profiles of the cell lines to identify markers that predict response and cellular functions associated with drug sensitivity. Results The concentrations of PG-11047 needed to inhibit growth of members of the panel of breast cell lines varied over a wide range, with basal-like cell lines being inhibited at lower concentrations than the luminal cell lines. Sensitive cell lines showed a significant decrease in S phase fraction at doses that produced little apoptosis. Correlation of the GI50 values with the omic profiles of the cell lines identified genomic, transcriptional and proteomic variables associated with response. Conclusions A 13-gene transcriptional marker set was developed as a predictor of response to PG-11047 that warrants clinical evaluation. Analyses of the pathways, networks and genes associated with response to PG-11047 suggest that response may be influenced by interferon signalling and differential inhibition of aspects of motility and epithelial to mesenchymal transition. See the related commentary by Benes and Settleman: http://www.biomedcentral.com/1741-7015/7/78

  3. A systems analysis of the chemosensitivity of breast cancer cells to the polyamine analogue PG-11047

    Energy Technology Data Exchange (ETDEWEB)

    Kuo, Wen-Lin; Das, Debopriya; Ziyad, Safiyyah; Bhattacharya, Sanchita; Gibb, William J.; Heiser, Laura M.; Sadanandam, Anguraj; Fontenay, Gerald V.; Hu, Zhi; Wang, Nicholas J.; Bayani, Nora; Feiler, Heidi S.; Neve, Richard M.; Wyrobek, Andrew J.; Spellman, Paul T.; Marton, Laurence J.; Gray, Joe W.

    2009-11-14

    Polyamines regulate important cellular functions and polyamine dysregulation frequently occurs in cancer. The objective of this study was to use a systems approach to study the relative effects of PG-11047, a polyamine analogue, across breast cancer cells derived from different patients and to identify genetic markers associated with differential cytotoxicity. A panel of 48 breast cell lines that mirror many transcriptional and genomic features present in primary human breast tumours were used to study the antiproliferative activity of PG-11047. Sensitive cell lines were further examined for cell cycle distribution and apoptotic response. Cell line responses, quantified by the GI50 (dose required for 50% relative growth inhibition) were correlated with the omic profiles of the cell lines to identify markers that predict response and cellular functions associated with drug sensitivity. The concentrations of PG-11047 needed to inhibit growth of members of the panel of breast cell lines varied over a wide range, with basal-like cell lines being inhibited at lower concentrations than the luminal cell lines. Sensitive cell lines showed a significant decrease in S phase fraction at doses that produced little apoptosis. Correlation of the GI50 values with the omic profiles of the cell lines identified genomic, transcriptional and proteomic variables associated with response. A 13-gene transcriptional marker set was developed as a predictor of response to PG-11047 that warrants clinical evaluation. Analyses of the pathways, networks and genes associated with response to PG-11047 suggest that response may be influenced by interferon signaling and differential inhibition of aspects of motility and epithelial to mesenchymal transition.

  4. The effects of selective serotonin reuptake inhibitors on platelet function in whole blood and platelet concentrates.

    Science.gov (United States)

    Reikvam, Anne-Grete; Hustad, Steinar; Reikvam, Håkon; Apelseth, Torunn Oveland; Nepstad, Ina; Hervig, Tor Audun

    2012-01-01

    Several studies report that patients who are treated with selective serotonin reuptake inhibitors (SSRIs) for depression may have increased risk of bleeding, particularly from the gastrointestinal tract. This may be related to low intraplatelet serotonin concentrations. Several blood banks do not store platelets from donors using SSRIs for transfusion, although the possible effects of SSRIs on platelet storage are not documented. We conducted a case-control pilot study of apheresis platelet concentrates prepared from donors using SSRIs (n=8) and from donors without medication (n=10). The platelet concentrates were stored for 5 days. Light transmission aggregometry (LTA), thrombelastography (TEG), and flow cytometric analyses were preformed for in vitro measurements of platelet function. Platelet function and platelet serotonin content were investigated in whole blood and in platelet concentrates stored for up to 5 days. LTA, TEG, and flow cytometric analysis of glycoprotein expression did not reveal any significant differences between the two groups. All 18 platelet concentrates performed well according to the standards set for platelet quality in relation to transfusion. Blood donors using SSRIs had significantly lower platelet serotonin compared to blood donors without medication. The results from our pilot study indicate that platelets from donors using SSRIs may be suitable for transfusion after storage for 5 days, but further laboratory and clinical studies are necessary to confirm this.

  5. Platelet aggregation and quality control of platelet concentrates produced in the Amazon Blood Bank

    Directory of Open Access Journals (Sweden)

    Maria José Dantas Coêlho

    2011-01-01

    Full Text Available BACKGROUND: The study of platelet aggregation is essential to assess in vitro platelet function by different platelet activation pathways. OBJECTIVE: To assess aggregation and biochemical parameters of random platelet concentrates produced at the Fundação HEMOAM using the quality control tests defined by law. METHODS: Whole blood samples from 80 donors and the respective platelet concentrate units were tested. Platelet concentrates were tested (platelet count, aggregation and pH on days 1, 3 and 5 of storage. Additionally a leukocyte count was done only on day 1 and microbiological tests on day 5 of storage. Collagen and adenosine diphosphate were used as inducing agonists for platelet aggregation testing. RESULTS: Donor whole blood had normal aggregation (aggregation with adenosine diphosphate = 67% and with collagen = 78%. The median aggregation in platelet concentrates with adenosine diphosphate was low throughout storage (18% on day 1, 7% on day 3 and 6% on day 5 and the median aggregation with collagen was normal only on day 1 and low thereafter (54.4% on day 1, 20.5% on day 3 and 9% on day 5. CONCLUSION: Although the results were within the norms required by law, platelet concentrates had low aggregation rates. We suggest the inclusion of a functional assessment test for the quality control of platelet concentrates for a more effective response to platelet replacement therapy.

  6. Ultrastructural studies of the gray platelet syndrome.

    Science.gov (United States)

    White, J G

    1979-05-01

    The gray platelet syndrome (GPS) is a rare inherited disorder in which peripheral blood platelets are relatively large, vacuolated, and almost devoid of cytoplasmic granulation. In the present study we have evaluated the ultrastructure and cytochemistry of platelets from 2 patients with the GPS to determine precisely which organelles are missing from their cells. The findings indicate that gray platelets contain normal numbers of mitochondria, dense bodies, peroxisomes, and lysosomes but specifically lack alpha-granules. Preliminary studies of megakaryocytes from 1 of the 2 patients suggest that the defect in granule formation may lie at the level of the Golgi zone.

  7. Identification of platelet refractoriness in oncohematologic patients

    Directory of Open Access Journals (Sweden)

    Aline Aparecida Ferreira

    2011-01-01

    Full Text Available OBJECTIVES: To identify the occurrence and the causes of platelet refractoriness in oncohematologic patients. INTRODUCTION: Platelet refractoriness (unsatisfactory post-transfusion platelet increment is a severe problem that impairs the treatment of oncohematologic patients and is not routinely investigated in most Brazilian services. METHODS: Forty-four episodes of platelet concentrate transfusion were evaluated in 16 patients according to the following parameters: corrected count increment, clinical conditions and detection of anti-platelet antibodies by the platelet immunofluorescence test (PIFT and panel reactive antibodies against human leukocyte antigen class I (PRA-HLA. RESULTS: Of the 16 patients evaluated (median age: 53 years, nine (56% were women, seven of them with a history of pregnancy. An unsatisfactory increment was observed in 43% of the transfusion events, being more frequent in transfusions of random platelet concentrates (54%. Platelet refractoriness was confirmed in three patients (19%, who presented immunologic and non-immunologic causes. Alloantibodies were identified in eight patients (50% by the PIFT and in three (19% by the PRA-HLA. Among alloimmunized patients, nine (64% had a history of transfusion, and three as a result of pregnancy (43%. Of the former, two were refractory (29%. No significant differences were observed, probably as a result of the small sample size. CONCLUSION: The high rate of unsatisfactory platelet increment, refractoriness and alloimmunization observed support the need to set up protocols for the investigation of this complication in all chronically transfused patients, a fundamental requirement for the guarantee of adequate management.

  8. Does bipolar pacemaker current activate blood platelets?

    DEFF Research Database (Denmark)

    Gjesdal, Grunde; Hansen, Annebirthe Bo; Brandes, Axel

    2009-01-01

    OBJECTIVE: The aim of this study was to investigate whether bipolar pacemaker current lead can activate blood platelets. The null hypothesis was that 1 minute of electrical stimulation of platelets would not influence their subsequent reactivity to adenosine diphosphate (ADP). BACKGROUND: Both...... platelets and muscle cells contain actin and myosin filaments, and both cells are activated following calcium influx. Muscle cells open their calcium channels and contract when exposed to an electric current. Current through a bipolar pacemaker lead will expose a small volume of blood, including platelets...

  9. Platelet cytoskeleton and its hemostatic role.

    Science.gov (United States)

    Cerecedo, Doris

    2013-12-01

    Upon vascular injury, platelets adhere to the exposed extracellular matrix, which triggers the platelet activation and aggregation to form a hemostatic plug to seal the wound. All of these events involve dramatic changes in shape because of the cytoskeleton reorganization. The versatility of the cytoskeleton's main elements depends on the biochemical nature of the elements, as well as on the associated proteins that confer multiple functions within the cell. The list of these associated proteins grows actively, increasing our knowledge concerning the complexity of platelet cytoskeleton machinery. The present review evidences the recently described platelet proteins that promote characteristic modifications in their cytoskeleton organization, with special focus on the dystrophin-glycoprotein complex.

  10. The internal rotation of the GW Vir star PG 0112+200 through the eyes of asteroseismology

    CERN Document Server

    Córsico, A H; Kawaler, S D; Bertolami, M M Miller; García-Berro, E

    2011-01-01

    We investigate the internal rotation profile of the GW Vir (PG1159-type) star PG 0122+200 by employing an asteroseismological model that closely reproduces the observed periods of this star. We adopt a forward approach and two inversion methods based on the rotational splitting of the pulsation frequencies to explore the properties of the rotation of PG 0122+200. We found evidence for differential rotation in this star.

  11. Platelet function alterations in dengue are associated with plasma leakage

    NARCIS (Netherlands)

    Michels, M.; Alisjahbana, B.; Groot, P.G. de; Indrati, A.R.; Fijnheer, R.; Puspita, M.; Dewi, I.M.; Wijer, L. van de; Boer, E.M. de; Roest, M.; Ven, A.J. van der; Mast, Q. de

    2014-01-01

    Severe dengue is characterised by thrombocytopenia, plasma leakage and bleeding. Platelets are important for preservation of endothelial integrity. We hypothesised that platelet activation with secondary platelet dysfunction contribute to plasma leakage. In adult Indonesian patients with acute dengu

  12. Mean platelet volume in euthyroid patients with Hashimoto's thyroiditis.

    Science.gov (United States)

    Carlioglu, Ayse; Timur, Ozge; Durmaz, Senay A; Ayhan, Mehmet E

    2015-04-01

    Mean platelet volume (MPV) is the measure of platelet size. MPV possibly is a simple way to estimate platelet activity. In this study, we aimed to investigate MPV levels in euthyroid Hashimoto's thyroiditis patients. Fifty-one euthyroid patients with Hashimoto's thyroiditis attending our outpatient clinic of the endocrinology department, and 51 age and BMI-matched healthy individuals were included in this study. All patients with euthyroid Hashimoto's thyroiditis were at euthyroid state. None of the study patients was subjected to levothyroxine replacement therapy. Anti-thyroid peroxidase (anti-TPO) antibody and anti-tiroglobulin antibody were positive. All the study participants were evaluated by biochemical and platelet parameters. There were no significant differences in age (33.88 ± 12.87 and 30.18 ± 12.43 years, respectively; P > 0.05) and BMI (23.55 ± 3.34 and 22.25 ± 3.65 kg/m, respectively, P > 0.05) between the study and the control groups. Anti-TPO and anti-tiroglobulin levels were significantly higher in the study group (anti-TPO 428.32 ± 668.39 IU/ml in the euthyroid Hashimoto's thyroiditis group; 14.85 ± 9.66 IU/ml in the control group, P = 0.001; anti-tiroglobulin 320.46 ± 796.05 IU/ml in the euthyroid Hashimoto's thyroiditis group, 21.28 ± 26.24 IU/ml in the control group, P = 0.09). There were no significant differences in terms of serum thyroid-stimulating hormone (TSH) (1.76 ± 0.79 and 1.85 ± 1.14 uIU/ml, respectively), FT3 (3.10 ± 0.37 and 3.29 ± 0.76 pg/ml, respectively) and FT4 (1.22 ± 0.42 and 1.46 ± 0.78 pg/ml, respectively) levels between the study and the control groups. Serum triglyceride levels were significantly higher in the study group than in the control group (133.81 ± 91.50 and 90.18 ± 41.15 mg/dl, respectively; P = 0.015). Mean MPV levels were significantly higher in the euthyroid Hashimoto's thyroiditis group than

  13. Aminoacyl-tRNA Synthetases in the Bacterial World.

    Science.gov (United States)

    Giegé, Richard; Springer, Mathias

    2016-05-01

    Aminoacyl-tRNA synthetases (aaRSs) are modular enzymes globally conserved in the three kingdoms of life. All catalyze the same two-step reaction, i.e., the attachment of a proteinogenic amino acid on their cognate tRNAs, thereby mediating the correct expression of the genetic code. In addition, some aaRSs acquired other functions beyond this key role in translation. Genomics and X-ray crystallography have revealed great structural diversity in aaRSs (e.g., in oligomery and modularity, in ranking into two distinct groups each subdivided in 3 subgroups, by additional domains appended on the catalytic modules). AaRSs show huge structural plasticity related to function and limited idiosyncrasies that are kingdom or even species specific (e.g., the presence in many Bacteria of non discriminating aaRSs compensating for the absence of one or two specific aaRSs, notably AsnRS and/or GlnRS). Diversity, as well, occurs in the mechanisms of aaRS gene regulation that are not conserved in evolution, notably between distant groups such as Gram-positive and Gram-negative Bacteria. The review focuses on bacterial aaRSs (and their paralogs) and covers their structure, function, regulation, and evolution. Structure/function relationships are emphasized, notably the enzymology of tRNA aminoacylation and the editing mechanisms for correction of activation and charging errors. The huge amount of genomic and structural data that accumulated in last two decades is reviewed, showing how the field moved from essentially reductionist biology towards more global and integrated approaches. Likewise, the alternative functions of aaRSs and those of aaRS paralogs (e.g., during cell wall biogenesis and other metabolic processes in or outside protein synthesis) are reviewed. Since aaRS phylogenies present promiscuous bacterial, archaeal, and eukaryal features, similarities and differences in the properties of aaRSs from the three kingdoms of life are pinpointed throughout the review and

  14. Actinobacterial acyl coenzyme A synthetases involved in steroid side-chain catabolism.

    Science.gov (United States)

    Casabon, Israël; Swain, Kendra; Crowe, Adam M; Eltis, Lindsay D; Mohn, William W

    2014-02-01

    Bacterial steroid catabolism is an important component of the global carbon cycle and has applications in drug synthesis. Pathways for this catabolism involve multiple acyl coenzyme A (CoA) synthetases, which activate alkanoate substituents for β-oxidation. The functions of these synthetases are poorly understood. We enzymatically characterized four distinct acyl-CoA synthetases from the cholate catabolic pathway of Rhodococcus jostii RHA1 and the cholesterol catabolic pathway of Mycobacterium tuberculosis. Phylogenetic analysis of 70 acyl-CoA synthetases predicted to be involved in steroid metabolism revealed that the characterized synthetases each represent an orthologous class with a distinct function in steroid side-chain degradation. The synthetases were specific for the length of alkanoate substituent. FadD19 from M. tuberculosis H37Rv (FadD19Mtb) transformed 3-oxo-4-cholesten-26-oate (kcat/Km = 0.33 × 10(5) ± 0.03 × 10(5) M(-1) s(-1)) and represents orthologs that activate the C8 side chain of cholesterol. Both CasGRHA1 and FadD17Mtb are steroid-24-oyl-CoA synthetases. CasG and its orthologs activate the C5 side chain of cholate, while FadD17 and its orthologs appear to activate the C5 side chain of one or more cholesterol metabolites. CasIRHA1 is a steroid-22-oyl-CoA synthetase, representing orthologs that activate metabolites with a C3 side chain, which accumulate during cholate catabolism. CasI had similar apparent specificities for substrates with intact or extensively degraded steroid nuclei, exemplified by 3-oxo-23,24-bisnorchol-4-en-22-oate and 1β(2'-propanoate)-3aα-H-4α(3″-propanoate)-7aβ-methylhexahydro-5-indanone (kcat/Km = 2.4 × 10(5) ± 0.1 × 10(5) M(-1) s(-1) and 3.2 × 10(5) ± 0.3 × 10(5) M(-1) s(-1), respectively). Acyl-CoA synthetase classes involved in cholate catabolism were found in both Actinobacteria and Proteobacteria. Overall, this study provides insight into the physiological roles of acyl-CoA synthetases in steroid

  15. Platelet-rich plasma preparation using three devices : Implications for platelet activation and platelet growth factor release

    NARCIS (Netherlands)

    Everts, Peter A. M.; Mahoney, Christine Brown; Hoffmann, Johannes J. M. L.; Schonberger, Jacques P. A. M.; Box, Henk A. M.; Van Zundert, Andre; Knape, Johannes T. A.

    2006-01-01

    Background: In this study, three commercial systems for the preparation of platelet-rich plasma (PRP) were compared and platelet growth factors release was measured. Methods: Ten healthy volunteers donated whole blood that was fractionated by a blood cell separator, and a table-top centrifuge to pre

  16. Hereditary sideroblastic anemia with associated platelet abnormalities.

    Science.gov (United States)

    Soslau, G; Brodsky, I

    1989-12-01

    A 62 year old male (R.H.) presented with a mild anemia (Hb 11-12 gm%) and a history of multiple hemorrhagic episodes. The marrow had 40-50% sideroblasts. Marrow chromosomes were normal. His wife was hematologically normal, while one daughter, age 30 years, had a sideroblastic anemia (Hb 11-12 gm%) with 40-50% sideroblasts in the marrow. Her anemia was first noted at age 15 years. Administration of vitamin B6 did not correct the anemia in either the father or daughter. Platelet abnormalities inherited jointly with this disorder are described for the first time. Both R.H. and his daughter had prolonged bleeding times, with normal PTT, PT times, fVIII:C, fVIII:Ag levels, and vWF multimers, which may rule out a von Willebrand's disease. They have normal platelet numbers but abnormally low platelet adhesiveness and greatly depressed ADP, collagen, and epinephrine responsiveness. Response to ristocetin was in the low normal range, and aggregation with thrombin was normal. While desmopressin completely normalized R.H.'s bleeding time, none of these platelet parameters were improved. No differences in the SDS PAGE protein patterns of RH platelets could be detected in comparison to normal samples. His platelets took up and released serotonin (5HT) normally, and electron micrographs defined no morphological abnormalities. However, no ATP was released from platelets activated with collagen, and when followed by thrombin about fourfold greater ATP was released by control platelets as compared to RH platelets. The dense granule fraction derived from RH platelets contained about 20% the level of ATP, 40% the level of ADP, and 50% the level of 5HT detected in a normal sample. The results indicate that the bleeding disorder is related to a non-classical heritable storage pool defect. The connection between the inherited sideroblastic anemia and platelet defects is obscure.

  17. Expression of glutamine synthetase in the mouse kidney: localization in multiple epithelial cell types and differential regulation by hypokalemia.

    Science.gov (United States)

    Verlander, Jill W; Chu, Diana; Lee, Hyun-Wook; Handlogten, Mary E; Weiner, I David

    2013-09-01

    Renal glutamine synthetase catalyzes the reaction of NH4+ with glutamate, forming glutamine and decreasing the ammonia available for net acid excretion. The purpose of the present study was to determine glutamine synthetase's specific cellular expression in the mouse kidney and its regulation by hypokalemia, a common cause of altered renal ammonia metabolism. Glutamine synthetase mRNA and protein were present in the renal cortex and in both the outer and inner stripes of the outer medulla. Immunohistochemistry showed glutamine synthetase expression throughout the entire proximal tubule and in nonproximal tubule cells. Double immunolabel with cell-specific markers demonstrated glutamine synthetase expression in type A intercalated cells, non-A, non-B intercalated cells, and distal convoluted tubule cells, but not in principal cells, type B intercalated cells, or connecting segment cells. Hypokalemia induced by feeding a nominally K+ -free diet for 12 days decreased glutamine synthetase expression throughout the entire proximal tubule and in the distal convoluted tubule and simultaneously increased glutamine synthetase expression in type A intercalated cells in both the cortical and outer medullary collecting duct. We conclude that glutamine synthetase is widely and specifically expressed in renal epithelial cells and that the regulation of expression differs in specific cell populations. Glutamine synthetase is likely to mediate an important role in renal ammonia metabolism.

  18. Regulation of expression from the glnA promoter of Escherichia coli in the absence of glutamine synthetase.

    OpenAIRE

    Rothstein, D M; Pahel, G; Tyler, B.; Magasanik, B

    1980-01-01

    One of the suspected regulators of glutamine synthetase [L-glutamate:ammonia ligase (ADP-forming), EC 6.3.1.2] in enteric bacteria is glutamine synthetase itself. We isolated Escherichia coli strains carrying fusions of the beta-galactosidase structural gene to the promoter of the glutamine synthetase gene, with the aid of the Casadaban Mud1 (ApR, lac, cts62) phage. Some aspects of regulation were retained in haploid fusion strains despite the absence of glutamine synthetase, whereas other as...

  19. Expression of acyl-CoA synthetase 5 reflects the state of villus architecture in human small intestine

    DEFF Research Database (Denmark)

    Gassler, Nikolaus; Kopitz, Jürgen; Tehrani, Arman

    2004-01-01

    . Screening of antibodies from a hybridoma library led to the identification of an acyl-CoA synthetase 5-specific monoclonal antibody. Protein synthesis, mRNA expression, and the enzyme activity of acyl-CoA synthetase 5 were studied by several methods in human small intestinal tissues with Crohn's disease...... or coeliac disease, respectively. Acyl-CoA synthetase 5 mRNA and protein levels were substantially reduced in injured small intestinal mucosa. Moreover, impaired synthesis of the acyl-CoA synthetase 5 protein was reflected by a decrease in intramucosal enzyme activity. Subtle changes of the acyl...

  20. Homology modeling and molecular docking studies of Bacillomycin and Iturin synthetases with novel ligands for the production of therapeutic lipopeptides.

    Science.gov (United States)

    Eswari, Jujjavarapu Satya; Dhagat, Swasti; Kaser, Shubham; Tiwari, Anoop

    2017-08-15

    Lipopeptide synthetases play an important role in the production of lipopeptides. Lipopeptides are molecules made up of peptides and fatty acid moieties and have shown to have a broad range of antimicrobial activity. As infectious diseases have caused severe health problems mainly resulting from the development of antibiotic resistant strains of disease causing microorganisms there is a need of alternatives to antibiotics. The lipopeptide synthetase of the corresponding lipopeptides can be used as templates to design these as drugs using computational techniques. The objective of this study was homology modeling and molecular docking of two lipopeptide synthetases, bacillomycin D synthetase and iturin A synthetase, with their ligands as a means of drug design. Schrödinger software was used for homology modeling and molecular docking. After the identification of ligands, molecular docking of these ligands with the lipopeptide (bacillomycin and iturin) synthetases was performed. The docking was tested on the parameters of docking score and glide energy. 5 out of 21 ligands were found to dock with bacillomycin D synthetase whereas 8 out of 20 ligands docked with the iturin A synthetase. The knowledge of the docking sites and docking characteristics of the lipopeptide synthetases mentioned in the paper with the ligands can provide advantages of high speed and reliability, reduced costs on chemicals and experiments and the ethical issues concerned with the use of animal models for screening of drug toxicity. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  1. Inherited human group IVA cytosolic phospholipase A2 deficiency abolishes platelet, endothelial, and leucocyte eicosanoid generation.

    Science.gov (United States)

    Kirkby, Nicholas S; Reed, Daniel M; Edin, Matthew L; Rauzi, Francesca; Mataragka, Stefania; Vojnovic, Ivana; Bishop-Bailey, David; Milne, Ginger L; Longhurst, Hilary; Zeldin, Darryl C; Mitchell, Jane A; Warner, Timothy D

    2015-11-01

    Eicosanoids are important vascular regulators, but the phospholipase A2 (PLA2) isoforms supporting their production within the cardiovascular system are not fully understood. To address this, we have studied platelets, endothelial cells, and leukocytes from 2 siblings with a homozygous loss-of-function mutation in group IVA cytosolic phospholipase A2 (cPLA2α). Chromatography/mass spectrometry was used to determine levels of a broad range of eicosanoids produced by isolated vascular cells, and in plasma and urine. Eicosanoid release data were paired with studies of cellular function. Absence of cPLA2α almost abolished eicosanoid synthesis in platelets (e.g., thromboxane A2, control 20.5 ± 1.4 ng/ml vs. patient 0.1 ng/ml) and leukocytes [e.g., prostaglandin E2 (PGE2), control 21.9 ± 7.4 ng/ml vs. patient 1.9 ng/ml], and this was associated with impaired platelet activation and enhanced inflammatory responses. cPLA2α-deficient endothelial cells showed reduced, but not absent, formation of prostaglandin I2 (prostacyclin; control 956 ± 422 pg/ml vs. patient 196 pg/ml) and were primed for inflammation. In the urine, prostaglandin metabolites were selectively influenced by cPLA2α deficiency. For example, prostacyclin metabolites were strongly reduced (18.4% of control) in patients lacking cPLA2α, whereas PGE2 metabolites (77.8% of control) were similar to healthy volunteer levels. These studies constitute a definitive account, demonstrating the fundamental role of cPLA2α to eicosanoid formation and cellular responses within the human circulation.

  2. Multiple alterations of platelet functions dominated by increased secretion in mice lacking Cdc42 in platelets

    DEFF Research Database (Denmark)

    Pleines, Irina; Eckly, Anita; Elvers, Margitta;

    2010-01-01

    formation and exocytosis in various cell types, but its exact function in platelets is not established. Here, we show that the megakaryocyte/platelet-specific loss of Cdc42 leads to mild thrombocytopenia and a small increase in platelet size in mice. Unexpectedly, Cdc42-deficient platelets were able to form...... reduced, suggesting increased clearing of the cells under physiologic conditions. These data point to novel multiple functions of Cdc42 in the regulation of platelet activation, granule organization, degranulation, and a specific role in GPIb signaling....

  3. Platelet-rich fibrin: Evolution of a second-generation platelet concentrate

    Directory of Open Access Journals (Sweden)

    Sunitha Raja V

    2008-01-01

    Full Text Available Platelet-rich plasma (PRP is a platelet concentrate that has been used widely to accelerate soft-tissue and hard-tissue healing. The preparation of PRP has been described by several authors. Platelet-rich fibrin (PRF was first described by Choukroun et al. in France. It has been referred to as a second-generation platelet concentrate, which has been shown to have several advantages over traditionally prepared PRP. Its chief advantages include ease of preparation and lack of biochemical handling of blood, which makes this preparation strictly autologous. This article describes the evolution of this novel platelet concentrate, referred to as PRF.

  4. Human platelets antigens influence the viral load of platelets after the interaction of the platelets with HCV and HIV in vitro

    Directory of Open Access Journals (Sweden)

    Rejane Maria Tommasini Grotto

    Full Text Available Abstract: INTRODUCTION: In this study, we evaluated hepatitis C virus (HCV and human immunodeficiency virus (HIV - platelet interactions in vitro as well as human platelets antigen (HPA polymorphisms. METHODS: Platelets were obtained from 100 healthy HPA-genotyped volunteer donors and incubated with HIV or HCV. The viral load after in vitro exposure was detected. RESULTS: The viral load in the platelets after exposure to the virus was higher in the HIV exposure than in the HCV exposure. CONCLUSIONS: HIV-platelet ligation could be more efficient than HCV-platelet interaction. Further, the HPA-1b allele seems to influence the interaction of platelets with HCV.

  5. Nitric oxide synthetase and Helicobacter pylori in patients undergoing appendicectomy.

    LENUS (Irish Health Repository)

    Kell, M R

    2012-02-03

    BACKGROUND: This study was designed to determine whether Helicobacter pylori forms part of the normal microenvironment of the appendix, whether it plays a role in the pathogenesis of acute appendicitis, and whether it is associated with increased expression of inducible nitric oxide synthetase (iNOS) in appendicular macrophages. METHODS: Serology for H. pylori was performed on 51 consecutive patients undergoing emergency appendicectomy. Appendix samples were tested for urease activity, cultured and stained for H. pylori, graded according to the degree of inflammatory infiltrate, and probed immunohistochemically for iNOS expression. RESULTS: The mean age of the patients was 21 (range 7-51) years. Seventeen patients (33 per cent) were seropositive for H. pylori but no evidence of H. pylori was found in any appendix specimen. However, an enhanced inflammatory cell infiltration was observed in seropositive patients (P < 0.04) and the expression of macrophage iNOS in the mucosa of normal and inflamed appendix specimens was increased (P < 0.01). CONCLUSION: H. pylori does not colonize the appendix and is unlikely to be a pathogenic stimulus for appendicitis. Priming effects on mucosal immunology downstream from the foregut may occur after infection with H. pylori.

  6. Cloning, expression, and purification of glutamine synthetase from Clostridum acetobutylicum

    Energy Technology Data Exchange (ETDEWEB)

    Usdin, K.P.; Zappe, H.; Jones, D.T.; Woods, D.R.

    1986-09-01

    A glutamine synthetase (GS) gene, glnA, from the gram-positive obligate anaerobe Clostridium acetobutylicum was cloned on recombinant plasmid pHZ200 and enabled Escherichia coli glnA deletion mutants to utilize (NH/sub 4/)/sub 2/ as a sole source of nitrogen. The cloned C. acetobutylicum gene was expressed from a regulatory region contained within the cloned DNA fragment. glnA expression was subject to nitrogen regulation in E. coli. This cloned glnA DNA did not enable an E. coli glnA ntrB ntrC deletion mutant to utilize arginine or low levels of glutamine as sole nitrogen sources, and failed to activate histidase activity in this strain which contained the Klebsiella aerogenes hut operon. The GS produced by pHZ200 was purified and had an apparent subunit molecular weight of approximately 59,000. There was no DNA or protein homology between the cloned C. acetobutylicum glnA gene and GS and the corresponding gene and GS from E. coli. The C. acetobutylicum GS was inhibited by Mg/sup 2 +/ in the ..gamma..-glutamyl transferase assay, but there was no evidence that the GS was adenylylated.

  7. Glutamine synthetase of Streptomyces cattleya: purification and regulation of synthesis.

    Science.gov (United States)

    Paress, P S; Streicher, S L

    1985-08-01

    Glutamine synthetase (GS; EC 6.3.1.2) from Streptomyces cattleya was purified using a single affinity-gel chromatography step, and some of its properties were determined. Levels of GS in S. cattleya cells varied by a factor of 8 depending upon the source of nitrogen in the growth medium. Of 24 nitrogen sources examined only glutamine or NH4Cl utilization resulted in very low GS activity. Addition of NH4Cl to a culture with high GS levels appeared to stop further synthesis and resulted in a progressive decrease in the specific activity of the enzyme. The GS inhibitor methionine sulphoximine (MSX) inhibited GS activity but had no effect on exponentially growing cells. The presence of MSX either lengthened or shortened the period between spore inoculation and initiation of exponential growth, depending on the source of nitrogen. In glutamine minimal medium MSX produced earlier and more efficient spore germination while in glutamate or nitrate minimal medium germination was delayed by its presence.

  8. Chitin synthetase in encysting Giardia lamblia and Entamoeba invadens

    Energy Technology Data Exchange (ETDEWEB)

    Das, S.; Gillin, F.D.

    1987-05-01

    Giardia lamblia (Gl) and Entamoeba invadens (Ei) are protozoan parasites with two morphologic stages in their life cycles. Motile trophozoites colonize the intestine of humans and reptiles respectively. Water resistant cysts, which can survive outside the host, transmit infection. In vitro cyst formation of Ei from trophozoites has been reported, and the authors have recently induced in vitro encystation of Gl. Although the cyst walls of both parasites contain chitin, it synthesis by encysting trophozoites has not been reported. The authors now show that encystation conditions greatly increase chitin synthetase (CS) specific activity (incorporation of /sup 3/H GlcNAc from UDP-GlcNAc into TCA-or alcohol-precipitable material). Extracts of encysting Gl incorporated 3.6 nmol/mg protein in 5 hr compared to < 0.005 in controls. Extracts of encysting Fi incorporated 4.8 n mol/mg protein, compared to 1.7 in the control. CS activity of both parasites requires preformed chitin. The Gl enzyme requires a reducing agent, is inhibited by digitonin and the CS inhibitors, polyoxin D and Nikkomycin, but not by tunicamycin. The product is digested by chitinase. Ei enzyme does not require a reducing agent and is stimulated by 1 mg/ml digitonin, but inhibited by higher concentrations. These studies demonstrate CS enzymes which may play important roles in encystation of Gl and Ei.

