WorldWideScience

Sample records for inhibit hemocyte aggregation

  1. The virus-like particles of a braconid endoparasitoid wasp, Meteorus pulchricornis, inhibit hemocyte spreading in its noctuid host, Pseudaletia separata.

    Science.gov (United States)

    Suzuki, M; Miura, K; Tanaka, T

    2008-06-01

    We previously reported that the virus-like particles of Meteorus pulchricornis (MpVLPs) are capable of inducing apoptosis by around 6h in the hemocytes of the host, Pseudaletia separata [Suzuki, M., Tanaka, T., 2006. Virus-like particles in venom of Meteorus pulchricornis induce host hemocyte apoptosis. Journal of Insect Physiology 52, 602-611], thereby protecting the oviposited egg. In the present study, we focused on analyses of the earlier events caused by the MpVLPs upon the host immune response, namely their effects on hemocyte spreading. After recognition and attachment on foreign substance, the granulocytes and plasmatocytes assemble focal complexes and focal adhesions and spread by protruding filopodia/lamellipodia. The well-spread, cultured hemocytes were subjected to MpVLPs exposure, and the morphological changes were observed. The granulocytes lost the focal complexes/adhesions visualized as phosphotyrosine clusters and retracted the filopodia/lamellipodia within 30min after exposure, while the plasmatocytes exhibited similar but distinct responses. The two hemocyte species prepared from either parasitized or MpVLP-injected hosts lost the ability to form both filopodia/lamellipodia and phosphotyrosine clusters. A caspase inhibitor, Z-VAD-FMK, did not affect these MpVLP-induced morphological changes, indicating that these earlier changes found in the hemocytes precede apoptosis. The present study together with our previous data has established that the attenuation of host immune defense by the MpVLPs comprises at least two temporally distinguishable phases: immediate and early inhibition of hemocyte spreading and the eventual induction of hemocyte apoptosis.

  2. Curcumin inhibits aggregation of alpha-synuclein.

    Science.gov (United States)

    Pandey, Neeraj; Strider, Jeffrey; Nolan, William C; Yan, Sherry X; Galvin, James E

    2008-04-01

    Aggregation of amyloid-beta protein (Abeta) is a key pathogenic event in Alzheimer's disease (AD). Curcumin, a constituent of the Indian spice Turmeric is structurally similar to Congo Red and has been demonstrated to bind Abeta amyloid and prevent further oligomerization of Abeta monomers onto growing amyloid beta-sheets. Reasoning that oligomerization kinetics and mechanism of amyloid formation are similar in Parkinson's disease (PD) and AD, we investigated the effect of curcumin on alpha-synuclein (AS) protein aggregation. In vitro model of AS aggregation was developed by treatment of purified AS protein (wild-type) with 1 mM Fe3+ (Fenton reaction). It was observed that the addition of curcumin inhibited aggregation in a dose-dependent manner and increased AS solubility. The aggregation-inhibiting effect of curcumin was next investigated in cell culture utilizing catecholaminergic SH-SY5Y cell line. A model system was developed in which the red fluorescent protein (DsRed2) was fused with A53T mutant of AS and its aggregation examined under different concentrations of curcumin. To estimate aggregation in an unbiased manner, a protocol was developed in which the images were captured automatically through a high-throughput cell-based screening microscope. The obtained images were processed automatically for aggregates within a defined dimension of 1-6 microm. Greater than 32% decrease in mutant alpha-synuclein aggregation was observed within 48 h subsequent to curcumin addition. Our data suggest that curcumin inhibits AS oligomerization into higher molecular weight aggregates and therefore should be further explored as a potential therapeutic compound for PD and related disorders.

  3. Immune responses of mussel hemocyte subpopulations are differentially regulated by enzymes of the PI 3-K, PKC, and ERK kinase families.

    Science.gov (United States)

    García-García, Erick; Prado-Alvarez, Maria; Novoa, Beatriz; Figueras, Antonio; Rosales, Carlos

    2008-01-01

    Various hemocyte cell types have been described in invertebrates, but for most species a functional characterization of different hemocyte cell types is still lacking. In order to characterize some immunological properties of mussel (Mytilus galloprovincialis) hemocytes, cells were separated by flow cytometry and their capacity for phagocytosis, production of reactive oxygen species (ROS), and production of nitric oxide (NO), was examined. Phosphatidylinositol 3-kinase (PI 3-K), protein kinase C (PKC), and extracellular signal-regulated kinase (ERK) inhibitors were also used to biochemically characterize these cell responses. Four morphologically distinct subpopulations, designated R1-R4, were detected. R1, R2, and R3 cells presented different levels of phagocytosis towards zymosan, latex beads, and two bacteria species. Similarly, R1 to R3, but not R4, cells produced ROS, while all subpopulations produced NO, in response to zymosan. Internalization of all phagocytic targets was blocked by PI 3-K inhibition. In addition, internalization of latex particles, but not of bacteria, was partially blocked by PKC or ERK inhibition. Interestingly, phagocytosis of zymosan was impaired by PKC, or ERK inhibitors, only in R2 cells. Zymosan-induced ROS production was blocked by PI 3-K inhibition, but not by PKC, or ERK inhibition. In addition, zymosan-stimulated NO production was affected by PI 3-K inhibition in R1 and R2, but not in R3 or R4 cells. NO production in all cell types was unaffected by PKC inhibition, but ERK inhibition blocked it in R2 cells. These data reveal the existence of profound functional and biochemical differences in mussel hemocytes and indicate that M. galloprovincialis hemocytes are specialized cells fulfilling specific tasks in the context of host defense.

  4. Gingival tissue-produced inhibition of platelet aggregation and the loss of inhibition in streptozotocin-induced diabetic rats

    Energy Technology Data Exchange (ETDEWEB)

    Kawamura, Keiichiroh; Tamai, Kazuharu; Shirakawa, Masaharu; Okamoto, Hiroshi; Dohi, Toshihiro; Tsujimoto, Akira

    1988-01-01

    Addition of medium incubated with normal rat gingival tissue to platelet-rich plasma inhibited ADP-induced platelet aggregation. The ability of rat gingiva to produce activity inhibiting platelet aggregation was enhanced by the addition of arachidonic acid. Diabetic rat gingiva failed to inhibit platelet aggregation but did produce the anti-platelet aggregating activity in the presence of arachidonic acid. Indomethacin blocked the production of anti-platelet aggregating activity. There was no difference in conversion of (1-/sup 14/C)arachidonic acid to prostaglandins by normal and diabetic rat gingiva. These results suggest that an arachidonic acid metabolite released from gingiva during incubation inhibits platelet aggregation, and the synthesis of the metabolite is impaired in diabetic rat gingiva. A decrease in availability of arachidonic acid may be a causal factor of the defect in diabetic rat gingiva.

  5. Gingival tissue-produced inhibition of platelet aggregation and the loss of inhibition in streptozotocin-induced diabetic rats

    International Nuclear Information System (INIS)

    Kawamura, Keiichiroh; Tamai, Kazuharu; Shirakawa, Masaharu; Okamoto, Hiroshi; Dohi, Toshihiro; Tsujimoto, Akira

    1988-01-01

    Addition of medium incubated with normal rat gingival tissue to platelet-rich plasma inhibited ADP-induced platelet aggregation. The ability of rat gingiva to produce activity inhibiting platelet aggregation was enhanced by the addition of arachidonic acid. Diabetic rat gingiva failed to inhibit platelet aggregation but did produce the anti-platelet aggregating activity in the presence of arachidonic acid. Indomethacin blocked the production of anti-platelet aggregating activity. There was no difference in conversion of [1- 14 C]arachidonic acid to prostaglandins by normal and diabetic rat gingiva. These results suggest that an arachidonic acid metabolite released from gingiva during incubation inhibits platelet aggregation, and the synthesis of the metabolite is impaired in diabetic rat gingiva. A decrease in availability of arachidonic acid may be a causal factor of the defect in diabetic rat gingiva. (author)

  6. Hemocyte characterization of Nasutitermes coxipoensis (Holmgren) (Isoptera: Termitidae) workers and hemocyte evaluation after parasitism by Metarhizium anisopliae

    International Nuclear Information System (INIS)

    Cunha, Franklin M.; Wanderley-Teixeira, Valeria; Albuquerque, Auristela C.; Lima, Elza A.L.A.

    2009-01-01

    We aimed to characterize the morphology and ultrastructure of hemocytes of Nasutitermes coxipoensis (Holmgren) workers and to quantify the cell types 24h, 48h and 72h after inoculation with Metarhizium anisopliae. Six hemocytes types were identified, plasmatocyte, granulocyte, spherulocyte, prohemocyte, adipohemocyte and eonocytoid Hemocytes did not present any morphological alteration at the several observation periods, but they did have a change in their abundance, as observed for spherulocytes, adipohemocytes and eonocytoids at all intervals, and for plasmatocytes and granulocytes at 48h after host inoculation. We argue on the possible reasons and implications of the observed changes. (author)

  7. 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.

  8. Osmoregulated Chloride Currents in Hemocytes from Mytilus galloprovincialis.

    Directory of Open Access Journals (Sweden)

    Monica Bregante

    Full Text Available We investigated the biophysical properties of the transport mediated by ion channels in hemocytes from the hemolymph of the bivalve Mytilus galloprovincialis. Besides other transporters, mytilus hemocytes possess a specialized channel sensitive to the osmotic pressure with functional properties similar to those of other transport proteins present in vertebrates. As chloride fluxes may play an important role in the regulation of cell volume in case of modifications of the ionic composition of the external medium, we focused our attention on an inwardly-rectifying voltage-dependent, chloride-selective channel activated by negative membrane potentials and potentiated by the low osmolality of the external solution. The chloride channel was slightly inhibited by micromolar concentrations of zinc chloride in the bath solution, while the antifouling agent zinc pyrithione did not affect the channel conductance at all. This is the first direct electrophysiological characterization of a functional ion channel in ancestral immunocytes of mytilus, which may bring a contribution to the understanding of the response of bivalves to salt and contaminant stresses.

  9. On the origin of the Biomphalaria glabrata hemocytes

    Directory of Open Access Journals (Sweden)

    Samaly dos Santos Souza

    2006-10-01

    Full Text Available A histologic, morphometric and ultrastructural study performed on Biomphalaria glabrata submitted to infection with Schistosoma mansoni miracidia failed to provide significant evidences that the so-called amebocyte-producing organ (APO is really the central organ for hemocyte production. In infected snails no general reactive changes appeared in the APO, the mitoses were seen only occasionally, and the possibility of cellular hyperplasia was ruled out by morphometric measurements. Under the electron microscope the APO cells presented an essentially epithelial structure, without features indicative of transition toward hemocytes. On the other hand, the present findings pointed to a multicentric origin for the mollusck hemocytes, as earlier studies had indicated. Dense foci of hemocyte collections appeared sometimes around disintegrating sporocysts and cercariae in several organs and tissues of the infected snails, including a curious accumulation of such cells inside the ventricular cavity of the heart. In the heart and other sites, features suggestive of transformation of vascular space endothelial lining cells into hemocytes were apparent. To some extent, the postulated multicentric origin for B. glabrata hemocytes recapitulates earlier embryologic findings in vertebrates, when mesenchymal vascular spaces generate the circulating and phagocytic blood cells.

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

    Science.gov (United States)

    Kemp, A S; Brown, S

    1980-01-01

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

  11. 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.

  12. Hemocyte-mediated phagocytosis differs between honey bee (Apis mellifera) worker castes.

    Science.gov (United States)

    Hystad, Eva Marit; Salmela, Heli; Amdam, Gro Vang; Münch, Daniel

    2017-01-01

    Honey bees as other insects rely on the innate immune system for protection against diseases. The innate immune system includes the circulating hemocytes (immune cells) that clear pathogens from hemolymph (blood) by phagocytosis, nodulation or encapsulation. Honey bee hemocyte numbers have been linked to hemolymph levels of vitellogenin. Vitellogenin is a multifunctional protein with immune-supportive functions identified in a range of species, including the honey bee. Hemocyte numbers can increase via mitosis, and this recruitment process can be important for immune system function and maintenance. Here, we tested if hemocyte mediated phagocytosis differs among the physiologically different honey bee worker castes (nurses, foragers and winter bees), and study possible interactions with vitellogenin and hemocyte recruitment. To this end, we adapted phagocytosis assays, which-together with confocal microscopy and flow cytometry-allow qualitative and quantitative assessment of hemocyte performance. We found that nurses are more efficient in phagocytic uptake than both foragers and winter bees. We detected vitellogenin within the hemocytes, and found that winter bees have the highest numbers of vitellogenin-positive hemocytes. Connections between phagocytosis, hemocyte-vitellogenin and mitosis were worker caste dependent. Our results demonstrate that the phagocytic performance of immune cells differs significantly between honey bee worker castes, and support increased immune competence in nurses as compared to forager bees. Our data, moreover, provides support for roles of vitellogenin in hemocyte activity.

  13. Hemocyte-mediated phagocytosis differs between honey bee (Apis mellifera worker castes.

    Directory of Open Access Journals (Sweden)

    Eva Marit Hystad

    Full Text Available Honey bees as other insects rely on the innate immune system for protection against diseases. The innate immune system includes the circulating hemocytes (immune cells that clear pathogens from hemolymph (blood by phagocytosis, nodulation or encapsulation. Honey bee hemocyte numbers have been linked to hemolymph levels of vitellogenin. Vitellogenin is a multifunctional protein with immune-supportive functions identified in a range of species, including the honey bee. Hemocyte numbers can increase via mitosis, and this recruitment process can be important for immune system function and maintenance. Here, we tested if hemocyte mediated phagocytosis differs among the physiologically different honey bee worker castes (nurses, foragers and winter bees, and study possible interactions with vitellogenin and hemocyte recruitment. To this end, we adapted phagocytosis assays, which-together with confocal microscopy and flow cytometry-allow qualitative and quantitative assessment of hemocyte performance. We found that nurses are more efficient in phagocytic uptake than both foragers and winter bees. We detected vitellogenin within the hemocytes, and found that winter bees have the highest numbers of vitellogenin-positive hemocytes. Connections between phagocytosis, hemocyte-vitellogenin and mitosis were worker caste dependent. Our results demonstrate that the phagocytic performance of immune cells differs significantly between honey bee worker castes, and support increased immune competence in nurses as compared to forager bees. Our data, moreover, provides support for roles of vitellogenin in hemocyte activity.

  14. Two Hemocyte Lineages Exist in Silkworm Larval Hematopoietic Organ

    OpenAIRE

    Nakahara, Yuichi; Kanamori, Yasushi; Kiuchi, Makoto; Kamimura, Manabu

    2010-01-01

    BACKGROUND: Insects have multiple hemocyte morphotypes with different functions as do vertebrates, however, their hematopoietic lineages are largely unexplored with the exception of Drosophila melanogaster. METHODOLOGY/PRINCIPAL FINDINGS: To study the hematopoietic lineage of the silkworm, Bombyx mori, we investigated in vivo and in vitro differentiation of hemocyte precursors in the hematopoietic organ (HPO) into the four mature hemocyte subsets, namely, plasmatocytes, granulocytes, oenocyto...

  15. Hemiuroid trematode sporocysts are undetected by hemocytes of their intermediate host, the ark cockle Anadara trapezia: potential role of surface carbohydrates in successful parasitism.

    Science.gov (United States)

    Kawasaki, Minami; Delamare-Deboutteville, Jerome; Dang, Cecile; Barnes, Andrew C

    2013-12-01

    In order to establish a successful relationship with their hosts, parasites must subvert or evade immune defences. Cockle Anadara trapezia and Sydney Rock oyster (SRO) Saccostrea glomerata live in the same location but only ark cockles are infected by sporocysts of hemiuroid trematode. This provides an opportunity to explore differing interactions between the parasite and the immune system of susceptible and refractive hosts. Rapid migration and encapsulation of sporocysts was observed by SRO hemocytes but not by cockle hemocytes. This migration/encapsulation was inhibited by N-acetylglucosamine or N-acetylgalactosamine but not by the other sugars, implicating specific surface carbohydrates in immune detection. Effector responses of hemocytes were investigated in vitro in terms of production of reactive oxygen production (ROS). Hemocytes of both species strongly reacted to Zymosan, but only SRO hemocytes responded to live sporocysts. Neither species' hemocytes produced ROS in the presence of dead/fixed sporocysts, and there was no suppression of Zymosan-induced respiratory burst by sporocysts. This suggests that immune escape is mediated by avoiding encapsulation, perhaps through molecular mimicry. Membrane-shaving with proteases indicated that sporocyst surface proteins are not a key factors in hemocytic detection. Surface carbohydrates of SRO and cockle hemocytes and of sporocysts were profiled with a panel of biotinylated lectins. This revealed substantial differences between cockle and SRO hemocytes, but greater similarity between cockle hemocytes and sporocysts. Results suggest that surface carbohydrates play an integral role in hemocyte immunorecognition and that surface carbohydrate molecular mimicry is a potential strategy for immune evasion in cockles by hemiuroid trematode sporocysts. Crown Copyright © 2013. Published by Elsevier Ltd. All rights reserved.

  16. Immune Defenses of the Invasive Apple Snail Pomacea canaliculata (Caenogastropoda, Ampullariidae: Phagocytic Hemocytes in the Circulation and the Kidney.