  9. Overexpression of glutamine synthetases confers transgenic rice herbicide resistance

    Institute of Scientific and Technical Information of China (English)

    Sun Hui; Huang Qiman; Su Jin

    2005-01-01

    Glutamine synthetase (GS, E.C.6.3.1.2) is a key enzyme involved in the assimilation of inorganic nitrogen in higher plants and gram-negative microorganisms. GS is the targeting enzyme of a herbicide phosphinothricin (PPT) or Basta. In order to generate PPT-resistant transgenic rice via overexpression of GS, we constructed a plant expression vector p2GS harboring two different isoenzymes GS1 and GS2 cDNAs under the control of constitutive promoters of rice Act1 and maize Ubiquitin(Ubi) genes. The p2GS was introduced into rice genome by Agrobacterium-mediated transformation and confirmed by PCR and Southern blot hybridization. GS-transgene expression was first detected by Northern blot analyses. Results from Basta test indicated that GS-transgenic plants can tolerate as high as 0.3% Basta solution. In addition, our results also demonstrated that GS overexpression conferred transformed rice calli PPT resistance. Thus, GS cassette can serve as a selective marker gene instead of bar cassette for selection of PPT transformants.

  10. Prostaglandin synthetase inhibitors in the treatment of nephrogenic diabetes insipidus.

    Science.gov (United States)

    Monn, E

    1981-01-01

    Two boys with classical NDI have been treated with prostaglandin synthetase inhibitors. A boy, 7 years old, was treated with low solute-load diet and diuretics from his first year of life. His main complaint was nocturnal enuresis. He responded within one day to indomethacin 25 mg twice daily, and the urine volume was reduced from 4 1/2--6 litre/day to 2 1/2--3 litre/day. There is almost no enuresis. A boy, 7 months old, had a basal daily urine volume of 1.6--1.8 litre. A low solute-load diet and diuretics reduced urine volume to 1 litre, but he still needed gastric tube feeding. With the addition of acetylsalicylic acid, 75 mg three times daily, the urine volume was reduced to 600 ml, and he needed no more tube feeding. Both boys are doing well on the above-mentioned regimens, and no side effects have been observed after 1 year of treatment.

  11. The first report of Japanese patients with asparagine synthetase deficiency.

    Science.gov (United States)

    Yamamoto, Takahiro; Endo, Wakaba; Ohnishi, Hidenori; Kubota, Kazuo; Kawamoto, Norio; Inui, Takehiko; Imamura, Atsushi; Takanashi, Jun-Ichi; Shiina, Masaaki; Saitsu, Hirotomo; Ogata, Kazuhiro; Matsumoto, Naomichi; Haginoya, Kazuhiro; Fukao, Toshiyuki

    2017-03-01

    Asparagine synthetase (ASNS) deficiency was recently discovered as a metabolic disorder of non-essential amino acids, and presents as severe progressive microcephaly, intellectual disorder, dyskinetic quadriplegia, and intractable seizures. Two Japanese children with progressive microcephaly born to unrelated patients were analyzed by whole exome sequencing and novel ASNS mutations were identified. The effects of the ASNS mutations were analyzed by structural evaluation and in silico predictions. We describe the first known Japanese patients with ASNS deficiency. Their clinical manifestations were very similar to reported cases of ASNS deficiency. Progressive microcephaly was noted during the prenatal period in patient 1 but only after birth in patient 2. Both patients had novel ASNS mutations: patient 1 had p.L145S transmitted from his mother and p.L247W which was absent from his mother, while patient 2 carried p.V489D and p.W541Cfs*5, which were transmitted from his mother and father, respectively. Three of the four mutations were predicted to affect protein folding, and in silico analyses suggested that they would be pathogenic. We report the first two Japanese patients with ASNS deficiency. Disease severity appears to vary among patients, as is the case for other non-essential amino acid metabolic disorders. Copyright © 2016 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

  12. The plastidial folylpolyglutamate synthetase and root apical meristem maintenance

    Science.gov (United States)

    Srivastava, Avinash C; Tang, Yuhong; Díaz de la Garza, Rocío I

    2011-01-01

    Folylpolyglutamate synthetase (FPGS) catalyzes the attachment of glutamate residues to the folate molecule in plants. Three isoforms of FPGS have been identified in Arabidopsis and these are localized in the plastid (AtDFB), mitochondria (AtDFC) and cytosol (AtDFD). We recently determined that mutants in the AtDFB (At5G05980) gene disrupt primary root development in Arabidopsis thaliana seedlings. Transient expression of AtDFB-green fluorescent protein (GFP) fusion under the control of the native AtDFB promoter in Nicotiana tabacum leaf epidermal cells verified the plastid localization of AtDFB. Furthermore, low concentrations of methotrexate (MTX), a compound commonly used as a folate antagonist in plant and mammalian cells induced primary root defects in wild type seedlings that were similar to atdfb. In addition, atdfb seedlings were more sensitive to MTX when compared to wild type. Quantitative (q) RT-PCR showed lower transcript levels of the mitochondrial and cytosolic FPGS in roots of 7-day-old atdfb seedling suggesting feedback regulation of AtDFB on the expression of other FPGS isoforms during early seedling development. The primary root defects of atdfb, which can be traced in part to altered quiescent center (QC) identity, pave the way for future studies that could link cell type specific folate and FPGS isoform requirements to whole organ development. PMID:21502816

  13. Secondary NAD+ deficiency in the inherited defect of glutamine synthetase.

    Science.gov (United States)

    Hu, Liyan; Ibrahim, Khalid; Stucki, Martin; Frapolli, Michele; Shahbeck, Noora; Chaudhry, Farrukh A; Görg, Boris; Häussinger, Dieter; Penberthy, W Todd; Ben-Omran, Tawfeg; Häberle, Johannes

    2015-11-01

    Glutamine synthetase (GS) deficiency is an ultra-rare inborn error of amino acid metabolism that has been described in only three patients so far. The disease is characterized by neonatal onset of severe encephalopathy, low levels of glutamine in blood and cerebrospinal fluid, chronic moderate hyperammonemia, and an overall poor prognosis in the absence of an effective treatment. Recently, enteral glutamine supplementation was shown to be a safe and effective therapy for this disease but there are no data available on the long-term effects of this intervention. The amino acid glutamine, severely lacking in this disorder, is central to many metabolic pathways in the human organism and is involved in the synthesis of nicotinamide adenine dinucleotide (NAD(+)) starting from tryptophan or niacin as nicotinate, but not nicotinamide. Using fibroblasts, leukocytes, and immortalized peripheral blood stem cells (PBSC) from a patient carrying a GLUL gene point mutation associated with impaired GS activity, we tested whether glutamine deficiency in this patient results in NAD(+) depletion and whether it can be rescued by supplementation with glutamine, nicotinamide or nicotinate. The present study shows that congenital GS deficiency is associated with NAD(+) depletion in fibroblasts, leukocytes and PBSC, which may contribute to the severe clinical phenotype of the disease. Furthermore, it shows that NAD(+) depletion can be rescued by nicotinamide supplementation in fibroblasts and leukocytes, which may open up potential therapeutic options for the treatment of this disorder.

  14. Enzymatic Production of Glutathione by Bifunctional γ-Glutamylcysteine Synthetase/Glutathione Synthetase Coupled with In Vitro Acetate Kinase-Based ATP Generation.

    Science.gov (United States)

    Jiang, Yu; Tao, Rongsheng; Shen, Zhengquan; Sun, Liangdong; Zhu, Fuyun; Yang, Sheng

    2016-12-01

    Glutathione (γ-glutamyl-L-cysteinylglycine, GSH) is a pharmaceutical compound often used in food additives and the cosmetics industry. GSH can be produced biologically from L-glutamic acid, L-cysteine, and glycine through an enzymatic process traditionally involving two sequential adenosine triphosphate (ATP)-dependent reactions catalyzed by γ-glutamylcysteine synthetase (γ-GCS or GSHI, EC 6.3.2.2) and GSH synthetase (GS or GSHII, EC 6.3.2.3). Here, we report the enzymatic production of GSH by recombinant cell-free bifunctional γ-glutamylcysteine synthetase/glutathione synthetase (γ-GCS-GS or GshF) coupled with in vitro acetate kinase-based ATP generation. GSH production by an acetate kinase-integrated Escherichia coli Rosetta(DE3) mutant expressing Streptococcus thermophilus GshF reached 18.3 ± 0.1 g l(-1) (59.5 ± 0.3 mM) within 3 h, with a molar yield of 0.75 ± 0.00 mol mol(-1) added cysteine and a productivity of 6.1 ± 0.0 g l(-1) h(-1). This is the highest GSH titer reported to date. This newly developed biocatalytic process offers a promising approach for meeting the industrial requirements for GSH production.

  15. Expansion of the neonatal platelet mass is achieved via an extension of platelet lifespan.

    Science.gov (United States)

    Liu, Zhi-Jian; Hoffmeister, Karin M; Hu, Zhongbo; Mager, Donald E; Ait-Oudhia, Sihem; Debrincat, Marlyse A; Pleines, Irina; Josefsson, Emma C; Kile, Benjamin T; Italiano, Joseph; Ramsey, Haley; Grozovsky, Renata; Veng-Pedersen, Peter; Chavda, Chaitanya; Sola-Visner, Martha

    2014-05-29

    The fetal/neonatal hematopoietic system must generate enough blood cells to meet the demands of rapid growth. This unique challenge might underlie the high incidence of thrombocytopenia among preterm neonates. In this study, neonatal platelet production and turnover were investigated in newborn mice. Based on a combination of blood volume expansion and increasing platelet counts, the platelet mass increased sevenfold during the first 2 weeks of murine life, a time during which thrombopoiesis shifted from liver to bone marrow. Studies applying in vivo biotinylation and mathematical modeling showed that newborn and adult mice had similar platelet production rates, but neonatal platelets survived 1 day longer in circulation. This prolonged lifespan fully accounted for the rise in platelet counts observed during the second week of murine postnatal life. A study of pro-apoptotic and anti-apoptotic Bcl-2 family proteins showed that neonatal platelets had higher levels of the anti-apoptotic protein Bcl-2 and were more resistant to apoptosis induced by the Bcl-2/Bcl-xL inhibitor ABT-737 than adult platelets. However, genetic ablation or pharmacologic inhibition of Bcl-2 alone did not shorten neonatal platelet survival or reduce platelet counts in newborn mice, indicating the existence of redundant or alternative mechanisms mediating the prolonged lifespan of neonatal platelets. © 2014 by The American Society of Hematology.

  16. [Platelet allo-antibodies identification strategies for preventing and managing platelet refractoriness].

    Science.gov (United States)

    Basire, A; Picard, C

    2014-11-01

    Platelet refractoriness is a serious complication for patients receiving recurrent platelet transfusions, which can be explained by non-immune and immune causes. Human Leukocyte Antigens (HLA) allo-immunization, especially against HLA class I, is the major cause for immune platelet refractoriness. To a lesser extent, allo-antibodies against specific Human Platelet Antigen (HPA) are also involved. Pregnancy, transplantation and previous transfusions can lead to allo-immune reaction against platelet antigens. After transfusion, platelet count is decreased by accelerated platelet destruction related to antibodies fixation on incompatible platelet antigens. New laboratory tests for allo-antibodies identification were developed to improve sensibility and specificity, especially with the LUMINEX(®) technology. The good use and interpretation of these antibodies assays can improve strategies for platelet refractoriness prevention and management with a patient adapted response. Compatible platelets units can be selected according to their identity with recipient typing or immune compatibility regarding HLA or HPA antibodies or HLA epitope compatibility. Prospective studies are needed to further confirm the clinical benefit of new allo-antibodies identification methods and consensus strategies for immune platelet refractoriness management.

  17. Platelet antibodies, activated platelets and serum leptin in childhood immune thrombocytopenic purpura.

    Science.gov (United States)

    Badrawy, Hosny; Elsayh, Khalid I; Zahran, Asmaa M; El-Ghazali, Mohamad Hamdy

    2013-01-01

    The aim of this study was to evaluate the levels of platelet-associated antibodies (PAIgG and PAIgM), activated platelets and serum leptin in children with acute immune thrombocytopenic purpura (ITP). The study included 40 patients with ITP and 40 healthy age- and sex-matched controls. PAIgG, PAIgM and activated platelet levels were estimated by flow cytometry, and serum leptin levels were estimated by ELISA. Activated platelets and serum leptin were significantly higher in the ITP patients than in the controls. The percentage and mean fluorescence intensity of PAIgG and PAIgM staining were significantly higher in the patients than in the controls. Serum leptin and activated platelet levels in patients with thrombocytopenia of brief duration were significantly lower than those in patients with thrombocytopenia of prolonged duration. The levels of activated platelets, serum leptin and PAIgG were positively correlated, and the levels of serum leptin, activated platelets and platelet counts were negatively correlated. The increased levels of activated platelets, serum leptin and platelet-associated antibodies in children with acute ITP suggest that these factors could play a role in ITP pathogenesis. Additionally, activated platelets and serum leptin could have prognostic significance in paediatric acute ITP. Copyright © 2013 S. Karger AG, Basel.

  18. Bulk fluid phase behaviour of colloidal platelet-sphere and platelet-polymer mixtures.

    Science.gov (United States)

    de las Heras, Daniel; Schmidt, Matthias

    2013-04-13

    Using a geometry-based fundamental measure density functional theory, we calculate bulk fluid phase diagrams of colloidal mixtures of vanishingly thin hard circular platelets and hard spheres. We find isotropic-nematic phase separation, with strong broadening of the biphasic region, upon increasing the pressure. In mixtures with large size ratio of platelet and sphere diameters, there is also demixing between two nematic phases with differing platelet concentrations. We formulate a fundamental measure density functional for mixtures of colloidal platelets and freely overlapping spheres, which represent ideal polymers, and use it to obtain phase diagrams. We find that, for low platelet-polymer size ratio, in addition to isotropic-nematic and nematic-nematic phase coexistence, platelet-polymer mixtures also display isotropic-isotropic demixing. By contrast, we do not find isotropic-isotropic demixing in hard-core platelet-sphere mixtures for the size ratios considered.

  19. IgG platelet antibodies in EDTA-dependent pseudothrombocytopenia bind to platelet membrane glycoprotein IIb.

    Science.gov (United States)

    Fiorin, F; Steffan, A; Pradella, P; Bizzaro, N; Potenza, R; De Angelis, V

    1998-08-01

    EDTA-dependent pseudothrombocytopenia (PTCP) consists of an inappropriate low platelet count caused by autoantibodies present in the serum samples reacting with platelets only in EDTA-anticoagulated blood. By using immunoprecipitation and Western blot techniques, we studied the immunochemical specificity of platelet agglutinating autoantibodies in the serum samples of 10 patients with PTCP. Furthermore, to evaluate a possible role of PTCP-associated IgG autoantibodies in increased platelet turnover, we assayed the plasma glycocalicin (GC) level and calculated the GC index for every patient. Our results provide direct evidence that an epitope located on platelet membrane glycoprotein IIb is recognized by PTCP-associated IgG antibodies; moreover GC levels in patients with EDTA-dependent PTCP were similar to control levels, thus excluding an increased platelet turnover. We conclude that antiplatelet antibodies directed against platelet cryptantigens are unlikely to have a major role in the increased removal of cells from circulation.

  20. Probe of Lorentz Invariance Violation effects and determination of the distance of PG 1553+113

    CERN Document Server

    Sanchez, D A; Couturier, C; Jacholkowska, A

    2015-01-01

    The high frequency peaked BL Lac object PG 1553+113 underwent a flaring event in 2012. The High Energy Stereoscopic System (H.E.S.S.) observed this source for two consecutive nights at very high energies (VHE, $E>$100~GeV). The data show an increase of a factor of three of the flux with respect to archival measurements with the same instrument and hints of intra-night variability. The data set has been used to put constraints on possible Lorentz invariance violation (LIV), manifesting itself as an energy dependence of the velocity of light in vacuum, and to set limits on the energy scale at which Quantum Gravity effects causing LIV may arise. With a new method to combine H.E.S.S. and Fermi large area telescope data, the previously poorly known redshift of PG 1555+113 has been determined to be close to the value derived from optical measurements.

  1. In-package P/G planes analysis and optimization based on transmission matrix method

    Institute of Scientific and Technical Information of China (English)

    Yin-jun WANG; Cheng ZHUO; Jun-yong DENG; Jin-fang ZHOU; Kang-sheng CHEN

    2008-01-01

    Power integrity (PI) has become a limiting factor for the chip's overall performance, and how to place in-package decoupling capacitors to improve a chip's PI performance has become a hot issue. In this paper, we propose an improved transmission matrix method (TMM) for fast decoupling capacitance allocation. An irregular grid partition mechanism is proposed, which helps speed up the impedance computation and complies better with the irregular power/ground (P/G) plane or planes with many vias and decoupling capacitors. Furthermore, we also ameliorate the computation procedure of the impedance matrix whenever decoupling capacitors are inserted or removed at specific ports. With the fast computation of impedance change, in-package decoupling capacitor allocation is done with an efficient change based method in the frequency domain. Experimental results show that our approach can gain about 5× speedup compared with a general TMM, and is efficient in restraining the noise on the P/G plane.

  2. Variability of Fe II in Two NLS1s, PG 1700+815 and NGC 4051

    Indian Academy of Sciences (India)

    Weihao Bian; Zhen Yang

    2011-03-01

    We analyze the spectral variability for two narrow line Seyfert 1 galaxies, PG 1700+518 and NGC 4051 using the spectral decomposition method. We focus on their optical Fe II variability to investigate the origin of Fe II in AGNs. For PG 1700+518, we find that the Fe II size is about 200 light-days, which is consistent with the H size derived from the empirical R–L relation. For NGC 4051, the [O III] 5007 Å flux is strongly correlated with continuum flux, suggesting that we should recalibrate the spectral flux on a scale defined by [O III] flux. The corrected light curves of Fe II, H, He II, (5100 Å) are given here. A detailed analysis will be given in the near future.

  3. The placental mammal ancestor and the post-K-Pg radiation of placentals.

    Science.gov (United States)

    O'Leary, Maureen A; Bloch, Jonathan I; Flynn, John J; Gaudin, Timothy J; Giallombardo, Andres; Giannini, Norberto P; Goldberg, Suzann L; Kraatz, Brian P; Luo, Zhe-Xi; Meng, Jin; Ni, Xijun; Novacek, Michael J; Perini, Fernando A; Randall, Zachary S; Rougier, Guillermo W; Sargis, Eric J; Silcox, Mary T; Simmons, Nancy B; Spaulding, Michelle; Velazco, Paúl M; Weksler, Marcelo; Wible, John R; Cirranello, Andrea L

    2013-02-01

    To discover interordinal relationships of living and fossil placental mammals and the time of origin of placentals relative to the Cretaceous-Paleogene (K-Pg) boundary, we scored 4541 phenomic characters de novo for 86 fossil and living species. Combining these data with molecular sequences, we obtained a phylogenetic tree that, when calibrated with fossils, shows that crown clade Placentalia and placental orders originated after the K-Pg boundary. Many nodes discovered using molecular data are upheld, but phenomic signals overturn molecular signals to show Sundatheria (Dermoptera + Scandentia) as the sister taxon of Primates, a close link between Proboscidea (elephants) and Sirenia (sea cows), and the monophyly of echolocating Chiroptera (bats). Our tree suggests that Placentalia first split into Xenarthra and Epitheria; extinct New World species are the oldest members of Afrotheria.

  4. Fractal and Euclidean descriptors of platelet shape.

    Science.gov (United States)

    Kraus, Max-Joseph; Neeb, Heiko; Strasser, Erwin F

    2014-01-01

    Platelet shape change is a dynamic membrane surface process that exhibits remarkable morphological heterogeneity. Once the outline of an irregular shape is identified and segmented from a digital image, several mathematical descriptors can be applied to numerical characterize the irregularity of the shapes surface. 13072 platelet outlines (PLO) were segmented automatically from 1928 microscopic images using a newly developed algorithm for the software product Matlab R2012b. The fractal dimension (FD), circularity, eccentricity, area and perimeter of each PLO were determined. 972 PLO were randomly assigned for computer-assisted manual measurement of platelet diameter as well as number, width and length of filopodia per platelet. FD can be used as a surrogate parameter for determining the roughness of the PLO and circularity can be used as a surrogate to estimate the number and length of filopodia. The relationship between FD and perimeter of the PLO reveals the existence of distinct groups of platelets with significant structural differences which may be caused by platelet activation. This new method allows for the standardized continuous numerical classification of platelet shape and its dynamic change, which is useful for the analysis of altered platelet activity (e.g. inflammatory diseases, contact activation, drug testing).

  5. Clinica use of platelet additive solutions.

    Science.gov (United States)

    van Rhenen, Dick J

    2007-12-01

    Randomised clinical trial (RCT) to study the clinical efficacy and safety of new platelet products using platelet additive solutions are scarce. In this paper a number of recent RCT's is discussed. It can be the start of a development where new transfusion products enter a RCT before the product is applied in clinical practice.

  6. Platelets in liver transplantation : Friend or foe?

    NARCIS (Netherlands)

    Pereboom, Ilona T. A.; Lisman, Ton; Porte, Robert J.

    2008-01-01

    Apart from the well-known role of blood platelets in hemostasis, there is emerging evidence that platelets have various nonhemostatic properties that play a critical role in inflammation, angiogenesis, tissue repair and regeneration, and ischemia/reperfusion (I/R) injury. All these processes may be

  7. Studies on megakaryopoiesis and platelet function

    NARCIS (Netherlands)

    Meinders, M.

    2015-01-01

    Platelets are blood circulating specialized subcellular fragments, which are produced by megakaryocytes. Platelets are essential for hemostasis and wound healing but also play a role in non-hemostatic processes such as the immune response or cancer metastasis. Considering the immediate precursors of

  8. Erythrocyte-platelet interaction in uncomplicated pregnancy.

    Science.gov (United States)

    Swanepoel, Albe C; Pretorius, Etheresia

    2014-12-01

    Maternal and fetal requirements during uncomplicated pregnancy are associated with changes in the hematopoietic system. Platelets and erythrocytes [red blood cells (RBCs)], and especially their membranes, are involved in coagulation, and their interactions may provide reasons for the changed hematopoietic system during uncomplicated pregnancy. We review literature regarding RBC and platelet membrane structure and interactions during hypercoagulability and hormonal changes. We then study interactions between RBCs and platelets in uncomplicated pregnancy, as their interactions may be one of the reasons for increased hypercoagulability during uncomplicated pregnancy. Scanning electron microscopy was used to study whole blood smears from 90 pregnant females in different phases of pregnancy. Pregnancy-specific interaction was seen between RBCs and platelets. Typically, one or more platelets interacted through platelet spreading and pseudopodia formation with a single RBC. However, multiple interactions with RBCs were also shown for a single platelet. Specific RBC-platelet interaction seen during uncomplicated pregnancy may be caused by increased estrogen and/or increased fibrinogen concentrations. This interaction may contribute to the hypercoagulable state associated with healthy and uncomplicated pregnancy and may also play a fundamental role in gestational thrombocytopenia.

  9. BETA-ADRENOBLOCKERS AND PLATELET AGGREGATION. CARVEDILOL

    Directory of Open Access Journals (Sweden)

    A. N. Zakirova

    2008-01-01

    Full Text Available Approaches evolution to studying of beta-blockers influence on platelet aggregation is reviewed. The current view on of beta-blocker antiplatelet effects is presented on the basis of physical and chemical drug properties (water repellency, dipole moment, molecular mass. Trail results on carvedilol influence on platelet aggregation are focused.

  10. Novel agents for anti-platelet therapy

    Directory of Open Access Journals (Sweden)

    Ji Xuebin

    2011-11-01

    Full Text Available Abstract Anti-platelet therapy plays an important role in the treatment of patients with thrombotic diseases. The most commonly used anti-platelet drugs, namely, aspirin, ticlopidine, and clopidogrel, are effective in the prevention and treatment of cardio-cerebrovascular diseases. Glycoprotein IIb/IIIa antagonists (e.g., abciximab, eptifibatide and tirofiban have demonstrated good clinical benefits and safety profiles in decreasing ischemic events in acute coronary syndrome. However, adverse events related to thrombosis or bleeding have been reported in cases of therapy with glycoprotein IIb/IIIa antagonists. Cilostazol is an anti-platelet agent used in the treatment of patients with peripheral ischemia, such as intermittent claudication. Presently, platelet adenosine diphosphate P2Y(12 receptor antagonists (e.g., clopidogrel, prasugrel, cangrelor, and ticagrelor are being used in clinical settings for their pronounced protective effects. The new protease-activated receptor antagonists, vorapaxar and atopaxar, potentially decrease the risk of ischemic events without significantly increasing the rate of bleeding. Some other new anti-platelet drugs undergoing clinical trials have also been introduced. Indeed, the number of new anti-platelet drugs is increasing. Consequently, the efficacy of these anti-platelet agents in actual patients warrants scrutiny, especially in terms of the hemorrhagic risks. Hopefully, new selective platelet inhibitors with high anti-thrombotic efficiencies and low hemorrhagic side effects can be developed.

  11. Performance evaluation of PL-11 platelet analyzer

    Institute of Scientific and Technical Information of China (English)

    张有涛

    2013-01-01

    Objective To evaluate and report the performance of PL-11 platelet analyzer. Methods Intravenous blood sam-ples anticoagulated with EDTA-K2 and sodium citrate were tested by the PL-11 platelet analyzer to evaluate the intra-assay and interassay coefficient of variation(CV),

  12. Platelet affinity for burro aorta collagen

    Energy Technology Data Exchange (ETDEWEB)

    Schneider, M.D.

    1977-10-01

    Despite ingenious concepts, there are no unequivocal clues as to what, when, and how some undefined biochemical factor(s) or constituent(s) that localizes in the arterial wall can precipitate a thromboatheromatous lesion or arterial disease. The present study focused on the extraction, partial purification, and characterization of a collagen-active platelet stimulator from the aortas of aged burros. The aggregator moiety in the aorta extracts invariably had a higher affinity for platelets in citrated platelet-rich plasma of human beings than for platelets of homologous burros. The platelet-aggregating factor(s) in the aorta extract was retained by incubation with ..cap alpha..-chymotrypsin. Platelet-aggregating activity was rapidly abolished after incubation with collagenase, as determined by platelet-aggregometry tests. Evidence based on light microscope and polysaccharide histochemical reactions indicates a probability that the intracellular amorphous matrix (PAS-positive) and filamentous components (PTAH-positive) expelled from smooth muscle cells disrupted during homogenization of the aorta may be a principal source of a precursor collagen species which is a potent inducer of platelet aggregation.

  13. The origin and function of platelet glycosyltransferases

    DEFF Research Database (Denmark)

    Wandall, Hans H; Rumjantseva, Viktoria; Sørensen, Anne Louise Tølbøll;

    2012-01-01

    Platelets are megakaryocyte subfragments that participate in hemostatic and host defense reactions and deliver pro- and anti-angiogenic factors throughout the vascular system. Platelets are anucleated cells and lack a complex secretory apparatus with distinct Golgi/endoplasmic reticulum compartme...

  14. Function of eltrombopag-induced platelets compared to platelets from control patients with immune thrombocytopenia.

    Science.gov (United States)

    Haselboeck, Johanna; Kaider, Alexandra; Pabinger, Ingrid; Panzer, Simon

    2013-04-01

    Data on the in vivo function of platelets induced by the thrombopoietin receptor agonist eltrombopag are scarce. To assess a possible influence of eltrombopag we compared platelet function of eltrombopag-treated immune thrombocytopenia (ITP) patients (group 1; n=10) after treatment response to that from control ITP patients (group 2; n=12). We further analysed platelet function at baseline and after one, three, and four weeks of eltrombopag treatment and estimated daily changes of platelet function during the eltrombopag-induced platelet rise. The formation of platelet-monocyte aggregates (PMA), P-selectin expression [MFI], and platelet adhesion under high shear conditions (surface coverage, SC) in vivo and after in vitro addition of agonists (ADP, TRAP-6, Collagen) were similar between both groups after response to eltrombopag treatment. Only TRAP-6 induced a lower SC in the eltrombopag group (p=0.03). All platelet function parameters except for Collagen-induced P-selectin expression changed significantly during treatment with eltrombopag. PMA, naïve and after addition of ADP or TRAP-6 increased with increasing platelet counts. P-selectin expression decreased, when measured without and upon addition of ADP, increased in the presence of TRAP-6, and remained unchanged after addition of Collagen. SC increased during the eltrombopag-induced platelet rise. All significant changes of platelet function correlated to changes in platelet counts. Two patients developed venous thromboses during eltrombopag treatment, but no association with any distinct single platelet function parameter or combinations thereof was identifiable. Thus, eltrombopag-induced platelets function similar to those from control ITP patients without discernible increased hyper-reactivity.

  15. A platelet monoclonal antibody inhibition assay for detection of glycoprotein IIb/IIIa-related platelet alloantibodies.

    Science.gov (United States)

    Reiner, A P; Teramura, G; Nelson, K A; Slichter, S J

    1995-08-18

    Post-transfusion purpura (PTP) and neonatal alloimmune thrombocytopenia (NAT) result from formation of alloantibodies to platelet membrane glycoprotein-associated antigens. The detection and identification of platelet-specific alloantibodies in patient sera is often complicated by the presence of co-existing HLA antibodies and/or more than one platelet specificity in the same serum. We describe a solid phase assay that specifically detects antibodies to platelet membrane associated alloantigens by measuring the ability of patient antisera to inhibit the binding of glycoprotein GPIIb or GPIIIa monoclonal antibodies to intact platelets. When tested in the GPIIIa assay against a panel of random platelet donors, the reactivities of two known PLAI antisera that also contained different HLA antibodies were highly correlated (r = 0.99) and allowed PLA phenotyping of the population. A standard direct binding platelet ELISA, on the other hand, was unable to accurately PLA phenotype the same population. The reactivities of two known Baka antisera (one containing additional anti-PLA2 and the other anti-Brb specificities) were highly correlated (r = 0.95) in the GPIIb assay, and Bak phenotype determination was similarly accomplished for a random platelet panel. Furthermore, a comparison of platelet phenotype results (using the monoclonal inhibition assay) and genotype results (using DNA analysis) for the PLA and Bak systems showed a concordance of 98% for 146 alleles tested. In conclusion, the platelet monoclonal antibody inhibition assay: (1) allows determination of platelet-specific alloantibodies in the presence of contaminating HLA antibodies and/or in sera containing multiple platelet alloantibodies; (2) allows accurate platelet phenotyping for the GPIIIa-associated PLA and GPIIb-associated Bak antigen systems; and (3) may be applicable to the detection of other known or even novel platelet glycoprotein-associated antigens.

  16. Array analysis of regional Pn and Pg wavefields from the Nevada Test Site

    Energy Technology Data Exchange (ETDEWEB)

    Leonard, M.A. (California Univ., Berkeley, CA (United States). Dept. of Geology and Geophysics Lawrence Berkeley Lab., CA (United States))

    1991-06-01

    Small-aperture high-frequency seismic arrays with dimensions of a few kilometers or less, can improve our ability to seismically monitor compliance with a low-yield Threshold Test Ban Treaty. This work studies the characteristics and effectiveness of array processing of the regional Pn and Pg wavefields generated by underground nuclear explosions at the Nevada Test Site. Waveform data from the explosion HARDIN (m{sub b} = 5.5) is recorded at a temporary 12-element, 3-component, 1.5 km-aperture array sited in an area of northern Nevada. The explosions VILLE (m{sub b} = 4.4) and SALUT (m{sub b} = 5.5) are recorded at two arrays sited in the Mojave desert, one a 96-element vertical-component 7 km-aperture array and the other a 155-element vertical-component 4 km-aperture array. Among the mean spectra for the m{sub b} = 5.5 events there are significant differences in low-frequency spectral amplitudes between array sites. The spectra become nearly identical beyond about 6 Hz. Spectral ratios are used to examine seismic source properties and the partitioning of energy between Pn and Pg. Frequency-wavenumber analysis at the 12-element array is used to obtain estimates of signal gain, phase velocity, and source azimuth. This analysis reveals frequency-dependent biases in velocity and azimuth of the coherent Pn and Pg arrivals. Signal correlation, the principal factor governing array performance, is examined in terms of spatial coherence estimates. The coherence is found to vary between the three sites. In all cases the coherence of Pn is greater than that for Pg. 81 refs., 92 figs., 5 tabs.

  17. Complete genome sequence of Mycoplasma bovis type strain PG45 (ATCC 25523).

    Science.gov (United States)

    Wise, Kim S; Calcutt, Michael J; Foecking, Mark F; Röske, Kerstin; Madupu, Ramana; Methé, Barbara A

    2011-02-01

    This complete and fully assembled genome sequence of Mycoplasma bovis type strain PG45 is the first available for this species and offers a framework for comparison with additional pathogenic isolates. The single circular chromosome of 1,003,404 bp reveals multiple gene sets and mechanisms involved in variable expression of surface antigens and the incursion of numerous and assorted mobile elements, despite its reduced size.

  18. Complete Genome Sequence of Mycoplasma bovis Type Strain PG45 (ATCC 25523)▿

    Science.gov (United States)

    Wise, Kim S.; Calcutt, Michael J.; Foecking, Mark F.; Röske, Kerstin; Madupu, Ramana; Methé, Barbara A.

    2011-01-01

    This complete and fully assembled genome sequence of Mycoplasma bovis type strain PG45 is the first available for this species and offers a framework for comparison with additional pathogenic isolates. The single circular chromosome of 1,003,404 bp reveals multiple gene sets and mechanisms involved in variable expression of surface antigens and the incursion of numerous and assorted mobile elements, despite its reduced size. PMID:21134966

  19. Children Beware! Children’s horror, PG-13 and the emergent Millennial pre-teen

    OpenAIRE

    Goncalves Antunes, Filipa

    2015-01-01

    Abstract This thesis is a study of the children’s horror trend of the 1980s and 1990s focused on the transformation of the concepts of childhood and horror. Specifically, it discusses the segmentation of childhood to include the pre-teen demographic, which emerges as a distinct Millennial figure, and the ramifications of this social and cultural shift both on the horror genre and the entertainment industry more broadly, namely through the introduction of the deeply impactful PG...

  20. Modulatory effect of coffee on platelet function.

    Science.gov (United States)

    Bhaskar, Shobha; Rauf, Arun A

    2010-01-01

    Blood platelets play a major role in cardiovascular disease (CVD) and thrombosis. Conflicting information exists regarding the effect of coffee consumption on the cardiovascular system. We have investigated whether the consumption of moderate amount of coffee affect platelet functions and primary hemostasis in vivo in normal and high fat diet fed rats. Coffee fed group showed significant (P production from membrane arachidonic acid and it was decreased in coffee treated group. Platelet aggregation studies with ADP, collagen, arachidonic acid and epinephrine showed significant (P coffee fed group. Scanning electron microscopic studies revealed that platelet aggregation tendency increased in HFD group and was reduced in coffee fed group. These results indicate that coffee is active in inhibiting platelet aggregation, a critical step involved in thrombosis.

  1. Platelet mitochondrial function and dysfunction: physiological consequences

    Energy Technology Data Exchange (ETDEWEB)

    Popov, D.

    2015-07-01

    There is a general trend in revisiting mitochondria using the up-to-date technologies that uncovered novel attributes of this organelle, such as the intracellular displacement to locations where an energy supply is needed, the dynamic shape changes and turnover, the initiation of signaling to the rest of the cell, and the ability to crosstalk with other cellular organelles. The in-depth scrutiny of platelet mitochondria role in health and pathology is included within this ongoing revisiting trend. The current article puts into a nutshell the most recent data on platelet mitochondria function and disease-related ion, focusing on generation of stress- and apoptosis-related signaling molecules, overproduction of reactive oxygen species during activation and disease, on the biomarker potential of platelets mitochondria, and their prospective exploitation in translational applications. These novel findings complete the physiological profile of platelets and could have potential therapeutic effectiveness in platelet-associated disorders.

  2. Platelets as immune cells in infectious diseases.

    Science.gov (United States)

    Speth, Cornelia; Löffler, Jürgen; Krappmann, Sven; Lass-Flörl, Cornelia; Rambach, Günter

    2013-11-01

    Platelets have been shown to cover a broad range of functions. Besides their role in hemostasis, they have immunological functions and thus participate in the interaction between pathogens and host defense. Platelets have a broad repertoire of receptor molecules that enable them to sense invading pathogens and infection-induced inflammation. Consequently, platelets exert antimicrobial effector mechanisms, but also initiate an intense crosstalk with other arms of the innate and adaptive immunity, including neutrophils, monocytes/macrophages, dendritic cells, B cells and T cells. There is a fragile balance between beneficial antimicrobial effects and detrimental reactions that contribute to the pathogenesis, and many pathogens have developed mechanisms to influence these two outcomes. This review aims to highlight aspects of the interaction strategies between platelets and pathogenic bacteria, viruses, fungi and parasites, in addition to the subsequent networking between platelets and other immune cells, and the relevance of these processes for the pathogenesis of infections.

  3. Platelet bioreactor-on-a-chip

    Science.gov (United States)

    Mazutis, Linas; Wu, Stephen; Sylman, Joanna L.; Ehrlicher, Allen; Machlus, Kellie R.; Feng, Qiang; Lu, Shijiang; Lanza, Robert; Neeves, Keith B.; Weitz, David A.; Italiano, Joseph E.

    2014-01-01

    Platelet transfusions total >2.17 million apheresis-equivalent units per year in the United States and are derived entirely from human donors, despite clinically significant immunogenicity, associated risk of sepsis, and inventory shortages due to high demand and 5-day shelf life. To take advantage of known physiological drivers of thrombopoiesis, we have developed a microfluidic human platelet bioreactor that recapitulates bone marrow stiffness, extracellular matrix composition, micro-channel size, hemodynamic vascular shear stress, and endothelial cell contacts, and it supports high-resolution live-cell microscopy and quantification of platelet production. Physiological shear stresses triggered proplatelet initiation, reproduced ex vivo bone marrow proplatelet production, and generated functional platelets. Modeling human bone marrow composition and hemodynamics in vitro obviates risks associated with platelet procurement and storage to help meet growing transfusion needs. PMID:25606631

  4. Platelet-rich plasma in otolaryngology.

    Science.gov (United States)

    Stavrakas, M; Karkos, P D; Markou, K; Grigoriadis, N

    2016-12-01

    Platelet-rich plasma is a novel material that is being used more frequently in many surgical specialties. A literature review on the current and potential uses of platelet-rich plasma in otolaryngology was performed. There is limited evidence on the use of platelet-rich plasma in otolaryngology compared with other specialties: only 11 studies on various subspecialties (otology, rhinology and laryngology) were included in the final review. Based on the limited number of studies, we cannot draw safe conclusions about the value of platelet-rich plasma in otolaryngology. Nevertheless, the available literature suggests that platelet-rich plasma holds promise for future research and may have a number of clinical applications.

  5. Finding Robust Assailant Using Optimization Functions (FiRAO-PG in Wireless Sensor Network

    Directory of Open Access Journals (Sweden)

    Piyush Kumar Shukla

    2015-01-01

    Full Text Available Wireless sensor network consists of hundreds or thousands of low cost, low power, and self-organizing tiny sensor nodes that are deployed within the sensor network. Sensor network is susceptible to physical attacks due to deprived power and restricted resource capability and is exposed to external environment for transmitting and receiving data. Node capture attack is one of the most menacing attack in the wireless sensor network and may be physically captured by an adversary for extracting confidential information regarding cryptographic keys, node’s unique id, and so forth, from its memory to eliminate the confidentiality and integrity of the wireless links. Node capture attack suffers from severe security breach and tremendous network cost. We propose an empirically designed multiple objectives node capture attack algorithm based on optimization functions as an effective solution against the attacking efficiency of node capture attack. Finding robust assailant optimization-particle swarm optimization and genetic algorithm (FiRAO-PG consists of multiple objectives: maximum node participation, maximum key participation, and minimum resource expenditure to find optimal nodes using PSO and GA. It will leverage a comprehensive tool to destroy maximum portion of the network realizing cost-effectiveness and higher attacking efficiency. The simulation results manifest that FiRAO-PG can provide higher fraction of compromised traffic than matrix algorithm (MA so the attacking efficiency of FiRAO-PG is higher.

  6. Infrared Time Lags for the Periodic Quasar PG 1302-102

    CERN Document Server

    Jun, Hyunsung D; Graham, Matthew J; Djorgovski, S G; Mainzer, Amy; Cutri, Roc M; Drake, Andrew J; Mahabal, Ashish A

    2015-01-01

    The optical light curve of the quasar PG 1302-102 at $z = 0.278$ shows a strong, smooth 5.2 yr periodic signal, detectable over a period of $\\sim 20$ yr. Although the interpretation of this phenomenon is still uncertain, the most plausible mechanisms involve a binary system of two supermassive black holes with a subparsec separation. At this close separation, the nuclear black holes in PG 1302-102 will likely merge within $\\sim 10^{5}$ yr due to gravitational wave emission alone. Here we report the rest-frame near-infrared time lags for PG 1302-102. Compiling data from {\\it WISE} and {\\it Akari}, we confirm that the periodic behavior reported in the optical light curve from Graham et al. (2015) is reproduced at infrared wavelengths, with best-fit observed-frame 3.4 and $4.6 \\mu$m time lags of $(2219 \\pm 153, 2408 \\pm 148)$ days for a near face-on orientation of the torus, or $(4103\\pm 153, 4292 \\pm 148)$ days for an inclined system with relativistic Doppler boosting in effect. The periodicity in the infrared ...

  7. NeuroPG: Open source software for optical pattern generation and data acquisition

    Directory of Open Access Journals (Sweden)

    Benjamin W. Avants

    2015-03-01

    Full Text Available Patterned illumination using a digital micromirror device (DMD is a powerful tool for optogenetics. Compared to a scanning laser, DMDs are inexpensive and can easily create complex illumination patterns. Combining these complex spatiotemporal illumination patterns with optogenetics allows DMD-equipped microscopes to probe neural circuits by selectively manipulating the activity of many individual cells or many subcellular regions at the same time. To use DMDs to study neural activity, scientists must develop specialized software to coordinate optical stimulation patterns with the acquisition of electrophysiological and fluorescence data. To meet this growing need we have developed an open source optical pattern generation software for neuroscience - NeuroPG - that combines, DMD control, sample visualization, and data acquisition in one application. Built on a MATLAB platform, NeuroPG can also process, analyze, and visualize data. The software is designed specifically for the Mightex Polygon400; however, as an open source package, NeuroPG can be modified to incorporate any data acquisition, imaging, or illumination equipment that is compatible with MATLAB’s Data Acquisition and Image Acquisition toolboxes.

  8. Mass extinction of birds at the Cretaceous-Paleogene (K-Pg) boundary.

    Science.gov (United States)

    Longrich, Nicholas R; Tokaryk, Tim; Field, Daniel J

    2011-09-13

    The effect of the Cretaceous-Paleogene (K-Pg) (formerly Cretaceous-Tertiary, K-T) mass extinction on avian evolution is debated, primarily because of the poor fossil record of Late Cretaceous birds. In particular, it remains unclear whether archaic birds became extinct gradually over the course of the Cretaceous or whether they remained diverse up to the end of the Cretaceous and perished in the K-Pg mass extinction. Here, we describe a diverse avifauna from the latest Maastrichtian of western North America, which provides definitive evidence for the persistence of a range of archaic birds to within 300,000 y of the K-Pg boundary. A total of 17 species are identified, including 7 species of archaic bird, representing Enantiornithes, Ichthyornithes, Hesperornithes, and an Apsaravis-like bird. None of these groups are known to survive into the Paleogene, and their persistence into the latest Maastrichtian therefore provides strong evidence for a mass extinction of archaic birds coinciding with the Chicxulub asteroid impact. Most of the birds described here represent advanced ornithurines, showing that a major radiation of Ornithurae preceded the end of the Cretaceous, but none can be definitively referred to the Neornithes. This avifauna is the most diverse known from the Late Cretaceous, and although size disparity is lower than in modern birds, the assemblage includes both smaller forms and some of the largest volant birds known from the Mesozoic, emphasizing the degree to which avian diversification had proceeded by the end of the age of dinosaurs.

  9. How many hot subdwarf stars were rejected from the PG survey?

    CERN Document Server

    Wade, R A; Green, R F

    2004-01-01

    The Palomar-Green (PG) survey for UV-excess objects selected objects with U-B<-0.46 for spectroscopic follow-up. The color selection was done from photographic photometry, with typical error sigma(U-B) = 0.38. Spectroscopic detection of the Ca II K line in color-selected candidates was thought to indicate that a metal-weak cool star (sdF-sdG) had entered the list owing to photometric errors. About 1100 such "K-line" stars were rejected on this basis from the final published PG catalog, as not having "genuine" UV excesses. However, another possibility is that some of these objects are composite (binary) stars, consisting of a hot subdwarf (sdB or sdO) and a cool companion (F-G-K). Recent interest in binary-star formation channels for sdB stars in particular has brought renewed attention to the issue of completeness of lists of known hot subdwarfs, especially ones with cool companions. In this contribution, we attempt to determine that nature of the "rejected" PG candidate stars, by assembling available info...

  10. Dynamic masses for the close PG1159 binary SDSSJ212531.92-010745.9

    CERN Document Server

    Schuh, S; Nagel, T

    2008-01-01

    SDSSJ212531.92-010745.9 is the first known PG1159 star in a close binary with a late main sequence companion allowing a dynamical mass determination. The system shows flux variations with a peak-to-peak amplitude of about 0.7 mag and a period of about 6.96h. In August 2007, 13 spectra of SDSSJ212531.92-010745.9 covering the full orbital phase range were taken at the TWIN 3.5m telescope at the Calar Alto Observatory (Alm\\'{e}ria, Spain). These confirm the typical PG1159 features seen in the SDSS discovery spectrum, together with the Balmer series of hydrogen in emission (plus other emission lines), interpreted as signature of the companion's irradiated side. A radial velocity curve was obtained for both components. Using co-added radial-velocity-corrected spectra, the spectral analysis of the PG1159 star is being refined. The system's lightcurve, obtained during three seasons of photometry with the G\\"ottingen 50cm and T\\"ubingen 80cm telescopes, was fitted with both the NIGHTFALL and PHOEBE binary simulation ...

  11. Spectroscopic Orbital Elements for the Helium-Rich Subdwarf Binary PG1544+488

    CERN Document Server

    Şener, H Tuğça

    2014-01-01

    PG1544+488 is an exceptional short-period spectroscopic binary containing two subdwarf B stars. It is also exceptional because the surfaces of both components are extremely helium-rich. We present a new analysis of spectroscopy of PG1544+488 obtained with the William Herschel Telescope. We obtain improved orbital parameters and atmospheric parameters for each component. The orbital period $P=0.496\\pm0.002$\\,d, dynamical mass ratio $M_{\\rm B}/M_{\\rm A}=0.911\\pm0.015$, and spectroscopic radius ratio $R_{\\rm B}/R_{\\rm A}=0.939\\pm0.004$ indicate a binary consisting of nearly identical twins. The data are insufficient to distinguish any difference in surface composition between the components, which are slightly metal-poor (1/3 solar) and carbon-rich (0.3% by number). The latter indicates that the hotter component, at least, has ignited helium. The best theoretical model for the origin of PG1544+488 is by the ejection of a common envelope from a binary system in which both components are giants with helium cores o...

  12. The rice proteogenomics database OryzaPG-DB: development, expansion and new features

    Directory of Open Access Journals (Sweden)

    Mohamed eHelmy

    2012-04-01

    Full Text Available Proteogenomics is the utilization of large-scale proteome data in genome annotation refinement. Our recently developed rice proteogenomics database (OryzaPG-DB is the first sustainable resource for rice shotgun-based proteogenomics, providing information on peptides identified in rice protein digested peptides measured by means of liquid chromatography-tandem mass spectrometry (LC-MS/MS, and mapping of the peptides to their genomic origins and the genomic novelty of each peptide. The sequences of the peptides, proteins, cDNAs and genes, and the gene annotations are available for download in FASTA and GFF3 formats, respectively. Further, an annotated visualization of the gene models, corresponding peptides and genomic novelty is available for each gene, and MS/MS spectra are available for each peptide. In this article, we discuss the utilization of OryzaPG-DB and report on its development, recent content expansions and newly added features in the current version (OryzaPG-DB v1.1.

  13. The far-ultraviolet spectra of two hot PG1159 stars

    CERN Document Server

    Werner, K; Kruk, J W

    2016-01-01

    PG1159 stars are hot, hydrogen-deficient (pre-) white dwarfs with atmospheres mainly composed of helium, carbon, and oxygen. The unusual surface chemistry is the result of a late helium-shell flash. Observed element abundances enable us to test stellar evolution models quantitatively with respect to their nucleosynthesis products formed near the helium-burning shell of the progenitor asymptotic giant branch stars. Because of the high effective temperatures (Teff), abundance determinations require ultraviolet spectroscopy and non-local thermodynamic equilibrium model atmosphere analyses. Up to now, we have presented results for the prototype of this spectral class and two cooler members (Teff in the range 85,000-140,000 K). Here we report on the results for two even hotter stars (PG1520+525 and PG1144+005, both with Teff = 150,000 K) which are the only two objects in this temperature-gravity region for which useful far-ultraviolet spectra are available, and revisit the prototype star. Previous results on the a...

  14. Tidal synchronization of the subdwarf B binary PG 0101+039

    CERN Document Server

    Geier, S; Heber, U; Randall, S K; Edelmann, H; Green, E M

    2007-01-01

    Tidally locked rotation is a frequently applied assumption that helps to measure masses of invisible compact companions in close binaries. The calculations of synchronization times are affected by large uncertainties in particular for stars with radiative envelopes calling for observational constraints. We aim at verifying tidally locked rotation for the binary PG 0101+039, a subdwarf B star + white dwarf binary from its tiny (0.025 %) light variations measured with the MOST satellite (Randall et al. 2005). Binary parameters were derived from the mass function, apparent rotation and surface gravity of PG 0101+039 assuming a canonical mass of 0.47 Mo and tidally locked rotation. The light curve was then synthesised and was found to match the observed amplitude well. We verified that the light variations are due to ellipsoidal deformation and that tidal synchronization is established for PG 0101+039. We conclude that this assumption should hold for all sdB binaries with orbital periods of less than half a day. ...

  15. Platelet derivatives in regenerative medicine: an update.

    Science.gov (United States)

    De Pascale, Maria Rosaria; Sommese, Linda; Casamassimi, Amelia; Napoli, Claudio

    2015-01-01

    Prior preclinical and clinical studies support the use of platelet-derived products for the treatment of soft and hard tissue lesions. These regenerative effects are controlled by autocrine and paracrine biomolecules including growth factors and cytokines contained in platelet alpha granules. Each growth factor is involved in a phase of the healing process, such as inflammation, collagen synthesis, tissue granulation, and angiogenesis collectively promoting tissue restitution. Platelet derivatives have been prepared as platelet-rich plasma, platelet gel, platelet-rich fibrin, and platelet eye drops. These products vary in their structure, growth factors, composition, and cytokine concentrations. Here, we review the current use of platelet-derived biological products focusing on the rationale for their use and the main requirements for their preparation. Variation in the apparent therapeutic efficacy may have resulted from a lack of reproducible, standardized protocols for preparation. Despite several individual studies showing favorable treatment effects, some randomized controlled trials as well as meta-analyses have found no constant clinical benefit from the application of platelet-derived products for prevention of tissue lesions. Recently, 3 published studies in dentistry showed an improvement in bone density. Seven published studies showed positive results in joint regeneration. Five published studies demonstrated an improvement in the wound healing, and an improvement of eye epithelial healing was observed in 2 reports. Currently, at least 14 ongoing clinical trials in phase 3 or 4 have been designed with large groups of treated patients (n > 100). Because the rationale of the therapy with platelet-derived compounds is still debated, a definitive insight can be acquired only when these large randomized trials will be completed.

  16. Structure of the prolyl-tRNA synthetase from the eukaryotic pathogen Giardia lamblia

    Energy Technology Data Exchange (ETDEWEB)

    Larson, Eric T.; Kim, Jessica E.; Napuli, Alberto J.; Verlinde, Christophe L. M. J.; Fan, Erkang; Zucker, Frank H.; Van Voorhis, Wesley C.; Buckner, Frederick S.; Hol, Wim G. J.; Merritt, Ethan A., E-mail: merritt@u.washington.edu [Medical Structural Genomics of Pathogenic Protozoa, (United States); University of Washington, Seattle, WA 98195 (United States)

    2012-09-01

    The structure of Giardia prolyl-tRNA synthetase cocrystallized with proline and ATP shows evidence for half-of-the-sites activity, leading to a corresponding mixture of reaction substrates and product (prolyl-AMP) in the two active sites of the dimer. The genome of the human intestinal parasite Giardia lamblia contains only a single aminoacyl-tRNA synthetase gene for each amino acid. The Giardia prolyl-tRNA synthetase gene product was originally misidentified as a dual-specificity Pro/Cys enzyme, in part owing to its unexpectedly high off-target activation of cysteine, but is now believed to be a normal representative of the class of archaeal/eukaryotic prolyl-tRNA synthetases. The 2.2 Å resolution crystal structure of the G. lamblia enzyme presented here is thus the first structure determination of a prolyl-tRNA synthetase from a eukaryote. The relative occupancies of substrate (proline) and product (prolyl-AMP) in the active site are consistent with half-of-the-sites reactivity, as is the observed biphasic thermal denaturation curve for the protein in the presence of proline and MgATP. However, no corresponding induced asymmetry is evident in the structure of the protein. No thermal stabilization is observed in the presence of cysteine and ATP. The implied low affinity for the off-target activation product cysteinyl-AMP suggests that translational fidelity in Giardia is aided by the rapid release of misactivated cysteine.

  17. Calcium regulates the expression of a Dictyostelium discoideum asparaginyl tRNA synthetase gene

    Indian Academy of Sciences (India)

    Jyoti K Jaiswal; Vidyanand Nanjundiah

    2003-12-01

    In a screen for calcium-regulated gene expression during growth and development of Dictyostelium discoideum we have identified an asparaginyl tRNA synthetase (ddAsnRS) gene, the second tRNA synthetase gene identified in this organism. The ddAsnRS gene shows many unique features. One, it is repressed by lowering cellular calcium, making it the first known calcium-regulated tRNA synthetase. Two, despite the calcium-dependence, its expression is unaltered during the cell cycle, making this the first D. discoideum gene to show a calcium-dependent but cell cycle phase-independent expression. Finally, the N-terminal domain of the predicted ddAsnRS protein shows higher sequence similarity to Glutaminyl tRNA synthetases than to other Asn tRNA synthetases. These unique features of the AsnRS from this primitive eukaryote not only point to a novel mechanism regulating the components of translation machinery and gene expression by calcium, but also hint at a link between the evolution of GlnRS and AsnRS in eukaryotes.

  18. The yeast VAS1 gene encodes both mitochondrial and cytoplasmic valyl-tRNA synthetases.

    Science.gov (United States)

    Chatton, B; Walter, P; Ebel, J P; Lacroute, F; Fasiolo, F

    1988-01-05

    S1 mapping on the VAS1 structural gene indicates the existence of two classes of transcripts initiating at distinct in-frame translation start codons. The longer class of VAS1 transcripts initiates upstream of both ATG codons located 138 base pairs away and the shorter class downstream of the first ATG. A mutation that destroys the first AUG on the long message results in respiratory deficiency but does not affect viability. Mutation of the ATG at position 139 leads to lethality because the initiating methionine codon of the essential cytoplasmic valyl-tRNA synthetase has been destroyed. N-terminal protein sequence data further confirm translation initiation at ATG-139 for the cytoplasmic valyl-tRNA synthetase. From these results, we conclude that the VAS1 single gene encodes both mitochondrial and cytoplasmic valyl-tRNA synthetases. The presequence of the mitochondrial valyl-tRNA synthetase shows amino acid composition but not the amphiphilic character of imported mitochondrial proteins. From mutagenesis of the ATG-139 we conclude that the presequence specifically targets the cytoplasmically synthesized mitochondrial valyl-tRNA synthetase to the mitochondrial outer membrane and prevents binding of the enzyme core to cytoplasmic tRNAVal.

  19. The effect of glial glutamine synthetase inhibition on recognition and temporal memories in the rat.

    Science.gov (United States)

    Kant, Deepika; Tripathi, Shweta; Qureshi, Munazah F; Tripathi, Shweta; Pandey, Swati; Singh, Gunjan; Kumar, Tankesh; Mir, Fayaz A; Jha, Sushil K

    2014-02-07

    The glutamate neurotransmitter is intrinsically involved in learning and memory. Glial glutamine synthetase enzyme synthesizes glutamine, which helps maintain the optimal neuronal glutamate level. However, the role of glutamine synthetase in learning and memory remains unclear. Using associative trace learning task, we investigated the effects of methionine sulfoximine (MSO) (glutamine synthetase inhibitor) on recognition and temporal memories. MSO and vehicle were injected (i.p.) three hours before training in separate groups of male Wistar rats (n=11). Animals were trained to obtain fruit juice after following a set of sequential events. Initially, house-light was presented for 15s followed by 5s trace interval. Thereafter, juice was given for 20s followed by 20s inter-presentation interval. A total of 75 presentations were made over five sessions during the training and testing periods. The average number of head entries to obtain juice per session and during individual phases at different time intervals was accounted as an outcome measure of recognition and temporal memories. The total head entries in MSO and vehicle treated animals were comparable on training and testing days. However, it was 174.90% (p=0.08), 270.61% (pGlutamine synthetase inhibition did not induce recognition memory deficit, while temporal memory was altered, suggesting that glutamine synthetase modulates some aspects of mnemonic processes.

  20. Glutamine Synthetase Sensitivity to Oxidative Modification during Nutrient Starvation in Prochlorococcus marinus PCC 9511.

    Science.gov (United States)

    Gómez-Baena, Guadalupe; Domínguez-Martín, María Agustina; Donaldson, Robert P; García-Fernández, José Manuel; Diez, Jesús

    2015-01-01

    Glutamine synthetase plays a key role in nitrogen metabolism, thus the fine regulation of this enzyme in Prochlorococcus, which is especially important in the oligotrophic oceans where this marine cyanobacterium thrives. In this work, we studied the metal-catalyzed oxidation of glutamine synthetase in cultures of Prochlorococcus marinus strain PCC 9511 subjected to nutrient limitation. Nitrogen deprivation caused glutamine synthetase to be more sensitive to metal-catalyzed oxidation (a 36% increase compared to control, non starved samples). Nutrient starvation induced also a clear increase (three-fold in the case of nitrogen) in the concentration of carbonyl derivatives in cell extracts, which was also higher (22%) upon addition of the inhibitor of electron transport, DCMU, to cultures. Our results indicate that nutrient limitations, representative of the natural conditions in the Prochlorococcus habitat, affect the response of glutamine synthetase to oxidative inactivating systems. Implications of these results on the regulation of glutamine synthetase by oxidative alteration prior to degradation of the enzyme in Prochlorococcus are discussed.

  1. Decreased TGF-β1 and VEGF Release in Cystic Fibrosis Platelets: Further Evidence for Platelet Defects in Cystic Fibrosis

    Science.gov (United States)

    Maloney, James P.; Narasimhan, Jayashree; Biller, Julie

    2016-01-01

    Purpose Cystic fibrosis (CF) patients suffer from chronic lung inflammation. This inflammation may activate platelets. There are limited data on the role of platelet-secreted cytokines in CF. Platelet cytokines with inflammatory effects include vascular endothelial growth factor (VEGF) and transforming growth factor-β1 (TGF-β1). As levels of these cytokines are tenfold greater in serum than plasma due to platelet release, serum levels may be one index of platelet content; but a more specific index is release during the aggregation of isolated platelets. We postulated that altered release of these platelet cytokines occurs in CF. Methods We obtained sera and plasma from CF outpatients (n=21) and from healthy controls (n=20), measured VEGF and TGF-β1, assessed for correlations with platelet number, analyzed cytokine release during platelet aggregation to collagen, and analyzed differences in maximal platelet aggregation. Results Platelet number and maximal aggregation levels were higher in CF. Plasma and serum levels of TGF-β1 and VEGF were higher in CF, but these levels were similar after adjusting for platelet number (serum cytokines correlated with platelet count). The release of VEGF and TGF-β1 during aggregation was decreased in CF platelets (by 52% and 29%, respectively). Conclusion Platelet release is not a source of the elevated blood proinflammatory cytokines TGF-β1 and VEGF in CF, as platelets from CF patients actually release less of these cytokines. These data provide further evidence for platelet defects in CF. PMID:27423781

  2. Breaking the mold: transcription factors in the anucleate platelet and platelet-derived microparticles

    Directory of Open Access Journals (Sweden)

    Katie L Lannan

    2015-02-01

    Full Text Available Platelets are small anucleate blood cells derived from megakaryocytes. In addition to their pivotal roles in hemostasis, platelets are the smallest, yet most abundant, immune cell and regulate inflammation, immunity, and disease progression. Although platelets lack DNA, and thus no functional transcriptional activities, they are nonetheless rich sources of RNAs, possess an intact spliceosome, and are thus capable of synthesizing proteins. Previously, it was thought that platelet RNAs and translational machinery were remnants from the megakaryocyte. We now know that the initial description of platelets as cellular fragments is an antiquated notion, as mounting evidence suggests otherwise. Therefore, it is reasonable to hypothesize that platelet transcription factors are not vestigial remnants from megakaryoctes, but have important, if only partly understood functions. Proteins play multiple cellular roles to minimize energy expenditure for maximum cellular function; thus, the same can be expected for transcription factors. In fact, numerous transcription factors have non-genomic roles, both in platelets and in nucleated cells. Our lab and others have discovered the presence and nongenomic roles of transcription factors in platelets, such as the nuclear factor kappa β (NFκB family of proteins and peroxisome proliferator activated receptor gamma (PPARγ. In addition to numerous roles in regulating platelet activation, functional transcription factors can be transferred to vascular and immune cells through platelet microparticles. This method of transcellular delivery of key immune molecules may be a vital mechanism by which platelet transcription factors regulate inflammation and immunity. At the very least, platelets are an ideal model cell to dissect out the nongenomic roles of transcription factors in nucleated cells. There is abundant evidence to suggest that transcription factors in platelets play key roles in regulating inflammatory and

  3. Platelet lysates produced from expired platelet concentrates support growth and osteogenic differentiation of mesenchymal stem cells.

    Directory of Open Access Journals (Sweden)

    Sandra Mjoll Jonsdottir-Buch

    Full Text Available BACKGROUND: Mesenchymal stem cells are promising candidates in regenerative cell therapy. Conventional culture methods involve the use of animal substances, specifically fetal bovine serum as growth supplement. Since the use of animal-derived products is undesirable for human applications, platelet lysates produced from human platelets are an attractive alternative. This is especially true if platelet lysates from already approved transfusion units at blood banks can be utilized. The purpose of this study was to produce human platelet lysates from expired, blood bank-approved platelet concentrates and evaluate their use as growth supplement in the culture of mesenchymal stem cells. METHODOLOGY/PRINCIPAL FINDINGS: In this study, bone marrow-derived mesenchymal stem cells were cultured with one of three culture supplements; fetal bovine serum, lysates from freshly prepared human platelet concentrates, or lysates from expired human platelet concentrates. The effects of these platelet-derived culture supplements on basic mesenchymal stem cell characteristics were evaluated. All cultures maintained the typical mesenchymal stem cell surface marker expression, trilineage differentiation potential, and the ability to suppress in vitro immune responses. However, mesenchymal stem cells supplemented with platelet lysates proliferated faster than traditionally cultured cells and increased the expression of the osteogenic marker gene RUNX-2; yet no difference between the use of fresh and expired platelet concentrates was observed. CONCLUSION/SIGNIFICANCE: Our findings suggest that human platelet lysates produced from expired platelet concentrates can be used as an alternative to fetal bovine serum for mesenchymal stem cell culture to the same extent as lysates from fresh platelets.

  4. Functional analysis of Leishmania cyclopropane fatty acid synthetase.

    Directory of Open Access Journals (Sweden)

    Samuel O Oyola

    Full Text Available The single gene encoding cyclopropane fatty acid synthetase (CFAS is present in Leishmania infantum, L. mexicana and L. braziliensis but absent from L. major, a causative agent of cutaneous leishmaniasis. In L. infantum, usually causative agent of visceral leishmaniasis, the CFAS gene is transcribed in both insect (extracellular and host (intracellular stages of the parasite life cycle. Tagged CFAS protein is stably detected in intracellular L. infantum but only during the early log phase of extracellular growth, when it shows partial localisation to the endoplasmic reticulum. Lipid analyses of L. infantum wild type, CFAS null and complemented parasites detect a low abundance CFAS-dependent C19Δ fatty acid, characteristic of a cyclopropanated species, in wild type and add-back cells. Sub-cellular fractionation studies locate the C19Δ fatty acid to both ER and plasma membrane-enriched fractions. This fatty acid is not detectable in wild type L. major, although expression of the L. infantum CFAS gene in L. major generates cyclopropanated fatty acids, indicating that the substrate for this modification is present in L. major, despite the absence of the modifying enzyme. Loss of the L. infantum CFAS gene does not affect extracellular parasite growth, phagocytosis or early survival in macrophages. However, while endocytosis is also unaffected in the extracellular CFAS nulls, membrane transporter activity is defective and the null parasites are more resistant to oxidative stress. Following infection in vivo, L. infantum CFAS nulls exhibit lower parasite burdens in both the liver and spleen of susceptible hosts but it has not been possible to complement this phenotype, suggesting that loss of C19Δ fatty acid may lead to irreversible changes in cell physiology that cannot be rescued by re-expression. Aberrant cyclopropanation in L. major decreases parasite virulence but does not influence parasite tissue tropism.