    Directory of Open Access Journals (Sweden)

    Juan A Cueto

    Full Text Available Hemocytes in the circulation and kidney islets, as well as their phagocytic responses to microorganisms and fluorescent beads, have been studied in Pomacea canaliculata, using flow cytometry, light microscopy (including confocal laser scanning microscopy and transmission electron microscopy (TEM. Three circulating hemocyte types (hyalinocytes, agranulocytes and granulocytes were distinguished by phase contrast microscopy of living cells and after light and electron microscopy of fixed material. Also, three different populations of circulating hemocytes were separated by flow cytometry, which corresponded to the three hemocyte types. Hyalinocytes showed a low nucleus/cytoplasm ratio, and no apparent granules in stained material, but showed granules of moderate electron density under TEM (L granules and at least some L granules appear acidic when labeled with LysoTracker Red. Both phagocytic and non-phagocytic hyalinocytes lose most (if not all L granules when exposed to microorganisms in vitro. The phagosomes formed differed whether hyalinocytes were exposed to yeasts or to Gram positive or Gram negative bacteria. Agranulocytes showed a large nucleus/cytoplasm ratio and few or no granules. Granulocytes showed a low nucleus/cytoplasm ratio and numerous eosinophilic granules after staining. These granules are electron dense and rod-shaped under TEM (R granules. Granulocytes may show merging of R granules into gigantic ones, particularly when exposed to microorganisms. Fluorescent bead exposure of sorted hemocytes showed phagocytic activity in hyalinocytes, agranulocytes and granulocytes, but the phagocytic index was significantly higher in hyalinocytes. Extensive hemocyte aggregates ('islets' occupy most renal hemocoelic spaces and hyalinocyte-like cells are the most frequent component in them. Presumptive glycogen deposits were observed in most hyalinocytes in renal islets (they also occur in the circulation but less frequently and may mean that

  17. Curcumin Inhibits Tau Aggregation and Disintegrates Preformed Tau Filaments in vitro.

    Science.gov (United States)

    Rane, Jitendra Subhash; Bhaumik, Prasenjit; Panda, Dulal

    2017-01-01

    The pathological aggregation of tau is a common feature of most of the neuronal disorders including frontotemporal dementia, Parkinson's disease, and Alzheimer's disease. The inhibition of tau aggregation is considered to be one of the important strategies for treating these neurodegenerative diseases. Curcumin, a natural polyphenolic molecule, has been reported to have neuroprotective ability. In this work, curcumin was found to bind to adult tau and fetal tau with a dissociation constant of 3.3±0.4 and 8±1 μM, respectively. Molecular docking studies indicated a putative binding site of curcumin in the microtubule-binding region of tau. Using several complementary techniques, including dynamic light scattering, thioflavin S fluorescence, 90° light scattering, electron microscopy, and atomic force microscopy, curcumin was found to inhibit the aggregation of tau. The dynamic light scattering analysis and atomic force microscopic images revealed that curcumin inhibits the oligomerization of tau. Curcumin also disintegrated preformed tau oligomers. Using Far-UV circular dichroism, curcumin was found to inhibit the β-sheets formation in tau indicating that curcumin inhibits an initial step of tau aggregation. In addition, curcumin inhibited tau fibril formation. Furthermore, the effect of curcumin on the preformed tau filaments was analyzed by atomic force microscopy, transmission electron microscopy, and 90° light scattering. Curcumin treatment disintegrated preformed tau filaments. The results indicated that curcumin inhibited the oligomerization of tau and could disaggregate tau filaments.

  18. Jaburetox-induced toxic effects on the hemocytes of Rhodnius prolixus (Hemiptera: Reduviidae).

    Science.gov (United States)

    Moyetta, Natalia R; Broll, Valquiria; Perin, Ana Paula A; Uberti, Augusto F; Coste Grahl, Matheus V; Staniscuaski, Fernanda; Carlini, Celia R; Fruttero, Leonardo L

    2017-10-01

    Jaburetox is a recombinant peptide derived from a Canavalia ensiformis urease that presents toxic effects upon several species of insects, phytopathogenic fungi and yeasts of medical importance. So far, no toxicity of Jaburetox to mammals has been shown. Previous reports have identified biochemical targets of this toxic peptide in insect models, although its mechanism of action is not completely understood. In this work, we aimed to characterize the effects of Jaburetox in hemolymphatic insect cells. For this purpose, the model insect and Chagas' disease vector Rhodnius prolixus was used. In vivo and in vitro experiments indicated that Jaburetox interacts with a subset of hemocytes and it can be found in various subcellular compartments. In insects injected with Jaburetox there was an increase in the gene expression of the enzymes UDP-N-acetylglucosamine pyrophosphorylase (UAP), chitin synthase and nitric oxide synthase (NOS). Nevertheless, the expression of NOS protein, the enzyme activities of UAP and acid phosphatase (a possible link between UAP and NOS) as well as the phosphorylation state of proteins remained unchanged upon the in vivo Jaburetox treatment. Nitric oxide (NO) imaging using fluorescent probes showed that Jaburetox augmented NO production in the hemocyte aggregates when compared to controls. Even though Jaburetox activated the hemocytes, as demonstrated by wheat germ agglutinin binding assays, the peptide did not lead to an increase of their phagocytic behavior. Taken together, these findings contribute to our understanding of toxic effects of Jaburetox, a peptide with biotechnological applications and a prospective tool for rational insect control. Copyright © 2017 Elsevier Inc. All rights reserved.

  19. Nattokinase improves blood flow by inhibiting platelet aggregation and thrombus formation

    OpenAIRE

    Jang, Ja-Young; Kim, Tae-Su; Cai, Jingmei; Kim, Jihyun; Kim, Youngeun; Shin, Kyungha; Kim, Kwang Sei; Park, Sung Kyeong; Lee, Sung-Pyo; Choi, Ehn-Kyoung; Rhee, Man Hee; Kim, Yun-Bae

    2013-01-01

    The effects of nattokinase on the in vitro platelet aggregation and in vivo thrombosis were investigated in comparison with aspirin. Rabbit platelet-rich plasma was incubated with nattokinase and aggregation inducers collagen and thrombin, and the platelet aggregation rate was analyzed. Nattokinase significantly inhibited both the collagen- and thrombin-induced platelet aggregations. Nattokinase also reduced thromboxane B2 formation from collagen-activated platelets in a concentration-depende...

  20. Mapuche Herbal Medicine Inhibits Blood Platelet Aggregation

    OpenAIRE

    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??M) and collagen- (2.0??g/mL) induced aggregations in human blood. These four species in respective extracts (in brackets) were Blechnum chilense (MeOH), Luma apiculata (H2O), Amomyrtus l...

  1. Two hemocyte lineages exist in silkworm larval hematopoietic organ.

    Science.gov (United States)

    Nakahara, Yuichi; Kanamori, Yasushi; Kiuchi, Makoto; Kamimura, Manabu

    2010-07-28

    Insects have multiple hemocyte morphotypes with different functions as do vertebrates, however, their hematopoietic lineages are largely unexplored with the exception of Drosophila melanogaster. To study the hematopoietic lineage of the silkworm, Bombyx mori, we investigated in vivo and in vitro differentiation of hemocyte precursors in the hematopoietic organ (HPO) into the four mature hemocyte subsets, namely, plasmatocytes, granulocytes, oenocytoids, and spherulocytes. Five days after implantation of enzymatically-dispersed HPO cells from a GFP-expressing transgenic line into the hemocoel of normal larvae, differentiation into plasmatocytes, granulocytes and oenocytoids, but not spherulocytes, was observed. When the HPO cells were cultured in vitro, plasmatocytes appeared rapidly, and oenocytoids possessing prophenol oxidase activity appeared several days later. HPO cells were also able to differentiate into a small number of granulocytes, but not into spherulocytes. When functionally mature plasmatocytes were cultured in vitro, oenocytoids were observed 10 days later. These results suggest that the hemocyte precursors in HPO first differentiate into plasmatocytes, which further change into oenocytoids. From these results, we propose that B. mori hemocytes can be divided into two major lineages, a granulocyte lineage and a plasmatocyte-oenocytoid lineage. The origins of the spherulocytes could not be determined in this study. We construct a model for the hematopoietic lineages at the larval stage of B. mori.

  2. Hemocyte responses of Dreissena polymorpha following a short-term in vivo exposure to titanium dioxide nanoparticles: Preliminary investigations

    Energy Technology Data Exchange (ETDEWEB)

    Couleau, Nicolas; Techer, Didier [Universite de Lorraine, Laboratoire des Interactions Ecotoxicologie, Biodiversite, Ecosystemes (LIEBE), CNRS UMR 7146, IUT Thionville-Yutz, Espace Cormontaigne, Yutz, F-57970 (France); Pagnout, Christophe [Universite de Lorraine, Laboratoire des Interactions Ecotoxicologie, Biodiversite, Ecosystemes (LIEBE), UMR 7146, Campus Bridoux, rue du General Delestraint, Metz, F-57070 (France); International Consortium for the Environmental Implications of Nanotechnology, iCEINT, http://www.i-ceint.org (France); Jomini, Stephane [Universite de Lorraine, Laboratoire des Interactions Ecotoxicologie, Biodiversite, Ecosystemes (LIEBE), UMR 7146, Campus Bridoux, rue du General Delestraint, Metz, F-57070 (France); Foucaud, Laurent; Laval-Gilly, Philippe; Falla, Jairo [Universite de Lorraine, Laboratoire des Interactions Ecotoxicologie, Biodiversite, Ecosystemes (LIEBE), CNRS UMR 7146, IUT Thionville-Yutz, Espace Cormontaigne, Yutz, F-57970 (France); Bennasroune, Amar, E-mail: amar.bennasroune@univ-metz.fr [Universite de Lorraine, Laboratoire des Interactions Ecotoxicologie, Biodiversite, Ecosystemes (LIEBE), CNRS UMR 7146, IUT Thionville-Yutz, Espace Cormontaigne, Yutz, F-57970 (France)

    2012-11-01

    The widespread use of titanium-based nanoparticles and their environmental release may pose a significant risk to aquatic organisms within freshwater ecosystems. Suspension-feeder invertebrates like bivalve molluscs represent a unique target group for nanoparticle toxicology. The aim of this work was to investigate the short-term responses of Dreissena polymorpha hemocytes after in vivo exposure to titanium dioxide nanoparticles (TiO{sub 2} NP). For this purpose, freshwater mussels were exposed to P25 TiO{sub 2} NP at the concentrations of 0.1, 1, 5 and 25 mg/L during 24 h. Viability, phagocytosis activity and mitogen activated protein kinase (MAPK) phosphorylation level of ERK 1/2 and p38 in hemocytes extracted from exposed mussels were compared to those from control specimens. Results demonstrated an inhibition of the phagocytosis activity after exposure to TiO{sub 2} NP at 0.1 and 1 mg/L. Similar trends, albeit less pronounced, were reported for higher concentrations of NP. Transmission electron microscopy showed for the first time the internalization of TiO{sub 2} NP into Dreissena polymorpha hemocytes. Besides, exposure to NP increased the ERK 1/2 phosphorylation levels in all treatments. Concerning the phosphorylation level of p38, only exposures to 5 and 25 mg/L of NP induced significant p38 activation in comparison to that of the control. Finally, these short-term effects observed at environmentally relevant concentrations highlighted the need for further studies concerning ecotoxicological evaluation of nanoparticle release into an aquatic environment. -- Highlights: Black-Right-Pointing-Pointer Phagocytosis inhibition at TiO{sub 2} NP exposure concentrations of 0.1 and 1 mg/L. Black-Right-Pointing-Pointer Internalization of TiO{sub 2} NP in freshwater mussel hemocytes. Black-Right-Pointing-Pointer Increased phosphorylation level of p38 and ERK 1/2 after in vivo exposure to TiO{sub 2} NP.

  3. Two hemocyte lineages exist in silkworm larval hematopoietic organ.

    Directory of Open Access Journals (Sweden)

    Yuichi Nakahara

    Full Text Available BACKGROUND: Insects have multiple hemocyte morphotypes with different functions as do vertebrates, however, their hematopoietic lineages are largely unexplored with the exception of Drosophila melanogaster. METHODOLOGY/PRINCIPAL FINDINGS: To study the hematopoietic lineage of the silkworm, Bombyx mori, we investigated in vivo and in vitro differentiation of hemocyte precursors in the hematopoietic organ (HPO into the four mature hemocyte subsets, namely, plasmatocytes, granulocytes, oenocytoids, and spherulocytes. Five days after implantation of enzymatically-dispersed HPO cells from a GFP-expressing transgenic line into the hemocoel of normal larvae, differentiation into plasmatocytes, granulocytes and oenocytoids, but not spherulocytes, was observed. When the HPO cells were cultured in vitro, plasmatocytes appeared rapidly, and oenocytoids possessing prophenol oxidase activity appeared several days later. HPO cells were also able to differentiate into a small number of granulocytes, but not into spherulocytes. When functionally mature plasmatocytes were cultured in vitro, oenocytoids were observed 10 days later. These results suggest that the hemocyte precursors in HPO first differentiate into plasmatocytes, which further change into oenocytoids. CONCLUSIONS/SIGNIFICANCE: From these results, we propose that B. mori hemocytes can be divided into two major lineages, a granulocyte lineage and a plasmatocyte-oenocytoid lineage. The origins of the spherulocytes could not be determined in this study. We construct a model for the hematopoietic lineages at the larval stage of B. mori.

  4. In vitro cultivation and cryopreservation of Babesia bigemina sporokinetes in hemocytes of Rhipicephalus microplus.

    Science.gov (United States)

    de Rezende, Jania; Rangel, Charles P; McIntosh, Douglas; Silveira, Júlia A G; Cunha, Nathalie C; Ramos, Carlos A N; Fonseca, Adivaldo H

    2015-09-15

    Cultures of tick hemocytes represent alternative cell lines for the isolation and cultivation of a variety of hemoparasites. The present study reports the development and evaluation of methods for the in vitro culture and maintenance of sporokinetes of Babesia bigemina in association with hemocytes of the tick Rhipicephalus microplus. Hemolymph, from engorged females infected with B. bigemina sporokinetes, was incubated at 28 °C in L15 culture medium supplemented with 40% fetal bovine serum. Adherence of hemocytes to flask surfaces and the development of B. bigemina sporokinetes commenced on the first day of cultivation. The protozoa demonstrated clear motility and the capacity to adhere to hemocyte membranes for up to 25 days, at which time the hemocytes began to show signs of degeneration. Examination of Giemsa stained hemocyte cultures, revealed the presence of pyriformis forms, as well as mature and immature sporokinetes with dark red nuclei, centralized or near the apical extremities. Sporokinetes harvested from culture supernatants were cryopreserved in liquid nitrogen. Inoculation of parasite-free hemocyte cultures with defrosted sporokinetes, demonstrated the viability and interaction of the protozoa with the hemocytes over 21 days. Cultured hemocytes of R. microplus hold potential for development as a tool in the study of host parasite interactions and as a substrate for the in vitro maintenance of B. bigemina sporokinetes. Copyright © 2015 Elsevier B.V. All rights reserved.

  5. [27- Hydroxycholesterol reverses estradiol induced inhibition of platelet aggregation in postmenopausal women].

    Science.gov (United States)

    Rocha, Gladys; Sierralta, Walter; Valladares, Luis

    2016-11-01

    The decline of estrogen levels increases cardiovascular risk in women. Platelets express estrogen receptors and 17β-estradiol- (E2) can produce a protective effect on thrombus formation. The hydroxylation of cholesterol generates several sterols and 27-hydroxycholesterol (27HC) predominates in circulation. To evaluate the effect of 27HC as an endogenous antagonist of the anti-aggregating properties of E2 in platelets of postmenopausal women. Platelet function of postmenopausal women was evaluated ex-vivo. Platelets pre-incubated with 27HC in the presence or absence of E2, were stimulated with collagen. Aggregation was evaluated using turbidimetry using a Chrono-log aggregometer. Collagen-stimulated platelet aggregation was significantly inhibited by E2. The inhibitory effect of E2 on collagen-stimulated platelet aggregation was significantly reversed in the presence of 27HC. The suppressive effect of E2 on platelet aggregation is inhibited by 27HC, which could contribute to increase cardiovascular risk in postmenopausal women.

  6. Inhibition of protein aggregation: supramolecular assemblies of arginine hold the key.

    Directory of Open Access Journals (Sweden)

    Utpal Das

    Full Text Available BACKGROUND: Aggregation of unfolded proteins occurs mainly through the exposed hydrophobic surfaces. Any mechanism of inhibition of this aggregation should explain the prevention of these hydrophobic interactions. Though arginine is prevalently used as an aggregation suppressor, its mechanism of action is not clearly understood. We propose a mechanism based on the hydrophobic interactions of arginine. METHODOLOGY: We have analyzed arginine solution for its hydrotropic effect by pyrene solubility and the presence of hydrophobic environment by 1-anilino-8-naphthalene sulfonic acid fluorescence. Mass spectroscopic analyses show that arginine forms molecular clusters in the gas phase and the cluster composition is dependent on the solution conditions. Light scattering studies indicate that arginine exists as clusters in solution. In the presence of arginine, the reverse phase chromatographic elution profile of Alzheimer's amyloid beta 1-42 (Abeta(1-42 peptide is modified. Changes in the hydrodynamic volume of Abeta(1-42 in the presence of arginine measured by size exclusion chromatography show that arginine binds to Abeta(1-42. Arginine increases the solubility of Abeta(1-42 peptide in aqueous medium. It decreases the aggregation of Abeta(1-42 as observed by atomic force microscopy. CONCLUSIONS: Based on our experimental results we propose that molecular clusters of arginine in aqueous solutions display a hydrophobic surface by the alignment of its three methylene groups. The hydrophobic surfaces present on the proteins interact with the hydrophobic surface presented by the arginine clusters. The masking of hydrophobic surface inhibits protein-protein aggregation. This mechanism is also responsible for the hydrotropic effect of arginine on various compounds. It is also explained why other amino acids fail to inhibit the protein aggregation.