  5. Antimalarial Benzoxaboroles Target Plasmodium falciparum Leucyl-tRNA Synthetase.

    Science.gov (United States)

    Sonoiki, Ebere; Palencia, Andres; Guo, Denghui; Ahyong, Vida; Dong, Chen; Li, Xianfeng; Hernandez, Vincent S; Zhang, Yong-Kang; Choi, Wai; Gut, Jiri; Legac, Jennifer; Cooper, Roland; Alley, M R K; Freund, Yvonne R; DeRisi, Joseph; Cusack, Stephen; Rosenthal, Philip J

    2016-08-01

    There is a need for new antimalarials, ideally with novel mechanisms of action. Benzoxaboroles have been shown to be active against bacteria, fungi, and trypanosomes. Therefore, we investigated the antimalarial activity and mechanism of action of 3-aminomethyl benzoxaboroles against Plasmodium falciparum Two 3-aminomethyl compounds, AN6426 and AN8432, demonstrated good potency against cultured multidrug-resistant (W2 strain) P. falciparum (50% inhibitory concentration [IC50] of 310 nM and 490 nM, respectively) and efficacy against murine Plasmodium berghei infection when administered orally once daily for 4 days (90% effective dose [ED90], 7.4 and 16.2 mg/kg of body weight, respectively). To characterize mechanisms of action, we selected parasites with decreased drug sensitivity by culturing with stepwise increases in concentration of AN6426. Resistant clones were characterized by whole-genome sequencing. Three generations of resistant parasites had polymorphisms in the predicted editing domain of the gene encoding a P. falciparum leucyl-tRNA synthetase (LeuRS; PF3D7_0622800) and in another gene (PF3D7_1218100), which encodes a protein of unknown function. Solution of the structure of the P. falciparum LeuRS editing domain suggested key roles for mutated residues in LeuRS editing. Short incubations with AN6426 and AN8432, unlike artemisinin, caused dose-dependent inhibition of [(14)C]leucine incorporation by cultured wild-type, but not resistant, parasites. The growth of resistant, but not wild-type, parasites was impaired in the presence of the unnatural amino acid norvaline, consistent with a loss of LeuRS editing activity in resistant parasites. In summary, the benzoxaboroles AN6426 and AN8432 offer effective antimalarial activity and act, at least in part, against a novel target, the editing domain of P. falciparum LeuRS.

  6. Blockade of Glutamine Synthetase Enhances Inflammatory Response in Microglial Cells

    Science.gov (United States)

    Palmieri, Erika M.; Menga, Alessio; Lebrun, Aurore; Hooper, Douglas C.; Butterfield, D. Allan

    2017-01-01

    Abstract Aims: Microglial cells are brain-resident macrophages engaged in surveillance and maintained in a constant state of relative inactivity. However, their involvement in autoimmune diseases indicates that in pathological conditions microglia gain an inflammatory phenotype. The mechanisms underlying this change in the microglial phenotype are still unclear. Since metabolism is an important modulator of immune cell function, we focused our attention on glutamine synthetase (GS), a modulator of the response to lipopolysaccharide (LPS) activation in other cell types, which is expressed by microglia. Results: GS inhibition enhances release of inflammatory mediators of LPS-activated microglia in vitro, leading to perturbation of the redox balance and decreased viability of cocultured neurons. GS inhibition also decreases insulin-mediated glucose uptake in microglia. In vivo, microglia-specific GS ablation enhances expression of inflammatory markers upon LPS treatment. In the spinal cords from experimental autoimmune encephalomyelitis (EAE), GS expression levels and glutamine/glutamate ratios are reduced. Innovation: Recently, metabolism has been highlighted as mediator of immune cell function through the discovery of mechanisms that (behind these metabolic changes) modulate the inflammatory response. The present study shows for the first time a metabolic mechanism mediating microglial response to a proinflammatory stimulus, pointing to GS activity as a master modulator of immune cell function and thus unraveling a potential therapeutic target. Conclusions: Our study highlights a new role of GS in modulating immune response in microglia, providing insights into the pathogenic mechanisms associated with inflammation and new strategies of therapeutic intervention. Antioxid. Redox Signal. 26, 351–363. PMID:27758118

  7. Functional interactions between a glutamine synthetase promoter and MYB proteins.

    Science.gov (United States)

    Gómez-Maldonado, Josefa; Avila, Concepción; Torre, Fernando; Cañas, Rafael; Cánovas, Francisco M; Campbell, Malcolm M

    2004-08-01

    In Scots pine (Pinus sylvestris), ammonium assimilation is catalysed by glutamine synthetase (GS) [EC 6.3.1.2], which is encoded by two genes, PsGS1a and PsGS1b. PsGS1b is expressed in the vascular tissue throughout the plant body, where it is believed to play a role in recycling ammonium released by various facets of metabolism. The mechanisms that may underpin the transcriptional regulation of PsGS1b were explored. The PsGS1b promoter contains a region that is enriched in previously characterized cis-acting elements, known as AC elements. Pine nuclear proteins bound these AC element-rich regions in a tissue-specific manner. As previous experiments had shown that R2R3-MYB transcription factors could interact with AC elements, the capacity of the AC elements in the PsGS1b promoter to interact with MYB proteins was examined. Two MYB proteins from loblolly pine (Pinus taeda), PtMYB1 and PtMYB4, bound to the PsGS1b promoter were able to activate transcription from this promoter in yeast, arabidopsis and pine cells. Immunolocalization experiments revealed that the two MYB proteins were most abundant in cells previously shown to accumulate PsGS1b transcripts. Immunoprecipitation analysis and supershift electrophoretic mobility shift assays implicated these same two proteins in the formation of complexes between pine nuclear extracts and the PsGS1b promoter. Given that these MYB proteins were previously shown to have the capacity to activate gene expression related to lignin biosynthesis, we hypothesize that they may function to co-regulate lignification, a process that places significant demands on nitrogen recycling, and GS, the major enzyme involved in the nitrogen recycling pathway.

  8. Platelet-TLR7 mediates host survival and platelet count during viral infection in the absence of platelet-dependent thrombosis.

    Science.gov (United States)

    Koupenova, Milka; Vitseva, Olga; MacKay, Christopher R; Beaulieu, Lea M; Benjamin, Emelia J; Mick, Eric; Kurt-Jones, Evelyn A; Ravid, Katya; Freedman, Jane E

    2014-07-31

    Viral infections have been associated with reduced platelet counts, the biological significance of which has remained elusive. Here, we show that infection with encephalomyocarditis virus (EMCV) rapidly reduces platelet count, and this response is attributed to platelet Toll-like receptor 7 (TLR7). Platelet-TLR7 stimulation mediates formation of large platelet-neutrophil aggregates, both in mouse and human blood. Intriguingly, this process results in internalization of platelet CD41-fragments by neutrophils, as assessed biochemically and visualized by microscopy, with no influence on platelet prothrombotic properties. The mechanism includes TLR7-mediated platelet granule release, translocation of P-selectin to the cell surface, and a consequent increase in platelet-neutrophil adhesion. Viral infection of platelet-depleted mice also led to increased mortality. Transfusion of wild-type, TLR7-expressing platelets into TLR7-deficient mice caused a drop in platelet count and increased survival post EMCV infection. Thus, this study identifies a new link between platelets and their response to single-stranded RNA viruses that involves activation of TLR7. Finally, platelet-TLR7 stimulation is independent of thrombosis and has implications to the host immune response and survival.

  9. Blood platelets in the progression of Alzheimer's disease.

    Directory of Open Access Journals (Sweden)

    Nina S Gowert

    Full Text Available Alzheimer's disease (AD is characterized by neurotoxic amyloid-ß plaque formation in brain parenchyma and cerebral blood vessels known as cerebral amyloid angiopathy (CAA. Besides CAA, AD is strongly related to vascular diseases such as stroke and atherosclerosis. Cerebrovascular dysfunction occurs in AD patients leading to alterations in blood flow that might play an important role in AD pathology with neuronal loss and memory deficits. Platelets are the major players in hemostasis and thrombosis, but are also involved in neuroinflammatory diseases like AD. For many years, platelets were accepted as peripheral model to study the pathophysiology of AD because platelets display the enzymatic activities to generate amyloid-ß (Aß peptides. In addition, platelets are considered to be a biomarker for early diagnosis of AD. Effects of Aß peptides on platelets and the impact of platelets in the progression of AD remained, however, ill-defined. The present study explored the cellular mechanisms triggered by Aß in platelets. Treatment of platelets with Aß led to platelet activation and enhanced generation of reactive oxygen species (ROS and membrane scrambling, suggesting enhanced platelet apoptosis. More important, platelets modulate soluble Aß into fibrillar structures that were absorbed by apoptotic but not vital platelets. This together with enhanced platelet adhesion under flow ex vivo and in vivo and platelet accumulation at amyloid deposits of cerebral vessels of AD transgenic mice suggested that platelets are major contributors of CAA inducing platelet thrombus formation at vascular amyloid plaques leading to vessel occlusion critical for cerebrovascular events like stroke.

  10. Brief Report: Platelet-Poor Plasma Serotonin in Autism

    Science.gov (United States)

    Anderson, George M.; Hertzig, Margaret E.; McBride, P. A.

    2012-01-01

    Possible explanations for the well-replicated platelet hyperserotonemia of autism include an alteration in the platelet's handling of serotonin (5-hydroxyserotonin, 5-HT) or an increased exposure of the platelet to 5-HT. Measurement of platelet-poor plasma (PPP) levels of 5-HT appears to provide the best available index of in vivo exposure of the…

  11. 21 CFR 864.5700 - Automated platelet aggregation system.

    Science.gov (United States)

    2010-04-01

    ... addition of an aggregating reagent to a platelet-rich plasma. (b) Classification. Class II (performance... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Automated platelet aggregation system. 864.5700... § 864.5700 Automated platelet aggregation system. (a) Identification. An automated platelet...

  12. Quality assessment of platelet concentrates prepared by platelet rich plasma-platelet concentrate, buffy coat poor-platelet concentrate (BC-PC and apheresis-PC methods

    Directory of Open Access Journals (Sweden)

    Singh Ravindra

    2009-01-01

    Full Text Available Background: Platelet rich plasma-platelet concentrate (PRP-PC, buffy coat poor-platelet concentrate (BC-PC, and apheresis-PC were prepared and their quality parameters were assessed. Study Design: In this study, the following platelet products were prepared: from random donor platelets (i platelet rich plasma - platelet concentrate (PRP-PC, and (ii buffy coat poor- platelet concentrate (BC-PC and (iii single donor platelets (apheresis-PC by different methods. Their quality was assessed using the following parameters: swirling, volume of the platelet concentrate, platelet count, WBC count and pH. Results: A total of 146 platelet concentrates (64 of PRP-PC, 62 of BC-PC and 20 of apheresis-PC were enrolled in this study. The mean volume of PRP-PC, BC-PC and apheresis-PC was 62.30±22.68 ml, 68.81±22.95 ml and 214.05±9.91 ml and ranged from 22-135 ml, 32-133 ml and 200-251 ml respectively. The mean platelet count of PRP-PC, BC-PC and apheresis-PC was 7.6±2.97 x 1010/unit, 7.3±2.98 x 1010/unit and 4.13±1.32 x 1011/unit and ranged from 3.2-16.2 x 1010/unit, 0.6-16.4 x 1010/unit and 1.22-8.9 x 1011/unit respectively. The mean WBC count in PRP-PC (n = 10, BC-PC (n = 10 and apheresis-PC (n = 6 units was 4.05±0.48 x 107/unit, 2.08±0.39 x 107/unit and 4.8±0.8 x 106/unit and ranged from 3.4 -4.77 x 107/unit, 1.6-2.7 x 107/unit and 3.2 - 5.2 x 106/unit respectively. A total of 26 units were analyzed for pH changes. Out of these units, 10 each were PRP-PC and BC-PC and 6 units were apheresis-PC. Their mean pH was 6.7±0.26 (mean±SD and ranged from 6.5 - 7.0 and no difference was observed among all three types of platelet concentrate. Conclusion: PRP-PC and BC-PC units were comparable in terms of swirling, platelet count per unit and pH. As expected, we found WBC contamination to be less in BC-PC than PRP-PC units. Variation in volume was more in BC-PC than PRP-PC units and this suggests that further standardization is required for preparation of BC

  13. Continuous recording of long-chain acyl-coenzyme A synthetase activity using fluorescently labeled bovine serum albumin

    DEFF Research Database (Denmark)

    Demant, Erland J.F.; Nystrøm, Birthe T.

    2001-01-01

    acyl-Coenzyme A, synthetase, activity assay, fluorescence recording, fatty acid probe, serum albumin, hydroxycoumarin, detergent, micelles, Pseudomonas fragi, rat liver microsomes......acyl-Coenzyme A, synthetase, activity assay, fluorescence recording, fatty acid probe, serum albumin, hydroxycoumarin, detergent, micelles, Pseudomonas fragi, rat liver microsomes...

  14. Methods and compositions for the production of orthogonal tRNA-aminoacyl tRNA synthetase pairs

    Energy Technology Data Exchange (ETDEWEB)

    Schultz, Peter G.; Wang, Lei; Anderson, John Christopher; Chin, Jason W.; Liu, David R.; Magliery, Thomas J.; Meggers, Eric L.; Mehl, Ryan Aaron; Pastrnak, Miro; Santoro, Stephen William; Zhang, Zhiwen

    2015-10-20

    This invention provides compositions and methods for generating components of protein biosynthetic machinery including orthogonal tRNAs, orthogonal aminoacyl-tRNA synthetases, and orthogonal pairs of tRNAs/synthetases. Methods for identifying orthogonal pairs are also provided. These components can be used to incorporate unnatural amino acids into proteins in vivo.

  15. Platelet thrombosis in cardiac-valve prostheses

    Energy Technology Data Exchange (ETDEWEB)

    Dewanjee, M.K.

    1989-01-01

    The contribution of platelets and clotting factors in thrombosis on cardiovascular prostheses had been quantified with several tracers. Thrombus formation in vivo could be measured semiquantitatively in animal models and patients with indium-111, Technetium-99m labeled platelets, iodine-123, iodine-131 labeled fibrinogen, and In-111 and Tc-99m labeled antibody to the fibrinogen-receptor on the platelet- membrane, or fibrin. The early studies demonstrated that certain platelet-inhibitors, e.g. sulfinpyrazone, aspirin or aspirin- persantine increased platelet survival time with mechanical valves implanted in the baboon model and patients. Thrombus localization by imaging is possible for large thrombus on thrombogenic surface of prosthesis in the acute phase. The majority of thrombus was found in the sewing ring (Dacron) in the acute phase in both the mechanical and tissue valves. The amount of retained thrombus in both mechanical and tissue valves in our one-day study in the dog model was similar (< 1% if injected In-111 platelets = 5 billion platelets). As the fibrous ingrowth covered the sewing ring, the thrombus formation decreased significantly. Only a small amount of thrombus was found on the leaflets at one month in both the dog and calf models. 38 refs., 9 figs., 5 tabs.

  16. Changes in platelet parameters in leukocytosis.

    Science.gov (United States)

    Ozturk, Nurinnisa; Baygutalp, Nurcan Kilic; Bakan, Ebubekir; Altas, Gulsum Feyza; Polat, Harun; Dorman, Emrullah

    2016-01-01

    In recent years, platelets are known to have a large variety of functions in many pathophysiological processes and their interaction with endothelial cells and leukocytes is known to play an important role in the pathophysiology of vascular inflammation. The aim of this study was to investigate the relationship between white blood cell count in conditions resulting in leukocytosis and platelet count and platelet parameters including mean platelet volume, platelet distribution width, and plateletcrit. White blood cell counts count and all platelet parameters were evaluated in 341 results of normal complete blood count (of which the white blood cell counts were within reference range, group 1) and 327 results of elevated white blood cell counts count (group 2). There was a significant difference between these two groups in PLT counts and PCT values, being higher in Group 2. However, there was no statistically significant difference between two groups in MPV and PDW values. On the other hand, there were statistically significant, but weak, correlations between the WBC and platelet counts in both groups (p<0.01, r=0.235 for group 1, p<0.05, r=0.116 for group 2). As a conclusion PLT count and PCT values increase in infectious conditions. This study and previous studies show that PLTs are employed in infectious conditions but the exact mechanism and the exact clinical importance of this response remains to be cleared by further studies.

  17. Identification of autoantibodies to tyrosil-tRNA synthetase in heart disfunctions

    Directory of Open Access Journals (Sweden)

    Ryabenko D. V.

    2010-09-01

    Full Text Available Aim. To investigate the levels of specific autoantibodies against tyrosyl-tRNA synthetase and its individual modules in the blood serum of people with heart failure caused by dilated cardiomyopathy, myocarditis and ischemic heart disease compared with healthy donors. Methods. Recombinant proteins were obtained using bacterial strains transformed with appropriate plasmid vectors and were purified by chromatography on Ni-NTA-agarose. The levels of specific autoantibodies were investigated by ELISA. Results. The increased levels of autoantibodies specific to tyrosyl-tRNA synthetase, its N-terminal catalytic module and non-catalytic C-module, were found in the blood serum of patients, compared with healthy donors. Conclusions. The results obtained demonstrate the possible role of tyrosyl-tRNA synthetase in adaptive changes of the myocardium in response to stress factors.

  18. 19-Year Follow-up of A Patient With Severe Glutathione Synthetase Deficiency

    Science.gov (United States)

    Atwal, Paldeep S.; Medina, Casey R.; Burrage, Lindsay C.; Sutton, V. Reid

    2016-01-01

    Glutathione synthetase deficiency is a rare autosomal recessive disorder resulting in low levels of glutathione and an increased susceptibility to oxidative stress. Patients with glutathione synthetase deficiency typically present in the neonatal period with hemolytic anemia, metabolic acidosis and neurological impairment. Lifelong treatment with antioxidants has been recommended in an attempt to prevent morbidity and mortality associated with the disorder. Here we present a 19-year-old female who was diagnosed with glutathione synthetase deficiency shortly after birth and who has been closely followed in our metabolic clinic. Despite an initial severe presentation, she has had normal intellectual development and few complications of her disorder with a treatment regimen that includes polycitra (citric acid, potassium citrate and sodium citrate), vitamin C, vitamin E and selenium. PMID:26984560

  19. Transcription factor TnrA inhibits the biosynthetic activity of glutamine synthetase in Bacillus subtilis.

    Science.gov (United States)

    Fedorova, Ksenia; Kayumov, Airat; Woyda, Kathrin; Ilinskaja, Olga; Forchhammer, Karl

    2013-05-02

    The Bacillus subtilis glutamine synthetase (GS) plays a dual role in cell metabolism by functioning as catalyst and regulator. GS catalyses the ATP-dependent synthesis of glutamine from glutamate and ammonium. Under nitrogen-rich conditions, GS becomes feedback-inhibited by high intracellular glutamine levels and then binds transcription factors GlnR and TnrA, which control the genes of nitrogen assimilation. While GS-bound TnrA is no longer able to interact with DNA, GlnR-DNA binding is shown to be stimulated by GS complex formation. In this paper we show a new physiological feature of the interaction between glutamine synthetase and TnrA. The transcription factor TnrA inhibits the biosynthetic activity of glutamine synthetase in vivo and in vitro, while the GlnR protein does not affect the activity of the enzyme.

  20. In vitro reactivation of in vivo ammonium-inactivated glutamine synthetase from Synechocystis sp. PCC 6803.

    Science.gov (United States)

    Mérida, A; Candau, P; Florencio, F J

    1991-12-16

    Glutamine synthetase from Synechocystis sp. strain PCC 6803 is inactivated by ammonium addition to cells growing with nitrate as the nitrogen source. The enzyme can be reactivated in vitro by different methods such as alkaline phosphatase treatment, but not phosphodiesterase, by raising the pH of the crude extract to values higher than 8, by increasing the ionic strength of the cell-free extract, or by preincubation with organic solvents, such as 2-propanol and ethanol. These results suggest that the loss of glutamine synthetase activity promoted by ammonium involves the non-covalent binding of a phosphorylated compound to the enzyme and support previous results that rule out the existence of an adenylylation/deadenylylation system functioning in the regulation of cyanobacterial glutamine synthetase.

  1. Analysis of aggregation of platelets in thrombosis

    Science.gov (United States)

    Ahuja, Suresh

    Platelets are key players in thrombus formation by first rolling over collagen bound von Willebrand factor followed by formation of a stable interaction with collagen. The first adhered platelets bind additional platelets until the whole injury is sealed off by a platelet aggregate. The coagulation system stabilizes the formed platelet plug by creating a tight fibrin network, and then wound contraction takes place because of morphological changes in platelets. Coagulation takes place by platelet activation and aggregation mainly through fibrinogen polymerization into fibrin fibers. The process includes multiple factors, such as thrombin, plasmin, and local shear-rate which regulate and control the process. Coagulation can be divided into two pathways: the intrinsic pathway and the extrinsic pathway. The intrinsic pathway is initiated by the exposure of a negatively charged. It is able to activate factor XII, using a complex reaction that includes prekallikrein and high-molecular-weight kininogen as cofactors.. Thrombin is the final enzyme that is needed to convert fibrinogen into fibrin. The extrinsic pathway starts with the exposure of tissue factor to the circulating blood, which is the major initiator of coagulation. There are several feedback loops that reinforce the coagulation cascade, resulting in large amounts of thrombin. It is dependent on the presence of pro-coagulant surfaces of cells expressing negatively charged phospholipids--which include phosphatidylserine (PS)--on their outer membrane. PS-bearing surfaces are able to increase the efficiency of the reactions by concentrating and co-localizing coagulation factors.. Aggregation of platelets are analyzed and compared to adhesion of platelet to erythrocyte and to endothelial cells. This abstract is replacing MAR16-2015-020003.

  2. Archaeal RibL: a new FAD synthetase that is air sensitive.

    Science.gov (United States)

    Mashhadi, Zahra; Xu, Huimin; Grochowski, Laura L; White, Robert H

    2010-10-12

    FAD synthetases catalyze the transfer of the AMP portion of ATP to FMN to produce FAD and pyrophosphate (PP(i)). Monofunctional FAD synthetases exist in eukaryotes, while bacteria have bifunctional enzymes that catalyze both the phosphorylation of riboflavin and adenylation of FMN to produce FAD. Analyses of archaeal genomes did not reveal the presence of genes encoding either group, yet the archaea contain FAD. Our recent identification of a CTP-dependent archaeal riboflavin kinase strongly indicated the presence of a monofunctional FAD synthetase. Here we report the identification and characterization of an archaeal FAD synthetase. Methanocaldococcus jannaschii gene MJ1179 encodes a protein that is classified in the nucleotidyl transferase protein family and was previously annotated as glycerol-3-phosphate cytidylyltransferase (GCT). The MJ1179 gene was cloned and its protein product heterologously expressed in Escherichia coli. The resulting enzyme catalyzes the adenylation of FMN with ATP to produce FAD and PP(i). The MJ1179-derived protein has been designated RibL to indicate that it follows the riboflavin kinase (RibK) step in the archaeal FAD biosynthetic pathway. Aerobically isolated RibL is active only under reducing conditions. RibL was found to require divalent metals for activity, the best activity being observed with Co(2+), where the activity was 4 times greater than that with Mg(2+). Alkylation of the two conserved cysteines in the C-terminus of the protein resulted in complete inactivation. RibL was also found to catalyze cytidylation of FMN with CTP, making the modified FAD, flavin cytidine dinucleotide (FCD). Unlike other FAD synthetases, RibL does not catalyze the reverse reaction to produce FMN and ATP from FAD and PP(i). Also in contrast to other FAD synthetases, PP(i) inhibits the activity of RibL.

  3. The peculiar optical-UV X-ray spectra of the X-ray weak quasar PG 0043+039

    CERN Document Server

    Kollatschny, W; Zetzl, M; Santos-Lleó, M; Rodríguez-Pascual, P M; Ballo, L; Talavera, A

    2016-01-01

    The object PG 0043+039 has been identified as a broad absorption line (BAL) quasar based on its UV spectra. However, this optical luminous quasar has not been detected before in deep X-ray observations, making it the most extreme X-ray weak quasar known today. This study aims to detect PG 0043+039 in a deep X-ray exposure. The question is what causes the extreme X-ray weakness of PG 0043+039? Does PG 0043+039 show other spectral or continuum peculiarities? We took simultaneous deep X-ray spectra with XMM-Newton, far-ultraviolet (FUV) spectra with the Hubble Space Telescope (HST) and optical spectra of PG 0043+039 with the Hobby-Eberly Telescope (HET) and Southern African Large Telescope (SALT) in July, 2013. We have detected PG 0043+039 in our X-ray exposure taken in 2013. We presented our first results in a separate paper (Kollatschny et al. 2015). PG 0043+039 shows an extreme {\\alpha}_ox gradient ({\\alpha}_ox =-2.37). Furthermore, we were able to verify an X-ray flux of this source in a reanalysis of the X-...

  4. Evaluation of platelet function using multiple electrode platelet aggregometry in dogs with septic peritonitis.

    Science.gov (United States)

    Li, Ronald H L; Chan, Daniel L

    2016-09-01

    To assess platelet function via multiple electrode platelet aggregometry (MEPA) in dogs with septic peritonitis and in healthy dogs. The secondary aim was to determine if there is prognostic significance to changes in platelet function observed in septic dogs. Prospective, observational cohort study conducted from January 2012 to March 2014. University teaching hospital. Twenty dogs with septic peritonitis and 23 healthy dogs. None. MEPA using arachidonic acid, adenosine diphosphate, and collagen (COL) as agonists was measured within 24 hours of diagnosis of sepsis. Compared to healthy dogs, platelet aggregation was reduced in dogs with septic peritonitis for all agonists (P peritonitis. Circulating platelets from dogs with septic peritonitis have diminished aggregation in response to multiple platelet agonists. MEPA may serve as an assessment tool for illness severity in this patient population. © Veterinary Emergency and Critical Care Society 2016.

  5. [Glycoproteins, inherited diseases of platelets, and the role of platelets in wound healing].

    Science.gov (United States)

    Nurden, Alan T; Nurden, Paquita

    2013-02-01

    Recognition that platelets have a glycocalyx rich in membrane glycoproteins prompted the discovery in France that inherited bleeding syndromes due to defects of platelet adhesion and aggregation were caused by deficiencies in major receptors at the platelet surface. Identification of the alpha IIb beta3 integrin prompted the development of powerful anti-thrombotic drugs that have gained worldwide use. Since these discoveries, the genetic causes of many other defects of platelet function and production have been elucidated, with the identification of an ADP receptor, P2 Y12, another widespread target for anti-thrombotic drugs. Discovery of the molecular basis of a rare disease of storage of biologically active proteins in platelet alpha-granules has been accompanied by the recognition of the roles of platelets in inflammation, the innate immune system and tissue repair, opening new avenues for therapeutic advances.

  6. Decrease in platelet activating factor stimulated phosphoinositide turnover during storage of human platelets in plasma

    Energy Technology Data Exchange (ETDEWEB)

    Carter, M.G.; Shukla, S.D. (Univ. of Missouri School of Medicine, Columbia (USA))

    1987-05-01

    Human platelet concentrate from the American Red Cross Blood Center was stored at 24{degree}C in a shaker and aliquots were taken out at time intervals aseptically. Platelet activating factor (PAF) stimulated turnover of phosphoinositide (PPI) was monitored by assaying {sup 32}P incorporation into phosphoinositides using platelet rich plasma (PRP). Platelets in PRP were incubated with 1 {times} 10{sup {minus}7} M PAF at 37{degree}C with gentle shaking and after 5 min their lipids were extracted and analysed by TLC for {sup 32}P-phosphoinositides. The percent stimulation of {sup 32}P incorporation by PAF (over control) into PPI was approximately 250, 100, 60, 25 and 20 on days 1, 2, 3, 5 and 6, respectively. This indicated a dramatic decrease in PAF responsive turnover of platelet PPI during storage. These findings have important implications in relation to PAF receptor activity and viability of platelets at different periods of storage.

  7. Platelets: at the nexus of antimicrobial defence.

    Science.gov (United States)

    Yeaman, Michael R

    2014-06-01

    Platelets have traditionally been viewed as fragmentary mediators of coagulation. However, recent molecular and cellular evidence suggests that they have multiple roles in host defence against infection. From first-responders that detect pathogens and rapidly deploy host-defence peptides, to beacons that recruit and enhance leukocyte functions in the context of infection, to liaisons that facilitate the T cell-B cell crosstalk that is required in adaptive immunity, platelets represent a nexus at the intersection of haemostasis and antimicrobial host defence. In this Review, I consider recent insights into the antimicrobial roles of platelets, which are mediated both directly and indirectly to integrate innate and adaptive immune responses to pathogens.

  8. Transcellular lipoxygenase metabolism between monocytes and platelets

    Energy Technology Data Exchange (ETDEWEB)

    Bigby, T.D.; Meslier, N. (Univ. of California, San Francisco (USA))

    1989-09-15

    We have examined the effects of co-culture and in vitro co-stimulation on lipoxygenase metabolism in monocytes and platelets. Monocytes were obtained from the peripheral blood of normal volunteers by discontinuous gradient centrifugation and adherence to tissue culture plastic. Platelets were obtained from the platelet-rich plasma of the same donor. When 10(9) platelets and 2.5 x 10(6) monocytes were co-stimulated with 1 microM A23187, these preparations released greater quantities of 12(S)-hydroxy-10-trans-5,8,14-cis-eicosatetraenoic acid, 5(S),12-(S)dihydroxy-6,10-trans-8,14-cis-eicosatetraenoic acid, and leukotriene C4, 5(S)-hydroxy-6(R)-S-glutathionyl-7,9-trans-11,14-cis-eicosatetraenoic (LTC4) when compared with monocytes alone. Release of arachidonic acid, 5-HETE, delta 6-trans-LTB4, and delta 6-trans-12-epi-LTB4 from monocytes was decreased in the presence of platelets. A dose-response curve was constructed and revealed that the above changes became evident when the platelet number exceeded 10(7). Dual radiolabeling experiments with 3H- and 14C-arachidonic acid revealed that monocytes provided arachidonic acid, 5-HETE, and LTA4 for further metabolism by the platelet. Monocytes did not metabolize platelet intermediates detectably. In addition, as much as 1.2 microM 12(S)-hydroxy-10-trans-5,8,14-cis-eicosatetraenoic acid and 12(S)-hydroperoxy-10-trans-5,8,14-cis-eicosatetraenoic acid had no effect on monocyte lipoxygenase metabolism. Platelets were capable of converting LTA4 to LTC4, but conversion of LTA4 to LTB4 was not detected. We conclude that the monocyte and platelet lipoxygenase pathways undergo a transcellular lipoxygenase interaction that differs from the interaction of the neutrophil and platelet lipoxygenase pathways. In this interaction monocytes provide intermediate substrates for further metabolic conversion by platelets in an unidirectional manner.

  9. The Chicxulub impact at the K-Pg boundary - search for traces of the projectile

    Science.gov (United States)

    Deutsch, A.

    2012-04-01

    One of the most interesting problems in the context of the end-Cretaceous Chicxulub impact is the question after the whererabouts of the main mass of the projectile. The nature of this >10 km-sized Chicxulub projectile was constrained by an anomaly in the chromium isotope 54 in the K-Pg deposit at Stevens Klint, Denmark, to a carbonaceous chondrite of type CM2 [1]. About 1.5 % of the estimated mass of the projectile has been detected world-wide in the K-Pg boundary layer; mainly in the form of platinum group elements (PGE) as well as other siderophile elements (Ni, Co ... ). A contamination by or even a major contribution of other "projectile" elements to the K-Pg event bed was rarely proposed. The few examples in the literature (cf. compilation in [2, 3]) used rare earth elements (REE) distribution patterns that are slightly inconsistent with REE patterns typical for the upper continental crust (UCC). Ejecta consisting of UCC target rocks is expected to form the overwhelming mass of the ejecta. In most K-Pg layers, however, the ejecta is diluted or even totally masked by a component of more local origin and with features of high-energy deposition mechanisms. Numerical models [4] indicate a deposition of >500km3 projectile material, corresponding to >2 x 10exp9 tons of mainly silica, iron, and magnesium in the K-Pg event bed. Detecting the "meteoritic" origin of these major elements, however, in a matrix of siliceous detritus, is practically impossible. Recent LA-ICP-MS analyses show that siliceous impact spherules - hydrated glass or altered to chlorite - in the Chicxulub event bed at various locations (e.g., Shell Creek, La Lajilla, La Popa) have REE patterns that are flat and un-fractionated, corresponding quite well to a typical CI-pattern. The REE abundances are chondritic to sub-chondritic. Mixing calculations indicate that the maximum REE contribution of UCC material to the REE budget of these spherules is on the order of 2 %, but usually much less. These

  10. Flow cytometric assessment of activation of peripheral blood platelets in dogs with normal platelet count and asymptomatic thrombocytopenia.

    Science.gov (United States)

    Żmigrodzka, M; Guzera, M; Winnicka, A

    2016-01-01

    Platelets play a crucial role in hemostasis. Their activation has not yet been evaluated in healthy dogs with a normal and low platelet count. The aim of this study was to determine the influence of activators on platelet activation in dogs with a normal platelet count and asymptomatic thrombocytopenia. 72 clinically healthy dogs were enrolled. Patients were allocated into three groups. Group 1 consisted of 30 dogs with a normal platelet count, group 2 included 22 dogs with a platelet count between 100 and 200×109/l and group 3 consisted of 20 dogs with a platelet count lower than 100×109/l. Platelet rich-plasma (PRP) was obtained from peripheral blood samples using tripotassium ethylenediaminetetraacetic acid (K3-EDTA) as anticoagulant. Next, platelets were stimulated using phorbol-12-myristate-13-acetate or thrombin, stabilized using procaine or left unstimulated. The expression of CD51 and CD41/CD61 was evaluated. Co-expression of CD41/CD61 and Annexin V served as a marker of platelet activation. The expression of CD41/CD61 and CD51 did not differ between the 3 groups. Thrombin-stimulated platelets had a significantly higher activity in dogs with a normal platelet count than in dogs with asymptomatic thrombocytopenia. Procaine inhibited platelet activity in all groups. In conclusion, activation of platelets of healthy dogs in vitro varied depending on the platelet count and platelet activator.

  11. Sequence determination and modeling of structural motifs for the smallest monomeric aminoacyl-tRNA synthetase.

    OpenAIRE

    Hou, Y M; Shiba, K; Mottes, C; Schimmel, P.

    1991-01-01

    Polypeptide chains of 19 previously studied Escherichia coli aminoacyl-tRNA synthetases are as large as 951 amino acids and, depending on the enzyme, have quaternary structures of alpha, alpha 2, alpha 2 beta 2, and alpha 4. These enzymes have been organized into two classes which are defined by sequence motifs that are associated with specific three-dimensional structures. We isolated, cloned, and sequenced the previously uncharacterized gene for E. coli cysteine-tRNA synthetase (EC 6.1.1.16...

  12. Phosphoribosylpyrophosphate synthetase of Escherichia coli, Identification of a mutant enzyme

    DEFF Research Database (Denmark)

    Hove-Jensen, Bjarne; Nygaard, Per

    1982-01-01

    From an Escherichia coli purine auxotroph a mutant defective in phosphoribosylpyrophosphate (PRib-PP) synthetase has been isolated and partially characterized. In contrast to the parental strain, the mutant was able to grow on nucleosides as purine source, whereas growth on purine bases was reduced......, stimulated the mutant enzyme. The activity of PRib-PP synthetase in crude extract was higher in the mutant than in the parent. When starved for purines an accumulation of PRib-PP was observed in the parent strain, while the pool decreased in the mutant. During pyrimidine starvation derepression of PRib...

  13. Reduced activity of glutamine synthetase in Rhodospirillum rubrum mutants lacking the adenylyltransferase GlnE.

    Science.gov (United States)

    Jonsson, Anders; Nordlund, Stefan; Teixeira, Pedro Filipe

    2009-10-01

    In the nitrogen-fixing bacterium Rhodospirillum rubrum, the GlnE adenylyltransferase (encoded by glnE) catalyzes reversible adenylylation of glutamine synthetase, thereby regulating nitrogen assimilation. We have generated glnE mutant strains that are unable to adenylylate glutamine synthetase (GS). Surprisingly, the activity of GS was lower in the mutants than in the wild type, even when grown in nitrogen-fixing conditions. Our results support the proposal that R. rubrum can only cope with the absence of an adenylylation system in the presence of lowered GS expression or activity. In general terms, this report also provides further support for the central role of GS in bacterial metabolism.

  14. An archaeal tRNA-synthetase complex that enhances aminoacylation under extreme conditions

    DEFF Research Database (Denmark)

    Godinic-Mikulcic, Vlatka; Jaric, Jelena; Hausmann, Corinne D;

    2011-01-01

    Aminoacyl-tRNA synthetases (aaRSs) play an integral role in protein synthesis, functioning to attach the correct amino acid with its cognate tRNA molecule. AaRSs are known to associate into higher-order multi-aminoacyl-tRNA synthetase complexes (MSC) involved in archaeal and eukaryotic translation...... in the catalytic efficiency of serine attachment to tRNA, but had no effect on the activity of MtArgRS. Further, the most pronounced improvements in the aminoacylation activity of MtSerRS induced by MtArgRS were observed under conditions of elevated temperature and osmolarity. These data indicate that formation...

  15. Truncated FAD synthetase for direct biocatalytic conversion of riboflavin and analogs to their corresponding flavin mononucleotides.

    Science.gov (United States)

    Iamurri, Samantha M; Daugherty, Ashley B; Edmondson, Dale E; Lutz, Stefan

    2013-12-01

    The preparation of flavin mononucleotide (FMN) and FMN analogs from their corresponding riboflavin precursors is traditionally performed in a two-step procedure. After initial enzymatic conversion of riboflavin to flavin adenine dinucleotide (FAD) by a bifunctional FAD synthetase, the adenyl moiety of FAD is hydrolyzed with snake venom phosphodiesterase to yield FMN. To simplify the protocol, we have engineered the FAD synthetase from Corynebacterium ammoniagenes by deleting its N-terminal adenylation domain. The newly created biocatalyst is stable and efficient for direct and quantitative phosphorylation of riboflavin and riboflavin analogs to their corresponding FMN cofactors at preparative-scale.

  16. Crystal structure of yeast FAD synthetase (Fad1) in complex with FAD.

    Science.gov (United States)

    Leulliot, Nicolas; Blondeau, Karine; Keller, Jenny; Ulryck, Nathalie; Quevillon-Cheruel, Sophie; van Tilbeurgh, Herman

    2010-05-21

    Flavin adenine dinucleotide (FAD) synthetase is an essential enzyme responsible for the synthesis of FAD by adenylation of riboflavin monophosphate (FMN). We have solved the 1.9 A resolution structure of Fad1, the yeast FAD synthetase, in complex with the FAD product in the active site. The structure of Fad1 shows it to be a member of the PP-ATPase superfamily. Important conformational differences in the two motifs involved in binding the phosphate moieties of FAD compared to the Candida glabrata FMNT ortholog suggests that this loop is dynamic and undergoes substantial conformational changes during its catalytic cycle.

  17. PgLOX6 encoding a lipoxygenase contributes to jasmonic acid biosynthesis and ginsenoside production in Panax ginseng

    Science.gov (United States)

    Rahimi, Shadi; Kim, Yu-Jin; Sukweenadhi, Johan; Zhang, Dabing; Yang, Deok-Chun

    2016-01-01

    Ginsenosides, the valuable pharmaceutical compounds in Panax ginseng, are triterpene saponins that occur mainly in ginseng plants. It was shown that in vitro treatment with the phytohormone jasmonic acid (JA) is able to increase ginsenoside production in ginseng plants. To understand the molecular link between JA biosynthesis and ginsenoside biosynthesis, we identified a JA biosynthetic 13-lipoxygenase gene (PgLOX6) in P. ginseng that promotes ginsenoside production. The expression of PgLOX6 was high in vascular bundles, which corresponds with expression of ginsenoside biosynthetic genes. Consistent with the role of PgLOX6 in synthesizing JA and promoting ginsenoside synthesis, transgenic plants overexpressing PgLOX6 in Arabidopsis had increased amounts of JA and methyl jasmonate (MJ), increased expression of triterpene biosynthetic genes such as squalene synthase (AtSS1) and squalene epoxidase (AtSE1), and increased squalene content. Moreover, transgenic ginseng roots overexpressing PgLOX6 had around 1.4-fold increased ginsenoside content and upregulation of ginsenoside biosynthesis-related genes including PgSS1, PgSE1, and dammarenediol synthase (PgDDS), which is similar to that of treatment with MJ. However, MJ treatment of transgenic ginseng significantly enhanced JA and MJ, associated with a 2.8-fold increase of ginsenoside content compared with the non-treated, non-transgenic control plant, which was 1.4 times higher than the MJ treatment effect on non-transgenic plants. These results demonstrate that PgLOX6 is responsible for the biosynthesis of JA and promotion of the production of triterpenoid saponin through up-regulating the expression of ginsenoside biosynthetic genes. This work provides insight into the role of JA in biosynthesizing secondary metabolites and provides a molecular tool for increasing ginsenoside production. PMID:27811076

  18. Induction and Synchronization of Estrus in Gilts with P.G.600

    Directory of Open Access Journals (Sweden)

    Ion Valeriu Caraba

    2014-11-01

    Full Text Available Normal 0 false false false EN-US X-NONE X-NONE MicrosoftInternetExplorer4 Recent developments in understanding the physiological mechanisms of reproduction control can be adapted to swine reproductive management. This article points out the procedures that can be used to induce estrus, in pre-pubescent and anestrus gilts, and heat synchronization. For estrus induction and heat synchronization, we used P.G. 600 commercial product (400 IU of PMSG and 200 IU of hCG, Intervet, Millsboro, DE. A total of 36 gilts, from Large White breed, were used, divided in two lots: pre-pubescent gilts (5months of age, no = 19 and gilts in anestrus (8 months of age, no = 17. The efficacy of hormonal P.G. 600 product was different for the two lots. Estrus manifestation rate was different between lots 73.68% of pre-pubescent gilts compared with 76.47% of anestrus gilts. The use of P.G. 600 hormonal product is effective in inducing and synchronizing estrus in gilts. /* Style Definitions */ table.MsoNormalTable {mso-style-name:"Table Normal"; mso-tstyle-rowband-size:0; mso-tstyle-colband-size:0; mso-style-noshow:yes; mso-style-priority:99; mso-style-qformat:yes; mso-style-parent:""; mso-padding-alt:0cm 5.4pt 0cm 5.4pt; mso-para-margin:0cm; mso-para-margin-bottom:.0001pt; mso-pagination:widow-orphan; font-size:11.0pt; font-family:"Calibri","sans-serif"; mso-ascii-font-family:Calibri; mso-ascii-theme-font:minor-latin; mso-fareast-font-family:"Times New Roman"; mso-fareast-theme-font:minor-fareast; mso-hansi-font-family:Calibri; mso-hansi-theme-font:minor-latin; mso-bidi-font-family:"Times New Roman"; mso-bidi-theme-font:minor-bidi;}

  19. The far-ultraviolet spectra of two hot PG 1159 stars

    Science.gov (United States)

    Werner, K.; Rauch, T.; Kruk, J. W.

    2016-09-01

    PG 1159 stars are hot, hydrogen-deficient (pre-) white dwarfs with atmospheres mainly composed of helium, carbon, and oxygen. The unusual surface chemistry is the result of a late helium-shell flash. Observed element abundances enable us to test stellar evolution models quantitatively with respect to their nucleosynthesis products formed near the helium-burning shell of the progenitor asymptotic giant branch stars. Because of the high effective temperatures (Teff), abundance determinations require ultraviolet spectroscopy and non-local thermodynamic equilibrium model atmosphere analyses. Up to now, we have presented results for the prototype of this spectral class and two cooler members (Teff in the range 85 000-140 000 K). Here we report on the results for two even hotter stars (PG 1520+525 and PG 1144+005, both with Teff = 150 000 K) which are the only two objects in this temperature-gravity region for which useful far-ultraviolet spectra are available, and revisit the prototype star. Previous results on the abundances of some species are confirmed, while results on others (Si, P, S) are revised. In particular, a solar abundance of sulphur is measured in contrast to earlier claims of a strong S deficiency that contradicted stellar evolution models. For the first time, we assess the abundances of Na, Al, and Cl with newly constructed non-LTE model atoms. Besides the main constituents (He, C, O), we determine the abundances (or upper limits) of N, F, Ne, Na, Al, Si, P, S, Cl, Ar, and Fe. Generally, good agreement with stellar models is found.

  20. Mass extinction of birds at the Cretaceous–Paleogene (K–Pg) boundary

    Science.gov (United States)

    Longrich, Nicholas R.; Tokaryk, Tim; Field, Daniel J.

    2011-01-01

    The effect of the Cretaceous-Paleogene (K-Pg) (formerly Cretaceous–Tertiary, K–T) mass extinction on avian evolution is debated, primarily because of the poor fossil record of Late Cretaceous birds. In particular, it remains unclear whether archaic birds became extinct gradually over the course of the Cretaceous or whether they remained diverse up to the end of the Cretaceous and perished in the K–Pg mass extinction. Here, we describe a diverse avifauna from the latest Maastrichtian of western North America, which provides definitive evidence for the persistence of a range of archaic birds to within 300,000 y of the K–Pg boundary. A total of 17 species are identified, including 7 species of archaic bird, representing Enantiornithes, Ichthyornithes, Hesperornithes, and an Apsaravis-like bird. None of these groups are known to survive into the Paleogene, and their persistence into the latest Maastrichtian therefore provides strong evidence for a mass extinction of archaic birds coinciding with the Chicxulub asteroid impact. Most of the birds described here represent advanced ornithurines, showing that a major radiation of Ornithurae preceded the end of the Cretaceous, but none can be definitively referred to the Neornithes. This avifauna is the most diverse known from the Late Cretaceous, and although size disparity is lower than in modern birds, the assemblage includes both smaller forms and some of the largest volant birds known from the Mesozoic, emphasizing the degree to which avian diversification had proceeded by the end of the age of dinosaurs. PMID:21914849

  1. Pathogen-Reduced, Extended Platelet Storage in Platelet Additive Solution (PAS)

    Science.gov (United States)

    2016-10-01

    concentrations will be performed to ensure the desired concentration was achieved. Platelet Additive Solutions are isotonic solutions used to replace a...Sherrill J. Slichter, MD CONTRACTING ORGANIZATION: Bloodworks Northwest Seattle, WA 98104 REPORT DATE: October 2016 TYPE OF REPORT: Annual...TITLE AND SUBTITLE Pathogen-Reduced, Extended Platelet Storage in Platelet Additive Solution (PAS) 5a. CONTRACT NUMBER W81XWH-12-1-0441 5b. GRANT

  2. Xanthohumol, a Prenylated Flavonoid from Hops (Humulus lupulus), Prevents Platelet Activation in Human Platelets

    OpenAIRE

    Ye-Ming Lee; Kuo-Hsien Hsieh; Wan-Jung Lu; Hsiu-Chu Chou; Duen-Suey Chou; Li-Ming Lien; Joen-Rong Sheu; Kuan-Hung Lin

    2012-01-01

    Xanthohumol is the principal prenylated flavonoid in the hop plant (Humulus lupulus L.). Xanthohumol was found to be a very potent cancer chemopreventive agent through regulation of diverse mechanisms. However, no data are available concerning the effects of xanthohumol on platelet activation. The aim of this paper was to examine the antiplatelet effect of xanthohumol in washed human platelets. In the present paper, xanthohumol exhibited more-potent activity in inhibiting platelet aggregation...

  3. Platelet Lysates Produced from Expired Platelet Concentrates Support Growth and Osteogenic Differentiation of Mesenchymal Stem Cells

    OpenAIRE

    Sandra Mjoll Jonsdottir-Buch; Ramona Lieder; Olafur Eysteinn Sigurjonsson

    2013-01-01

    BACKGROUND: Mesenchymal stem cells are promising candidates in regenerative cell therapy. Conventional culture methods involve the use of animal substances, specifically fetal bovine serum as growth supplement. Since the use of animal-derived products is undesirable for human applications, platelet lysates produced from human platelets are an attractive alternative. This is especially true if platelet lysates from already approved transfusion units at blood banks can be utilized. The purpose ...

  4. Revascularization of Immature Necrotic Teeth: Platelet rich Fibrin an Edge over Platelet rich Plasma

    OpenAIRE

    Neelam Mittal; Isha Narang

    2012-01-01

    Introduction: Revascularization is one such entity that has found its clinical application in the field of endodontics for the manage-ment of immature permanent necrotic teeth. The protocols for revascularization of such teeth focus especially on delivery of stem cells and scaffolds in a nonsurgical manner rather than concentrated growth micro molecules.The hypothesis: This article proposes the role of platelet concentrates such as platelet rich fibrin (PRF) and platelet rich plasma (PRP) in ...

  5. Platelet lipidomics: a modern day perspective on lipid discovery and characterization in platelets

    OpenAIRE

    O’Donnell, Valerie B.; Murphy, Robert C.; Watson, Steve P.

    2014-01-01

    Lipids are diverse families of biomolecules that perform essential structural and signaling roles in platelets. Their formation and metabolism is tightly controlled by enzymes and signal transduction pathways, and their dysregulation leads to significant defects in platelet function and disease. Platelet activation is associated with significant changes to membrane lipids, and formation of diverse bioactive lipids that play essential roles in hemostasis. In recent years, new generation mass s...

  6. Platelet-rich fibrin matrix for facial plastic surgery.

    Science.gov (United States)

    Sclafani, Anthony P; Saman, Masoud

    2012-05-01

    Platelets are known primarily for their role in hemostasis, but there is increasing interest in the effect of platelets on wound healing. Platelet isolates such as platelet-rich plasma have been advocated to enhance and accelerate wound healing. This article describes the use of a novel preparation, platelet-rich fibrin matrix (PRFM), for facial plastic surgery applications such as volume augmentation, fat transfer supplementation, and as an adjunct to open surgical procedures.

  7. Platelet interaction with bacterial toxins and secreted products.

    Science.gov (United States)

    Shannon, Oonagh

    2015-01-01

    Bacteria that enter the bloodstream will encounter components of the cellular and soluble immune response. Platelets contribute to this response and have emerged as an important target for bacterial pathogens. Bacteria produce diverse extracellular proteins and toxins that have been reported to modulate platelet function. These interactions can result in complete or incomplete platelet activation or inhibition of platelet activation, depending on the bacteria and bacterial product. The nature of the platelet response may be highly relevant to disease pathogenesis.

  8. Evaluation of platelet thromboxane radioimmunoassay method to measure platelet life-span: Comparison with /sup 111/indium-platelet method

    Energy Technology Data Exchange (ETDEWEB)

    Vallabhajosula, S.; Machac, J.; Badimon, L.; Lipszyc, H.; Goldsmith, S.J.; Fuster, V.

    1985-05-01

    The platelet activation during radiolabeling in vitro with Cr-51 and In-111 may affect the platelet life-span (PLS) in vivo. A new RIA method to measure PLS is being evaluated. Aspirin inhibits platelet thromboxane (TxA/sub 2/) by acetylating cyclooxygenase. The time required for the TxA/sub 2/ levels to return towards control values depends on the rate of new platelets entering circulation and is a measure of PLS. A single dose of aspirin (150mg) was given to 5 normal human subjects. Blood samples were collected for 2 days before aspirin and daily for 10 days. TxA/sub 2/ production in response to endogenous thrombin was studied by allowing 1 ml blood sample to clot at 37/sup 0/C for 90 min. Serum TxB/sub 2/ (stable breakdown product of Tx-A/sub 2/) levels determined by RIA technique. The plot of TxB/sub 2/ levels (% control) against time showed a gradual increase. The PLS calculated by linear regression analysis assuming a 2-day lag period before cyclooxygenase recovery is 9.7 +- 2.37. In the same 5 subjects, platelets from a 50ml blood sample were labeled with /sup 111/In-tropolone in 2 ml autologous plasma. Starting at 1 hr after injection of labeled platelets, 10 blood samples were obtained over a 8 day period. The PLS calculated based on a linear regression analysis is 10.2 +. 1.4. The PLS measured from the rate of platelet disappearance from circulation and the rate of platelet regeneration into circulation are quite comparable in normal subjects. TxA/sub 2/ regeneration RIA may provide a method to measure PLS without administering radioactivity to patient.

  9. Correlation of exon 3 β-catenin mutations with glutamine synthetase staining patterns in hepatocellular adenoma and hepatocellular carcinoma.

    Science.gov (United States)

    Hale, Gillian; Liu, Xinxin; Hu, Junjie; Xu, Zhong; Che, Li; Solomon, David; Tsokos, Christos; Shafizadeh, Nafis; Chen, Xin; Gill, Ryan; Kakar, Sanjay

    2016-11-01

    The current clinical practice is based on the assumption of strong correlation between diffuse glutamine synthetase expression and β-catenin activation in hepatocellular adenoma and hepatocellular carcinoma. This high correlation is based on limited data and may represent an oversimplification as glutamine synthetase staining patterns show wide variability in clinical practice. Standardized criteria for interpreting diverse glutamine synthetase patterns, and the association between each pattern and β-catenin mutations is not clearly established. This study examines the correlation between glutamine synthetase staining patterns and β-catenin mutations in 15 typical hepatocellular adenomas, 5 atypical hepatocellular neoplasms and 60 hepatocellular carcinomas. Glutamine synthetase staining was classified into one of the three patterns: (a) diffuse homogeneous: moderate-to-strong cytoplasmic staining in >90% of lesional cells, without a map-like pattern, (b) diffuse heterogeneous: moderate-to-strong staining in 50-90% of lesional cells, without a map-like pattern, and (c) patchy: moderate-to-strong staining in glutamine synthetase staining (homogeneous or heterogeneous), an exon 3 β-catenin mutation was detected in 33% (2/6) of typical hepatocellular adenoma, 75% (3/4) of atypical hepatocellular neoplasm and 17% (8/47) of hepatocellular carcinomas. An exon 3 mutation was also observed in 15% (2/13) of hepatocellular carcinomas with patchy glutamine synthetase staining. The results show a modest correlation between diffuse glutamine synthetase immunostaining and exon 3 β-catenin mutations in hepatocellular adenoma and hepatocellular carcinoma with discrepancy rates >50% in both hepatocellular adenoma and hepatocellular carcinoma. The interpretation of β-catenin activation based on glutamine synthetase staining should be performed with caution, and the undetermined significance of various glutamine synthetase patterns should be highlighted in pathology reports.

  10. Single-step separation of platelets from whole blood coupled with digital quantification by interfacial platelet cytometry (iPC).

    Science.gov (United States)

    Basabe-Desmonts, L; Ramstrom, S; Meade, G; O'Neill, S; Riaz, A; Lee, L P; Ricco, A J; Kenny, D

    2010-09-21

    We report the efficient single-step separation of individual platelets from unprocessed whole blood, enabling digital quantification of platelet function using interfacial platelet cytometry (iPC) on a chip. iPC is accomplished by the precision micropatterning of platelet-specific protein surfaces on solid substrates. By separating platelets from whole blood using specific binding to protein spots of a defined size, iPC implements a simple incubate-and-rinse approach, without sample preparation, that enables (1) the study of platelets in the physiological situation of interaction with a protein surface, (2) the choice of the number of platelets bound on each protein spot, from one to many, (3) control of the platelet-platelet distance, including the possibility to study noninteracting single platelets, (4) digital quantification (counting) of platelet adhesion to selected protein matrices, enabling statistical characterization of platelet subpopulations from meaningfully large numbers of single platelets, (5) the study of platelet receptor expression and spatial distribution, and (6) a detailed study of the morphology of isolated single platelets at activation levels that can be manipulated. To date, we have demonstrated 1-4 of the above list. Platelets were separated from whole blood using iPC with fibrinogen, von Willebrand factor (VWF), and anti-CD42b antibody printed "spots" ranging from a fraction of one to several platelet diameters (2-24 μm). The number of platelets captured per spot depends strongly on the protein matrix and the surface area of the spot, together with the platelet volume, morphology, and activation state. Blood samples from healthy donors, a May-Hegglin-anomaly patient, and a Glanzmann's Thrombasthenia patient were analyzed via iPC to confirm the specificity of the interaction between protein matrices and platelets. For example, the results indicate that platelets interact with fibrinogen spots only through the fibrinogen receptor (

  11. Metal abundances in PG1159 stars from Chandra and FUSE spectroscopy

    CERN Document Server

    Werner, K; Dreizler, S; Rauch, T; Barstow, M A; Kruk, J W

    2002-01-01

    We investigate FUSE spectra of three PG1159 stars and do not find any evidence for iron lines. From a comparison with NLTE models we conclude a deficiency of 1-1.5 dex. We speculate that iron was transformed into heavier elements. A soft X-ray Chandra spectrum of the unique H- and He-deficient star H1504+65 is analyzed. We find high neon and magnesium abundances and confirm that H1504+65 is the bare core of either a C-O or a O-Ne-Mg white dwarf.

  12. OPTIMIZATION OF MANNANASE PRODUCTION FROM STREPTOMYCES SP. PG-08-03 IN SUBMERGED FERMENTATION

    Directory of Open Access Journals (Sweden)

    Preeti Bhoria

    Full Text Available Streptomyces sp. PG-08-3 was isolated from the desert of Rajasthan (India. The organism produced mannanase (15 Umg-1 protein in the presence of 0.5% guar gum as a sole carbon source in minimal media by submerged fermentation (SmF. Enzyme production was enhanced by 7.3-fold when 0.5% soyabean meal and 0.25% of leucine were added to the minimal media. Increasing the guar gum concentration in the media by 0.1-1.0% resulted in linearly enhanced the production of mannanase.

  13. Line partitions of internal points to a conic in PG(2,q)

    OpenAIRE

    2006-01-01

    All sets of lines providing a partition of the set of internal points to a conic C in PG(2,q), q odd, are determined. There exist only three such linesets up to projectivities, namely the set of all nontangent lines to C through an external point to C, the set of all nontangent lines to C through a point in C, and, for square q, the set of all nontangent lines to C belonging to a Baer subplane with at least 5 common points with C. This classification theorem is the analogous of a classical re...

  14. VERITAS OBSERVATIONS OF THE BL LAC OBJECT PG 1553+113

    Energy Technology Data Exchange (ETDEWEB)

    Aliu, E. [Department of Physics and Astronomy, Barnard College, Columbia University, NY 10027 (United States); Archer, A.; Beilicke, M.; Buckley, J. H.; Bugaev, V. [Department of Physics, Washington University, St. Louis, MO 63130 (United States); Aune, T. [Department of Physics and Astronomy, University of California, Los Angeles, CA 90095 (United States); Barnacka, A. [Harvard-Smithsonian Center for Astrophysics, 60 Garden Street, Cambridge, MA 02138 (United States); Behera, B.; Chen, X. [DESY, Platanenallee 6, 15738 Zeuthen (Germany); Benbow, W.; Cerruti, M. [Fred Lawrence Whipple Observatory, Harvard-Smithsonian Center for Astrophysics, Amado, AZ 85645 (United States); Berger, K. [Department of Physics and Astronomy and the Bartol Research Institute, University of Delaware, Newark, DE 19716 (United States); Bird, R. [School of Physics, University College Dublin, Belfield, Dublin 4 (Ireland); Byrum, K. [Argonne National Laboratory, 9700 South Cass Avenue, Argonne, IL 60439 (United States); Cardenzana, J. V; Dickinson, H. J. [Department of Physics and Astronomy, Iowa State University, Ames, IA 50011 (United States); Ciupik, L. [Astronomy Department, Adler Planetarium and Astronomy Museum, Chicago, IL 60605 (United States); Connolly, M. P. [School of Physics, National University of Ireland Galway, University Road, Galway (Ireland); Cui, W. [Department of Physics and Astronomy, Purdue University, West Lafayette, IN 47907 (United States); Dumm, J. [School of Physics and Astronomy, University of Minnesota, Minneapolis, MN 55455 (United States); and others

    2015-01-20

    We present results from VERITAS observations of the BL Lac object PG 1553+113 spanning the years 2010, 2011, and 2012. The time-averaged spectrum, measured between 160 and 560 GeV, is well described by a power law with a spectral index of 4.33 ± 0.09. The time-averaged integral flux above 200 GeV measured for this period was (1.69 ± 0.06) × 10{sup –11} photons cm{sup –2} s{sup –1}, corresponding to 6.9% of the Crab Nebula flux. We also present the combined γ-ray spectrum from the Fermi Large Area Telescope and VERITAS covering an energy range from 100 MeV to 560 GeV. The data are well fit by a power law with an exponential cutoff at 101.9 ± 3.2 GeV. The origin of the cutoff could be intrinsic to PG 1553+113 or be due to the γ-ray opacity of our universe through pair production off the extragalactic background light (EBL). Given lower limits to the redshift of z > 0.395 based on optical/UV observations of PG 1553+113, the cutoff would be dominated by EBL absorption. Conversely, the small statistical uncertainties of the VERITAS energy spectrum have allowed us to provide a robust upper limit on the redshift of PG 1553+113 of z ≤ 0.62. A strongly elevated mean flux of (2.50 ± 0.14) × 10{sup –11} photons cm{sup –2} s{sup –1} (10.3% of the Crab Nebula flux) was observed during 2012, with the daily flux reaching as high as (4.44±0.71)×10{sup −11} photons cm{sup −2} s{sup −1} (18.3% of the Crab Nebula flux) on MJD 56048. The light curve measured during the 2012 observing season is marginally inconsistent with a steady flux, giving a χ{sup 2} probability for a steady flux of 0.03%.

  15. A proof of the linearity conjecture for k-blocking sets in PG(n, p3), p prime

    CERN Document Server

    Lavrauw, Michel; Van de Voorde, Geertrui

    2012-01-01

    In this paper, we show that a small minimal k-blocking set in PG(n, q3), q = p^h, h >= 1, p prime, p >=7, intersecting every (n-k)-space in 1 (mod q) points, is linear. As a corollary, this result shows that all small minimal k-blocking sets in PG(n, p^3), p prime, p >=7, are Fp-linear, proving the linearity conjecture (see [7]) in the case PG(n, p3), p prime, p >= 7.

  16. Thrombopoietin induces p-selectin expression on platelets and subsequent platelet/leukocyte interactions.

    Science.gov (United States)

    Tibbles, Heather E; Navara, Christopher S; Hupke, Michael A; Vassilev, Alexei O; Uckun, Fatih M

    2002-04-12

    Ligation of thrombopoietin (TPO) to the platelet c-Mpl receptor induces numerous biochemical pathways in the absence of aggregation. Two forms of recombinant TPO are currently in clinical trials for the treatment of thrombocytopenia. This study focuses on the effects of the full-length recombinant human TPO (rhTPO) on platelets in a whole blood system. Platelet-leukocyte associations (PLAs) were visualized following rhTPO stimulation as CD42b/CD 45 double positive clusters by FACS analysis. Treatment of washed platelets with rhTPO induced granule release and expression of the leukocyte adhesion receptor P-selectin (CD 62P) in the absence of aggregation and calcium mobilization. RhTPO also induced platelet-leukocyte interactions in whole blood. Following stimulation, leukocytes were recruited by platelets through P-selectin in a calcium-dependent manner. rhTPO stimulates platelet-leukocyte associations in whole blood through expression of platelet P-selectin. To our knowledge, this is the first report that identifies TPO as a promoter of platelet-leukocyte interactions.