  7. Nattokinase improves blood flow by inhibiting platelet aggregation and thrombus formation.

    Science.gov (United States)

    Jang, Ja-Young; Kim, Tae-Su; Cai, Jingmei; Kim, Jihyun; Kim, Youngeun; Shin, Kyungha; Kim, Kwang Sei; Park, Sung Kyeong; Lee, Sung-Pyo; Choi, Ehn-Kyoung; Rhee, Man Hee; Kim, Yun-Bae

    2013-12-01

    The effects of nattokinase on the in vitro platelet aggregation and in vivo thrombosis were investigated in comparison with aspirin. Rabbit platelet-rich plasma was incubated with nattokinase and aggregation inducers collagen and thrombin, and the platelet aggregation rate was analyzed. Nattokinase significantly inhibited both the collagen- and thrombin-induced platelet aggregations. Nattokinase also reduced thromboxane B2 formation from collagen-activated platelets in a concentration-dependent manner. Rats were orally administered with nattokinase for 1 week, and their carotid arteries were exposed. Arterial thrombosis was induced by applying 35% FeCl3-soaked filter paper for 10 min, and the blood flow was monitored with a laser Doppler probe. Nattokinase delayed the FeCl3-induced arterial occlusion in a dose-dependent manner, doubling the occlusion time at 160 mg/kg. In addition, a high dose (500 mg/kg) of nattokinase fully prevented the occlusion, as achieved with aspirin (30 mg/kg). The results indicate that nattokinase extracted from fermented soybean inhibit platelet aggregation by blocking thromboxane formation, and thereby delay thrombosis following oxidative arterial wall injury. Therefore, it is suggested that nattokinase could be a good candidate without adverse effects for the improvement of blood flow.

  8. Vitamin k3 inhibits protein aggregation: Implication in the treatment of amyloid diseases.

    Science.gov (United States)

    Alam, Parvez; Chaturvedi, Sumit Kumar; Siddiqi, Mohammad Khursheed; Rajpoot, Ravi Kant; Ajmal, Mohd Rehan; Zaman, Masihuz; Khan, Rizwan Hasan

    2016-05-27

    Protein misfolding and aggregation have been associated with several human diseases such as Alzheimer's, Parkinson's and familial amyloid polyneuropathy etc. In this study, anti-fibrillation activity of vitamin k3 and its effect on the kinetics of amyloid formation of hen egg white lysozyme (HEWL) and Aβ-42 peptide were investigated. Here, in combination with Thioflavin T (ThT) fluorescence assay, circular dichroism (CD), transmission electron microscopy and cell cytotoxicity assay, we demonstrated that vitamin k3 significantly inhibits fibril formation as well as the inhibitory effect is dose dependent manner. Our experimental studies inferred that vitamin k3 exert its neuro protective effect against amyloid induced cytotoxicity through concerted pathway, modifying the aggregation formation towards formation of nontoxic aggregates. Molecular docking demonstrated that vitamin k3 mediated inhibition of HEWL and Aβ-42 fibrillogenesis may be initiated by interacting with proteolytic resistant and aggregation prone regions respectively. This work would provide an insight into the mechanism of protein aggregation inhibition by vitamin k3; pave the way for discovery of other small molecules that may exert similar effect against amyloid formation and its associated neurodegenerative diseases.

  9. Ocean Acidification Affects Hemocyte Physiology in the Tanner Crab (Chionoecetes bairdi)

    Science.gov (United States)

    Meseck, Shannon L.; Alix, Jennifer H.; Swiney, Katherine M.; Long, W. Christopher; Wikfors, Gary H.; Foy, Robert J.

    2016-01-01

    We used flow cytometry to determine if there would be a difference in hematology, selected immune functions, and hemocyte pH (pHi), under two different, future ocean acidification scenarios (pH = 7.50, 7.80) compared to current conditions (pH = 8.09) for Chionoecetes bairdi, Tanner crab. Hemocytes were analyzed after adult Tanner crabs were held for two years under continuous exposure to acidified ocean water. Total counts of hemocytes did not vary among control and experimental treatments; however, there were significantly greater number of dead, circulating hemocytes in crabs held at the lowest pH treatment. Phagocytosis of fluorescent microbeads by hemocytes was greatest at the lowest pH treatment. These results suggest that hemocytes were dying, likely by apoptosis, at a rate faster than upregulated phagocytosis was able to remove moribund cells from circulation at the lowest pH. Crab hemolymph pH (pHe) averaged 8.09 and did not vary among pH treatments. There was no significant difference in internal pH (pHi) within hyalinocytes among pH treatments and the mean pHi (7.26) was lower than the mean pHe. In contrast, there were significant differences among treatments in pHi of the semi-granular+granular cells. Control crabs had the highest mean semi-granular+granular pHi compared to the lowest pH treatment. As physiological hemocyte functions changed from ambient conditions, interactions with the number of eggs in the second clutch, percentage of viable eggs, and calcium concentration in the adult crab shell was observed. This suggested that the energetic costs of responding to ocean acidification and maintaining defense mechanisms in Tanner crab may divert energy from other physiological processes, such as reproduction. PMID:26859148

  10. Structural insights into mechanisms for inhibiting amyloid β42 aggregation by non-catechol-type flavonoids.

    Science.gov (United States)

    Hanaki, Mizuho; Murakami, Kazuma; Akagi, Ken-ichi; Irie, Kazuhiro

    2016-01-15

    The prevention of 42-mer amyloid β-protein (Aβ42) aggregation is promising for the treatment of Alzheimer's disease. We previously described the site-specific inhibitory mechanism for Aβ42 aggregation by a catechol-type flavonoid, (+)-taxifolin, targeting Lys16,28 after its autoxidation. In contrast, non-catechol-type flavonoids (morin, datiscetin, and kaempferol) inhibited Aβ42 aggregation without targeting Lys16,28 with almost similar potencies to that of (+)-taxifolin. We herein provided structural insights into their mechanisms for inhibiting Aβ42 aggregation. Physicochemical analyses revealed that their inhibition did not require autoxidation. The (1)H-(15)N SOFAST-HMQC NMR of Aβ42 in the presence of morin and datiscetin revealed the significant perturbation of chemical shifts of His13,14 and Gln15, which were close to the intermolecular β-sheet region, Gln15-Ala21. His13,14 also played a role in radical formation at Tyr10, thereby inducing the oxidation of Met35, which has been implicated in Aβ42 aggregation. These results suggest the direct interaction of morin and datiscetin with the Aβ42 monomer. Although only kaempferol was oxidatively-degraded during incubation, its degradation products as well as kaempferol itself suppressed Aβ42 aggregation. However, neither kaempferol nor its decomposed products perturbed the chemical shifts of the Aβ42 monomer. Aggregation experiments using 1,1,1,3,3,3-hexafluoro-2-propanol-treated Aβ42 demonstrated that kaempferol and its degradation products inhibited the elongation rather than nucleation phase, implying that they interacted with small aggregates of Aβ42, but not with the monomer. In contrast, morin and datiscetin inhibited both phases. The position and number of hydroxyl groups on the B-ring of non-catechol-type flavonoids could be important for their inhibitory potencies and mechanisms against Aβ42 aggregation. Copyright © 2015 Elsevier Ltd. All rights reserved.

  11. Reactive oxygen species in unstimulated hemocytes of the pacific oyster Crassostrea gigas: a mitochondrial involvement.

    Directory of Open Access Journals (Sweden)

    Ludovic Donaghy

    Full Text Available The Pacific oyster Crassostrea gigas is a sessile bivalve mollusc whose homeostasis relies, at least partially, upon cells circulating in hemolymph and referred to as hemocytes. Oyster's hemocytes have been reported to produce reactive oxygen species (ROS, even in absence of stimulation. Although ROS production in bivalve molluscs is mostly studied for its defence involvement, ROS may also be involved in cellular and tissue homeostasis. ROS sources have not yet been described in oyster hemocytes. The objective of the present work was to characterize the ROS sources in unstimulated hemocytes. We studied the effects of chemical inhibitors on the ROS production and the mitochondrial membrane potential (Δψ(m of hemocytes. First, this work confirmed the specificity of JC-10 probe to measure Δψ(m in oyster hemocytes, without being affected by ΔpH, as reported in mammalian cells. Second, results show that ROS production in unstimulated hemocytes does not originate from cytoplasmic NADPH-oxidase, nitric oxide synthase or myeloperoxidase, but from mitochondria. In contrast to mammalian cells, incubation of hemocytes with rotenone (complex I inhibitor had no effect on ROS production. Incubation with antimycin A (complex III inhibitor resulted in a dose-dependent ROS production decrease while an over-production is usually reported in vertebrates. In hemocytes of C. gigas, the production of ROS seems similarly dependent on both Δψ(m and ΔpH. These findings point out differences between mammalian models and bivalve cells, which warrant further investigation about the fine characterization of the electron transfer chain and the respective involvement of mitochondrial complexes in ROS production in hemocytes of bivalve molluscs.

  12. Effect of gamma irradiation on the hemocyte-mediated immune response of Aedes aegypti against microfilariae

    International Nuclear Information System (INIS)

    Christensen, B.M.; Huff, B.M.; Li, J.

    1990-01-01

    The effect of gamma irradiation on the melanotic encapsulation response of Aedes aegypti black eye Liverpool strain against inoculated Dirofilaria immitis microfilariae (mff) was assessed at 1, 2, 3, and 6 days postinoculation (PI). Mosquitoes received 6000 rad from a 137Cs source (Shepard Mark I irradiator) at 3 days postemergence and were inoculated with 15-20 mff 24 hr later. These mosquitoes were compared to nonirradiated controls that also were inoculated with 15-20 mff at 3 days postemergence. The immune response was significantly reduced in irradiated mosquitoes as compared with controls at all days PI. Although the response was significantly inhibited compared with controls, irradiated mosquitoes were still capable of eliciting a response against 69% of recovered mff at 6 days PI. External gamma irradiation did not significantly affect the proliferation of hemocytes associated with the melanotic encapsulation response of A. aegypti. The number of circulating hemocytes increased in irradiated mosquitoes in response to inoculated mff in a manner similar to nonirradiated, inoculated controls. Hemocyte monophenol oxidase activity, however, was significantly reduced in gamma-irradiated mosquitoes at 12 hr PI as compared with controls. The reduced immunological capacity of irradiated mosquitoes might be related to an interference with gene activity required for the synthesis or activation of enzymes that are directly or indirectly involved in the biochemical processes associated with the production of melanotic substances that sequester mff

  13. Honey bee hemocyte profiling by flow cytometry.

    Science.gov (United States)

    Marringa, William J; Krueger, Michael J; Burritt, Nancy L; Burritt, James B

    2014-01-01

    Multiple stress factors in honey bees are causing loss of bee colonies worldwide. Several infectious agents of bees are believed to contribute to this problem. The mechanisms of honey bee immunity are not completely understood, in part due to limited information about the types and abundances of hemocytes that help bees resist disease. Our study utilized flow cytometry and microscopy to examine populations of hemolymph particulates in honey bees. We found bee hemolymph includes permeabilized cells, plasmatocytes, and acellular objects that resemble microparticles, listed in order of increasing abundance. The permeabilized cells and plasmatocytes showed unexpected differences with respect to properties of the plasma membrane and labeling with annexin V. Both permeabilized cells and plasmatocytes failed to show measurable mitochondrial membrane potential by flow cytometry using the JC-1 probe. Our results suggest hemolymph particulate populations are dynamic, revealing significant differences when comparing individual hive members, and when comparing colonies exposed to diverse conditions. Shifts in hemocyte populations in bees likely represent changing conditions or metabolic differences of colony members. A better understanding of hemocyte profiles may provide insight into physiological responses of honey bees to stress factors, some of which may be related to colony failure.

  14. Recognition between symbiotic Vibrio fischeri and the hemocytes of Euprymna scolopes

    Science.gov (United States)

    Nyholm, Spencer V.; Stewart, Jennifer J.; Ruby, Edward G.; McFall-Ngai, Margaret J.

    2008-01-01

    Summary The light-organ crypts of the squid Euprymna scolopes permit colonization exclusively by the luminous bacterium Vibrio fischeri. Because the crypt interior remains in contact with seawater, the squid must not only foster the specific symbiosis but also continue to exclude other bacteria. Investigation of the role of the innate immune system in these processes revealed that macrophage-like hemocytes isolated from E. scolopes recognized and phagocytosed V. fischeri less than other closely related bacterial species common to the host’s environment. Interestingly, phagocytes isolated from hosts that had been cured of their symbionts bound five-times more V. fischeri cells than those from uncured hosts. No such change in the ability to bind other species of bacteria was observed, suggesting that the host adapts specifically to V. fischeri. Deletion of the gene encoding OmpU, the major outer membrane protein of V. fischeri, increased binding by hemocytes from uncured animals to the level observed for hemocytes from cured animals. Co-incubation with wild-type V. fischeri reduced this binding, suggesting they produce a factor that complements the mutant’s defect. Analyses of the phagocytosis of bound cells by fluorescence-activated cell sorting (FACS) indicated that, once binding to hemocytes had occurred, V. fischeri cells are phagocytosed as effectively as other bacteria. Thus, discrimination by this component of the squid immune system occurs at the level of hemocyte binding, and this response: (i) is modified by previous exposure to the symbiont and, (ii) relies on outer membrane and/or secreted components of the symbionts. These data suggest that regulation of host hemocyte binding by the symbiont may be one of many factors that contribute to specificity in this association. PMID:19196278

  15. Targeting tumor multicellular aggregation through IGPR-1 inhibits colon cancer growth and improves chemotherapy.

    Science.gov (United States)

    Woolf, N; Pearson, B E; Bondzie, P A; Meyer, R D; Lavaei, M; Belkina, A C; Chitalia, V; Rahimi, N

    2017-09-18

    Adhesion to extracellular matrix (ECM) is crucially important for survival of normal epithelial cells as detachment from ECM triggers specific apoptosis known as anoikis. As tumor cells lose the requirement for anchorage to ECM, they rely on cell-cell adhesion 'multicellular aggregation' for survival. Multicellular aggregation of tumor cells also significantly determines the sensitivity of tumor cells to the cytotoxic effects of chemotherapeutics. In this report, we demonstrate that expression of immunoglobulin containing and proline-rich receptor-1 (IGPR-1) is upregulated in human primary colon cancer. Our study demonstrates that IGPR-1 promotes tumor multicellular aggregation, and interfering with its adhesive function inhibits multicellular aggregation and, increases cell death. IGPR-1 supports colon carcinoma tumor xenograft growth in mouse, and inhibiting its activity by shRNA or blocking antibody inhibits tumor growth. More importantly, IGPR-1 regulates sensitivity of tumor cells to the chemotherapeutic agent, doxorubicin/adriamycin by a mechanism that involves doxorubicin-induced AKT activation and phosphorylation of IGPR-1 at Ser220. Our findings offer novel insight into IGPR-1's role in colorectal tumor growth, tumor chemosensitivity, and as a possible novel anti-cancer target.

  16. Changes in blood aggregation with differences in molecular weight and degree of deacetylation of chitosan

    International Nuclear Information System (INIS)

    Hattori, Hidemi; Ishihara, Masayuki

    2015-01-01

    Because the molecular weight (Mw) and degree of deacetylation (DDA) of chitosan can vary depending on the purification method, the identification of appropriate chitosan structures is important for developing more effective hemostatic agents. In this study, the influence of varying Mw and DDA of chitosan on blood aggregation was characterized by 10 types of chitosan with different Mw and DDA, including oligomers. The highest aggregation of whole blood, washed erythrocytes and platelets in platelet-rich plasma (PRP) were observed in chitosan with Mw of 8.6 kDa or more and with DDA of 75 to 88%. However, chitosan with too high Mw (247 kDa) inhibited the aggregation of whole blood, washed erythrocytes and PRP at high chitosan concentration. At certain concentrations, chitosan with 75–85% DDA and 50–190 kDa and chitosan with 87.6% DDA and 247 kDa both aggregated proteins in PRP. Chitosan oligomer did not affect blood aggregation. The results suggested that the aggregation by chitosan depended on the interaction of positively charged chitosan with negatively charged erythrocytes, platelets and plasma protein. It seemed that a suitable balance of positive charge in chitosan and negative charge in hemocytes and some kinds of proteins was important. To develop a hemostatic with effective blood aggregation, the chitosan should not be limited to a single Mw and a single DDA but may be a mixed chitosan with wide range of Mw (8.6–247 kDa) and DDA of 75 to 88%. (paper)

  17. α-Synuclein aggregation, seeding and inhibition by scyllo-inositol

    Energy Technology Data Exchange (ETDEWEB)

    Ibrahim, Tarek [Biological Sciences, Sunnybrook Research Institute (Canada); Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, M4N 3M5, ON (Canada); McLaurin, JoAnne, E-mail: jmclaurin@sri.utoronto.ca [Biological Sciences, Sunnybrook Research Institute (Canada); Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, M4N 3M5, ON (Canada)

    2016-01-15

    Recent literature demonstrates the accelerated aggregation of α-synuclein, a protein implicated in the pathogenesis of Parkinson's disease (PD), by the presence of preformed fibrillar conformers in vitro. Furthermore, these preformed fibrillar seeds are suggested to accelerate pathological induction in vivo when injected into the brains of mice. Variation in the results of in vivo studies is proposed to be caused by α-synuclein conformational variants. To investigate the impact of amino acid sequence on seeding efficiency, human and mouse α-synuclein seeds, which vary at 7 amino acid residues, were generated and cross-seeding kinetics studied. Using transmission electron microscopy (TEM), we confirmed that mouse α-synuclein aggregated more rapidly than human α-synuclein. Subsequently, we determined that seeding of human and mouse α-synuclein was more rapid in the presence of seeds generated from the same species. In addition, an established amyloid inhibitor, scyllo-inositol, was examined for potential inhibitory effects on α-synuclein aggregation. TEM analysis of protein:inhibitor assays demonstrated that scyllo-inositol inhibits the aggregation of α-synuclein, suggesting the therapeutic potential of the small molecule in PD. - Highlights: • Mouse α-syn fibrillizes in a significantly shorter timeframe than human α-syn. • Seeding of monomers is more efficient when seeds originate from the same species. • scyllo-Inositol has anti-aggregation effects on mouse and human α-syn.

  18. Red Wine Inhibits Aggregation and Increases ATP-diphosphohydrolase (CD39) Activity of Rat Platelets in Vitro.

    Science.gov (United States)

    Caiazzo, Elisabetta; Tedesco, Idolo; Spagnuolo, Carmela; Russo, Gian Luigi; Ialenti, Armando; Cicala, Carla

    2016-06-01

    Moderate consumption of red wine has been shown to exert a peculiar cardioprotective effect compared with other alcoholic beverages; inhibition of platelet aggregation seems to be one of the mechanisms underlying this beneficial effect. CD39/ATP-diphosphohydrolase is an integral membrane glycoprotein metabolizing ATP and ADP to AMP; in concert with CD73/ecto-5'-nucleotidase, it contributes to extracellular adenosine accumulation. CD39 is considered a key modulator of thrombus formation; it inhibits platelet aggregation by promoting ADP hydrolysis. There is evidence that red wine consumption increases CD39 activity in platelets from streptozotocin-induced diabetic rats. Here we show that two kinds of Aglianico red wines inhibit aggregation and increase ATP--and ADPase activity in rat platelets.

  19. New insights from the oyster Crassostrea rhizophorae on bivalve circulating hemocytes.

    Directory of Open Access Journals (Sweden)

    Mauro de Freitas Rebelo

    Full Text Available Hemocytes are the first line of defense of the immune system in invertebrates, but despite their important role and enormous potential for the study of gene-environment relationships, research has been impeded by a lack of consensus on their classification. Here we used flow cytometry combined with histological procedures, histochemical reactions and transmission electron microscopy to characterize the hemocytes from the oyster Crassostrea rhizophorae. Transmission electron microscopy revealed remarkable morphological characteristics, such as the presence of membranous cisternae in all mature cells, regardless of size and granulation. Some granular cells contained many cytoplasmic granules that communicated with each other through a network of channels, a feature never previously described for hemocytes. The positive reactions for esterase and acid phosphatase also indicated the presence of mature cells of all sizes and granule contents. Flow cytometry revealed a clear separation in complexity between agranular and granular populations, which could not be differentiated by size, with cells ranging from 2.5 to 25 µm. Based on this evidence we suggest that, at least in C. rhizophorae, the different subpopulations of hemocytes may in reality be different stages of one type of cell, which accumulates granules and loses complexity (with no reduction in size as it degranulates in the event of an environmental challenge.

  20. Vibrio cholerae interactions with Mytilus galloprovincialis hemocytes mediated by serum components.

    Directory of Open Access Journals (Sweden)

    Laura eCanesi

    2013-12-01

    Full Text Available Edible bivalves (e.g., mussels, oysters can accumulate large amount of bacteria in their tissues and act as passive carriers of pathogens to humans. Bacterial persistence inside bivalves depends, at least in part, on hemolymph anti-bacterial activity that is exerted by both serum soluble factors and phagocytic cells (i.e., the hemocytes. It was previously shown that Mytilus galloprovincialis hemolymph serum contains opsonins that mediate D-mannose-sensitive interactions between hemocytes and V. cholerae O1 El Tor bacteria that carry the Mannose–Sensitive Hemagglutinin (MSHA. These opsonins enhance phagocytosis and killing of vibrios by facilitating their binding to hemocytes. Since V. cholerae strains not carrying the MSHA ligand (O1 classical, non O1/O139 are present in coastal water and can be entrapped by mussels, we studied whether in mussel serum, in addition to opsonins directed towards MSHA, other components can mediate opsonization of these bacteria. By comparing interactions of O1 classical and non O1/O139 strains with hemocytes in ASW and serum, it was found that M. galloprovincialis serum contains components that increase by at approximately two fold their adhesion to, association with and killing by hemocytes. Experiments conducted with high and low molecular mass fractions obtained by serum ultrafiltration indicated that these compounds have molecular mass higher than 5000 Da. Serum exposure to high temperature (80°C abolished its opsonizing capability suggesting that the involved serum active components are of protein nature. Further studies are needed to define the chemical properties and specificity of both the involved bacterial ligands and hemolymph opsonins. This information will be central not only to better understand V. cholerae ecology, but also to improve current bivalve depuration practices and properly protect human health.

  1. Concholepas hemocyanin biosynthesis takes place in the hepatopancreas, with hemocytes being involved in its metabolism.

    Science.gov (United States)

    Manubens, Augusto; Salazar, Fabián; Haussmann, Denise; Figueroa, Jaime; Del Campo, Miguel; Pinto, Jonathan Martínez; Huaquín, Laura; Venegas, Alejandro; Becker, María Inés

    2010-12-01

    Hemocyanins are copper-containing glycoproteins in some molluscs and arthropods, and their best-known function is O(2) transport. We studied the site of their biosynthesis in the gastropod Concholepas concholepas by using immunological and molecular genetic approaches. We performed immunohistochemical staining of various organs, including the mantle, branchia, and hepatopancreas, and detected C. concholepas hemocyanin (CCH) molecules in circulating and tissue-associated hemocytes by electron microscopy. To characterize the hemocytes, we purified them from hemolymph. We identified three types of granular cells. The most abundant type was a phagocyte-like cell with small cytoplasmic granules. The second type contained large electron-dense granules. The third type had vacuoles containing hemocyanin molecules suggesting that synthesis or catabolism occurred inside these cells. Our failure to detect cch-mRNA in hemocytes by reverse transcription with the polymerase chain reaction (RT-PCR) led us to propose that hemocytes instead played a role in CCH metabolism. This hypothesis was supported by colloidal gold staining showing hemocyanin molecules in electron-dense granules inside hemocytes. RT-PCR analysis, complemented by in situ hybridization analyses with single-stranded antisense RNAs as specific probes, demonstrated the presence of cch-mRNA in the hepatopancreas; this was consistent with the specific hybridization signal and confirmed the hepatopancreas as the site of CCH synthesis. Finally, we investigated the possibility that CCH catabolism in hemocytes was involved in the host immune response and in the generation of secondary metabolites such as antimicrobial peptides and phenoloxidase.

  2. Inhibition of neuronal cell–cell adhesion measured by the microscopic aggregation assay and impedance sensing

    NARCIS (Netherlands)

    Wiertz, Remy; Marani, Enrico; Rutten, Wim

    2010-01-01

    Microscopic aggregation assay and impedance sensing (IS) were used to monitor a change in in vitro neuron–neuron adhesion in response to blocking of cell adhesion molecules. By blocking neuron–neuron adhesion, migration and aggregation of neuronal cells can be inhibited. This leads to better control

  3. Hydroxychavicol, a novel betel leaf component, inhibits platelet aggregation by suppression of cyclooxygenase, thromboxane production and calcium mobilization.

    Science.gov (United States)

    Chang, M C; Uang, B J; Tsai, C Y; Wu, H L; Lin, B R; Lee, C S; Chen, Y J; Chang, C H; Tsai, Y L; Kao, C J; Jeng, J H

    2007-09-01

    Platelet hyperactivity is important in the pathogenesis of cardiovascular diseases. Betel leaf (PBL) is consumed by 200-600 million betel quid chewers in the world. Hydroxychavicol (HC), a betel leaf component, was tested for its antiplatelet effect. We tested the effect of HC on platelet aggregation, thromboxane B(2) (TXB(2)) and reactive oxygen species (ROS) production, cyclooxygenase (COX) activity, ex vivo platelet aggregation and mouse bleeding time and platelet plug formation in vivo. The pharmacokinetics of HC in rats was also assessed. HC inhibited arachidonic acid (AA) and collagen-induced platelet aggregation and TXB(2) production. HC inhibited the thrombin-induced TXB(2) production, but not platelet aggregation. SQ29548, suppressed collagen- and thrombin-induced TXB(2) production, but not thrombin-induced platelet aggregation. HC also suppressed COX-1/COX-2 enzyme activity and the AA-induced ROS production and Ca(2+) mobilization. HC further inhibited the ex vivo platelet aggregation of platelet-rich plasma (>100 nmole/mouse) and prolonged platelet plug formation (>300 nmole/mouse) in mesenteric microvessels, but showed little effect on bleeding time in mouse tail. Moreover, pharmacokinetics analysis found that more than 99% of HC was metabolized within 3 min of administration in Sprague-Dawley rats in vivo. HC is a potent COX-1/COX-2 inhibitor, ROS scavenger and inhibits platelet calcium signaling, TXB(2) production and aggregation. HC could be a potential therapeutic agent for prevention and treatment of atherosclerosis and other cardiovascular diseases through its anti-inflammatory and antiplatelet effects, without effects on haemostatic functions.

  4. Endogenous growth factor stimulation of hemocyte proliferation induces resistance to Schistosoma mansoni challenge in the snail host.

    Science.gov (United States)

    Pila, Emmanuel A; Gordy, Michelle A; Phillips, Valerie K; Kabore, Alethe L; Rudko, Sydney P; Hanington, Patrick C

    2016-05-10

    Digenean trematodes are a large, complex group of parasitic flatworms that infect an incredible diversity of organisms, including humans. Larval development of most digeneans takes place within a snail (Gastropoda). Compatibility between snails and digeneans is often very specific, such that suitable snail hosts define the geographical ranges of diseases caused by these worms. The immune cells (hemocytes) of a snail are sentinels that act as a crucial barrier to infection by larval digeneans. Hemocytes coordinate a robust and specific immunological response, participating directly in parasite killing by encapsulating and clearing the infection. Hemocyte proliferation and differentiation are influenced by unknown digenean-specific exogenous factors. However, we know nothing about the endogenous control of hemocyte development in any gastropod model. Here, we identify and functionally characterize a progranulin [Biomphalaria glabrata granulin (BgGRN)] from the snail B. glabrata, a natural host for the human blood fluke Schistosoma mansoni Granulins are growth factors that drive proliferation of immune cells in organisms, spanning the animal kingdom. We demonstrate that BgGRN induces proliferation of B. glabrata hemocytes, and specifically drives the production of an adherent hemocyte subset that participates centrally in the anti-digenean defense response. Additionally, we demonstrate that susceptible B. glabrata snails can be made resistant to infection with S. mansoni by first inducing hemocyte proliferation with BgGRN. This marks the functional characterization of an endogenous growth factor of a gastropod mollusc, and provides direct evidence of gain of resistance in a snail-digenean infection model using a defined factor to induce snail resistance to infection.

  5. Parsley extract inhibits in vitro and ex vivo platelet aggregation and prolongs bleeding time in rats.

    Science.gov (United States)

    Gadi, Dounia; Bnouham, Mohamed; Aziz, Mohammed; Ziyyat, Abderrahim; Legssyer, Abdelkhaleq; Legrand, Chantal; Lafeve, Françoise Fauvel; Mekhfi, Hassane

    2009-08-17

    Many cardiovascular diseases are associated with an increase in blood platelet activity. In Morocco, parsley (Petroselinum crispum, Apiaceae) is one of the medicinal herbs used to treat cardiovascular diseases such as arterial hypertension. In this study, crude aqueous extract (CAE) of parsley was evaluated for its anti-platelet activity in experimental animals on platelet aggregation in vitro and ex vivo; and on bleeding time in vivo. The in vitro aggregation was monitored after pre-incubation of platelets with CAE. The bleeding time and ex vivo aggregation were performed after oral treatment. CAE inhibited dose dependently platelet aggregation in vitro induced by thrombin, ADP, collagen and epinephrine. The oral administration of CAE (3g/kg) inhibited significantly (pparsley may be benefit in the normalization of platelet hyperactivation, in the nutritional prevention of cardiovascular diseases and are potentially interesting in the development of new prevention strategies.

  6. Dark chocolate inhibits platelet aggregation in healthy volunteers.

    Science.gov (United States)

    Innes, Andrew J; Kennedy, Gwen; McLaren, Margaret; Bancroft, Anne J; Belch, Jill J F

    2003-08-01

    Cardiovascular disease is a leading cause of death in the UK. The flavonoids found in cocoa may produce a cardio-protective role for chocolate with a high cocoa content. Thirty healthy volunteers were randomised to receive 100 g of white, milk or dark chocolate, and assessments of platelet function were undertaken on venous blood samples before and after chocolate consumption. White and milk chocolate had no significant effect on platelets. However dark chocolate inhibited collagen-induced platelet aggregation in platelet rich plasma. In the future dark chocolate may have a role in prevention of cardiovascular and thromboembolic diseases.

  7. Inhibition of Alzheimer amyloid {beta} aggregation by polyvalent trehalose

    Energy Technology Data Exchange (ETDEWEB)

    Miura, Yoshiko; You, Chouga [School of Materials Science, Japan Advanced Institute of Science and Technology, 1-1 Asahidai, Nomi, Ishikawa 923-1292 (Japan); Ohnishi, Reiko [Department of Molecular Design and Engineering, Graduate School of Engineering, Nagoya University, Furo-cho, Chikusa-ku, Nagoya 464-8603 (Japan)], E-mail: miuray@jaist.ac.jp

    2008-04-15

    A glycopolymer carrying trehalose was found to suppress the formation of amyloid fibrils from the amyloid {beta} peptide (1-42) (A{beta}), as evaluated by thioflavin T assay and atomic force microscopy. Glycopolymers carrying sugar alcohols also changed the aggregation properties of A{beta}, and the inhibitory effect depended on the type of sugar and alkyl side chain. Neutralization activity was confirmed by in vitro assay using HeLa cells. The glycopolymer carrying trehalose strongly inhibited amyloid formation and neutralized cytotoxicity.

  8. Morphologic, cytometric and functional characterization of the common octopus (Octopus vulgaris) hemocytes.

    Science.gov (United States)

    Castellanos-Martínez, S; Prado-Alvarez, M; Lobo-da-Cunha, A; Azevedo, C; Gestal, C

    2014-05-01

    The hemocytes of Octopus vulgaris were morphologically and functionally characterized. Light and electron microscopy (TEM and SEM), and flow cytometry analyses revealed the existence of two hemocyte populations. Large granulocytes showed U-shaped nucleus, a mean of 11.6 μm±1.2 in diameter with basophilic granules, polysaccharide and lysosomic deposits in the cytoplasm. Small granulocytes measured a mean of 8.1 μm±0.7 in diameter, and have a round nucleus occupying almost the entire cell and few or not granules in the cytoplasm. Flow cytometry analysis showed that large granulocytes are the principal cells that develop phagocytosis of latex beads (rising up to 56%) and ROS after zymosan stimulation. Zymosan induced the highest production of both ROS and NO. This study is the first tread towards understanding the O. vulgaris immune system by applying new tools to provide a most comprehensive morpho-functional study of their hemocytes. Copyright © 2013 Elsevier Ltd. All rights reserved.

  9. Hemocyte characterization of Nasutitermes coxipoensis (Holmgren) (Isoptera: Termitidae) workers and hemocyte evaluation after parasitism by Metarhizium anisopliae; Caracterizacao dos hemocitos de operarios de Nasutitermes coxipoensis (Holmgren) (Isoptera: Termitidae) e avaliacao hemocitaria apos parasitismo por Metarhizium anisopliae

    Energy Technology Data Exchange (ETDEWEB)

    Cunha, Franklin M.; Wanderley-Teixeira, Valeria; Albuquerque, Auristela C. [Universidade Federal Rural de Pernambuco (UFRPE), Recife, PE (Brazil). Programa de Pos-Graduacao em Entomologia Agricola], e-mail: ukento@yahoo.com.br; Teixeira, Alvaro A.C. [Universidade Federal Rural de Pernambuco (UFRPE), Recife, PE (Brazil). Dept. de Morfologia e Fisiologia Animal], e-mail: valeria@dmfa.ufrpe.br, e-mail: auritermes@yahoo.com.br; Alves, Luiz C. [Universidade Federal de Pernambuco (UFPE), Recife, PE (Brazil). Lab. de Imunopatologia Keizo Asami (LIKA); Lima, Elza A.L.A. [Universidade Federal de Pernambuco (UFPE), Recife, PE (Brazil). Dept. de Micologia. Lab. de Controle Biologico

    2009-03-15

    We aimed to characterize the morphology and ultrastructure of hemocytes of Nasutitermes coxipoensis (Holmgren) workers and to quantify the cell types 24h, 48h and 72h after inoculation with Metarhizium anisopliae. Six hemocytes types were identified, plasmatocyte, granulocyte, spherulocyte, prohemocyte, adipohemocyte and eonocytoid Hemocytes did not present any morphological alteration at the several observation periods, but they did have a change in their abundance, as observed for spherulocytes, adipohemocytes and eonocytoids at all intervals, and for plasmatocytes and granulocytes at 48h after host inoculation. We argue on the possible reasons and implications of the observed changes. (author)

  10. Understanding the Role of Host Hemocytes in a Squid/Vibrio Symbiosis Using Transcriptomics and Proteomics

    Directory of Open Access Journals (Sweden)

    Andrew J. Collins

    2012-05-01

    Full Text Available The symbiosis between the squid, Euprymna scolopes, and the bacterium, Vibrio fischeri, serves as a model for understanding interactions between beneficial bacteria and animal hosts. The establishment and maintenance of the association is highly specific and depends on the selection of V. fischeri and exclusion of non-symbiotic bacteria from the environment. Current evidence suggests that the host’s cellular innate immune system, in the form of macrophage-like hemocytes, helps to mediate host tolerance of V. fischeri. To begin to understand the role of hemocytes in this association, we analyzed these cells by high-throughput 454 transcriptomic and liquid chromatography/ tandem mass spectrometry (LC-MS/MS proteomic analyses. 454 high-throughput sequencing produced 650,686 reads totaling 279.9 Mb while LC-MS/MS analyses of circulating hemocytes putatively identified 702 unique proteins. Several receptors involved with the recognition of microbial associated molecular patterns (MAMPs were identified. Among these was a complete open reading frame (ORF to a putative peptidoglycan recognition protein (EsPGRP5 that has conserved residues for amidase activity. Assembly of the hemocyte transcriptome showed EsPGRP5 had high coverage, suggesting it is among the 5% most abundant transcripts in circulating hemocytes. Other transcripts and proteins identified included members of the conserved NFκB signaling pathway, putative members of the complement pathway, the carbohydrate binding protein galectin, and cephalotoxin. Quantitative PCR of complement-related genes, cephalotoxin, EsPGRP5, and a nitric oxide synthase showed differential expression in circulating hemocytes isolated from adult squid with colonized light organs compared to those for which the symbionts were removed. These data suggest that the presence of the symbiont influences gene expression of the cellular innate immune system of the host.