  17. Platelets and erythrocyte-bound platelets bind infectious HIV-1 in plasma of chronically infected patients.

    Science.gov (United States)

    Beck, Zoltan; Jagodzinski, Linda L; Eller, Michael A; Thelian, Doris; Matyas, Gary R; Kunz, Anjali N; Alving, Carl R

    2013-01-01

    Chronic HIV-1 infection is associated with persistent viremia in most patients, but it remains unclear how free virus may survive the potential hostile effects of plasma. We investigated whether sites might exist on the surfaces of circulating blood cells for protection of infectious HIV-1 particles. Red blood cells (RBC) either from blood of uninfected normal individuals, or from blood obtained without EDTA from chronically infected HIV-1 patients, invariably contained a small number of RBC having attached platelets as determined by flow cytometry, light microscopy, and immunofluorescence microscopy. After mixing normal RBC with platelet-rich plasma, discrete populations of RBC, platelets, and complexes of platelets attached to RBC were purified by fluorescence-activated cell sorting. Upon incubation of purified cells or platelets with HIV-1 followed by washing and co-incubation with CD4-positive peripheral blood mononuclear cells (PBMC), platelets, and platelet-RBC complexes, but not platelet-free RBC, caused infection of PBMC. Infection was prevented by pre-treating the platelet-RBC complexes with EDTA. Plasma and RBC (comprising a RBC/platelet-RBC mixture) from chronically infected patients with low viral loads were also co-incubated with PBMC ex vivo to determine the presence of infectious HIV-1. All freshly isolated plasmas from the HIV-1-infected donors, obtained in the absence of anticoagulant, were noninfectious. Interestingly, the RBC from most of the patients caused cell-cell infection of PBMC that was prevented by stripping the RBC with EDTA. A monoclonal antibody to DC-SIGN partially inhibited cell-cell HIV-1 infection of PBMC by normal RBC pre-incubated with platelets and HIV-1. We conclude: (a) platelet-free EDTA-free plasma from chronically infected HIV-1 patients, although containing viral RNA, is an environment that lacks detectable infectious HIV-1; (b) platelets and platelet-RBC complexes, but not purified RBC, bind infectious HIV-1; (c) DC

  18. Platelets and erythrocyte-bound platelets bind infectious HIV-1 in plasma of chronically infected patients.

    Directory of Open Access Journals (Sweden)

    Zoltan Beck

    Full Text Available Chronic HIV-1 infection is associated with persistent viremia in most patients, but it remains unclear how free virus may survive the potential hostile effects of plasma. We investigated whether sites might exist on the surfaces of circulating blood cells for protection of infectious HIV-1 particles. Red blood cells (RBC either from blood of uninfected normal individuals, or from blood obtained without EDTA from chronically infected HIV-1 patients, invariably contained a small number of RBC having attached platelets as determined by flow cytometry, light microscopy, and immunofluorescence microscopy. After mixing normal RBC with platelet-rich plasma, discrete populations of RBC, platelets, and complexes of platelets attached to RBC were purified by fluorescence-activated cell sorting. Upon incubation of purified cells or platelets with HIV-1 followed by washing and co-incubation with CD4-positive peripheral blood mononuclear cells (PBMC, platelets, and platelet-RBC complexes, but not platelet-free RBC, caused infection of PBMC. Infection was prevented by pre-treating the platelet-RBC complexes with EDTA. Plasma and RBC (comprising a RBC/platelet-RBC mixture from chronically infected patients with low viral loads were also co-incubated with PBMC ex vivo to determine the presence of infectious HIV-1. All freshly isolated plasmas from the HIV-1-infected donors, obtained in the absence of anticoagulant, were noninfectious. Interestingly, the RBC from most of the patients caused cell-cell infection of PBMC that was prevented by stripping the RBC with EDTA. A monoclonal antibody to DC-SIGN partially inhibited cell-cell HIV-1 infection of PBMC by normal RBC pre-incubated with platelets and HIV-1. We conclude: (a platelet-free EDTA-free plasma from chronically infected HIV-1 patients, although containing viral RNA, is an environment that lacks detectable infectious HIV-1; (b platelets and platelet-RBC complexes, but not purified RBC, bind infectious HIV

  19. The expression levels of platelet adhesive receptors in PRP derived platelet concentrates during storage

    Directory of Open Access Journals (Sweden)

    Fatemeh Nassaji

    2016-04-01

    Full Text Available Background: Major platelet adhesive receptors that contribute significantly to thrombus formation include platelet receptor glycoprotein Ibα (GPIbα of the GPIb-IX-V complex and platelet glycoprotein VI (GPVI. GPIbα plays a crucial role in platelet tethering to sub-endothelial matrix, which initiates thrombus formation at arterial shear rates, whereas GPVI is critically involved in platelets firm adhesion to the site of injury regardless of shear condition. During storage, platelets experience some changes that deleteriously affect the expression levels of platelet receptors, which in turn can alter platelet functional behaviors. Considering the important roles of GPIbα and GPVI in platelet adhesion, it seems that any dramatic changes in the expression levels of these receptors can influence adhesive function of transfused platelets. Thereby examining GPIbα and GPVI expression during the storage of platelet concentrates may provide some useful information about the functional quality of these products after transfusion. Methods: In our experimental study, 5 PRP-platelet concentrates were randomly obtained from Iranian Blood Transfusion Organization (IBTO. All the platelet products met the standard quality assessment based on AABB (American Association of Blood Banks guidelines. Washed platelets were subjected to flowcytometry analysis for the evaluation of GPIbα and GPVI receptor expression in day 1, 3 and 5 after storage. Data were presented as mean fluorescence intensity (MFI and analyzed by Kruskal-Wallis test with Dunn’s multiple comparison test. Results: The GPIbα expression on first day (MFI=86±5.9 was reduced three days after storage (MFI= 69±6.9. The expression levels continued to reduce until day 5 in which GPIbα expression was markedly decreased to (MFI= 61±7.7 (P= 0.0094. GPVI expression on the days 1, 3 and 5 after storage were 20.6±3.3, 24±2.5 and 14±4.9, respectively. The results showed a significant decrease of

  20. Understanding platelet generation from megakaryocytes: implications for in vitro-derived platelets.

    Science.gov (United States)

    Sim, Xiuli; Poncz, Mortimer; Gadue, Paul; French, Deborah L

    2016-03-10

    Platelets are anucleate cytoplasmic discs derived from megakaryocytes that circulate in the blood and have major roles in hemostasis, thrombosis, inflammation, and vascular biology. Platelet transfusions are required to prevent the potentially life-threatening complications of severe thrombocytopenia seen in a variety of medical settings including cancer therapy, trauma, and sepsis. Platelets used in the clinic are currently donor-derived which is associated with concerns over sufficient availability, quality, and complications due to immunologic and/or infectious issues. To overcome our dependence on donor-derived platelets for transfusion, efforts have been made to generate in vitro-based platelets. Work in this area has advanced our understanding of the complex processes that megakaryocytes must undergo to generate platelets both in vivo and in vitro. This knowledge has also defined the challenges that must be overcome to bring in vitro-based platelet manufacturing to a clinical reality. This review will focus on our understanding of committed megakaryocytes and platelet release in vivo and in vitro, and how this knowledge can guide the development of in vitro-derived platelets for clinical application.

  1. Donor demographic and laboratory predictors of single donor platelet yield

    Directory of Open Access Journals (Sweden)

    R. Arun

    2013-10-01

    Full Text Available Background: Platelet transfusions are essential to prevent morbidity and mortality in patients who are severely thrombocytopenic and are at risk of spontaneous bleeding. Platelets are currently obtained either by fractionation of whole blood or by platelet apheresis. The quality of single donor platelets (SDP in terms of yield influences platelet recovery in the recipient and allows prolonging intervals between transfusions. Material and Methods: Donor demographic and laboratory data were analyzed prior to performing plateletpheresis to identify donor factors that influence platelet yield. The study was conducted on 130 healthy, first-time plateletpheresis donors over a period of 4 years. The plateletpheresis procedures were performed using Fresenius Kabi COM.TEC and Hemonetics MCS plus separator. A relationship between pre-donation donor variables and yield of platelets was studied using the Pearson correlation. Results: The mean platelet yield was 3.160.62x1011 per unit. A positive correlation was observed between platelet yield and pre-donation platelet count, body mass index (BMI; Kg/m2 of the donor, while a negative correlation was observed between age and the platelet yield. Conclusion: Donor pre-donation platelet count, BMI and donor age influence platelet yield. Young healthy donors with a high platelet count and better BMI can give a better platelet yield in the SDP.

  2. 布氏乳杆菌PG-7去除胆固醇和抗氧化能力的研究%Study on Cholesterol-Lowering and Antioxidative Function of Lactobacillus buchneri PG-7

    Institute of Scientific and Technical Information of China (English)

    岳寿松; 尤升波; 游银伟; 王翠萍; 朱友峰; 邹晓凤

    2013-01-01

    A strain PG - 7 of lactic acid bacteria was isolated from picked garlic, which had the property of cholesterol - lowering as 58. 1% , radical - scavenging rate of DPPH and superoxide anion radical as 91.7% and 16. 2% , respectively. The 16S rDAN gene sequences for strain PG - 7 was amplified and se-quenced. The results showed that the complete 16S rDAN gene sequence was 1 638 bp. A phylogenetic tree was constructed by comparing its 16S rDAN sequence with other relative bacteria species in the GenBank database. The strain PG - 7 and Lactobacillus buchneri constituted a branch with the similarity value as 99% , so PG - 7 was identified as Lactobacillus buchneri.%从糖蒜中筛选分离到的一株具有降胆固醇和抗氧化能力的产乳酸菌株PG-7,该菌对胆固醇的去除率为58.1%,对DPPH自由基和超氧自由基的清除率分别为91.7%和16.2%.克隆了PG-7的16S rDNA序列,并以其同源性为基础构建了相关属种的系统发育树.结果表明,该菌16S rDNA序列全长1 638 bp,BLAST显示该菌株与乳杆菌属同源;PG-7菌株在进化关系上与布氏乳杆菌属(Lactobacillus buchneri)聚成一族.将其鉴定为布氏乳杆菌属,命名为:Lactobacillus buchneri PG-7.

  3. Propranolol modifies platelet serotonergic mechanisms in rats.

    Science.gov (United States)

    Zółtowski, R; Pawlak, R; Matys, T; Pietraszek, M; Buczko, W

    2002-06-01

    Though the mechanisms for the vascular actions of vasodilatory beta-blockers are mostly determined, some of their interactions with monoaminergic systems are not elucidated. Because there are evidences supporting a possible involvement of serotonin (5-HT) in the actions of beta-blockers, we studied the effect of propranolol on peripheral serotonergic mechanisms in normotensive and Goldblatt two-kidney - one clip (2K1C) hypertensive rats. In both groups of animals propranolol decreased systolic blood pressure, significantly increased whole blood serotonin concentration and at the same time it decreased platelet serotonin level. The uptake of the amine by platelets from hypertensive animals was lower than that of normotensive animals and it was decreased by propranolol only in the latter. In both groups propranolol inhibited potentiation of ADP-induced platelet aggregation by serotonin. In conclusion, this study provides evidence that propranolol modifies platelet serotonergic mechanisms in normotensive and renal hypertensive rats.

  4. Activation of human platelets by misfolded proteins

    NARCIS (Netherlands)

    Herczenik, E.; Bouma, B.; Korporaal, J.A.; Strangi, R.; Zeng, Q.; Gros, P.; van Eck, M.; van Berkel, T.J.C.; Gebbink, M.F.B.G.; Akkerman, J.W.N.

    2007-01-01

    Objective: Protein misfolding diseases result from the deposition of insoluble protein aggregates that often contain fibrils called amyloid. Amyloids are found in Alzheimer disease, atherosclerosis, diabetes mellitus, and systemic amyloidosis,which are diseases where platelet activation might be

  5. Mapuche herbal medicine inhibits blood platelet aggregation.

    Science.gov (United States)

    Falkenberg, Susan Skanderup; Tarnow, Inge; Guzman, Alfonso; Mølgaard, Per; Simonsen, Henrik Toft

    2012-01-01

    12 plant species traditionally used by the Mapuche people in Chile to treat wounds and inflammations have been evaluated for their direct blood platelet inhibition. Seven of the 12 tested plant species showed platelet inhibitory effect in sheep blood, and four of these were also able to inhibit the ADP- (5.0 μM) and collagen- (2.0 μg/mL) induced aggregations in human blood. These four species in respective extracts (in brackets) were Blechnum chilense (MeOH), Luma apiculata (H(2)O), Amomyrtus luma (DCM : MeOH 1 : 1) and Cestrum parqui (DCM : MeOH 1 : 1). The platelet aggregating inhibitory effects of A. luma (DCM : MeOH 1 : 1), and L. apiculata (H(2)O) were substantial and confirmed by inhibition of platelet surface activation markers.

  6. Mapuche Herbal Medicine Inhibits Blood Platelet Aggregation

    Directory of Open Access Journals (Sweden)

    Susan Skanderup Falkenberg

    2012-01-01

    Full Text Available 12 plant species traditionally used by the Mapuche people in Chile to treat wounds and inflammations have been evaluated for their direct blood platelet inhibition. Seven of the 12 tested plant species showed platelet inhibitory effect in sheep blood, and four of these were also able to inhibit the ADP- (5.0 μM and collagen- (2.0 μg/mL induced aggregations in human blood. These four species in respective extracts (in brackets were Blechnum chilense (MeOH, Luma apiculata (H2O, Amomyrtus luma (DCM : MeOH 1 : 1 and Cestrum parqui (DCM : MeOH 1 : 1. The platelet aggregating inhibitory effects of A. luma (DCM : MeOH 1 : 1, and L. apiculata (H2O were substantial and confirmed by inhibition of platelet surface activation markers.

  7. Relationship between platelet parameters and sudden ...

    African Journals Online (AJOL)

    Relationship between platelet parameters and sudden sensorineural hearing loss: a ... Data source: A PubMed, Science Direct, Scopus, OVID, EMBASE and ... relationship of PDW and SSNHL but due to the limited studies on this subject more ...

  8. Effects of drugs on platelet function.

    Science.gov (United States)

    Morse, E E

    1977-01-01

    Numerous drugs and chemicals affect the function of human blood platelets. The mechanism of action of some medications is partly understood. Aspirin is the most frequently involved drug. It appears to interfere with the platelet release reaction by acetylation of a platelet membrane protein which may be involved in the synthesis of prostaglandins. Other anti-inflammatory drugs, including indomethacin, phenylbutazone, ibuprophen (Motrin) and clonixin, also interfere with the release reaction but have a shorter acting course than aspirin. Some drugs stimulate adenylcyclase (gliclazide) or block phosphodiesterase, (dipyridamole, caffeine) both of which actions lead to an increase in adenosine cyclic 3':5' monophosphate (cAMP) and decrease aggregation by adenosine diphosphate (ADP). These interactions should be known to clinical scientists since patients using these medicaments may manifest abnormal platelet function tests in the laboratory and mild hemorrhagic syndromes in the clinic.

  9. Physiopathology of blood platelets and development of platelet substitutes. Progress report, August 1, 1975--July 31, 1976

    Energy Technology Data Exchange (ETDEWEB)

    Baldini, M G

    1976-04-28

    Progress is reported on studies on the physiology of blood platelets in thrombocytopenic patients and rabbits. Methods for the detection of platelet antibodies and the preservation of platelets in vitro were investigated. Studies on the effect of low doses of x irradiation (up to 1000 R) on platelet function indicate that platelets exposed to ionizing radiation have increased functional activity. A list is included of publications that report the results of the studies in detail.

  10. Inherited human group IVA cytosolic phospholipase A2 deficiency abolishes platelet, endothelial, and leucocyte eicosanoid generation

    Science.gov (United States)

    Kirkby, Nicholas S.; Reed, Daniel M.; Edin, Matthew L.; Rauzi, Francesca; Mataragka, Stefania; Vojnovic, Ivana; Bishop-Bailey, David; Milne, Ginger L.; Longhurst, Hilary; Zeldin, Darryl C.; Mitchell, Jane A.; Warner, Timothy D.

    2016-01-01

    Eicosanoids are important vascular regulators, but the phospholipase A2 (PLA2) isoforms supporting their production within the cardiovascular system are not fully understood. To address this, we have studied platelets, endothelial cells, and leukocytes from 2 siblings with a homozygous loss-of-function mutation in group IVA cytosolic phospholipase A2 (cPLA2α). Chromatography/mass spectrometry was used to determine levels of a broad range of eicosanoids produced by isolated vascular cells, and in plasma and urine. Eicosanoid release data were paired with studies of cellular function. Absence of cPLA2α almost abolished eicosanoid synthesis in platelets (e.g., thromboxane A2, control 20.5 ± 1.4 ng/ml vs. patient 0.1 ng/ml) and leukocytes [e.g., prostaglandin E2 (PGE2), control 21.9 ± 7.4 ng/ml vs. patient 1.9 ng/ml], and this was associated with impaired platelet activation and enhanced inflammatory responses. cPLA2α-deficient endothelial cells showed reduced, but not absent, formation of prostaglandin I2 (prostacyclin; control 956 ± 422 pg/ml vs. patient 196 pg/ml) and were primed for inflammation. In the urine, prostaglandin metabolites were selectively influenced by cPLA2α deficiency. For example, prostacyclin metabolites were strongly reduced (18.4% of control) in patients lacking cPLA2α, whereas PGE2 metabolites (77.8% of control) were similar to healthy volunteer levels. These studies constitute a definitive account, demonstrating the fundamental role of cPLA2α to eicosanoid formation and cellular responses within the human circulation.—Kirkby, N. S., Reed, D. M., Edin, M. L., Rauzi, F., Mataragka, S., Vojnovic, I., Bishop-Bailey, D., Milne, G. L., Longhurst, H., Zeldin, D. C., Mitchell, J. A., Warner, T. D. Inherited human group IVA cytosolic phospholipase A2 deficiency abolishes platelet, endothelial, and leucocyte eicosanoid generation. PMID:26183771

  11. Asteroseismology of hot pre-white dwarf stars: the case of the DOV stars PG 2131+066 and PG 1707+427, and the PNNV star NGC 1501

    CERN Document Server

    Córsico, A H; Bertolami, M M Miller; García--Berro, E

    2009-01-01

    We present an asteroseismological study on the two high-gravity pulsating PG1159 (GW Vir or DOV) stars, PG 2131+066 and PG 1707+427, and on the pulsating [WCE] star NGC 1501. We compute adiabatic $g$-mode pulsation periods on PG1159 evolutionary models with stellar masses ranging from 0.530 to 0.741 Msun. These models take into account the complete evolution of progenitor stars, through the thermally pulsing AGB phase, and born-again episode. We constrain the stellar mass of PG 2131+066, PG 1707+427 and NGC 1501 by comparing the observed period spacing with the asymptotic period spacing and with the average of the computed period spacings. We also employ the individual observed periods in search of representative seismological models for each star. This work closes our short series of asteroseismological studies on pulsating pre-white dwarf stars. Our results demonstrate the usefulness of asteroseismology for probing the internal structure and evolutionary status of pre-white dwarf stars. In particular, aster...

  12. Platelet Glycoprotein lb-1X and Malignancy

    Science.gov (United States)

    2011-09-01

    patient with systemic lupus erythematosus . Am J Hematol 2001; 67:262-67. 20. Arthur JF, Dunkley S and Andrews RK. Platelet glycoprotein VI-related...Moroi M. Antibody against platelet membrane glyco- protein VI in a patient with systemic lupus erythematosus . Am J Hematol 2001; 67: 262–7. 9 Arthur JF...Approved OMB No. 0704-0188 Public reporting burden for this collection of information is estimated to average 1 hour per response, including the

  13. Dengue virus binding and replication by platelets.

    Science.gov (United States)

    Simon, Ayo Y; Sutherland, Michael R; Pryzdial, Edward L G

    2015-07-16

    Dengue virus (DENV) infection causes ∼200 million cases of severe flulike illness annually, escalating to life-threatening hemorrhagic fever or shock syndrome in ∼500,000. Although thrombocytopenia is typical of both mild and severe diseases, the mechanism triggering platelet reduction is incompletely understood. As a probable initiating event, direct purified DENV-platelet binding was followed in the current study by quantitative reverse transcription-polymerase chain reaction and confirmed antigenically. Approximately 800 viruses specifically bound per platelet at 37°C. Fewer sites were observed at 25°C, the blood bank storage temperature (∼350 sites), or 4°C, known to attenuate virus cell entry (∼200 sites). Dendritic cell-specific intercellular adhesion molecule-3-grabbing nonintegrin (DC-SIGN) and heparan sulfate proteoglycan were implicated as coreceptors because only the combination of anti-DC-SIGN and low-molecular-weight heparin prevented binding. Interestingly, at 37°C and 25°C, platelets replicated the positive sense single-stranded RNA genome of DENV by up to ∼4-fold over 7 days. Further time course experiments demonstrated production of viral NS1 protein, which is known to be highly antigenic in patient serum. The infectivity of DENV intrinsically decayed in vitro, which was moderated by platelet-mediated generation of viable progeny. This was shown using a transcription inhibitor and confirmed by freeze-denatured platelets being incapable of replicating the DENV genome. For the first time, these data demonstrate that platelets directly bind DENV saturably and produce infectious virus. Thus, expression of antigen encoded by DENV is a novel consideration in the pathogen-induced thrombocytopenia mechanism. These results furthermore draw attention to the possibility that platelets may produce permissive RNA viruses in addition to DENV.

  14. Platelet dynamics in three-dimensional simulation of whole blood.

    Science.gov (United States)

    Vahidkhah, Koohyar; Diamond, Scott L; Bagchi, Prosenjit

    2014-06-03

    A high-fidelity computational model using a 3D immersed boundary method is used to study platelet dynamics in whole blood. We focus on the 3D effects of the platelet-red blood cell (RBC) interaction on platelet margination and near-wall dynamics in a shear flow. We find that the RBC distribution in whole blood becomes naturally anisotropic and creates local clusters and cavities. A platelet can enter a cavity and use it as an express lane for a fast margination toward the wall. Once near the wall, the 3D nature of the platelet-RBC interaction results in a significant platelet movement in the transverse (vorticity) direction and leads to anisotropic platelet diffusion within the RBC-depleted zone or cell-free layer (CFL). We find that the anisotropy in platelet motion further leads to the formation of platelet clusters, even in the absence of any platelet-platelet adhesion. The transverse motion, and the size and number of the platelet clusters are observed to increase with decreasing CFL thickness. The 3D nature of the platelet-RBC collision also induces fluctuations in off-shear plane orientation and, hence, a rotational diffusion of the platelets. Although most marginated platelets are observed to tumble just outside the RBC-rich zone, platelets further inside the CFL are observed to flow with an intermittent dynamics that alters between sliding and tumbling, as a result of the off-shear plane rotational diffusion, bringing them even closer to the wall. To our knowledge, these new findings are based on the fundamentally 3D nature of the platelet-RBC interaction, and they underscore the importance of using cellular-scale 3D models of whole blood to understand platelet margination and near-wall platelet dynamics.

  15. Whole Earth Telescope observations of the pulsating subdwarf B star PG 0014+067

    CERN Document Server

    Vuckovic, M; O'Toole, S; Csubry, Z; Baran, A; Zola, S; Moskalik, P; Klumpe, E W; Riddle, R; O'Brien, M S; Mullally, F; Wood, M A; Wilkat, V; Zhou, A Y; Reed, M D; Terndrup, D M; Sullivan, D J; Kim, S L; Chen, W P; Chen, C W; Hsiao, W S; Sanchawala, K; Lee, H T; Jiang, X J; Janulis, R; Siwak, M; Ogloza, W; Paparo, M; Bognár, Z; Sodor, A; Handler, G; Lorenz, D; Steininger, B; Silvotti, R; Vauclair, G; Oreiro, R; Ostensen, R; Bronowska, A; Castanheira, B G; Kepler, S O; Fraga, L; Shipman, H L; Provencal, J L; Childers, D

    2006-01-01

    PG 0014+067 is one of the most promising pulsating subdwarf B stars for seismic analysis, as it has a rich pulsation spectrum. The richness of its pulsations, however, poses a fundamental challenge to understanding the pulsations of these stars, as the mode density is too complex to be explained only with radial and nonradial low degree (l < 3) p-modes without rotational splittings. One proposed solution, for the case of PG 0014+067 in particular, assigns some modes with high degree (l=3). On the other hand, theoretical models of sdB stars suggest that they may retain rapidly rotating cores, and so the high mode density may result from the presence of a few rotationally-split triplet (l=1), quintuplet (l=2) modes, along with radial (l=0) p-modes. To examine alternative theoretical models for these stars, we need better frequency resolution and denser longitude coverage. Therefore, we observed this star with the Whole Earth Telescope for two weeks in October 2004. In this paper we report the results of Whol...

  16. SDSSJ212531.92-010745.9 - the first definite PG1159 close binary system

    CERN Document Server

    Nagel, T; Kusterer, D J; Stahn, T; H"ugelmeyer, S D; Dreizler, S; Gänsicke, B T; Schreiber, M R

    2006-01-01

    The archival spectrum of SDSSJ212531.92-010745.9 shows not only the typical signature of a PG1159 star, but also indicates the presence of a companion. Our aim was the proof of the binary nature ofthis object and the determination of its orbital period.We performed time-series photometry of SDSSJ212531.92-010745.9. We observed the object during 10 nights, spread over one month, with the Tuebingen 80cm and the Goettingen 50cm telescopes. We fitted the observed light curve with a sine and simulated the light curve of this system with the nightfall program. Furthermore, we compared the spectrum of SDSSJ212531.92-010745.9 with NLTE models, the results of which also constrain the light curve solution. An orbital period of 6.95616(33)h with an amplitude of 0.354(3)mag is derived from our observations. A pulsation period could not be detected. For the PG1159 star we found, as preliminary results from comparison with our NLTE models, Teff about 90000K, log g about 7.60, and the abundance ratio C/He = 0.05 by number f...

  17. Can pulsating PG1159 stars place constraints on the occurrence of core overshooting?

    CERN Document Server

    Corsico, A H

    2005-01-01

    The present letter is aimed at exploring the influence of overshooting during the central helium burning in pre-white dwarf progenitors on the pulsational properties of PG1159 stars. To this end we follow the complete evolution an intermediate-mass white dwarf progenitor from the zero age main sequence through the thermally pulsing and born-again phases to the domain of the PG1159 stars. Our results suggest that the presence of mode-trapping features in the period spacings of these hot pulsating stars could result from structure in the carbon-oxygen core. We find in particular that in order to get enough core structure consistent with observational demands, the occurrence of overshoot episodes during the central helium burning is needed. This conclusion is valid for thick helium envelopes like those predicted by our detailed evolutionary calculations. If the envelope thickness were substantially smaller, then the occurrence of core overshooting would be more difficult to disentangle from the effects related t...

  18. New Estimates of Time Delays in the Gravitationally Lensed System PG1115+080

    CERN Document Server

    Shimanovskay, E; Artamonov, B

    2015-01-01

    We analyze all publicly available long-term optical observations of the gravitationally lensed quasar PG1115+080 for the purpose of estimating time delays between its four components. In particular, the light curves of PG1115+080 components obtained in 2001-2006 at Maidanak observatory (Uzbekistan) (Tsvetkova et. al. 2010} are considered. We find that the linear trend is observed in 2006 in light curves of all four components with fast variations only in the A1 and C components that can be due to microlensing and observational errors. Application of the MCCF method (Oknyansky 1993) to the photometric data obtained in 2004-2005 gives values of time delays $\\tau_{BC} = 22^{+2}_{-3}$, $\\tau_{AC} = 12^{+2}_{-1}$ and $\\tau_{BA} = 10^{+2}_{-3}$ days, which are in agreement with the results received earlier by Schechter and Barkana for 1995-1996 light curves with two different methods of statistic analysis. However, our estimates of $\\tau_{BA}$ and $\\tau_{BC}$ differ from the values received by the group of Vakulik ...

  19. VERITAS Observations of the BL Lac Object PG 1553+113

    CERN Document Server

    Aliu, E; Aune, T; Barnacka, A; Behera, B; Beilicke, M; Benbow, W; Berger, K; Bird, R; Buckley, J H; Bugaev, V; Byrum, K; Cardenzana, J V; Cerruti, M; Chen, X; Ciupik, L; Connolly, M P; Cui, W; Dickinson, H J; Dumm, J; Eisch, J D; Errando, M; Falcone, A; Federici, S; Feng, Q; Finley, J P; Fortin, P; Fortson, L; Furniss, A; Galante, N; Gillanders, G H; Griffin, S; Griffiths, S T; Grube, J; Gyuk, G; Håkansson, N; Hanna, D; Holder, J; Hughes, G; Humensky, T B; Johnson, C A; Kaaret, P; Kertzman, P Kar M; Khassen, Y; Kieda, D; Krawczynski, H; Krennrich, F; Kumar, S; Lang, M J; Madhavan, A; McArthur, S; McCann, A; Meagher, K; Millis, J; Moriarty, P; Nieto, D; de Bhróithe, A O'Faoláin; Ong, R A; Orr, M; Otte, A N; Park, N; Perkins, J S; Pohl, M; Popkow, A; Prokoph, H; Pueschel, E; Quinn, J; Ragan, K; Rajotte, J; Reyes, L C; Reynolds, P T; Richards, G T; Roache, E; Sembroski, G H; Shahinyan, K; Staszak, D; Telezhinsky, I; Tucci, J V; Tyler, J; Varlotta, A; Vassiliev, V V; Wakely, S P; Weinstein, A; Welsing, R; Wilhelm, A; Williams, D A; Zitzer, B

    2014-01-01

    We present results from VERITAS observations of the BL Lac object PG 1553+113 spanning the years 2010, 2011, and 2012. The time-averaged spectrum, measured between 160 and 560\\,GeV, is well described by a power law with a spectral index of $4.33 \\pm 0.09$. The time-averaged integral flux above $200\\,$GeV measured for this period was $(1.69 \\pm 0.06) \\times 10^{-11} \\, \\mathrm{ph} \\, \\mathrm{cm}^{-2} \\, \\mathrm{s}^{-1}$, corresponding to 6.9\\% of the Crab Nebula flux. We also present the combined $\\gamma$-ray spectrum from the Fermi Large Area Telescope and VERITAS covering an energy range from 100~MeV to 560~GeV. The data are well fit by a power law with an exponential cutoff at $\\rm {101.9 \\pm 3.2 \\, \\mathrm{GeV}} $. The origin of the cutoff could be intrinsic to PG~1553+113 or be due to the $\\gamma$-ray opacity of our universe through pair production off the extragalactic background light (EBL). Given lower limits to the redshift of $\\rm z \

  20. Designing matrix organizations that work: Lessons from the P&G case

    Directory of Open Access Journals (Sweden)

    Ronald Jean Degen

    2010-08-01

    Full Text Available The matrix organization concept emerged from the US aerospace industry in the 1960s and was adopted by many companies in the early 1970s. In the late 1970s and early 1980s many companies were experiencing trouble with its operation and many argued like Peters & Waterman in their bestseller In search of excellence in 1982 (p. 306 that the matrix was too complex to work properly. Galbraith (2009, p. 10-14 explains that the reason for the problems were that the matrix in these organizations was wrongly adopted, hastily installed, and inappropriately implemented. He explains that adopting a matrix structure requires a collaborative organization form, proper power, and accountability distribution, complementing changes to the information systems, planning and budgeting process, the performance evaluation and bonus system, and so on. The purpose of this paper is to illustrate why companies adopted the matrix, what problems they had, the solutions for these problems based on Galbraith (2009 and other authors like Davis & Lawrence (1977, and the state of the art of matrix structure design today like the P&G front-back hybrid matrix organization. To illustrate the historical evolution of organization structure to the simple matrix and then to more complex matrix organizations we used the P&G case (Piskorski & Spadini 2007.

  1. Proving strong magnetic fields near to the central black hole in the quasar PG0043+039 via cyclotron lines

    CERN Document Server

    Kollatschny, W; Zetzl, M; Santos-Lleo, M; Rodriguez-Pascual, P M; Ballo, L

    2015-01-01

    The optical luminous quasar PG0043+039 has not been detected before in deep X-ray observations indicating the most extreme optical-to-X-ray slope index ${\\alpha}_{ox}$ of all quasars. This study aims to detect PG0043+039 in a deep X-ray exposure. Furthermore, we wanted to check out whether this object shows specific spectral properties in other frequency bands. We took deep X-ray (XMM-Newton), far-ultraviolet (HST), and optical (HET, SALT telescopes) spectra of PG0043+039 simultaneously in July 2013. We just detected PG0043+039 in our deep X-ray exposure. The steep ${\\alpha}_{ox} = -2.37 {\\pm} 0.05$ gradient is consistent with an unusual steep gradient $F_{\

  2. Probing the internal rotation of pre-white dwarf stars with asteroseismology: the case of PG 122+200

    CERN Document Server

    Córsico, A H; Kawaler, S D; Bertolami, M M Miller; García--Berro, E; Kepler, S O

    2011-01-01

    We put asteroseismological constraints on the internal rotation profile of the GW Vir (PG1159-type) star PG 0122+200. To this end we employ a state-of-the-art asteroseismological model for this star and we assess the expected frequency splittings induced by rotation adopting a forward approach in which we compare the theoretical frequency separations with the observed ones assuming different types of plausible internal rotation profiles. We also employ two asteroseismological inversion methods for the inversion of the rotation profile of PG 0122+200. We find evidence for differential rotation in this star. We demonstrate that the frequency splittings of the rotational multiplets exhibited by PG 0122+200 are compatible with a rotation profile in which the central regions are spinning about 2.4 times faster than the stellar surface.

  3. In vivo function of Pgβglu-1 in the release of acetophenones in white spruce

    Directory of Open Access Journals (Sweden)

    Melissa H. Mageroy

    2017-07-01

    Full Text Available Eastern spruce budworm (Choristoneura fumiferiana Clemens (ESBW is a major forest pest which feeds on young shoots of white spruce (Picea glauca and can cause landscape level economic and ecological losses. Release of acetophenone metabolites, piceol and pungenol, from their corresponding glycosides, picein and pungenin, can confer natural resistance of spruce to ESBW. A beta-glucosidase gene, Pgβglu-1, was recently discovered and the encoded enzyme was characterized in vitro to function in the release of the defensive acetophenone aglycons. Here we describe overexpression of Pgβglu-1 in a white spruce genotype whose metabolome contains the glucosylated acetophenones, but no detectable amounts of the aglycons. Transgenic overexpression of Pgβglu-1 resulted in release of the acetophenone aglycons in planta. This work provides in vivo evidence for the function of Pgβglu-1.

  4. [The role of blood platelets in infections].

    Science.gov (United States)

    Micota, Bartłomiej; Sadowska, Beata; Różalska, Barbara

    2015-05-17

    Platelets are primarily associated with their main function, hemostasis, although it is known that these cells also exhibit biological activity in cancer progression, inflammation and infectious processes. During infection platelets, due to the expression of specific receptors - Toll-like receptors (TLRs) - which recognize molecular patterns associated with pathogens - pathogen-associated molecular patterns (PAMPs) - are activated by the presence of microorganism components and/or substances released from damaged cells/tissue. Further antimicrobial activity of platelets is based on their capacity for phagocytosis, generation of reactive oxygen species (ROS), and the synthesis, storage and release of proteins/peptides with antimicrobial activity. Another mechanism of platelet action is their immunomodulatory activity. It is based mainly on the ability to secrete chemotactic factors allowing the accumulation of professional immunocompetent cells at the site of infection, thus enhancing the effective eradication of an infectious agent. In chronic infections, platelets, due to release of numerous growth factors and various cytokines, support mechanisms of acquired immunity. They accelerate the maturation of dendritic cells, stimulate B cells to be immunoglobulin-producing plasma cells and potentiate the activity of T cells. Unfortunately, in certain situations (the existence of specific risk factors) the interaction of microorganisms with activated platelets may also be the cause of pathology within the cardiovascular system.

  5. Effects of irradiation on platelet function

    Energy Technology Data Exchange (ETDEWEB)

    Rock, G.; Adams, G.A.; Labow, R.S.

    1988-09-01

    Current medical practice involves the irradiation of blood components, including platelet concentrates, before their administration to patients with severe immunosuppression. The authors studied the effect of irradiation on in vitro platelet function and the leaching of plasticizers from the bag, both immediately and after 5 days of storage. The platelet count, white cell count, pH, glucose, lactate, platelet aggregation and release reaction, and serotonin uptake were not altered by the irradiation of random-donor or apheresis units with 2000 rads carried out at 0 and 24 hours and 5 days after collection. The leaching of di(2-ethylhexyl)phthalate from the plastic bags followed by the conversion to mono(2-ethylhexyl)phthalate was not increased by irradiation. Therefore, it is possible to irradiate platelet concentrates on the day of collection and subsequently store them for at least 5 days while maintaining in vitro function. This procedure could have considerable benefit for blood banks involved in the provision of many platelet products.