  11. Ultrastructural and functional characterization of circulating hemocytes from Galleria mellonella larva: Cell types and their role in the innate immunity.

    Science.gov (United States)

    Wu, Gongqing; Liu, Yi; Ding, Ying; Yi, Yunhong

    2016-08-01

    Galleria mellonella larvae have been widely used as a model to study the virulence of various human pathogens. Hemocytes play important roles in the innate immune response of G. mellonella. In this study, the hemocytes of G. mellonella larvae were analyzed by transmission electron microscope, light microscope, and cytochemistry. The cytological and morphological analyses revealed four types of hemocytes; Plasmatocytes, granular cells, spherule cells and oenocytoids. Differential hemocyte counts showed that under our conditions plasmatocytes and granular cells were the most abundant circulating cell types in the hemolymph. We also investigated the role of different types of hemocytes in the cellular and humoral immune defenses. The in-vivo experiment showed that plasmatocytes, granular cells and oenocytoids phagocytized FITC-labelled Escherichia coli bacteria in larvae of G. mellonella, whereas the granular cells exhibited the strongest phagocytic ability against these microbial cells. After incubation with L-DOPA, plasmatocytes, granular cells and oenocytoids are stained brown, indicating the presence of phenoloxidase activity. These results shed new light on our understanding of the immune function of G. mellonella hemocytes. Copyright © 2016 Elsevier Ltd. All rights reserved.

  12. Hemocyte-mediated phagocytosis and melanization in the mosquito Armigeres subalbatus following immune challenge by bacteria.

    Science.gov (United States)

    Hillyer, Julián F; Schmidt, Shelley L; Christensen, Bruce M

    2003-07-01

    Mosquitoes are important vectors of disease. These insects respond to invading organisms with strong cellular and humoral immune responses that share many similarities with vertebrate immune systems. The strength and specificity of these responses are directly correlated to a mosquito's ability to transmit disease. In the current study, we characterized the hemocytes (blood cells) of Armigeres subalbatus by morphology (ultrastructure), lectin binding, enzyme activity, immunocytochemistry, and function. We found four hemocyte types: granulocytes, oenocytoids, adipohemocytes, and thrombocytoids. Granulocytes contained acid phosphatase activity and bound the exogenous lectins Helix pomatia agglutinin, Galanthus nivalis lectin, and wheat germ agglutinin. Following bacteria inoculation, granulocytes mounted a strong phagocytic response as early as 5 min postexposure. Bacteria also elicited a hemocyte-mediated melanization response. Phenoloxidase, the rate-limiting enzyme in the melanization pathway, was present exclusively in oenocytoids and in many of the melanotic capsules enveloping bacteria. The immune responses mounted against different bacteria were not identical; gram(-) Escherichia coli were predominantly phagocytosed and gram(+) Micrococcus luteus were melanized. These studies implicate hemocytes as the primary line of defense against bacteria.

  13. Bombyx mori and Aedes aegypti form multi-functional immune complexes that integrate pattern recognition, melanization, coagulants, and hemocyte recruitment.

    Science.gov (United States)

    Phillips, Dennis R; Clark, Kevin D

    2017-01-01

    The innate immune system of insects responds to wounding and pathogens by mobilizing multiple pathways that provide both systemic and localized protection. Key localized responses in hemolymph include melanization, coagulation, and hemocyte encapsulation, which synergistically seal wounds and envelop and destroy pathogens. To be effective, these pathways require a targeted deposition of their components to provide protection without compromising the host. Extensive research has identified a large number of the effectors that comprise these responses, but questions remain regarding their post-translational processing, function, and targeting. Here, we used mass spectrometry to demonstrate the integration of pathogen recognition proteins, coagulants, and melanization components into stable, high-mass, multi-functional Immune Complexes (ICs) in Bombyx mori and Aedes aegypti. Essential proteins common to both include phenoloxidases, apolipophorins, serine protease homologs, and a serine protease that promotes hemocyte recruitment through cytokine activation. Pattern recognition proteins included C-type Lectins in B. mori, while A. aegypti contained a protein homologous to Plasmodium-resistant LRIM1 from Anopheles gambiae. We also found that the B. mori IC is stabilized by extensive transglutaminase-catalyzed cross-linking of multiple components. The melanization inhibitor Egf1.0, from the parasitoid wasp Microplitis demolitor, blocked inclusion of specific components into the IC and also inhibited transglutaminase activity. Our results show how coagulants, melanization components, and hemocytes can be recruited to a wound surface or pathogen, provide insight into the mechanism by which a parasitoid evades this immune response, and suggest that insects as diverse as Lepidoptera and Diptera utilize similar defensive mechanisms.

  14. Transient expression of protein tyrosine phosphatases encoded in Cotesia plutellae bracovirus inhibits insect cellular immune responses

    Science.gov (United States)

    Ibrahim, Ahmed M. A.; Kim, Yonggyun

    2008-01-01

    Several immunosuppressive factors are associated with parasitism of an endoparasitoid wasp, Cotesia plutellae, on the diamondback moth, Plutella xylostella. C. plutellae bracovirus (CpBV) encodes a large number of putative protein tyrosine phosphatases (PTPs), which may play a role in inhibiting host cellular immunity. To address this inhibitory hypothesis of CpBV-PTPs, we performed transient expression of individual CpBV-PTPs in hemocytes of the beet armyworm, Spodoptera exigua, and analyzed their cellular immune responses. Two different forms of CpBV-PTPs were chosen and cloned into a eukaryotic expression vector under the control of the p10 promoter of baculovirus: one with the normal cysteine active site (CpBV-PTP1) and the other with a mutated active site (CpBV-PTP5). The hemocytes transfected with CpBV-PTP1 significantly increased in PTP activity compared to control hemocytes, but those with CpBV-PTP5 exhibited a significant decrease in the PTP activity. All transfected hemocytes exhibited a significant reduction in both cell spreading and encapsulation activities compared to control hemocytes. Co-transfection of CpBV-PTP1 together with its double-stranded RNA reduced the messenger RNA (mRNA) level of CpBV-PTP1 and resulted in recovery of both hemocyte behaviors. This is the first report demonstrating that the polydnaviral PTPs can manipulate PTP activity of the hemocytes to interrupt cellular immune responses.

  15. The ascidian Styela plicata hemocytes as a potential biomarker of marine pollution: In vitro effects of seawater and organic mercury.

    Science.gov (United States)

    Parrinello, D; Bellante, A; Parisi, M G; Sanfratello, M A; Indelicato, S; Piazzese, D; Cammarata, M

    2017-02-01

    Toxic metals, such as mercury, contribute substantially to anthropogenic pollution in many estuarine environments. Animals living in those environments, particularly invertebrate filter feeders like tunicates, can be used as bioindicators. In an attempt to identify cellular markers for revealing pollution, this study examined in vitro the effects of different concentrations of methyl mercury on Styela plicata hemocytes. The harvested hemocytes from S. plicata that were exposed to the metal had a significant mortality, cellular count and morphometric alterations. These findings provided evidence of MeHg immunotoxic effects on S. plicata, resulting in hemocyte death and morphological changes induced by cytoskeleton alterations. Thus, a morphometric cellular parameter, such as spreading ability, was used as a complementary method for differentiation between hemocytes treated with a marine solution (as a negative control) and hemocytes incubated with methylmercury and/or Sicilian seawater samples. Copyright © 2016 Elsevier Inc. All rights reserved.

  16. Soluble Aβ aggregates can inhibit prion propagation.

    Science.gov (United States)

    Sarell, Claire J; Quarterman, Emma; Yip, Daniel C-M; Terry, Cassandra; Nicoll, Andrew J; Wadsworth, Jonathan D F; Farrow, Mark A; Walsh, Dominic M; Collinge, John

    2017-11-01

    Mammalian prions cause lethal neurodegenerative diseases such as Creutzfeldt-Jakob disease (CJD) and consist of multi-chain assemblies of misfolded cellular prion protein (PrP C ). Ligands that bind to PrP C can inhibit prion propagation and neurotoxicity. Extensive prior work established that certain soluble assemblies of the Alzheimer's disease (AD)-associated amyloid β-protein (Aβ) can tightly bind to PrP C , and that this interaction may be relevant to their toxicity in AD. Here, we investigated whether such soluble Aβ assemblies might, conversely, have an inhibitory effect on prion propagation. Using cellular models of prion infection and propagation and distinct Aβ preparations, we found that the form of Aβ assemblies which most avidly bound to PrP in vitro also inhibited prion infection and propagation. By contrast, forms of Aβ which exhibit little or no binding to PrP were unable to attenuate prion propagation. These data suggest that soluble aggregates of Aβ can compete with prions for binding to PrP C and emphasize the bidirectional nature of the interplay between Aβ and PrP C in Alzheimer's and prion diseases. Such inhibitory effects of Aβ on prion propagation may contribute to the apparent fall-off in the incidence of sporadic CJD at advanced age where cerebral Aβ deposition is common. © 2017 The Authors.

  17. Use of Biomphalaria glabrata hemocytes as a biomarker of exposure to ionizing radiation

    Energy Technology Data Exchange (ETDEWEB)

    Silva, Hianna A.M.F.; Lima, Maira V.; Sa, Jose L.F.; Siqueira, Williams N.; Luna Filho, Ricardo L.C.; Melo, Larissa S.A.; Morais, Vinicius H.T.; Melo, Ana M.M.A., E-mail: hiannaamfs@gmail.com, E-mail: mairavasconceloslima@gmail.com, E-mail: luismuma6@gmail.com, E-mail: williams.wns@gmail.com, E-mail: ricardolclf@hotmail.com, E-mail: larissamelo.pe@gmail.com, E-mail: viniciushtmorais@hotmail.com, E-mail: amdemelo@hotmail.com [Universidade Federal de Pernambuco (UFPE), Recife, PE (Brazil). Departamento de Biofisica e Radiobiologia

    2017-11-01

    The increase of the applications of ionizing radiation in several areas and sectors of modern society has given rise to a greater probability of occurrence of accidents. These accidental occurrences have revealed the need for methods that provide quantitative data on the radiation doses absorbed by biological systems. The mollusk Biomphalaria glabrata presents as a good bioindicator in several works referenced in the literature. In this way, the objective of this work was to evaluate the morphological and quantitative alterations of hemocytes of the Biomphalaria glabrata exposed to ionizing radiation. For the experiments, adult mollusks of the species B. glabrata pigmented were used. The selected mollusks were divided into six groups: five submitted to doses of 10, 20, 30, 40, 50 Gy of {sup 60}Co gamma radiation and the control group. After 48 h, the slides were prepared and then read in a microscope. Quantitative analysis showed a decrease in the total number of hemocytes after irradiation. In the cell classification, a higher number of hyalinocytes were observed in relation to the number of granulocytes, except for the animals exposed to a dose of 30 Gy. The presence of micronuclei and binucleations were observed at all doses used. Apoptosis was observed at doses starting at 30 Gy. Therefore, it is possible to conclude that the morphological and quantitative analysis of B. glabrata hemocytes provided significant data for the identification of biological damage caused by ionizing radiation, allowing the beginning of standardization of the morphological alteration counting technique in B. glabrata hemocytes as An environmental biomarker for the action of physical agents. (author)

  18. Use of Biomphalaria glabrata hemocytes as a biomarker of exposure to ionizing radiation

    International Nuclear Information System (INIS)

    Silva, Hianna A.M.F.; Lima, Maira V.; Sa, Jose L.F.; Siqueira, Williams N.; Luna Filho, Ricardo L.C.; Melo, Larissa S.A.; Morais, Vinicius H.T.; Melo, Ana M.M.A.

    2017-01-01

    The increase of the applications of ionizing radiation in several areas and sectors of modern society has given rise to a greater probability of occurrence of accidents. These accidental occurrences have revealed the need for methods that provide quantitative data on the radiation doses absorbed by biological systems. The mollusk Biomphalaria glabrata presents as a good bioindicator in several works referenced in the literature. In this way, the objective of this work was to evaluate the morphological and quantitative alterations of hemocytes of the Biomphalaria glabrata exposed to ionizing radiation. For the experiments, adult mollusks of the species B. glabrata pigmented were used. The selected mollusks were divided into six groups: five submitted to doses of 10, 20, 30, 40, 50 Gy of "6"0Co gamma radiation and the control group. After 48 h, the slides were prepared and then read in a microscope. Quantitative analysis showed a decrease in the total number of hemocytes after irradiation. In the cell classification, a higher number of hyalinocytes were observed in relation to the number of granulocytes, except for the animals exposed to a dose of 30 Gy. The presence of micronuclei and binucleations were observed at all doses used. Apoptosis was observed at doses starting at 30 Gy. Therefore, it is possible to conclude that the morphological and quantitative analysis of B. glabrata hemocytes provided significant data for the identification of biological damage caused by ionizing radiation, allowing the beginning of standardization of the morphological alteration counting technique in B. glabrata hemocytes as An environmental biomarker for the action of physical agents. (author)

  19. Immune responses and ultrastructural changes of hemocytes in freshwater crab Sinopotamon henanense exposed to elevated cadmium

    Energy Technology Data Exchange (ETDEWEB)

    Qin Qin [College of Life Science, Shanxi University, Taiyuan, Shanxi, 030006 (China); Central Laboratory, Shanxi Provincial People' s Hospital, Taiyuan, Shanxi, 030012 (China); Qin Shengjuan [College of Life Science, Shanxi University, Taiyuan, Shanxi, 030006 (China); Wang Lan, E-mail: lanwang@sxu.edu.cn [College of Life Science, Shanxi University, Taiyuan, Shanxi, 030006 (China); Lei Wenwen [College of Life Science, Shanxi University, Taiyuan, Shanxi, 030006 (China)

    2012-01-15

    Cadmium (Cd) is one of the most toxic heavy metals that can impact immunological parameters in aquatic animals. To investigate the immunotoxicity and ultrastructural changes of hemocytes, specimens of Sinopotamon henanense were exposed to different concentrations of cadmium and the differences in immunologic parameters between Cd exposure groups and control groups were investigated. Total hemocyte count (THC) in Cd-exposure groups were decreased significantly when compared with the control groups, especially in the groups treated with higher Cd concentrations and longer exposure time, while no significant differences were observed in the proportions of the three types of hemocytes. Phenoloxidase (PO) activities were significantly higher in Cd-exposure groups than the control groups. Superoxide dismutase (SOD) activities gradually increased in 7.25 and 14.5 mg L{sup -1} Cd groups, but in other higher Cd groups, they showed first increase and following decrease with the exposure time prolonged. Acid phosphatase (ACP) activities were induced at 48 h, and then decreased, while alkaline phosphatase (AKP) activities increased gradually until 96 h. Electron microscopic results showed that nucleus, mitochondria and rough endoplasm recutulum (rER) of three types of hemocytes were sensitive to acute Cd toxicity. In Cd-exposed groups, chromatin condensation, nucleus deformation and nucleus envelope rupture were noted. Additionally, mitochondrial dilation and rER degranulation were observed in Cd-treated crabs. These results suggested that immune response and organelles of hemocyte of S. henanense were impacted by Cd exposure, and the changes of these immunologic parameters reflect changes in crab immune response capability consequent to Cd exposure.

  20. Immune responses and ultrastructural changes of hemocytes in freshwater crab Sinopotamon henanense exposed to elevated cadmium

    International Nuclear Information System (INIS)

    Qin Qin; Qin Shengjuan; Wang Lan; Lei Wenwen

    2012-01-01

    Cadmium (Cd) is one of the most toxic heavy metals that can impact immunological parameters in aquatic animals. To investigate the immunotoxicity and ultrastructural changes of hemocytes, specimens of Sinopotamon henanense were exposed to different concentrations of cadmium and the differences in immunologic parameters between Cd exposure groups and control groups were investigated. Total hemocyte count (THC) in Cd-exposure groups were decreased significantly when compared with the control groups, especially in the groups treated with higher Cd concentrations and longer exposure time, while no significant differences were observed in the proportions of the three types of hemocytes. Phenoloxidase (PO) activities were significantly higher in Cd-exposure groups than the control groups. Superoxide dismutase (SOD) activities gradually increased in 7.25 and 14.5 mg L −1 Cd groups, but in other higher Cd groups, they showed first increase and following decrease with the exposure time prolonged. Acid phosphatase (ACP) activities were induced at 48 h, and then decreased, while alkaline phosphatase (AKP) activities increased gradually until 96 h. Electron microscopic results showed that nucleus, mitochondria and rough endoplasm recutulum (rER) of three types of hemocytes were sensitive to acute Cd toxicity. In Cd-exposed groups, chromatin condensation, nucleus deformation and nucleus envelope rupture were noted. Additionally, mitochondrial dilation and rER degranulation were observed in Cd-treated crabs. These results suggested that immune response and organelles of hemocyte of S. henanense were impacted by Cd exposure, and the changes of these immunologic parameters reflect changes in crab immune response capability consequent to Cd exposure.

  1. Inhibition of Platelet Aggregation by Supernates from Stored Red Blood Cells

    Science.gov (United States)

    2010-04-01

    450 μl of blood or 450 μl of platelet rich plasma (PRP) was mixed with 225 μl of supernate plus 225 μl of Tyrode’s buffer and incubated for ten... platelet counts, prothrombin time, activated partial thromboplastin time, fibrinogen, fibrin split products, and FVIII:Rag also measured 30 minutes...RTO-MP-HFM-182 22 - 1 Inhibition of Platelet Aggregation by Supernates from Stored Red Blood Cells Dr. Steve J. McFaul, LT Frederick A

  2. Flavonoids purified from parsley inhibit human blood platelet aggregation and adhesion to collagen under flow.

    Science.gov (United States)

    Gadi, Dounia; Bnouham, Mohamed; Aziz, Mohammed; Ziyyat, Abderrahim; Legssyer, Abdelkhaleq; Bruel, Arlette; Berrabah, Mohamed; Legrand, Chantal; Fauvel-Lafeve, Françoise; Mekhfi, Hassane

    2012-08-10

    Blood platelets are directly involved in both haemostatic and pathologic thrombotic processes, through their adhesion, secretion and aggregation. In this study, we investigated the effect of genins (aglycone flavonoids without sugar group) isolated from parsley (Petroselinum crispum) leaves in vitro on human platelet aggregation and adhesion to a collagen-coated surface under physiologic flow conditions. The aggregation and adhesion studies were monitored after pre-incubation of platelets with genins. Genins inhibited dose dependently aggregation induced by thrombin, ADP and collagen. The strongest effect was observed in collagen induced aggregation (IC50 = 0.08 ± 0.01 mg/ml). The HPLC identification of genins compounds revealed the presence of keampferol, apigenin and other not identified compounds. The aggregation tests showed that these compounds have anti-aggregating activity. In addition, adhesion of human platelets to collagen was greatly decreased (over 75 %) by genins (0.3 mg/ml). While the mechanism by which genins act is unclear, we suggest that these compounds may interfere with a multiple target step in the haemostasis process. These results show that genins isolated from parsley has a potent antiplatelet activity. It may be an important source of beneficial antiplatelet compounds that decrease thrombosis and cardiovascular diseases.

  3. Phagocytic activities of hemocytes from the deep-sea symbiotic mussels Bathymodiolus japonicus, B. platifrons, and B. septemdierum.

    Science.gov (United States)

    Tame, Akihiro; Yoshida, Takao; Ohishi, Kazue; Maruyama, Tadashi

    2015-07-01

    Deep-sea mytilid mussels harbor symbiotic bacteria in their gill epithelial cells that are horizontally or environmentally transmitted to the next generation of hosts. To understand the immune defense system in deep-sea symbiotic mussels, we examined the hemocyte populations of the symbiotic Bathymodiolus mussel species Bathymodiolus japonicus, Bathymodiolus platifrons, and Bathymodiolus septemdierum, and characterized three types of hemocytes: agranulocytes (AGs), basophilic granulocytes (BGs), and eosinophilic granulocytes (EGs). Of these, the EG cells were the largest (diameter, 8.4-10.0 μm) and had eosinophilic cytoplasm with numerous eosinophilic granules (diameter, 0.8-1.2 μm). Meanwhile, the BGs were of medium size (diameter, 6.7-8.0 μm) and contained small basophilic granules (diameter, 0.3-0.4 μm) in basophilic cytoplasm, and the AGs, the smallest of the hemocytes (diameter, 4.8-6.0 μm), had basophilic cytoplasm lacking granules. A lectin binding assay revealed that concanavalin A bound to all three hemocyte types, while wheat germ agglutinin bound exclusively to EGs and BGs. The total hemocyte population densities within the hemolymph of all three Bathymodiolus mussel species were similar (8.4-13.3 × 10(5) cells/mL), and the percentages of circulating AGs, BGs, and EGs in the hemolymph of these organisms were 44.7-48.5%, 14.3-17.6%, and 34.3-41.0%, respectively. To analyze the functional differences between these hemocytes, the phagocytic activity and post-phagocytic phagosome-lysosome fusion events were analyzed in each cell type using a fluorescent Alexa Fluor(®) 488-conjugated Escherichia coli bioparticle and a LysoTracker(®) lysosomal marker, respectively. While the AGs exhibited no phagocytic activity, both types of granulocytes were phagocytic. Of the three hemocyte types, the EGs exhibited the highest level of phagocytic activity as well as rapid phagosome-lysosome fusion, which occurred within 2 h of incubation. Meanwhile, the BGs showed

  4. Effects of cadmium on aneuploidy and hemocyte parameters in the Pacific oyster, Crassostrea gigas

    International Nuclear Information System (INIS)

    Bouilly, Karine; Gagnaire, Beatrice; Bonnard, Marc; Thomas-Guyon, Helene; Renault, Tristan; Miramand, Pierre; Lapegue, Sylvie

    2006-01-01

    Pacific oysters, Crassostrea gigas, are commonly reared in estuaries where they are exposed to anthropogenic pollution. Much research has been made on the toxicity of cadmium to aquatic organisms because the compound recurrently contaminates their environment. Our study examined the influence of cadmium on aneuploidy level (lowered chromosome number in a percentage of somatic cells) and hemocyte parameters in C. gigas at different stages of life. Adults and juveniles were exposed to two different concentrations of cadmium. The first concentration applied was equivalent to a peak value found in Marennes-Oleron bay (Charente-Maritime, France; 50 ng L -1 ) and the second was 10 times higher (500 ng L -1 ). Exposure to 50 ng L -1 cadmium caused a significant decrease in the survival time of C. gigas, but exposure to 500 ng L -1 surprisingly affected the survival time positively. Significant differences in aneuploidy level were observed between the cadmium treatments and the control in adults but not in juveniles or the offspring of the adult groups. The effects of cadmium on hemocyte parameters were analyzed by flow cytometry. Several hemocyte parameters increased significantly after 21 days of cadmium exposure and subsequently decreased. Phenoloxidase-like activity, evaluated by spectrophotometry, varied over the time of the experiment and increased after 66 days of contact with 500 ng L -1 cadmium. Taken together, cadmium at environmentally relevant concentrations seems to have only moderate effects on aneuploidy and hemocyte parameters

  5. Co-aggregation and growth inhibition of probiotic lactobacilli and clinical isolates of mutans streptococci: An in vitro study

    DEFF Research Database (Denmark)

    Keller, Mette Kirstine; Hassl F, Pamela; Stecks N-Blicks, Christina

    2011-01-01

    -free and caries-susceptible individuals. Conclusions. The selected lactobacilli displayed co-aggregation activity and inhibited growth of clinical mutans streptococci. The growth inhibition was strain-specific and dependent on pH and cell concentration. The findings indicate that the outcome of lactobacilli...

  6. A New Platelet-Aggregation-Inhibiting Factor Isolated from Bothrops moojeni Snake Venom

    Directory of Open Access Journals (Sweden)

    Bruna Barbosa de Sousa

    2017-01-01

    Full Text Available This work reports the purification and functional characterization of BmooPAi, a platelet-aggregation-inhibiting factor from Bothrops moojeni snake venom. The toxin was purified by a combination of three chromatographic steps (ion-exchange on DEAE-Sephacel, molecular exclusion on Sephadex G-75, and affinity chromatography on HiTrap™ Heparin HP. BmooPAi was found to be a single-chain protein with an apparent molecular mass of 32 kDa on 14% SDS-PAGE, under reducing conditions. Sequencing of BmooPAi by Edman degradation revealed the amino acid sequence LGPDIVPPNELLEVM. The toxin was devoid of proteolytic, haemorrhagic, defibrinating, or coagulant activities and induced no significant oedema or hyperalgesia. BmooPAi showed a rather specific inhibitory effect on ristocetin-induced platelet aggregation in human platelet-rich plasma, whereas it had little or no effect on platelet aggregation induced by collagen and adenosine diphosphate. The results presented in this work suggest that BmooPAi is a toxin comprised of disintegrin-like and cysteine-rich domains, originating from autolysis/proteolysis of PIII SVMPs from B. moojeni snake venom. This toxin may be of medical interest because it is a platelet aggregation inhibitor, which could potentially be developed as a novel therapeutic agent to prevent and/or treat patients with thrombotic disorders.

  7. Comparative venom toxicity between Pteromalus puparum and Nasonia vitripennis (Hymenoptera: Pteromalidae) toward the hemocytes of their natural hosts, non-target insects and cultured insect cells.

    Science.gov (United States)

    Zhang, Zhong; Ye, Gong-Yin; Cai, Jun; Hu, Cui

    2005-09-01

    Crude venoms from two parasitoid species, Pteromalus puparum and Nasonia vitripennis (Hymenoptera: Pteromalidae) were assayed for biological activities toward hemocytes from two species of their natural hosts and eight species of their non-natural hosts as well as two lines of cultured Lepidoptera cells, respectively. By inhibiting the spreading and viability of insect hemocytes, the venom from P. puparum displayed significantly higher activities toward plasmatocytes and granular cells from both larvae and pupae of two natural hosts, Pieris rapae and Papilio xuthus, and lower activity toward those from Spodoptera litura, Musca domestica and Sarcophaga peregrina. However, no effect was found towards any type of hemocytes from other five insects tested, namely, Ectropis oblique, Galleria mellonella, Sesamia inferens, Bombyx mori and Parnara guttata. In contrast, the venom from N. vitripennis showed a narrower range of targeted insects. It appeared to have highly adverse effects on the spreading and viability of plasmatocytes and granular cells only from the natural hosts, M. domestica and S. peregrina, little toxicity to cells from P. rapae and P. xuthus, and no effect on any of the other insects tested. Pteromalus puparum venom also apparently presented a high ability to block the spreading of Tn-5B1-4 cells derived from Trichoplusia ni, and high cytotoxicity to the cells and Ha cells derived from Helicoverpa armigera. Nasonia vitripennis venom, however, only had a marked lethal effect to Ha cells. In addition, the possibility that the host range of a defined parasitoid could be assessed using our method of treating hemocytes from candidate insects with venom in vitro, and the potential of our venoms tested in the development of bio-insecticides, insect-resistant transgenic plants, are discussed.

  8. β-Amyloid-derived pentapeptide RIIGLa inhibits Aβ1-42 aggregation and toxicity

    International Nuclear Information System (INIS)

    Fueloep, Livia; Zarandi, Marta; Datki, Zsolt; Soos, Katalin; Penke, Botond

    2004-01-01

    Pr-IIGL a , a derivative of the tetrapeptide β-amyloid 31-34 (Aβ 31-34 ), exerts controversial effects: it is toxic in a neuroblastoma culture, but it protects glial cells from the cytotoxic action of Aβ 1-42 . For an understanding of this phenomenon, a new pentapeptide, RIIGL a was synthetized, and both compounds were studied by different physicochemical and biological methods. Transmission electron microscopic (TEM) studies revealed that Pr-IIGL a forms fibrillar aggregates, whereas RIIGL a does not form fibrils. Congo red binding studies furnished the same results. Aggregated Pr-IIGL a acts as a cytotoxic agent in neuroblastoma cultures, but RIIGL a does not display inherent toxicity. RIIGL a co-incubated with Aβ 1-42 inhibits the formation of mature amyloid fibres (TEM studies) and reduces the cytotoxic effect of fibrillar Aβ 1-42 . These results indicate that RIIGL a is an effective inhibitor of both the aggregation and the toxic effects of Aβ 1-42 and can serve as a lead compound for the design of novel neuroprotective peptidomimetics

  9. Mechanism by which DHA inhibits the aggregation of KLVFFA peptides: A molecular dynamics study

    Science.gov (United States)

    Zhou, Hong; Liu, Shengtang; Shao, Qiwen; Ma, Dongfang; Yang, Zaixing; Zhou, Ruhong

    2018-03-01

    Docosahexaenoic acid (DHA) is one of the omega-3 polyunsaturated fatty acids, which has shown promising applications in lowering Aβ peptide neurotoxicity in vitro by preventing aggregation of Aβ peptides and relieving accumulation of Aβ fibrils. Unfortunately, the underlying molecular mechanisms of how DHA interferes with the aggregation of Aβ peptides remain largely enigmatic. Herein, aggregation behaviors of amyloid-β(Aβ)16-21 peptides (KLVFFA) with or without the presence of a DHA molecule were comparatively studied using extensive all-atom molecular dynamics simulations. We found that DHA could effectively suppress the aggregation of KLVFFA peptides by redirecting peptides to unstructured oligomers. The highly hydrophobic and flexible nature of DHA made it randomly but tightly entangled with Leu-17, Phe-19, and Phe-20 residues to form unstructured but stable complexes. These lower-ordered unstructured oligomers could eventually pass through energy barriers to form ordered β-sheet structures through large conformational fluctuations. This study depicts a microscopic picture for understanding the role and mechanism of DHA in inhibition of aggregation of Aβ peptides, which is generally believed as one of the important pathogenic mechanisms of Alzheimer's disease.

  10. The immune response of hemocytes of the insect Oncopeltus fasciatus against the flagellate Phytomonas serpens.

    Directory of Open Access Journals (Sweden)

    Thiago L Alves e Silva

    Full Text Available The genus Phytomonas includes parasites that are etiological agents of important plant diseases, especially in Central and South America. These parasites are transmitted to plants via the bite of an infected phytophagous hemipteran. Despite the economic impact of these parasites, many basic questions regarding the genus Phytomonas remain unanswered, such as the mechanism by which the parasites cope with the immune response of the insect vector. In this report, using a model of systemic infection, we describe the function of Oncopeltus fasciatus hemocytes in the immune response towards the tomato parasite Phytomonas serpens. Hemocytes respond to infection by trapping parasites in nodular structures and phagocytizing the parasites. In electron microscopy of hemocytes, parasites were located inside vacuoles, which appear fused with lysosomes. The parasites reached the O. fasciatus salivary glands at least six hours post-infection. After 72 hours post-infection, many parasites were attached to the salivary gland outer surface. Thus, the cellular responses did not kill all the parasites.

  11. Morphological and functional characterization of hemocytes from two deep-sea vesicomyid clams Phreagena okutanii and Abyssogena phaseoliformis.

    Science.gov (United States)

    Tame, Akihiro; Ozawa, Genki; Maruyama, Tadashi; Yoshida, Takao

    2018-03-01

    Deep-sea vesicomyid clams harboring intracellular symbiotic sulfur-oxidizing bacteria are often dominant in chemosynthetic animal communities. Although they are known to have erythrocytes, little is known about other hemocytes. To investigate the types and roles of various hemocytes in vesicomyid clams, we performed morphological, histochemical and functional characterization of the hemocytes in two species, Phreagena okutanii, collected from 873 to 978 m depth, and Abyssogena phaseoliformis, from 5199 to 5355 m. Both were found to have three types of hemocytes: erythrocytes (ERCs), eosinophilic granulocytes (EGs), and basophilic granulocytes (BGs). The ERCs contain hemoglobin in the cytoplasm, with basophilic vacuoles containing acid polysaccharide, neutral lipids, and peroxidase. The EGs were found to contain acid polysaccharides and eosinophilic granules containing lysosomal enzymes, acid and alkaline phosphatases, chloroacetate esterase, and peroxidase. Although BGs had some basophilic granules with alkaline phosphatase, they lacked acid phosphatase and acid polysaccharides. The EGs and BGs were shown to have phagocytic ability, while the ERCs exhibited no phagocytosis. The EGs showed higher phagocytic activity as well as a higher phagosome-lysosome fusion rate than BGs. The hemocytes of the two vesicomyid species differed in the intracellular structures. In A. phaseoliformis, ERCs additionally contained neutral polysaccharides in vacuoles and had vesicles with acinus-like acidic mucus in the cytoplasm, neither of which were observed in P. okutanii. The eosinophilic granules in the EGs had heteromorphically-elongated shapes containing homogeneously electron-dense material in P. okutanii, but were more spherical and composed of fibrous structures in A. phaseoliformis. The difference in hemocytes between the two clams seems to be reflective of phylogenetically differentiated lineages adapting to differing conditions in their respective deep-sea environments

  12. INFLUENCE OF SEASONAL FACTORS ON OYSTER HEMOCYTE KILLING OF VIBRIO PARAHEMOLYTICUS

    Science.gov (United States)

    Seasonal variation of cellular defenses of oyster Crassostrea virginica against Vibrio parahaemolyticus were examined from June 1997 to December 1998 using a recently developed bactericidal assay that utilizes a tetrazolium dye. Mean hemocyte numbers, plasma lysozyme, and P. mari...

  13. IN VITRO KILLING OF PERKINSUS MARINUS BY HEMOCYTES OF OYSTERS CRASSOSTREA VIRGINICA

    Science.gov (United States)

    A colorimetric microbicidal assay was adapted, optimized and applied in experiments to characterize the in vitro capacity of eastern oyster (Crassostrea virginica) hemocytes to kill cultured isolates of Perkinsus marinus, a protozoan parasite causing a highly destructive disease...

  14. Immunomodulation by different types of N-oxides in the hemocytes of the marine bivalve Mytilus galloprovincialis.

    Directory of Open Access Journals (Sweden)

    Caterina Ciacci

    Full Text Available The potential toxicity of engineered nanoparticles (NPs for humans and the environment represents an emerging issue. Since the aquatic environment represents the ultimate sink for NP deposition, the development of suitable assays is needed to evaluate the potential impact of NPs on aquatic biota. The immune system is a sensitive target for NPs, and conservation of innate immunity represents an useful basis for studying common biological responses to NPs. Suspension-feeding invertebrates, such as bivalves, are particularly at risk to NP exposure, since they have extremely developed systems for uptake of nano and microscale particles integral to intracellular digestion and cellular immunity. Evaluation of the effects of NPs on functional parameters of bivalve immunocytes, the hemocytes, may help understanding the major toxic mechanisms and modes of actions that could be relevant for different NP types in aquatic organisms.In this work, a battery of assays was applied to the hemocytes of the marine bivalve Mytilus galloprovincialis to compare the in vitro effects of different n-oxides (n-TiO(2, n-SiO(2, n-ZnO, n-CeO(2 chosen on the basis of their commercial and environmental relevance. Physico-chemical characterization of both primary particles and NP suspensions in artificial sea water-ASW was performed. Hemocyte lysosomal and mitochondrial parameters, oxyradical and nitric oxide production, phagocytic activity, as well as NP uptake, were evaluated. The results show that different n-oxides rapidly elicited differential responses hemocytes in relation to their chemical properties, concentration, behavior in sea water, and interactions with subcellular compartments. These represent the most extensive data so far available on the effects of NPs in the cells of aquatic organisms. The results indicate that Mytilus hemocytes can be utilized as a suitable model for screening the potential effects of NPs in the cells of aquatic invertebrates, and may

  15. Plasminogen-induced aggregation of PANC-1 cells requires conversion to plasmin and is inhibited by endogenous plasminogen activator inhibitor-1.