  6. Treatment of osteochondral injuries with platelet gel

    Directory of Open Access Journals (Sweden)

    Marcus Vinicius Danieli

    2014-12-01

    Full Text Available OBJECTIVES: Treatments for injured articular cartilage have not advanced to the point that efficient regeneration is possible. However, there has been an increase in the use of platelet-rich plasma for the treatment of several orthopedic disorders, including chondral injuries. Our hypothesis is that the treatment of chondral injuries with platelet gel results in higher-quality repair tissue after 180 days compared with chondral injuries not treated with gel. METHODS: A controlled experimental laboratory study was performed on 30 male rabbits to evaluate osteochondral injury repair after treatment with or without platelet gel. Osteochondral injuries were surgically induced in both knees of each rabbit at the medial femoral condyle. The left knee injury was filled with the platelet gel, and the right knee was not treated. Microscopic analysis of both knee samples was performed after 180 days using a histological grading scale. RESULTS: The only histological evaluation criterion that was not significantly different between treatments was metachromasia. The group that was treated with platelet gel exhibited superior results in all other criteria (cell morphology, surface regularity, chondral thickness and repair tissue integration and in the total score. CONCLUSION: The repair tissue was histologically superior after 180 days in the study group treated with platelet gel compared with the group of untreated injuries.

  7. Lymphocyte-platelet crosstalk in Graves' disease.

    Science.gov (United States)

    Kuznik, Boris I; Vitkovsky, Yuri A; Gvozdeva, Olga V; Solpov, Alexey V; Magen, Eli

    2014-03-01

    Platelets can modulate lymphocytes' role in the pathophysiology of thyroid autoimmune diseases. The present study was performed to clarify the status of platelet-lymphocyte subpopulations aggregation in circulating blood in patients with Graves' disease (GD). One hundred and fifty patients with GD (GD group) and 45 hyperthyroid patients with toxic multinodular goiter (TMG group) were recruited in the study. Control group consisted 150 healthy subjects. Immunophenotyping of lymphocytes was performed by flow cytometry. Detection of lymphocyte-platelet aggregates (LPAs) was done using light microscope after Ficoll-gradient centrifugation. The group of GD patients exhibited reduced CD8 lymphocyte and higher CD19 cell counts compared with TMG group and healthy controls. A greater number of activated CD3, HLA-DR+ lymphocytes were observed in GD than in TMG group and control group. GD group was characterized by lower blood platelet count (232 ± 89 × 10 cells/µL) than TMG group (251 ± 97 × 10 cells/µL; P < 0.05) and control group (262 ± 95 × 10 cells/µL; P < 0.05). In GD group, more platelet-bound lymphocytes (332 ± 91 /µL) were found than that in TMG group (116 ± 67/µL, P < 0.005) and control group (104 ± 58 /µL; P < 0.001). GD is associated with higher levels of activated lymphocytes and lymphocyte-platelet aggregates.

  8. A new ibuprofen derivative inhibits platelet aggregation and ROS mediated platelet apoptosis.

    Directory of Open Access Journals (Sweden)

    Kodagahalli S Rakesh

    Full Text Available Thrombocytopenia is a serious issue connected with the pathogenesis of several human diseases including chronic inflammation, arthritis, Alzheimer's disease, cardiovascular diseases (CVDs and other oxidative stress-associated pathologies. The indiscriminate use of antibiotics and other biological drugs are reported to result in thrombocytopenia, which is often neglected during the treatment regime. In addition, augmented oxidative stress induced by drugs and pathological conditions has also been shown to induce thrombocytopenia, which seems to be the most obvious consequence of elevated rate of platelet apoptosis. Thus, blocking oxidative stress-induced platelet apoptosis would be of prime importance in order to negotiate thrombocytopenia and associated human pathologies. The current study presents the synthesis and platelet protective nature of novel ibuprofen derivatives. The potent anti-oxidant ibuprofen derivative 4f was selected for the study and the platelet protective efficacy and platelet aggregation inhibitory property has been demonstrated. The compound 4f dose dependently mitigates the oxidative stress-induced platelet apoptosis in both platelet rich plasma and washed platelets. The platelet protective nature of compound 4f was determined by assessing various apoptotic markers such as ROS generation, cytosolic Ca2+ levels, PS externalization, cytochrome C translocation, Caspase activation, mitochondrial membrane depolarization, cytotoxicity, LDH leakage and tyrosine phosphorylation of cytosolic proteins. Furthermore, compound 4f dose dependently ameliorated agonist induced platelet aggregation. Therefore, compound 4f can be estimated as a potential candidate in the treatment regime of pathological disorders associated with platelet activation and apoptosis. In addition, compound 4f can be used as an auxiliary therapeutic agent in pathologies associated with thrombocytopenia.

  9. Assessment of quality of platelets preserved in plasma and platelet additive solution: A Malaysian experience

    Directory of Open Access Journals (Sweden)

    Munirah Binti Mokhtar

    2016-01-01

    Full Text Available Background: A use of platelet additives solution (PAS improves storage conditions so as to give increased shelf life to platelets and to maintain hemostatic function. Objective: The present study was aimed to compare in vitro quality of platelet rich plasma (PRP-derived platelet concentrate (PC during extended period of storage in plasma and in additive solution (Composol PS and Fresenius. Study Design: Randomized 19 PCs each were used in the study for plasma and PAS as the storage medium. The measurement parameters, including pH, total white blood cell (WBC count, total platelet count, and platelet activation rate, were studied on day 1, day 5, and day 8 of the storage period. The sterility test was carried out on the eighth day of storage. Results: pH of PC suspended in PAS was significantly lower as compared to that in plasma (P < 0.001 for all the three days of sampling. The WBC count, both in plasma and in PAS, showed an acceptable values of being <0.2 Χ 10 9 /unit during the storage period. Platelet count in PAS was higher as compared to that in plasma, though it was not statistically significant. While both the groups showed increased platelet activation rate during the storage, the PCs suspended in PAS showed significantly higher platelet activation rate (p0.001. Results from sterility test showed no bacterial growth in the PCs in both the groups. Conclusion: Most parameters studied on platelet storage in suspending medium of native plasma and PAS remained well within the acceptable limits. However, the pH values and platelet activation rate significantly differed in PAS as compared with plasma.

  10. Studies on platelet function in bronchial asthma Part 2. Production of 12-hydroxyeicosatetraenoic acid from platelets and the platelet-lymphocyte interaction in bronchial asthmatics

    OpenAIRE

    角南, 宏二

    1992-01-01

    To clarify the role of platelets in the pathogenesis of bronchial asthma, the production of 12-hydroxyeicosatetraenoic acid(12HETE) from platelets of asthmatics was examined by high performance liquid chromatography(HPLC). The effect of platelets on lymphocyte function was also studied by lymphocyte blastogenesis. The results were as follows : 1) The production of 12HETE from platelets of asthmatics were significantly higher than that of normal subjects(p

  11. Regulation of Amidase Formation in Mutants from Pseudomonas aeruginosa PAO Lacking Glutamine Synthetase Activity

    NARCIS (Netherlands)

    Janssen, Dick B.; Herst, Patricia M.; Joosten, Han M.L.J.; Drift, Chris van der

    1982-01-01

    The formation of amidase was studied in mutants from Pseudomonas aeruginosa PAO lacking glutamine synthetase activity. It appeared that catabolite repression of amidase synthesis by succinate was partially relieved when cellular growth was limited by glutamine. Under these conditions, a correlation

  12. The PRPP Synthetase Spectrum: What Does it Demonstrate About Nucleotide Syndromes?

    NARCIS (Netherlands)

    Duley, J.A.; Christodoulou, J.; Brouwer, A.P.M. de

    2011-01-01

    Defects in X-linked phosphoribosylpyrophosphate synthetase 1 (PRPS1) manifest as follows: (1) PRS-I enzyme "superactivity" (gain-of-function mutations affecting allosteric regions); (2) PRS-I overexpression (which may be linked to miRNA mutation); (3) severe PRS-I deficiency/Arts syndrome (missense

  13. β-Lactam formation by a non-ribosomal peptide synthetase during antibiotic biosynthesis.

    Science.gov (United States)

    Gaudelli, Nicole M; Long, Darcie H; Townsend, Craig A

    2015-04-16

    Non-ribosomal peptide synthetases are giant enzymes composed of modules that house repeated sets of functional domains, which select, activate and couple amino acids drawn from a pool of nearly 500 potential building blocks. The structurally and stereochemically diverse peptides generated in this manner underlie the biosynthesis of a large sector of natural products. Many of their derived metabolites are bioactive such as the antibiotics vancomycin, bacitracin, daptomycin and the β-lactam-containing penicillins, cephalosporins and nocardicins. Penicillins and cephalosporins are synthesized from a classically derived non-ribosomal peptide synthetase tripeptide (from δ-(L-α-aminoadipyl)-L-cysteinyl-D-valine synthetase). Here we report an unprecedented non-ribosomal peptide synthetase activity that both assembles a serine-containing peptide and mediates its cyclization to the critical β-lactam ring of the nocardicin family of antibiotics. A histidine-rich condensation domain, which typically performs peptide bond formation during product assembly, also synthesizes the embedded four-membered ring. We propose a mechanism, and describe supporting experiments, that is distinct from the pathways that have evolved to the three other β-lactam antibiotic families: penicillin/cephalosporins, clavams and carbapenems. These findings raise the possibility that β-lactam rings can be regio- and stereospecifically integrated into engineered peptides for application as, for example, targeted protease inactivators.

  14. Augmenting ureagenesis in patients with partial carbamyl phosphate synthetase 1deficiency with N-carbamylglutamate

    Science.gov (United States)

    Ah Mew, Nicholas; McCarter, Robert; Daikhin, Yevgeny; Lichter, Uta; Nissim, Ilana; Yudkoff, Marc; Tuchman, and Mendel

    2014-01-01

    Identical studies employing stable isotopes were performed before and after a 3-day trial of oral N-carbamylglutamate (NCG) in 5 subjects with late onset carbamyl phosphate synthetase deficiency. NCG augmented ureagenesis and decreased plasma ammonia in 4 of 5 subjects. There was marked improvement in nitrogen metabolism with long-term NCG administration in one subject. PMID:24880889

  15. Augmenting ureagenesis in patients with partial carbamyl phosphate synthetase 1deficiency with N-carbamylglutamate

    OpenAIRE

    Ah Mew, Nicholas; McCarter, Robert; Daikhin, Yevgeny; Lichter, Uta; Nissim, Ilana; Yudkoff, Marc; Tuchman, and Mendel

    2014-01-01

    Identical studies employing stable isotopes were performed before and after a 3-day trial of oral N-carbamylglutamate (NCG) in 5 subjects with late onset carbamyl phosphate synthetase deficiency. NCG augmented ureagenesis and decreased plasma ammonia in 4 of 5 subjects. There was marked improvement in nitrogen metabolism with long-term NCG administration in one subject.

  16. Studies towards the synthesis of ATP analogs as potential glutamine synthetase inhibitors

    CSIR Research Space (South Africa)

    Salisu, S

    2011-05-01

    Full Text Available -1 Synthetic Communications, 41: 2216?2225 DOI: 10.1080/00397911.2010.501473 Studies Towards the Synthesis of ATP Analogs as Potential Glutamine Synthetase Inhibitors Sheriff Salisu a , Colin Kenyon b & Perry T. Kaye a a Department of Chemistry...

  17. Glutamine synthetase sequence evolution in the mycobacteria and their use as molecular markers for Actinobacteria speciation

    Directory of Open Access Journals (Sweden)

    Wiid Ian JF

    2009-02-01

    Full Text Available Abstract Background Although the gene encoding for glutamine synthetase (glnA is essential in several organisms, multiple glnA copies have been identified in bacterial genomes such as those of the phylum Actinobacteria, notably the mycobacterial species. Intriguingly, previous reports have shown that only one copy (glnA1 is essential for growth in M. tuberculosis, while the other copies (glnA2, glnA3 and glnA4 are not. Results In this report it is shown that the glnA1 and glnA2 encoded glutamine synthetase sequences were inherited from an Actinobacteria ancestor, while the glnA4 and glnA3 encoded GS sequences were sequentially acquired during Actinobacteria speciation. The glutamine synthetase sequences encoded by glnA4 and glnA3 are undergoing reductive evolution in the mycobacteria, whilst those encoded by glnA1 and glnA2 are more conserved. Conclusion Different selective pressures by the ecological niche that the organisms occupy may influence the sequence evolution of glnA1 and glnA2 and thereby affecting phylogenies based on the protein sequences they encode. The findings in this report may impact the use of similar sequences as molecular markers, as well as shed some light on the evolution of glutamine synthetase in the mycobacteria.

  18. Regulation of Amidase Formation in Mutants from Pseudomonas aeruginosa PAO Lacking Glutamine Synthetase Activity

    NARCIS (Netherlands)

    Janssen, Dick B.; Herst, Patricia M.; Joosten, Han M.L.J.; Drift, Chris van der

    1982-01-01

    The formation of amidase was studied in mutants from Pseudomonas aeruginosa PAO lacking glutamine synthetase activity. It appeared that catabolite repression of amidase synthesis by succinate was partially relieved when cellular growth was limited by glutamine. Under these conditions, a correlation

  19. Noncoding RNA of Glutamine Synthetase I Modulates Antibiotic Production in Streptomyces coelicolor A3(2)

    OpenAIRE

    D'Alia, Davide; Nieselt, Kay; Steigele, Stephan; Mueller, Jonas; Verburg, Ilse; Takano, Eriko; Alia, Davide D’; Müller, Jonas

    2010-01-01

    Overexpression of antisense chromosomal cis-encoded noncoding RNAss (ncRNAs) in glutamine synthetase I resulted in a decrease in growth, protein synthesis, and antibiotic production in Streptomyces coelicolor. In addition, we predicted 3,597 cis-encoded ncRNAs and validated 13 of them experimentally, including several ncRNAs that are differentially expressed in bacterial hormone-defective mutants.

  20. A novel therapeutic target for peripheral nerve injury-related diseases: aminoacyl-tRNA synthetases

    Directory of Open Access Journals (Sweden)

    Byung Sun Park

    2015-01-01

    Full Text Available Aminoacyl-tRNA synthetases (AminoARSs are essential enzymes that perform the first step of protein synthesis. Beyond their original roles, AminoARSs possess non-canonical functions, such as cell cycle regulation and signal transduction. Therefore, AminoARSs represent a powerful pharmaceutical target if their non-canonical functions can be controlled. Using AminoARSs-specific primers, we screened mRNA expression in the spinal cord dorsal horn of rats with peripheral nerve injury created by sciatic nerve axotomy. Of 20 AminoARSs, we found that phenylalanyl-tRNA synthetase beta chain (FARSB, isoleucyl-tRNA synthetase (IARS and methionyl-tRNA synthetase (MARS mRNA expression was increased in spinal dorsal horn neurons on the injured side, but not in glial cells. These findings suggest the possibility that FARSB, IARS and MARS, as a neurotransmitter, may transfer abnormal sensory signals after peripheral nerve damage and become a new target for drug treatment.

  1. ISOLATION AND CHARACTERIZATION OF THE RAT GENE FOR CARBAMOYLPHOSPHATE SYNTHETASE-I

    NARCIS (Netherlands)

    VANDENHOFF, MJB; VANDEZANDE, LPWGM; DINGEMANSE, MA; DAS, AT; LABRUYERE, W; MOORMAN, AFM; CHARLES, R; LAMERS, WH; Jacobus Mgn Van De Zande, Louis

    1995-01-01

    Carbamoylphosphate synthetase I (CbmPS) is first expressed in rat hepatocytes shortly before birth. After birth, expression of CbmPS gradually becomes confined to the hepatocytes surrounding the portal veins. To obtain insight into the spatiotemporal regulation of its expression, the rat CbmPS gene

  2. Draft Genome Sequences of Five Novel Polyketide Synthetase-Containing Mouse Escherichia coli Strains

    Science.gov (United States)

    Mannion, Anthony; Shen, Zeli; Feng, Yan; Garcia, Alexis

    2016-01-01

    We report herein the draft genomes of five novel Escherichia coli strains isolated from surveillance and experimental mice housed at MIT and the Whitehead Institute and describe their genomic characteristics in context with the polyketide synthetase (PKS)-containing pathogenic E. coli strains NC101, IHE3034, and A192PP.

  3. Structure of the gene encoding phosphoribosylpyrophosphate synthetase (prsA>) in Salmonella typhimurium

    DEFF Research Database (Denmark)

    Bower, Stanley G.; Hove-Jensen, Bjarne; Switzer, Robert L.

    1988-01-01

    The Salmonella typhimurium gene prsA, which encodes phosphoribosylpyrophosphate synthetase, has been cloned, and the nucleotide sequence has been determined. The amino acid sequence derived from the S. typhimurium gene is 99% identical to the derived Escherichia coli sequence and 47% identical to...

  4. Effects of univalent cations on the activity of particulate starch synthetase.

    Science.gov (United States)

    Nitsos, R E; Evans, H J

    1969-09-01

    An investigation was made to determine the univalent cation requirements of starch synthetase from a variety of plant species of economic importance. The particulate enzyme from sweet corn was shown to have an absolute requirement for potassium, with the optimum activation occurring at 0.05 M KCl. Rubidium, cesium, and ammonium were 80% as effective as potassium while sodium and lithium were respectively 21% and 8% as effective as potassium. The K(A) for potassium was determined to be 6 mM. In the case of the particulate starch synthetase from wheat, bush beans, field corn, soybeans, peas, or potatoes, considerable stimulation of enzyme activity was obtained by the addition of potassium to the reaction mixture. In these studies, low enzyme activity was observed in the absence of added potassium, but the content of endogenous univalent cations in the reactions may be sufficient to account for the activities observed. Anions of various types had no effect on starch synthetase activity. Divalent cations produced slight activation in the presence or absence of potassium. All efforts to show a potassium requirement for glycogen synthetase from rat liver have been negative.

  5. Changes in Activities of Glutamine Synthetase during Grain Filling and Their Relation to Rice Quality

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    Four japonica rice varieties differed in cooking and eating qualities were used in a pot experiment to study the relationship between the activities of glutamine synthetase during grain filling and rice quality. The activities of glutamine synthetase gradually increased and then declined as a single peak curve in the course of grain filling. The 15th day after heading was a turning point, before which the enzymatic activities in the inferior rice varieties with high protein content were higher than those in the superior rice varietie with low protein content, and after which it was converse. The activity of glutamine synthetase in grain was correlated with the taste meter value, peak viscosity and breakdown negatively at the early stage of grain filling whereas positively at the middle and late stages. Moreover, it was correlated with the protein content of rice grain and setback positively at the early stage and negatively at the middle and late stages. The correlation degree varied with the course of grain filling. From 15 days to 20 days after heading was a critical stage, in which the direction of correlation between the activity of glutamine synthetase and taste meter value and RVA properties of rice changed.

  6. 2'-phosphodiesterase and 2',5'-oligoadenylate synthetase activities in the lowest metazoans, sponge [porifera

    DEFF Research Database (Denmark)

    Saby, Emilie; Poulsen, Jesper Buchhave; Justesen, Just;

    2009-01-01

    Sponges [porifera], the most ancient metazoans, contain modules related to the vertebrate immune system, including the 2′,5′-oligoadenylate synthetase (OAS). The components of the antiviral 2′,5′-oligoadenylate (2–5A) system (OAS, 2′-Phosphodiesterase (2′-PDE) and RNAse L) of vertebrates have...

  7. Purification and properties of phosphoribosyl-diphosphate synthetase from Bacillus subtilis

    DEFF Research Database (Denmark)

    Arnvig, Kirsten; Hove-Jensen, Bjarne; Switzer, Robert L.

    1990-01-01

    Phosphoribosyl-diphosphate (PPRibP) synthetase from Bacillus subtiliis has been purified to near homogeneity from an Escherichia coli Δprs strain bearing the cloned B. subtilis prs gene, encoding PPRibP synthentase, on a plasmid. The Mr of the subunit (34,000) and its amino-terminal amino acid...

  8. Effect of glutamine synthetase inhibition on brain and interorgan ammonia metabolism in bile duct ligated rats

    DEFF Research Database (Denmark)

    Fries, Andreas W; Dadsetan, Sherry; Keiding, Susanne

    2014-01-01

    Ammonia has a key role in the development of hepatic encephalopathy (HE). In the brain, glutamine synthetase (GS) rapidly converts blood-borne ammonia into glutamine which in high concentrations may cause mitochondrial dysfunction and osmolytic brain edema. In astrocyte-neuron cocultures and brains...

  9. Platelets kill intraerythrocytic malarial parasites and mediate survival to infection.

    Science.gov (United States)

    McMorran, Brendan J; Marshall, Vikki M; de Graaf, Carolyn; Drysdale, Karen E; Shabbar, Meriam; Smyth, Gordon K; Corbin, Jason E; Alexander, Warren S; Foote, Simon J

    2009-02-01

    Platelets play a critical role in the pathogenesis of malarial infections by encouraging the sequestration of infected red blood cells within the cerebral vasculature. But platelets also have well-established roles in innate protection against microbial infections. We found that purified human platelets killed Plasmodium falciparum parasites cultured in red blood cells. Inhibition of platelet function by aspirin and other platelet inhibitors abrogated the lethal effect human platelets exert on P. falciparum parasites. Likewise, platelet-deficient and aspirin-treated mice were more susceptible to death during erythrocytic infection with Plasmodium chabaudi. Both mouse and human platelets bind malarial-infected red cells and kill the parasite within. These results indicate a protective function for platelets in the early stages of erythrocytic infection distinct from their role in cerebral malaria.

  10. Growth inhibition and stability of PgAFP from Penicillium chrysogenum against fungi common on dry-ripened meat products.

    Science.gov (United States)

    Delgado, Josué; Acosta, Raquel; Rodríguez-Martín, Andrea; Bermúdez, Elena; Núñez, Félix; Asensio, Miguel A

    2015-07-16

    Dry-ripened foods favor the development of a superficial fungal population that may include toxigenic molds. To combat unwanted molds, an antifungal protein from Penicillium chrysogenum (PgAFP) can be useful. The aim of the present work was to study the antimicrobial activity of PgAFP against microorganisms common in dry-ripened foods, and to evaluate its sensitivity to proteolytic enzymes and heat treatments that may be applied to foods, as well as to different pH values. The inhibitory effect of the purified protein on 38 microbial strains grown in culture medium was determined. PgAFP sensitivity to various proteases, heat treatments, and preincubation at different pH values was tested by means of the residual activity on selected reference strains. Inhibitory activity of PgAFP against unwanted molds was tested in a dry-fermented sausage. This protein exhibited potent inhibitory activity against unwanted molds, including the main mycotoxin-producing species of Aspergillus and Penicillium of concern for dry-ripened foods. PgAFP withstood most proteases, intense heat and a wide range of pH values. PgAFP efficiently reduced counts of A. flavus and P. restrictum inoculated on a dry-fermented sausage. This protein can be of interest to control hazardous molds in dry-ripened foods.

  11. Triplatin, a platelet aggregation inhibitor from the salivary gland of the triatomine vector of Chagas disease, binds to TXA(2) but does not interact with glycoprotein PVI.

    Science.gov (United States)

    Ma, Dongying; Assumpção, Teresa C F; Li, Yuan; Andersen, John F; Ribeiro, José; Francischetti, Ivo M B

    2012-01-01

    Salivary glands from haematophagous animals express a notable diversity of negative modulators of platelet function. Triplatin is an inhibitor of collagen-induced platelet aggregation which has been described as an antagonist of glycoprotein VI (GPVI). Because triplatin displays sequence homology to members of the lipocalin family of proteins, we investigated whether triplatin mechanism of action could be explained by interaction with pro-haemostatic prostaglandins. Our results demonstrate that triplatin inhibits platelet aggregation induced by low doses of collagen, thromboxane A2 (TXA(2)) mimetic (U46619), and arachidonic acid (AA). On the other hand, it does not inhibit platelet aggregation by convulxin, PMA, or low-dose ADP. Isothermal titration calorimetry (ITC) revealed that triplatin binds AA, cTXA(2), TXB(2), U46619 or prostaglandin (PG)H(2) mimetic (U51605). Consistent with its ligand specificity, triplatin induces relaxation of rat aorta contracted with U46619. Triplatin also interacts with PGF(2α) and PGJ(2), but not with leukotrienes, AA or biogenic amines. Surface plasmon resonance experiments failed to demonstrate interaction of triplatin with GPVI; it also did to inhibit platelet adhesion to fibrillar or soluble collagen. Because triplatin displays sequence similarity to apolipoprotein D (ApoD) - a lipocalin associated with high-density lipoprotein, ApoD was tested as a putative TXA(2)-binding molecule. ITC failed to demonstrate binding of ApoD to all prostanoids described above, or to AA. Furthermore, ApoD was devoid of inhibitory properties towards platelets activation by AA, collagen, or U46619. In conclusion, triplatin mechanism of action has been elucidated without ambiguity as a novel TXA(2)- and PGF(2α)- binding protein. It conceivably blocks platelet aggregation and vasoconstriction, thus contributing to successful blood feeding at the vector-host interface.

  12. Resveratrol preserves the function of human platelets stored for transfusion.

    Science.gov (United States)

    Lannan, Katie L; Refaai, Majed A; Ture, Sara K; Morrell, Craig N; Blumberg, Neil; Phipps, Richard P; Spinelli, Sherry L

    2016-03-01

    Stored platelets undergo biochemical, structural and functional changes that lead to decreased efficacy and safety of platelet transfusions. Not only do platelets acquire markers of activation during storage, but they also fail to respond normally to agonists post-storage. We hypothesized that resveratrol, a cardioprotective antioxidant, could act as a novel platelet storage additive to safely prevent unwanted platelet activation during storage, while simultaneously preserving normal haemostatic function. Human platelets treated with resveratrol and stored for 5 d released less thromboxane B2 and prostaglandin E2 compared to control platelets. Resveratrol preserved the ability of platelets to aggregate, spread and respond to thrombin, suggesting an improved ability to activate post-storage. Utilizing an in vitro model of transfusion and thromboelastography, clot strength was improved with resveratrol treatment compared to conventionally stored platelets. The mechanism of resveratrol's beneficial actions on stored platelets was partly mediated through decreased platelet apoptosis in storage, resulting in a longer half-life following transfusion. Lastly, an in vivo mouse model of transfusion demonstrated that stored platelets are prothrombotic and that resveratrol delayed vessel occlusion time to a level similar to transfusion with fresh platelets. We show resveratrol has a dual ability to reduce unwanted platelet activation during storage, while preserving critical haemostatic function.

  13. Platelet inhibition by nitrite is dependent on erythrocytes and deoxygenation.

    Directory of Open Access Journals (Sweden)

    Sirada Srihirun

    Full Text Available BACKGROUND: Nitrite is a nitric oxide (NO metabolite in tissues and blood, which can be converted to NO under hypoxia to facilitate tissue perfusion. Although nitrite is known to cause vasodilation following its reduction to NO, the effect of nitrite on platelet activity remains unclear. In this study, the effect of nitrite and nitrite+erythrocytes, with and without deoxygenation, on platelet activity was investigated. METHODOLOGY/FINDING: Platelet aggregation was studied in platelet-rich plasma (PRP and PRP+erythrocytes by turbidimetric and impedance aggregometry, respectively. In PRP, DEANONOate inhibited platelet aggregation induced by ADP while nitrite had no effect on platelets. In PRP+erythrocytes, the inhibitory effect of DEANONOate on platelets decreased whereas nitrite at physiologic concentration (0.1 µM inhibited platelet aggregation and ATP release. The effect of nitrite+erythrocytes on platelets was abrogated by C-PTIO (a membrane-impermeable NO scavenger, suggesting an NO-mediated action. Furthermore, deoxygenation enhanced the effect of nitrite as observed from a decrease of P-selectin expression and increase of the cGMP levels in platelets. The ADP-induced platelet aggregation in whole blood showed inverse correlations with the nitrite levels in whole blood and erythrocytes. CONCLUSION: Nitrite alone at physiological levels has no effect on platelets in plasma. Nitrite in the presence of erythrocytes inhibits platelets through its reduction to NO, which is promoted by deoxygenation. Nitrite may have role in modulating platelet activity in the circulation, especially during hypoxia.

  14. Stability of lyophilized human platelets loaded with small molecule carbohydrates.

    Science.gov (United States)

    Wang, J X; Yang, C; Wan, W; Liu, M X; Ren, S P; Quan, G B; Han, Y

    2011-01-01

    Long-term preservation of platelets is a great challenge for blood transfusion centers, due to the required narrow storage temperature arange (22 ± 2 degree C). Short shelf life and potential bacterial growth often lead to the shortage of high-quality platelets. Freeze-dried preservation is thus believed to be a potential solution for long-term platelet storage without losing the hemostasis function. Here we report a new platelet preservation method, which uses small molecule carbohydrates to extend storage time and to maintain platelet function. The activities of lyophilized platelets that were stabilized with small molecule carbohydrate (e.g., cell viability, mean platelet volume, activation characteristics, and aggregation kinetics) were maintained after storage of 30, 60, and 90 days at room temperature, 4 degree C, and -20 degree C. The recovery of freeze-dried platelets was 87 percent in comparison to fresh platelets. The mean platelet volume of rehydrated platelets increased (from 6.8 fl to 8.0 fl). About 40 percent of rehydrated platelets was in the early-activated stage (PCA-1 positive) and 30 percent was in the terminal-activated stage (CD62P positive). The cell viability was about 60 percent as measured with CMFDA vital probes. The aggregation rate of rehydrated platelets after 90-day storage was similar to fresh platelets stored at 22 degree C ± 2 degree C.

  15. Platelet production in hypoxic and RBC-transfused mice

    Energy Technology Data Exchange (ETDEWEB)

    McDonald, T.P.

    1978-01-01

    Platelet production rates were studied in hypoxic, red blood cell (RBC) transfused, and normal mice. In addition, platelet depletion was induced in some of the mice by injection of rabbit anti-mouse platelet serum (RAMPS) to stimulate platelet production. Hypoxia alone caused an increase in haematocrit and platelet count at 1 to 3 d, followed by a decrease in platelet counts to below normal values at 6 to 7 d. On the other hand, RBC transfusion caused increased haematocrit and decreased platelet count of mice at 1 to 4 d, with a return of platelet counts to normal by 5 to 6 d. Normal mice and mice transfused with RBC responded to platelet depletion with rebound-thrombocytosis with maximum platelet production 3 to 5 d later and elevated platelet counts on day 5 to 6. However, platelet production in platelet-depleted mice exposed to hypoxia was less marked, and platelet counts did not reach normal levels. The data are consistent with the hypothesis that hypoxia causes thrombocytopenia by stem cell competition between erythroid and megakaryocytic cell lines and/or inhibition of thrombopoietin production.

  16. Platelet activation determines the severity of thrombocytopenia in dengue infection

    Science.gov (United States)

    Ojha, Amrita; Nandi, Dipika; Batra, Harish; Singhal, Rashi; Annarapu, Gowtham K.; Bhattacharyya, Sankar; Seth, Tulika; Dar, Lalit; Medigeshi, Guruprasad R.; Vrati, Sudhanshu; Vikram, Naval K.; Guchhait, Prasenjit

    2017-01-01

    Thrombocytopenia is common in patients with dengue virus (DENV) infections. With a focus on understanding the possible mechanism of thrombocytopenia in DENV infections we described a direct correlation between activation and depletion of platelets in patients. Our data showed a sharp decrease in platelet counts at day 4 of fever in patients. The high DENV genome copies in platelets correlated directly with the elevated platelet activation along with increased binding of complement factor C3 and IgG on their surface at day 4. Recovery in platelet count was observed on day 10 through day 6 and 8 with simultaneous decrease in platelet activation markers. Further, our in vitro data supported the above observations describing a concentration-dependent increase in platelet activation by DENV serotype-2. The high copy number of DENV2 genome in the platelet pellet correlated directly with platelet activation, microparticle generation and clot formation. Furthermore the DENV2-activated platelets were phagocytosed in large numbers by the monocytes. The DENV2-mediated lysis and clearance of platelets were abrogated in presence of platelet activation inhibitor, prostacyclin. These observations collectively suggest that platelet activation status is an important determinant of thrombocytopenia in dengue infections. A careful strategy of inactivation of platelets may rescue them from rapid destruction during DENV infections. PMID:28139770

  17. EFFECT OF UP-REGULATION OF S-ADOMET SYNTHETASE ON TAXOL-INDUCED APOPTOSIS IN HUMAN BREAST CANCER CELLS

    Institute of Scientific and Technical Information of China (English)

    Chen Lirong; Zheng Shu; Fan Weimin; Zhang Suzhan

    1998-01-01

    Objective:To investigate the gene regulation of taxolinduced apoptosis. Methods: Northern blot hybridization,enzyme activity assay of S-AdoMet synthetase and flow cytometry were performed in the investigation of expression in the Mrna level and biological action of SAdoMet synthetase in taxol-induced apoptosis in human breast cancer cell line (Bcap 37). Results: Up-regulation of S-AdoMet synthetase expression was resulted by taxol treatment and the expression peaked at 48hours. Moreover,the up-regulation of S-AdoMet synthetase was associated with cytotoxicity of antimicrotubule agents including taxol and colchicine.Inhibition rate of S-AdoMet synthetase activity by 1%DMSO was 34% in taxol-treated cells and 14% in taxoluntreated cells compared to control groups, respectively.Posttreatment with 1% DMSO following pretreatment with individual antitumor agent for 3 hrs promoted apoptotic cell death of taxol-,colchicine-,and adriamycintreated Bcap37 cells. Conclusion : The induction of apoptosis enhanced by post-treatment with DMSO in taxol-treated cells is probably linked to its inhibition on enzyme activity of S-AdoMet synthetase ,suggesting that the increased expression of S-AdoMet synthetase possibly plays an important role in protecting cells from DNA fragmentation in taxol-induced apoptosis.