    Science.gov (United States)

    Deshet, Naamit; Lupu-Meiri, Monica; Espinoza, Ingrid; Fili, Oded; Shapira, Yuval; Lupu, Ruth; Gershengorn, Marvin C; Oron, Yoram

    2008-09-01

    PANC-1 cells express proteinase-activated receptors (PARs)-1, -2, and respond to their activation by transient elevation of cytosolic [Ca(2+)] and accelerated aggregation (Wei et al., 2006, J Cell Physiol 206:322-328). We studied the effect of plasminogen (PGN), an inactive precursor of the PAR-1-activating protease, plasmin (PN) on aggregation of pancreatic adenocarcinoma (PDAC) cells. A single dose of PGN time- and dose-dependently promoted PANC-1 cells aggregation in serum-free medium, while PN did not. PANC-1 cells express urokinase plasminogen activator (uPA), which continuously converted PGN to PN. This activity and PGN-induced aggregation were inhibited by the uPA inhibitor amiloride. PGN-induced aggregation was also inhibited by alpha-antiplasmin and by the PN inhibitor epsilon-aminocaproic acid (EACA). Direct assay of uPA activity revealed very low rate, markedly enhanced in the presence of PGN. Moreover, in PGN activator inhibitor 1-deficient PANC-1 cells, uPA activity and PGN-induced aggregation were markedly potentiated. Two additional human PDAC cell lines, MiaPaCa and Colo347, were assayed for PGN-induced aggregation. Both cell lines responded by aggregation and exhibited PGN-enhanced uPA activity. We hypothesized that the continuous conversion of PGN to PN by endogenous uPA is limited by PN's degradation and negatively controlled by endogenously produced PAI-1. Indeed, we found that PANC-1 cells inactivate PN with t1/2 of approximately 7 h, while the continuous addition of PN promoted aggregation. Our data suggest that PANC-1 cells possess intrinsic, PAI-1-sensitive mechanism for promotion of aggregation and differentiation by prolonged exposure to PGN and, possibly, additional precursors of PARs agonists.

  16. Pacific oyster (Crassostrea gigas) hemocyte are not affected by a mixture of pesticides in short-term in vitro assays.

    Science.gov (United States)

    Moreau, Pierrick; Burgeot, Thierry; Renault, Tristan

    2014-04-01

    Pesticides are frequently detected in estuaries among the pollutants found in estuarine and coastal areas and may have major ecological consequences. They could endanger organism growth, reproduction, or survival. In the context of high-mortality outbreaks affecting Pacific oysters, Crassostrea gigas, in France since 2008, it appears of importance to determine the putative effects of pesticides on oyster susceptibility to infectious agents. Massive mortality outbreaks reported in this species, mainly in spring and summer, may suggest an important role played by the seasonal use of pesticides and freshwater input in estuarine areas where oyster farms are frequently located. To understand the impact of some pesticides detected in French waters, their effects on Pacific oyster hemocytes were studied through short-term in vitro experiments. Bivalve immunity is mainly supported by hemocytes eliminating pathogens by phagocytosis and producing compounds including lysosomal enzymes and antimicrobial molecules. In this study, oyster hemocytes were incubated with a mixture of 14 pesticides and metaldehyde alone, a molecule used to eliminate land mollusks. Hemocyte parameters including dead/alive cells, nonspecific esterase activities, intracytoplasmic calcium, lysosome number and activity, and phagocytosis were monitored by flow cytometry. No significant effect of pesticides tested at different concentrations was reported on oyster hemocytes maintained in vitro for short-term periods in the present study. It could be assumed that these oyster cells were resistant to pesticide exposure in tested conditions and developing in vivo assays appears as necessary to better understand the effects of pollutants on immune system in mollusks.

  17. Hemocyte quantitative changes in Anticarsia gemmatalis (Lepidoptera: Noctuidae larvae infected by AgMNPV

    Directory of Open Access Journals (Sweden)

    Fábio Goulart de Andrade

    2010-04-01

    Full Text Available The initial effects of the infection by AgMNPV in the total and differential counts of the hemocytes in Anticarsia gemmatalis (Lepidoptera: Noctuidae larvae were studied. The total number of the hemocytes did not decrease in infected larvae, as it occurred in non infected larvae. In infected larvae, the hemocyte types showed the following frequencies: plasmatocytes - 47.8%, esferulocytes - 25.9%, granulocytes - 15.8%, oenocytoids - 7.2%, prohemocytes - 2.8%, vermicytes - 0,5%. Only the percentage of the granulocytes was different among infected and non infected larvae, indicating that these cells responded quickly to the initial viral infection. These results showed the effective role of the hemocytes in the response of the A. gemmatalis to the infection by AgMNPV. The comprehension of the immunological mechanisms of this insect is an important tool to understand its biological control.Os efeitos iniciais da infecção por AgMNPV nas contagens total e diferencial dos hemócitos em Anticarsia gemmatalis (Lepidoptera: Noctuidae foram estudados. O número total de hemócitos não diminuiu nas larvas infectadas, como ocorreu nas larvas não infectadas. Nas larvas infectadas, os tipos de hemócitos apresentaram as seguintes freqüências: plasmatócitos - 47,8%, esferulócitos - 25,9%, granulócitos - 15,8%, oenocitóides - 7,2%, prohemócitos - 2,8%, vermiformes - 0,5%. Apenas a porcentagem de granulócitos foi diferente entre larvas infectadas e não infectadas, indicando que estas células responderam rapidamente à infecção viral inicial. Estes resultados mostraram o papel efetivo que dos hemócitos na resposta de A. gemmatalis à infecção por AgMNPV. A compreensão dos mecanismos imunológicos deste inseto é uma ferramenta importante para compreender seu controle biológico.

  18. Progranulin inhibits platelet aggregation and prolongs bleeding time in rats.

    Science.gov (United States)

    Al-Yahya, A M; Al-Masri, A A; El Eter, E A; Hersi, A; Lateef, R; Mawlana, O

    2018-05-01

    Several adipokines secreted by adipose tissue have an anti-thrombotic and anti-atherosclerotic function. Recently identified adipokine progranulin was found to play a protective role in atherosclerosis. Bearing in mind the central role of platelets in inflammation and atherosclerosis, we aimed, in this study, to examine the effect of progranulin on platelet function and coagulation profile in rats. Healthy male albino Wistar rats weighing (250-300 g) were divided into 4 groups. Three groups were given increasing doses of progranulin (0.001 µg, 0.01 µg, and 0.1 µg) intraperitoneally, while the control group received phosphate-buffered saline (PBS). Bleeding time, prothrombin time, activated partial thromboplastin time and platelet aggregation responses to adenosine diphosphate and arachidonic acid were assessed. Administration of progranulin resulted in a significant inhibition of platelet aggregation in response to both adenosine diphosphate, and arachidonic acid. Bleeding time, prothrombin time and activated partial thromboplastin time were significantly prolonged in all groups that received progranulin, in particular, the 0.1 µg dose, in comparison to the control group. This preliminary data is first suggesting that the antiplatelet and anticoagulant action of progranulin could have a physiological protective function against thrombotic disorders associated with obesity and atherosclerosis. However, these results merit further exploration.

  19. The inhibition of IGF-1 signaling promotes proteostasis by enhancing protein aggregation and deposition.

    Science.gov (United States)

    Moll, Lorna; Ben-Gedalya, Tziona; Reuveni, Hadas; Cohen, Ehud

    2016-04-01

    The discovery that the alteration of aging by reducing the activity of the insulin/IGF-1 signaling (IIS) cascade protects nematodes and mice from neurodegeneration-linked, toxic protein aggregation (proteotoxicity) raises the prospect that IIS inhibitors bear therapeutic potential to counter neurodegenerative diseases. Recently, we reported that NT219, a highly efficient IGF-1 signaling inhibitor, protects model worms from the aggregation of amyloid β peptide and polyglutamine peptides that are linked to the manifestation of Alzheimer's and Huntington's diseases, respectively. Here, we employed cultured cell systems to investigate whether NT219 promotes protein homeostasis (proteostasis) in mammalian cells and to explore its underlying mechanisms. We found that NT219 enhances the aggregation of misfolded prion protein and promotes its deposition in quality control compartments known as "aggresomes." NT219 also elevates the levels of certain molecular chaperones but, surprisingly, reduces proteasome activity and impairs autophagy. Our findings show that IGF-1 signaling inhibitors in general and NT219 in particular can promote proteostasis in mammalian cells by hyperaggregating hazardous proteins, thereby bearing the potential to postpone the onset and slow the progression of neurodegenerative illnesses in the elderly.-Moll, L., Ben-Gedalya, T., Reuveni, H., Cohen, E. The inhibition of IGF-1 signaling promotes proteostasis by enhancing protein aggregation and deposition. © FASEB.

  20. Virus-like particles in venom of Meteorus pulchricornis induce host hemocyte apoptosis.

    Science.gov (United States)

    Suzuki, M; Tanaka, T

    2006-06-01

    Ultrastructural studies on the reproductive tract and venom apparatus of a female braconid, Meteorus pulchricornis, revealed that the parasitoid lacks the calyx region in its oviduct, but possesses a venom gland with two venom gland filaments and a venom reservoir filled with white and cloudy fluid. Its venom gland cell is concaved and has a lumen filled with numerous granules. Transmisson electron microscopic (TEM) observation revealed that virus-like particles (VLPs) were produced in venom gland cells. The virus-like particle observed in M. pulchricornis (MpVLP) is composed of membranous envelopes with two different parts: a high-density core and a whitish low-density part. The VLPs of M. pulchricornis is also found assembling ultimately in the lumen of venom gland cell. Microvilli were found thrusting into the lumen of the venom gland cell and seem to aid in driving the matured MpVLPs to the common duct of the venom gland filament. Injection of MpVLPs into non-parasitized Pseudaletia separata hosts induced apoptosis in hemocytes, particularly granulocytes (GRs). Rate of apoptosis induced in GRs peaked 48h after VLP injection. While a large part of the GR population collapsed due to apoptosis caused by MpVLPs, the plasmatocyte population was minimally affected. The capacity of MpVLPs to cause apoptosis in host's hemocytes was further demonstrated by a decrease ( approximately 10-fold) in ability of host hemocytes to encapsulate fluorescent latex beads when MpVLPs were present. Apparently, the reduced encapsulation ability was due to a decrease in the GR population resulting from MpVLP-induced apoptosis.

  1. TAT improves in vitro transportation of fortilin through midgut and into hemocytes of white shrimp Litopenaeus vannamei

    Science.gov (United States)

    Zhou, Yi; Zhang, Wenbing; Mai, Kangsen; Xu, Wei; Zhang, Yanjiao; Ai, Qinghui; Wang, Xiaojie

    2012-06-01

    Fortilin is a multifunctional protein implicated in many important cellular processes. Since injection of Pm-fortilin reduces shrimp mortality caused by white spot syndrome virus (WSSV), there is potential application of fortilin in shrimp culture. In the present study, in order to improve trans-membrane transportation efficiency, the protein transduction domain of the transactivator of transcription (TAT) peptide was fused to fortilin. The Pichia pastoris yeast expression system, which is widely accepted in animal feeds, was used for production of recombinant fusion protein. Green fluorescence protein (GFP) was selected as a reporter because of its intrinsic visible fluorescence. The fortilin, TAT and GFP fusion protein were constructed. Their trans-membrane transportation efficiency and effects on immune response of shrimp were analyzed in vitro. Results showed that TAT peptide improved in vitro uptake of fortilin into the hemocytes and midgut of Litopenaeus vannamei. The phenoloxidase (PO) activity of hemocytes incubated with GFP-Fortilin or GFP-Fortilin-TAT was significantly increased compared with that in the control without expressed fortilin. The PO activity of hemocytes incubated with 200 μg mL-1 GFP-Fortilin-TAT was significantly higher than that in the group with the same concentration of GFP-Fortilin. Hemocytes incubated with GFP-Fortilin-TAT at all concentrations showed significantly higher nitric oxide synthase (NOS) activity than those in the control or in the GFP-Fortilin treatment. The present in vitro study indicated that TAT fusion protein improved the immune effect of fortilin.

  2. Prolongation of bleeding time and inhibition of platelet aggregation by low-dose acetylsalicylic acid in patients with cerebrovascular disease

    DEFF Research Database (Denmark)

    Boysen, G; Boss, A H; Ødum, Niels

    1984-01-01

    the bleeding time averaged 11.2 minutes in contrast to 7.0 minutes in the placebo group, p less than 0.001. This study confirms our previous findings of platelet inhibition by low-dose acetylsalicylic acid in patients with cerebrovascular disease. The prolongation of the bleeding time demonstrates that we......Platelet aggregation and bleeding time was measured in 43 cerebrovascular patients participating in a controlled double-blind study of low-dose acetylsalicylic acid. In 19 patients with satisfactory inhibition of the platelet aggregation obtained by 50 to 70 mg acetylsalicylic acid per day...... are dealing not merely with an in vitro phenomenon but with a significant in vivo effect. The study provides the rationale for clinical evaluations of low-dose acetylsalicylic acid in stroke prophylaxis....

  3. Selective inhibition of aggregation/fibrillation of bovine serum albumin by osmolytes: Mechanistic and energetics insights.

    Directory of Open Access Journals (Sweden)

    Moumita Dasgupta

    Full Text Available Bovine serum albumin (BSA is an important transport protein of the blood and its aggregation/fibrillation would adversely affect its transport ability leading to metabolic disorder. Therefore, understanding the mechanism of fibrillation/aggregation of BSA and design of suitable inhibitor molecules for stabilizing its native conformation, are of utmost importance. The qualitative and quantitative aspects of the effect of osmolytes (proline, hydroxyproline, glycine betaine, sarcosine and sorbitol on heat induced aggregation/fibrillation of BSA at physiological pH (pH 7.4 have been studied employing a combination of fluorescence spectroscopy, Rayleigh scattering, isothermal titration calorimetry (ITC, dynamic light scattering (DLS and transmission electron microscopy (TEM. Formation of fibrils by BSA under the given conditions was confirmed from increase in fluorescence emission intensities of Thioflavin T over a time period of 600 minutes and TEM images. Absence of change in fluorescence emission intensities of 8-Anilinonaphthalene-1-sulfonic acid (ANS in presence of native and aggregated BSA signify the absence of any amorphous aggregates. ITC results have provided important insights on the energetics of interaction of these osmolytes with different stages of the fibrillar aggregates of BSA, thereby suggesting the possible modes/mechanism of inhibition of BSA fibrillation by these osmolytes. The heats of interaction of the osmolytes with different stages of fibrillation of BSA do not follow a trend, suggesting that the interactions of stages of BSA aggregates are osmolyte specific. Among the osmolytes used here, we found glycine betaine to be supporting and promoting the aggregation process while hydroxyproline to be maximally efficient in suppressing the fibrillation process of BSA, followed by sorbitol, sarcosine and proline in the following order of their decreasing potency: Hydroxyproline> Sorbitol> Sarcosine> Proline> Glycine betaine.

  4. The hemocytes of Panstrogyllus Megistus (Hemiptera: Reduviidae Os hemócitos de Panstrongylus megistus (Hemiptera: Reduviidae

    Directory of Open Access Journals (Sweden)

    Margherita Anna Barracco

    1987-09-01

    Full Text Available Five hemocyte types were identified in the hemolymph of Panstrongylus megistus by phase contrast and common light microscopy using some histochemical methods. These are: Prohemocytes, small cells presenting a great nucleus/cytoplasm ratio; Plasmatocytes, the most numerous hemocytes, are polymorphic cells mainly characterized by a large amount of lysosomes; Granulocytes, hemocytes very similar to plasmatocytes which contain cytoplasmic granules and are especially rich in polysaccharides; Oenocytoids, cells presenting a small nucleus and a thick cytoplasm; they show many small round vacuoles when observed in Giemsa smears and many cytoplasmic granules under phase microscopy; Adipohemocytes, very large hemocytes, presenting many fat droplet inclusions which could correspond to free fat bodies which entered the hemolymph. Only prohemocytes and plasmatocytes can be clearly classified; all the other hemocyte types have a more ambiguous classification.Cinco tipos de hemócitos foram identificados na hemolinfa de Panstrongylus megistus através da microscopia de constraste de fase e de luz, usando alguns testes histoquímicos: Pró-hemócitos-células pequenas que mostram uma grande relação núcleocitoplasmática; Plasmotócitos-células polimporficas, que se caracterizam principalmente pela sua grande abundância em lisossomos - são os hemócitos mais numerosos; Granulócitos-células muito semelhantes aos plasmatócitos que contêm grânulos citoplasmáticos particularmente ricos em polissacarídeos; Enocitóides-hemócitos que apresentam um núcleo pequeno e cujo citoplasma basofílico revela-se muito denso e homogênio - mostram uma série de pequenos vacúolos esféricos quando observados nos esfregaços corados pelo Giemsa, mas a microscopia de fase revela uma grande quantidade de pequenos grânulo ao invés de vacúolos; Adipo-hemócitos-hemócitos muito grandes que contêm uma grande quantidade de inclusões lípicas - poderiam corresponder a

  5. Effect of dopamine injection on the hemocyte count and prophenoloxidase system of the white shrimp Litopenaeus vannamei

    Science.gov (United States)

    Pan, Luqing; Hu, Fawen; Zheng, Debin

    2011-09-01

    Effects of dopamine injection on the hemocyte count, phenoloxidase activity, serine proteinase activity, proteinase inhibitor activity and α2-macroglobulin-like activity in L. vannamei were studied. Results showed that dopamine injection resulted in a significant effect on the parameters measured ( P < 0.05), while no significant difference was observed in the control group (0.85% NaCl). In the experimental groups, the hemocyte count reached the minimum in 3 h; granular and semi-granular cells became stable after 12 h and hyaline cells and the total hemocyte count became stable after 18 h. Phenoloxidase activity reached the minimum in 6 h, and then became stable after 9 h. Serine protease activity and proteinase inhibitor activity reached the minimum in 3 h, and α2-macroglobulin-like activity reached the maximum in 3 h, and all the three parameters became stable after 12 h. The results suggest that the activating mechanisms of the proPO system triggered by dopamine are different from those triggered by invasive agents or spontaneously activated under a normal physical condition.