  18. The effect of portacaval anastomosis on the expression of glutamine synthetase and ornithine aminotransferase in perivenous hepatocytes.

    Science.gov (United States)

    da Silva, Robin; Levillain, Oliver; Brosnan, John T; Araneda, Silvia; Brosnan, Margaret E

    2013-05-01

    There is functional zonation of metabolism across the liver acinus, with glutamine synthetase restricted to a narrow band of cells around the terminal hepatic venules. Portacaval anastomosis, where there is a major rerouting of portal blood flow from the portal vein directly to the vena cava bypassing the liver, has been reported to result in a marked decrease in the activity of glutamine synthetase. It is not known whether this represents a loss of perivenous hepatocytes or whether there is a specific loss of glutamine synthetase. To answer this question, we have determined the activity of glutamine synthetase and another enzyme from the perivenous compartment, ornithine aminotransferase, as well as the immunochemical localization of both glutamine synthetase and ornithine aminotransferase in rats with a portacaval shunt. The portacaval shunt caused a marked decrease in glutamine synthetase activity and an increase in ornithine aminotransferase activity. Immunohistochemical analysis showed that the glutamine synthetase and ornithine aminotransferase proteins maintained their location in the perivenous cells. These results indicate that there is no generalized loss of perivenous hepatocytes, but rather, there is a significant alteration in the expression of these proteins and hence metabolism in this cell population.

  19. Anti-platelet Therapy Resistance – Concept, Mechanisms and Platelet Function Tests in Intensive Care Facilities

    Directory of Open Access Journals (Sweden)

    Mărginean Alina

    2016-01-01

    Full Text Available It is well known that critically ill patients require special attention and additional consideration during their treatment and management. The multiple systems and organ dysfunctions, typical of the critical patient, often results in different patterns of enteral absorption in these patients. Anti-platelet drugs are the cornerstone in treating patients with coronary and cerebrovascular disease. Dual anti-platelet therapy with aspirin and clopidogrel is the treatment of choice in patients undergoing elective percutaneous coronary interventions and is still widely used in patients with acute coronary syndromes. However, despite the use of dual anti-platelet therapy, some patients continue to experience cardiovascular ischemic events. Recurrence of ischemic events is partly attributed to the fact that some patients have poor inhibition of platelet reactivity despite treatment. These patients are considered low- or nonresponders to therapy. The underlying mechanisms leading to resistance are not yet fully elucidated and are probably multifactorial, cellular, genetic and clinical factors being implicated. Several methods have been developed to asses platelet function and can be used to identify patients with persistent platelet reactivity, which have an increased risk of thrombosis. In this paper, the concept of anti-platelet therapy resistance, the underlying mechanisms and the methods used to identify patients with low responsiveness to anti-platelet therapy will be highlighted with a focus on aspirin and clopidogrel therapy and addressing especially critically ill patients.

  20. Molecular cloning and characterization of glutamine synthetase, a tegumental protein from Schistosoma japonicum.

    Science.gov (United States)

    Qiu, Chunhui; Hong, Yang; Cao, Yan; Wang, Fei; Fu, Zhiqiang; Shi, Yaojun; Wei, Meimei; Liu, Shengfa; Lin, Jiaojiao

    2012-12-01

    Glutamine synthetase catalyzes the synthesis of glutamine, providing nitrogen for the production of purines, pyrimidines, amino acids, and other compounds required in many pivotal cellular events. Herein, a full-length cDNA encoding Schistosoma japonicum glutamine synthetase (SjGS) was isolated from 21-day schistosomes. The entire open reading frame of SjGS contains a 1,095-bp coding region corresponding to 364 amino acids with a calculated molecular weight of 40.7 kDa. NCBIP blast shows that the putative amino acid of SjGS contains a classic β-grasp domain and a catalytic domain of glutamine synthetase. The relative mRNA expression of SjGS was evaluated in 7-, 13-, 21-, 28-, 35-, and 42-day worms of S. japonicum in the final host and higher expression at day 21, and 42 worms were observed. This protein was also detected in worm extracts using Western blot. Immunofluorescence studies indicated that the SjGS protein was mainly distributed on tegument and parenchyma in 28-day adult worms. The recombinant glutamine synthetase with a molecular weight of 45 kDa was expressed in Escherichia coli and purified in its active form. The enzyme activity of the recombinant protein was 3.30 ± 0.67 U.μg-1. The enzyme activity was highly stable over a wide range of pH (6-9) and temperature (25-40 °C) under physiological conditions. The transcription of SjGS was upregulated in praziquantel-treated worms at 2-, 4-, and 24-h posttreatment compared with the untreated control. As a first step towards the clarification of the role of glutamine synthetase in schistosome species, we have cloned and characterized cDNAs encoding SjGS in S. japonicum, and the data presented suggest that SjGS is an important molecule in the development of the schistosome.

  1. Regulation of the intersubunit ammonia tunnel in Mycobacterium tuberculosis glutamine-dependent NAD[superscript +] synthetase

    Energy Technology Data Exchange (ETDEWEB)

    Chuenchor, Watchalee; Doukov, Tzanko I.; Resto, Melissa; Chang, Andrew; Gerratana, Barbara (SSRL); (Maryland)

    2012-08-31

    Glutamine-dependent NAD{sup +} synthetase is an essential enzyme and a validated drug target in Mycobacterium tuberculosis (mtuNadE). It catalyses the ATP-dependent formation of NAD{sup +} from NaAD{sup +} (nicotinic acid-adenine dinucleotide) at the synthetase active site and glutamine hydrolysis at the glutaminase active site. An ammonia tunnel 40 {angstrom} (1 {angstrom} = 0.1 nm) long allows transfer of ammonia from one active site to the other. The enzyme displays stringent kinetic synergism; however, its regulatory mechanism is unclear. In the present paper, we report the structures of the inactive glutaminase C176A variant in an apo form and in three synthetase-ligand complexes with substrates (NaAD{sup +}/ATP), substrate analogue {l_brace}NaAD{sup +}/AMP-CPP (adenosine 5'-[{alpha},{beta}-methylene]triphosphate){r_brace} and intermediate analogues (NaAD{sup +}/AMP/PPi), as well as the structure of wild-type mtuNadE in a product complex (NAD{sup +}/AMP/PPi/glutamate). This series of structures provides snapshots of the ammonia tunnel during the catalytic cycle supported also by kinetics and mutagenesis studies. Three major constriction sites are observed in the tunnel: (i) at the entrance near the glutaminase active site; (ii) in the middle of the tunnel; and (iii) at the end near the synthetase active site. Variation in the number and radius of the tunnel constrictions is apparent in the crystal structures and is related to ligand binding at the synthetase domain. These results provide new insight into the regulation of ammonia transport in the intermolecular tunnel of mtuNadE.

  2. Nephropathy in type 1 diabetes is associated with increased circulating activated platelets and platelet hyperreactivity

    DEFF Research Database (Denmark)

    Tarnow, Inge; Michelson, Alan D.; Barnard, Marc R.;

    2009-01-01

    Patients with diabetes mellitus (DM) have increased platelet activation compared to non-diabetic controls. Platelet hyperreactivity has been associated with adverse cardiovascular outcomes in Type 2 DM, and with diabetic nephropathy. We investigated the relationship between platelet activation...... and nephropathy in Type 1 DM. Patients with Type 1 DM and diabetic nephropathy (n = 35), age- and sex-matched Type 1 DM patients with persistent normoalbuminuria (n = 51), and healthy age- and sex-matched controls (n = 30) were studied. Platelet surface P-selectin, platelet surface activated GPIIb/IIIa, monocyte...... to 0.5 or 20 microM ADP) was higher in nephropathy patients compared with normoalbuminuric patients (P = 0.027), and non-diabetic controls (P = 0.0057). NPAs were higher in nephropathy patients compared to normoalbuminuric patients (P = 0.0088). MPAs were higher in nephropathy patients compared to non-diabetic...

  3. A General Aspect of Platelet Rich Plasma

    Directory of Open Access Journals (Sweden)

    Onur ORAL

    2015-08-01

    Full Text Available The aim of this scientific paper is to introduce Platelet Rich Plasma (PRP cure method by people who never heard about it. People can hurt their selves, thus they can have damaged tissue; for instance broken bone, a scar or a wounded area. Furthe rmore damaged tissue can be a cartilage tissue, which takes very long time to heal. Platelets, those exist in the veins as thrombus, come up to repair those damaged tissues. However, platelets would be insufficient to cure damaged area in a short time. At this point PRP cure method give a hand to the healing process. By centrifuging people’s own blood via special kits, platelets can be separated from blood cells as plasma. That plasma’s platelet density is 3 - 5 times greater than that blood’s platelet densit y. Afterwards PRP method is implemented by injection of plasma to the damaged area or tissue. After implementation of 2 - 4 sessions per week, damaged tissue can be regenerated. It is fast healing method because densified platelet plasma is used; and it is s afe because that plasma is obtained from people’s own blood. PRP can be implemented on many areas; for instance on dentistry, sports medicine, different kind of surgeries such as plastic, vascular or orthopedic and so on. When soccer players brake their le gs, their sports life come to the end, but what if their broken legs was healed better and faster than general healing process? To sum up, PRP is very safe and the future of healing process.

  4. Calcium-binding proteins from human platelets

    Energy Technology Data Exchange (ETDEWEB)

    Gogstad, G.O.; Krutnes, M.B.; Solum, N.O.

    1983-06-01

    Calcium-binding platelet proteins were examined by crossed immunoelectrophoresis of solubilized platelets against antibodies to whole platelets followed by incubation of the immunoplates with /sup 45/Ca/sup 2 +/ and autoradiography. When the immunoplates had been pretreated with EDTA at pH 9.0 in order to remove divalent cations, three immunoprecipitates were markedly labelled with /sup 45/Ca/sup 2 +/. These corresponded to the glycoprotein IIb-IIIa complex, glycoprotein Ia and a presently unidentified antigen termed G18. These antigens were membrane-bound and surface-oriented. When an excess of EDTA was introduced in the incubation media the results revealed that the glycoprotein IIb-IIIa complex and antigen G18, but not glycoprotein Ia, contained sites with a stronger affinity for calcium than has EDTA at pH 7.4. Immunoprecipitates of the separate glycoproteins IIb and IIIa both bound calcium in the same manner as the glycoprotein IIb-IIIa complex. As another approach, platelet-rich plasma was incubated with /sup 45/Ca/sup 2 +/ prior to crossed immunoelectrophoresis of the solubilized platelets. A single immunoprecipitate was weakly labelled. This did not correspond to any of the immunoprecipitates which were visible after staining with Coomassie blue. The labelling of this antigen was markedly increased when the platelet-rich plasma had been preincubated with EDTA and in this case a weak labelling of the glycoprotein IIB-IIIa precipitate also became apparent. No increased incorporation of calcium occured in any of these immunoprecipitates when the platelets were aggregated with ADP in the presence of /sup 45/Ca/sup 2 +/.

  5. Platelets of patients with chronic kidney disease demonstrate deficient platelet reactivity in vitro

    Directory of Open Access Journals (Sweden)

    van Bladel Esther R

    2012-09-01

    Full Text Available Abstract Background In patients with chronic kidney disease studies focusing on platelet function and properties often are non-conclusive whereas only few studies use functional platelet tests. In this study we evaluated a recently developed functional flow cytometry based assay for the analysis of platelet function in chronic kidney disease. Methods Platelet reactivity was measured using flow cytometric analysis. Platelets in whole blood were triggered with different concentrations of agonists (TRAP, ADP, CRP. Platelet activation was quantified with staining for P-selectin, measuring the mean fluorescence intensity. Area under the curve and the concentration of half-maximal response were determined. Results We studied 23 patients with chronic kidney disease (9 patients with cardiorenal failure and 14 patients with end stage renal disease and 19 healthy controls. Expression of P-selectin on the platelet surface measured as mean fluorescence intensity was significantly less in chronic kidney disease patients compared to controls after maximal stimulation with TRAP (9.7 (7.9-10.8 vs. 11.4 (9.2-12.2, P = 0.032, ADP (1.6 (1.2-2.1 vs. 2.6 (1.9-3.5, P = 0.002 and CRP (9.2 (8.5-10.8 vs. 11.5 (9.5-12.9, P = 0.004. Also the area under the curve was significantly different. There was no significant difference in half-maximal response between both groups. Conclusion In this study we found that patients with chronic kidney disease show reduced platelet reactivity in response of ADP, TRAP and CRP compared to controls. These results contribute to our understanding of the aberrant platelet function observed in patients with chronic kidney disease and emphasize the significance of using functional whole blood platelet activation assays.

  6. Platelet receptor polymorphisms do not influence Staphylococcus aureus-platelet interactions or infective endocarditis.

    Science.gov (United States)

    Daga, Shruti; Shepherd, James G; Callaghan, J Garreth S; Hung, Rachel K Y; Dawson, Dana K; Padfield, Gareth J; Hey, Shi Y; Cartwright, Robyn A; Newby, David E; Fitzgerald, J Ross

    2011-03-01

    Cardiac vegetations result from bacterium-platelet adherence, activation and aggregation, and are associated with increased morbidity and mortality in infective endocarditis. The GPIIb/IIIa and FcγRIIa platelet receptors play a central role in platelet adhesion, activation and aggregation induced by endocarditis pathogens such as Staphylococcus aureus, but the influence of known polymorphisms of these receptors on the pathogenesis of infective endocarditis is unknown. We determined the GPIIIa platelet antigen Pl(A1/A2) and FcγRIIa H131R genotype of healthy volunteers (n = 160) and patients with infective endocarditis (n = 40), and investigated the influence of these polymorphisms on clinical outcome in infective endocarditis and S. aureus-platelet interactions in vitro. Platelet receptor genotype did not correlate with development of infective endocarditis, vegetation characteristics on echocardiogram or the composite clinical end-point of embolism, heart failure, need for surgery or mortality (P > 0.05 for all), even though patients with the GPIIIa Pl(A1/A1) genotype had increased in vivo platelet activation (P = 0.001). Furthermore, neither GPIIIa Pl(A1/A2) nor FcγRIIa H131R genotype influenced S. aureus-induced platelet adhesion, activation or aggregation in vitro (P > 0.05). Taken together, our data suggest that the GPIIIa and FcγRIIa platelet receptor polymorphisms do not influence S. aureus-platelet interactions in vitro or the clinical course of infective endocarditis.

  7. Platelet receptor polymorphisms do not influence Staphylococcus aureus–platelet interactions or infective endocarditis

    Science.gov (United States)

    Daga, Shruti; Shepherd, James G.; Callaghan, J. Garreth S.; Hung, Rachel K.Y.; Dawson, Dana K.; Padfield, Gareth J.; Hey, Shi Y.; Cartwright, Robyn A.; Newby, David E.; Fitzgerald, J. Ross

    2011-01-01

    Cardiac vegetations result from bacterium–platelet adherence, activation and aggregation, and are associated with increased morbidity and mortality in infective endocarditis. The GPIIb/IIIa and FcγRIIa platelet receptors play a central role in platelet adhesion, activation and aggregation induced by endocarditis pathogens such as Staphylococcus aureus, but the influence of known polymorphisms of these receptors on the pathogenesis of infective endocarditis is unknown. We determined the GPIIIa platelet antigen PlA1/A2 and FcγRIIa H131R genotype of healthy volunteers (n = 160) and patients with infective endocarditis (n = 40), and investigated the influence of these polymorphisms on clinical outcome in infective endocarditis and S. aureus–platelet interactions in vitro. Platelet receptor genotype did not correlate with development of infective endocarditis, vegetation characteristics on echocardiogram or the composite clinical end-point of embolism, heart failure, need for surgery or mortality (P > 0.05 for all), even though patients with the GPIIIa PlA1/A1 genotype had increased in vivo platelet activation (P = 0.001). Furthermore, neither GPIIIa PlA1/A2 nor FcγRIIa H131R genotype influenced S. aureus-induced platelet adhesion, activation or aggregation in vitro (P > 0.05). Taken together, our data suggest that the GPIIIa and FcγRIIa platelet receptor polymorphisms do not influence S. aureus–platelet interactions in vitro or the clinical course of infective endocarditis. PMID:21044892

  8. Exploring the Powerful Ionised Wind in the Seyfert Galaxy PG1211+143

    Science.gov (United States)

    Pounds, Ken

    2013-10-01

    Highly-ionised high-speed winds in AGN (UFOs) were first detected with XMM-Newton a decade ago, and are now established as a key factor in the study of SMBH accretion, and in the growth and metal enrichment of their host galaxies. However, information on the ionisation and dynamical structure, and the ultimate fate of UFOs remains very limited. We request a 600ks extended XMM-Newton study of the prototype UFO PG1211+143 in AO-13, to obtain high quality EPIC and RGS spectra, to map the flow structure and variability, while seeking evidence for the anticipated interaction with the ISM and possible conversion of the energetic wind to a momentum-driven flow.

  9. KAJIAN SISTEM PENGUKURAN KINERJA PABRIK GULA (STUDI KASUS : PG SUBANG JAWA BARAT

    Directory of Open Access Journals (Sweden)

    Rohmatulloh Rohmatulloh

    2011-08-01

    Full Text Available Normal 0 false false false MicrosoftInternetExplorer4 The best apllying practice of performance management can lead to increase business competitiveness. The objective of this study was to describe of how performance measurement systems that has been conducted at PG Subang West Java to achive success areas of sugarcane factory. The systems was built to adopt from integrated dynamic performance systems (IDPMS model. The models integrates of four functional areas : corporate management, plant management, shop floor, and process improvement teams (bina sarana tani and lab. QC. Each fungsional areas were linked through the specification, reporting, and dynamic updating of the defined areas of success, performance measure, and performance standard. Understanding  interrelationships of performance measurements provides the foundation for more focused improvement efforts

  10. An exploratory study of the hard X-ray variability properties of PG quasars with RXTE

    CERN Document Server

    Guainazzi, M; Giallongo, E; Laor, A; Elvis, M; Siemiginowska, A L

    2000-01-01

    We have monitored with the RXTE PCA the variability pattern of the 2-20 keV flux in four PG quasars (QSOs) from the Laor et al. (1994) sample. Six observations of each target at regular intervals of 1 day were performed. The sample comprises objects with extreme values of Balmer line width (and hence soft X-ray steepness) and spans about one order of magnitude in luminosity. The most robust result is that the variability amplitude decreases as energy increases. Several options for a possible ultimate driver of the soft and hard X-ray variability, such as the influx rate of Comptonizing relativistic particles, instabilities in the accretion flow or the number of X-ray active sites, are consistent with our results.

  11. 露凝而白,昼夜平分——Pg.lost

    Institute of Scientific and Technical Information of China (English)

    高尔吉亚

    2007-01-01

    @@ 在Pg.lost的Myspace首页的"Influences"栏目上一溜排开了一群熟悉的名字,全是Post Rock界响当当的名字,再来看看那抽象的唱片封套设计,不需要拆开唱片,你已经基本揣摩出其中会是什么模样了.值得一提的是,这又是一个来自瑞典的乐队,这也再次颠覆了Indie Pop迷们对瑞典的传统印象,音乐与国家无关,虽然一个国家或民族会在创作音乐中带有自身的气质,但并不证明绝对.

  12. Models of Five Absorption Line Systems Along the Line of Sight Toward PG0117+213

    CERN Document Server

    Masiero, J R; Ding, J; Churchill, C W; Kacprzak, G G

    2005-01-01

    We present our investigation into the physical conditions of the gas in five intervening quasar absorption line systems along the line of sight toward the quasar PG 0117+213, with redshifts of z=0.57, z=0.72, z=1.04, z=1.32 and z=1.34. Photoionization modeling of HST, Keck I, and Palomar data, using the code Cloudy, is employed to derive densities and metallicities of the multiple phases of gas required to fit the absorption profile for each system. We discuss the implications of these models for galaxy evolution, including the interpretation of ``CIV deficiency'' and damped Lyman alpha absorbers (DLAs), and the relationships between galaxy morphology, galaxy luminosity, and absorption signature.

  13. Arterial supply to the cloacal bursa of Hybro PG lineage hens (Gallus gallus

    Directory of Open Access Journals (Sweden)

    Frederico Ozanam Carneiro e Silva

    2009-12-01

    Full Text Available A study was carried out on the origin, number and disposition of the arterial vessels and their branches which irrigated the cloacal bursas of 30 hens (Gallus gallus of the Hybro PG lineage. First of all, the left isquiadic artery from the samples was cannulated and injected with a 50% colored solution of Neoprene latex “450”; then, we continued the experiment with dissection whose results confi rmed that the cloacal bursa was supplied by direct branches from the left and right internal pudendal arteries and bursocloacal arteries in 100% of the cases, varying only in terms of the numbers and disposition of their branches. There were also some branches from the median caudal artery (23% and left external pudendal (3.33%. The total number of branches varied from 1 to 4 and their distribution was unique in each sample.

  14. Possible Quasi-Periodic Gamma-ray Emission from Blazar PG 1553+113

    Science.gov (United States)

    Thompson, David; Cutini, Sara; Ciprini, Stefano; Larsson, Stefan; Stamerra, Antonio; Fermi Large Area Telescope Collaboration

    2017-01-01

    We report an update on a possible gamma-ray and multiwavelength nearly periodic oscillation in an active galactic nucleus. Data from the Fermi Large Area Telescope exhibit an apparent quasi-periodicity in the gamma-ray flux (E > 100 MeV) from the GeV/TeV BL Lac object PG 1553+113. The indication of a 2.18 +/- 0.08 year period gamma-ray cycle is strengthened by correlated oscillations observed in radio and optical fluxes, through data collected in the Owens Valley Radio Observatory, Tuorla, Katzman Automatic Imaging Telescope, and Catalina Sky Survey monitoring programs and Swift-UVOT. Further long-term multiwavelength monitoring of this blazar may discriminate among the possible explanations for this quasi-periodicity.

  15. Evidence for Quasi-periodic Modulation in the Gamma-ray Blazar PG 1553+113

    CERN Document Server

    Ackermann, M; Albert, A; Atwood, W B; Baldini, L; Ballet, J; Barbiellini, G; Bastieri, D; Gonzalez, J Becerra; Bellazzini, R; Bissaldi, E; Blandford, R D; Bloom, E D; Bonino, R; Bottacini, E; Bregeon, J; Bruel, P; Buehler, R; Buson, S; Caliandro, G A; Cameron, R A; Caputo, R; Caragiulo, M; Caraveo, P A; Cavazzuti, E; Cecchi, C; Chekhtman, A; Chiang, J; Chiaro, G; Ciprini, S; Cohen-Tanugi, J; Conrad, J; Cutini, S; D'Ammando, F; De Angelis, A; De Palma, F; Desiante, R; Di Venere, L; Dominguez, A; Drell, P S; Favuzzi, C; Fegan, S J; Ferrara, E C; Focke, W B; Fuhrmann, L; Fukazawa, Y; Fusco, P; Gargano, F; Gasparrini, D; Giglietto, N; Giommi, P; Giordano, F; Giroletti, M; Godfrey, G; Green, D; Grenier, I A; Grove, J E; Guiriec, S; Harding, A K; Hays, E; Hewitt, J W; Hill, A B; Horan, D; Jogler, T; Johannesson, G; Johnson, A S; Kamae, T; Kuss, M; Larsson, S; Latronico, L; Li, J; Li, L; Longo, F; Loparco, F; Lott, B; Lovellette, M N; Lubrano, P; Magill, J; Maldera, S; Manfreda, A; Max-Moerbeck, W; Mayer, M; Mazziotta, M N; Mcenery, J E; Michelson, P F; Mizuno, T; Monzani, M E; Morselli, A; Moskalenko, I V; Murgia, S; Nuss, E; Ohno, M; Ohsugi, T; Ojha, R; Omodei, N; Orlando, E; Ormes, J F; Paneque, D; Pearson, T J; Perkins, J S; Perri, M; Pesce-Rollins, M; Petrosian, V; Piron, F; Pivato, G; Porter, T A; Raino', S; Rando, R; Razzano, M; Readhead, A; Reimer, A; Reimer, O; Schulz, A; Sgro', C; Siskind, E J; Spada, F; Spandre, G; Spinelli, P; Suson, D J; Takahashi, H; Thayer, J B; Thompson, D J; Tibaldo, L; Torres, D F; Tosti, G; Troja, E; Uchiyama, Y; Vianello, G; Wood, K S; Wood, M; Zimmer, S; Berdyugin, A; Corbet, R H D; Hovatta, T; Lindfors, E; Nilsson, K; Reinthal, R; Sillanpaa, A; Stamerra, A; Takalo, L O; Valtonen, M J

    2015-01-01

    We report for the first time a gamma-ray and multiwavelength nearly-periodic oscillation in an active galactic nucleus. Using the Fermi Large Area Telescope (LAT) we have discovered an apparent quasi-periodicity in the gamma-ray flux (E>100 MeV) from the GeV/TeV BL Lac object PG 1553+113. The marginal significance of the 2.18 +/- 0.08 year-period gamma-ray cycle, seen in 3.5 oscillation maxima observed, is corroborated by correlated oscillations observed in radio and optical fluxes, through data collected in the OVRO, Tuorla, KAIT, and CSS monitoring programs and Swift UVOT. The optical cycle appearing in sim 10 years of data has a similar period, while the 15 GHz oscillation is less regular. Further long-term multi-wavelength monitoring of this blazar may discriminate among the possible explanations for this quasi-periodicity.

  16. Spectral properties of the Narrow-Line Seyfert 1 Quasar PG1211+143

    CERN Document Server

    Janiuk, A; Madejski, G M; Janiuk, Agnieszka; Czerny, Bozena; Madejski, Grzegorz M.

    2001-01-01

    We propose a theoretical model to explain the spectrum of the quasar PG1211+143 emitted in the Optical/X-ray bands. In particular, we suggest that the inner accretion disk may develop a warm, optically thick skin, which produces a profound emission feature observed in the soft X-ray band. This is well modelled with the Comptonized black body emission. The same warm, mildly ionized medium may also be responsible for the hard X-ray reflection and the presence of the iron $K_{\\alpha}$ line. However, in our model it still remains an open question, whether the seed photons for Comptonization come from the cold accretion disc or from the hotter plasma. High resolution spectroscopy available through the Chandra and XMM data may provide now an independent test of the physical conditions in the Comptonizing and reflecting warm skin.

  17. Surface lipoproteome of Mycoplasma hominis PG21 and differential expression after contact with human dendritic cells.

    Science.gov (United States)

    Goret, Julien; Le Roy, Chloé; Touati, Arabella; Mesureur, Jennifer; Renaudin, Hélène; Claverol, Stéphane; Bébéar, Cécile; Béven, Laure; Pereyre, Sabine

    2016-01-01

    To assess the lipoproteins that are involved in the interaction between Mycoplasma hominis and human dendritic cells. The surface lipoproteome of M. hominis PG21 was characterized by using Triton X-114 extraction and LC-MS/MS identification. The transcriptional changes in lipoprotein genes upon contact with human dendritic cells were determined by using reverse transcription quantitative PCR after identification of reference genes suitable for normalization. A large-scale overexpression of lipoprotein genes was observed with 21 upregulated transcripts. Seven genes of unknown function were M. hominis species specific and six genes were putatively associated with increased nutrient capture from the host cell and adhesion. M. hominis regulates lipoprotein gene expression and may use species-specific mechanisms during the host colonization process.

  18. PG 1002+506: a Be Star Apparently at Z > +10 KPC

    Science.gov (United States)

    Ringwald, F. A.; Rolleston, W. R. J.; Saffer, R. A.; Thorstensen, John R.

    1997-12-01

    PG 1002+506 is found to be a Be star, one of two so far found by the Palomar-Green survey. Its spectrum is classified as a B5+/- 1 Ve, with T_eff = 14,900 +/- 1200, log g = 4.2 +/- 0.2, and v sin i = 340 +/- 50 km s(-1) . At b = +51(deg) , its height above the Galactic plane would therefore be Z = +10.8 kpc, putting this apparently young, rapidly rotating star well into the Galactic halo. Its heliocentric radial velocity is found to be -2 +/- 15 km s(-1) , consistent with either having been formed in the Galactic disk and subsequently ejected, or having been formed in the halo.

  19. LptO (PG0027) Is Required for Lipid A 1-Phosphatase Activity in Porphyromonas gingivalis W50.

    Science.gov (United States)

    Rangarajan, Minnie; Aduse-Opoku, Joseph; Hashim, Ahmed; McPhail, Graham; Luklinska, Zofia; Haurat, M Florencia; Feldman, Mario F; Curtis, Michael A

    2017-06-01

    Porphyromonas gingivalis produces outer membrane vesicles (OMVs) rich in virulence factors, including cysteine proteases and A-LPS, one of the two lipopolysaccharides (LPSs) produced by this organism. Previous studies had suggested that A-LPS and PG0027, an outer membrane (OM) protein, may be involved in OMV formation. Their roles in this process were examined by using W50 parent and the ΔPG0027 mutant strains. Inactivation of PG0027 caused a reduction in the yield of OMVs. Lipid A from cells and OMVs of P. gingivalis W50 and the ΔPG0027 mutant strains were analyzed by matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS). Lipid A from W50 cells contained bis-P-pentaacyl, mono-P-pentaacyl, mono-P-tetraacyl, non-P-pentaacyl, and non-P-tetraacyl species, whereas lipid A from ΔPG0027 mutant cells contained only phosphorylated species; nonphosphorylated species were absent. MALDI-TOF/TOF tandem MS of mono-P-pentaacyl (m/z 1,688) and mono-P-tetraacyl (m/z 1,448) lipid A from ΔPG0027 showed that both contained lipid A 1-phosphate, suggesting that the ΔPG0027 mutant strain lacked lipid A 1-phosphatase activity. The total phosphatase activities in the W50 and the ΔPG0027 mutant strains were similar, whereas the phosphatase activity in the periplasm of the ΔPG0027 mutant was lower than that in W50, supporting a role for PG0027 in lipid A dephosphorylation. W50 OMVs were enriched in A-LPS, and its lipid A did not contain nonphosphorylated species, whereas lipid A from the ΔPG0027 mutant (OMVs and cells) contained similar species. Thus, OMVs in P. gingivalis are apparently formed in regions of the OM enriched in A-LPS devoid of nonphosphorylated lipid A. Conversely, dephosphorylation of lipid A through a PG0027-dependent process is required for optimal formation of OMVs. Hence, the relative proportions of nonphosphorylated and phosphorylated lipid A appear to be crucial for OMV formation in this organism.IMPORTANCE Gram

  20. Magnetically Driven Accretion Disk Winds and Ultra-fast Outflows in PG 1211+143

    Science.gov (United States)

    Fukumura, Keigo; Tombesi, Francesco; Kazanas, Demosthenes; Shrader, Chris; Behar, Ehud; Contopoulos, Ioannis

    2015-05-01

    We present a study of X-ray ionization of MHD accretion-disk winds in an effort to constrain the physics underlying the highly ionized ultra-fast outflows (UFOs) inferred by X-ray absorbers often detected in various sub classes of Seyfert active galactic nuclei (AGNs). Our primary focus is to show that magnetically driven outflows are indeed physically plausible candidates for the observed outflows accounting for the AGN absorption properties of the present X-ray spectroscopic observations. Employing a stratified MHD wind launched across the entire AGN accretion disk, we calculate its X-ray ionization and the ensuing X-ray absorption-line spectra. Assuming an appropriate ionizing AGN spectrum, we apply our MHD winds to model the absorption features in an XMM-Newton/EPIC spectrum of the narrow-line Seyfert, PG 1211+143. We find, through identifying the detected features with Fe Kα transitions, that the absorber has a characteristic ionization parameter of log (ξc[erg cm s-1]) ≃ 5-6 and a column density on the order of NH ≃ 1023 cm-2 outflowing at a characteristic velocity of vc/c ≃ 0.1-0.2 (where c is the speed of light). The best-fit model favors its radial location at rc ≃ 200 Ro (Ro is the black hole’s innermost stable circular orbit), with an inner wind truncation radius at Rt ≃ 30 Ro. The overall K-shell feature in the data is suggested to be dominated by Fe xxv with very little contribution from Fe xxvi and weakly ionized iron, which is in good agreement with a series of earlier analyses of the UFOs in various AGNs, including PG 1211+143.