  6. Small stress molecules inhibit aggregation and neurotoxicity of prion peptide 106-126

    International Nuclear Information System (INIS)

    Kanapathipillai, Mathumai; Ku, Sook Hee; Girigoswami, Koyeli; Park, Chan Beum

    2008-01-01

    In prion diseases, the posttranslational modification of host-encoded prion protein PrP c yields a high β-sheet content modified protein PrP sc , which further polymerizes into amyloid fibrils. PrP106-126 initiates the conformational changes leading to the conversion of PrP c to PrP sc . Molecules that can defunctionalize such peptides can serve as a potential tool in combating prion diseases. In microorganisms during stressed conditions, small stress molecules (SSMs) are formed to prevent protein denaturation and maintain protein stability and function. The effect of such SSMs on PrP106-126 amyloid formation is explored in the present study using turbidity, atomic force microscopy (AFM), and cellular toxicity assay. Turbidity and AFM studies clearly depict that the SSMs-ectoine and mannosylglyceramide (MGA) inhibit the PrP106-126 aggregation. Our study also connotes that ectoine and MGA offer strong resistance to prion peptide-induced toxicity in human neuroblastoma cells, concluding that such molecules can be potential inhibitors of prion aggregation and toxicity

  7. Oxidative stress parameters induced by exposure to either cadmium or 17β-estradiol on Mytilus galloprovincialis hemocytes. The role of signaling molecules

    Energy Technology Data Exchange (ETDEWEB)

    Koutsogiannaki, Sophia [Laboratory of Animal Physiology, Zoology Department, School of Biology, Faculty of Science, Aristotle University of Thessaloniki, 54124 Thessaloniki (Greece); Franzellitti, Silvia [University of Bologna, Interdepartment Centre for Environmental Science Research, via S. Alberto 163, 48123 Ravenna (Italy); Fabbri, Elena [University of Bologna, Interdepartment Centre for Environmental Science Research, via S. Alberto 163, 48123 Ravenna (Italy); University of Bologna, Department of Biological, Geological, and Environmental Sciences, via Selmi 3, 40100 Bologna (Italy); Kaloyianni, Martha, E-mail: kaloyian@bio.auth.gr [Laboratory of Animal Physiology, Zoology Department, School of Biology, Faculty of Science, Aristotle University of Thessaloniki, 54124 Thessaloniki (Greece)

    2014-01-15

    Highlights: •Oxidative parameters in Mytilus galloprovincialis hemocytes were measured. •Comparison between cadmium and 17β-estradiol cytotoxicity is discussed. •NHE, PKC, PI3-K, NADPH oxidase, NO synthase, JNK involvement was observed. •Protective role of cAMP is suggested. •Signaling molecules studied could constitute novel biomarkers. -- Abstract: The aim of the present study was to determine and compare the possible effects of exposure to an estrogen, 17β-estradiol and to a metal, cadmium on oxidative parameters of Mytilus galloprovincialis hemocytes and to elucidate the signaling pathways that probably mediate the studied effects exerted by these two chemicals. In addition, it was of interest to investigate if the studied parameters could constitute biomarkers for aquatic pollution monitoring. Our results suggest that micromolar concentrations of either cadmium or 17β-estradiol affected the redox status of mussels by modulating oxidative parameters and antioxidant enzymes gene expression in mussel M. galloprovincialis hemocytes. In particular, our results showed that treatment of hemocytes with either 5 μM of cadmium chloride or with 25 nM of 17β-estradiol for 30 min caused significant increased ROS production; this led to oxidative damage exemplified by significant increased DNA damage, protein carbonylation and lipid peroxidation, as well as increased mRNA levels of the antioxidant enzymes catalase (CAT), superoxide dismoutase (SOD) and glutathione S-transferase (GST). Furthermore, our results suggest that either cadmium or 17β-estradiol signal is mediated either through one of the already known pathways initiated by photatidyl-inositol 3-kinase (PI3 K) and reaching Na{sup +}/H{sup +} exchanger (NHE) probably through protein kinase C (PKC) or a kinase-mediated signaling pathway that involves in most of the cases NHE, PKC, Ca{sup 2+}-dependent PKC isoforms, PI3-K, NADPH oxidase, nitric oxide (NO) synthase, c-Jun N-terminal kinase (JNK) and

  8. Oxidative stress parameters induced by exposure to either cadmium or 17β-estradiol on Mytilus galloprovincialis hemocytes. The role of signaling molecules

    International Nuclear Information System (INIS)

    Koutsogiannaki, Sophia; Franzellitti, Silvia; Fabbri, Elena; Kaloyianni, Martha

    2014-01-01

    Highlights: •Oxidative parameters in Mytilus galloprovincialis hemocytes were measured. •Comparison between cadmium and 17β-estradiol cytotoxicity is discussed. •NHE, PKC, PI3-K, NADPH oxidase, NO synthase, JNK involvement was observed. •Protective role of cAMP is suggested. •Signaling molecules studied could constitute novel biomarkers. -- Abstract: The aim of the present study was to determine and compare the possible effects of exposure to an estrogen, 17β-estradiol and to a metal, cadmium on oxidative parameters of Mytilus galloprovincialis hemocytes and to elucidate the signaling pathways that probably mediate the studied effects exerted by these two chemicals. In addition, it was of interest to investigate if the studied parameters could constitute biomarkers for aquatic pollution monitoring. Our results suggest that micromolar concentrations of either cadmium or 17β-estradiol affected the redox status of mussels by modulating oxidative parameters and antioxidant enzymes gene expression in mussel M. galloprovincialis hemocytes. In particular, our results showed that treatment of hemocytes with either 5 μM of cadmium chloride or with 25 nM of 17β-estradiol for 30 min caused significant increased ROS production; this led to oxidative damage exemplified by significant increased DNA damage, protein carbonylation and lipid peroxidation, as well as increased mRNA levels of the antioxidant enzymes catalase (CAT), superoxide dismoutase (SOD) and glutathione S-transferase (GST). Furthermore, our results suggest that either cadmium or 17β-estradiol signal is mediated either through one of the already known pathways initiated by photatidyl-inositol 3-kinase (PI3 K) and reaching Na + /H + exchanger (NHE) probably through protein kinase C (PKC) or a kinase-mediated signaling pathway that involves in most of the cases NHE, PKC, Ca 2+ -dependent PKC isoforms, PI3-K, NADPH oxidase, nitric oxide (NO) synthase, c-Jun N-terminal kinase (JNK) and cyclic adenosine

  9. Multitarget trehalose-carnosine conjugates inhibitaggregation, tune copper(II) activity and decrease acrolein toxicity.

    Science.gov (United States)

    Grasso, Giuseppa Ida; Bellia, Francesco; Arena, Giuseppe; Satriano, Cristina; Vecchio, Graziella; Rizzarelli, Enrico

    2017-07-28

    Increasing evidence is accumulating, showing that neurodegenerative disorders are somehow associated with the toxicity of amyloid aggregates, metal ion dyshomeostasis as well as with products generated by oxidative stress. Within the biological oxidation products, acrolein does have a prominent role. A promising strategy to deal with the above neurogenerative disorders is to use multi-functions bio-molecules. Herein, we show how a class of bio-conjugates takes advantage of the antiaggregating, antioxidant and antiglycating properties of trehalose and carnosine. Their ability to sequester acrolein and to inhibit both self- and metal-induced aggregation is here reported. The copper(II) coordination properties of a new trehalose-carnosine conjugate and the relative antioxidant effects have also been investigated. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  10. [Functional morphology of blowfly Calliphora vicina hemocytes].

    Science.gov (United States)

    Kind, T V

    2012-01-01

    In the hemolymph of Calliphora seven types of hemocytes were revealed. These are prohemocytes, which are the stem cells, stable and unstable hyaline cells, thrombocytoids, spindle cells, juvenile plasmatocytes and plasmatocytes I-IV, which represent sequential stages of one cell line differentiation were registered. The margin between them is completion of the crop emptying and beginning of wandering stage. In the feeding and crop emptying larvae take place rising of hyaline cells, thrombocytoids and hyaline cells amount with parallel growth of their defense function. The second wave of hemogenesis occur in the end of crop emptying period. It is accompanied by burst of plasmatocyte I production with their subsequent differentiation to plasmatocytes II-IV. Production of stable hyaline cells and respectively prothrombocytoids may be regulated not only by hormonal background but also by inorganic or organic particles invaded into the hemocel. Three types of hemocytes are involved in loosing of hemolymph from alien particles, notably thrombocytoids, juvenile plasmatocytes and plasmatocytes I and II. Thrombocytoids are responsible for parasitic eggs encapsulation. In addition they can phagocytize tiny organic and inorganic particles. Juvenile plasmatocytes respond to alien invasion almost as quickly as thrombocytoids at the onset of invasion. Plasmatocytes I and II start phagocytosis more slowly, hours post invasion, frequently accumulating the particles previously catched by thrombocytoids. Plasmatocytes I can absorb foreign particles and group in morules and can also surround filled thrombocytoids forming distinctive capsules. Both morules and capsules are temporary structures and disintegrate some hours lately. It is supposed the existence of three levels of immune defence: the fast response reaction of thrombocytoids and juvenile plasmatocytes and slow cellular reactions of plasmatocytes I. They are prerequisites for more extensive humoral response.

  11. In vivo effects of metaldehyde on Pacific oyster, Crassostrea gigas: comparing hemocyte parameters in two oyster families.

    Science.gov (United States)

    Moreau, Pierrick; Burgeot, Thierry; Renault, Tristan

    2015-06-01

    Pollutants via run-off into the ocean represent a potential threat to marine organisms, especially bivalves such as oysters living in coastal environments. These organisms filter large volumes of seawater and may accumulate contaminants within their tissues. Pesticide contamination in water could have a direct or indirect toxic action on tissues or cells and could induce alteration of immune system. Bivalve immunity is mainly supported by hemocytes and participates directly by phagocytosis to eliminate pathogens. Some studies have shown that pesticides can reduce immune defences and/or modify genomes in vertebrates and invertebrates. Metaldehyde is used to kill slugs, snails and other terrestrial gastropods. Although metaldehyde has been detected in surface waters, its effects on marine bivalves including the Pacific oyster, Crassostrea gigas, have never been studied. Given the mode of action of this molecule and its targets (molluscs), it could be potentially more toxic to oysters than other pesticides (herbicides, fungicides, insecticides, etc.). Effects of metaldehyde on oyster hemocyte parameters were thus monitored through in vivo experiments based on a short-term exposure. In this work, metaldehyde at 0.1 μg/L, which corresponds to an average concentration detected in the environment, modulated hemocyte activities of Pacific oysters after an in vivo short-term contact. Individuals belonging to two families showed different behaviours for some hemocyte activities after contamination by metaldehyde. These results suggested that effects of pollutants on oysters may differ from an individual to another in relation to genetic diversity. Finally, it appears essential to take an interest in the effects of metaldehyde on a wide variety of aquatic invertebrates including those that have a significant economic impact.

  12. Apoptosis of hemocytes from lions-paw scallop Nodipecten subnodosus induced with paralyzing shellfish poison from Gymnodinium catenatum.

    Science.gov (United States)

    Estrada, Norma; Ascencio, Felipe; Shoshani, Liora; Contreras, Rubén G

    2014-12-01

    The toxic dinoflagellate Gymnodinium catenatum produces paralyzing shellfish poisons (PSPs) that are consumed and accumulated by bivalves. Previously, we recorded a decrease in hemocytes 24h after injection of PSPs (gonyautoxin 2/3 epimers, GTX2/3) in the adductor muscle in the lions-paw scallop Nodipecten subnodosus. In this work, qualitative and quantitative analyses, in in vivo and in vitro experiments, revealed that the lower count of hemocytes results from cells undergoing typical apoptosis when exposed to GTX 2/3 epimers. This includes visible morphological alterations of the cytoplasmic membrane, damage to the nuclear membrane, condensation of chromatin, DNA fragmentation, and release of DNA fragments into the cytoplasm. Induction of apoptosis was accompanied by phosphatidylserine exposure to the outer cell membrane and activation of cysteine-aspartic proteases, caspase 3 and caspase 8. Addition of an inhibitor of caspase to the medium suppressed activation in hemocytes exposed to the toxins, suggesting that cell death was induced by a caspase-dependent apoptotic pathway. The results are important for future investigation of the scallop's immune system and should provide new insights into apoptotic processes in immune cells of scallops exposed to PSPs. Copyright © 2014 Elsevier GmbH. All rights reserved.

  13. RNA-Seq Study of Microbially Induced Hemocyte Transcripts from Larval Heliothis virescens (Lepidoptera: Noctuidae

    Directory of Open Access Journals (Sweden)

    Kent S. Shelby

    2012-08-01

    Full Text Available Larvae of the tobacco budworm are major polyphagous pests throughout the Americas. Development of effective microbial biopesticides for this and related noctuid pests has been stymied by the natural resistance mediated innate immune response. Hemocytes play an early and central role in activating and coordinating immune responses to entomopathogens. To approach this problem we completed RNA-seq expression profiling of hemocytes collected from larvae following an in vivo challenge with bacterial and fungal cell wall components to elicit an immune response. A de novo exome assembly was constructed by combination of sequence tags from all treatments. Sequence tags from each treatment were aligned separately with the assembly to measure expression. The resulting table of differential expression had > 22,000 assemblies each with a distinct combination of annotation and expression. Within these assemblies > 1,400 were upregulated and > 1,500 downregulated by immune activation with bacteria or fungi. Orthologs to innate immune components of other insects were identified including pattern recognition, signal transduction pathways, antimicrobial peptides and enzymes, melanization and coagulation. Additionally orthologs of components regulating hemocytic functions such as autophagy, apoptosis, phagocytosis and nodulation were identified. Associated cellular oxidative defenses and detoxification responses were identified providing a comprehensive snapshot of the early response to elicitation.

  14. Hemocyte parameters of the Pacific oyster Crassostrea gigas a year after the Hebei Spirit oil spill off the west coast of Korea

    Science.gov (United States)

    Donaghy, Ludovic; Hong, Hyun-Ki; Lee, Hee-Jung; Jun, Je-Cheon; Park, Young-Je; Choi, Kwang-Sik

    2010-12-01

    In marine bivalves, hemocytes support various physiological functions, including immune defense, nutrient transport, shell repair, and homeostatic maintenance. Although the effects of marine contaminants on the immunological functions of bivalves have been extensively investigated, the impacts of oil spills are not well understood. Therefore, we investigated hemocyte parameters in the Pacific oyster Crassostrea gigas 13 months after the Hebei Spirit oil spill (December 2007) off the west coast of Korea. The parameters studied included hemocyte concentration and mortality, relative proportion of hemocyte populations, and immunological functions such as phagocytosis and oxidative activity using flow cytometry. These immune-related parameters in oysters damaged by the oil spill were also compared to control oysters that were collected from an area unaffected by the spill. The flow cytometry study indicated that granulocyte population, phagocytic capacity, and reactive oxygen species production in oysters exposed to crude oil 13 months prior were depressed compared to the unexposed control oysters. Our data suggest that immunocompetence in oysters affected by the oil spill had not fully recovered 1 year after the accident, although more detailed studies on the physiology and disease resistance should be performed.

  15. Macrocarpal C isolated from Eucalyptus globulus inhibits dipeptidyl peptidase 4 in an aggregated form.

    Science.gov (United States)

    Kato, Eisuke; Kawakami, Kazuhiro; Kawabata, Jun

    2018-12-01

    Dipeptidyl peptidase 4 (DPP-4) inhibitors are used for the treatment of type-2 diabetes mellitus. Various synthetic inhibitors have been developed to date, and plants containing natural DPP-4 inhibitors have also been identified. Here, 13 plant samples were tested for their DPP-4 inhibitory activity. Macrocarpals A-C were isolated from Eucalyptus globulus through activity-guided fractionation and shown to be DPP-4 inhibitors. Of these, macrocarpal C showed the highest inhibitory activity, demonstrating an inhibition curve characterised by a pronounced increase in activity within a narrow concentration range. Evaluation of macrocarpal C solution by turbidity, nuclear magnetic resonance spectroscopy and mass spectrometry indicated its aggregation, which may explain the characteristics of the inhibition curve. These findings will be valuable for further study of potential small molecule DPP-4 inhibitors.

  16. Characterization of myosin light chain in shrimp hemocytic phagocytosis.

    Science.gov (United States)

    Han, Fang; Wang, Zhiyong; Wang, Xiaoqing

    2010-11-01

    Myosin light chain, a well-known cytoskeleton gene, regulates multiple processes that are involved in material transport, muscle shrink and cell division. However, its function in phagocytosis against invading pathogens in crustacean remains unknown. In this investigation, a myosin light chain gene was obtained from Marsupenaeus japonicus shrimp. The full-length cDNA of this gene was of 766 bp and an open reading frame (ORF) of 462 bp encoding a polypeptide of 153 amino acids. The myosin light chain protein was expressed in Escherichia coli and purified. Subsequently the specific antibody was raised using the purified GST fusion protein. As revealed by immuno-electron microscopy, the myosin light chain protein was only expressed in the dark bands of muscle. In the present study, the myosin light chain gene was up-regulated in the WSSV-resistant shrimp as revealed by real-time PCR and western blot. And the phagocytic percentage and phagocytic index using FITC-labeled Vibrio parahemolyticus were remarkably increased in the WSSV-resistant shrimp, suggesting that the myosin light chain protein was essential in hemocytic phagocytosis. On the other hand, RNAi assays indicated that the phagocytic percentage and phagocytic index were significantly decreased when the myosin light chain gene was silenced by sequence-specific siRNA. These findings suggested that myosin light chain protein was involved in the regulation of hemocytic phagocytosis of shrimp. Copyright 2010 Elsevier Ltd. All rights reserved.

  17. Benzbromarone, Quercetin, and Folic Acid Inhibit Amylin Aggregation

    Directory of Open Access Journals (Sweden)

    Laura C. López

    2016-06-01

    Full Text Available Human Amylin, or islet amyloid polypeptide (hIAPP, is a small hormone secreted by pancreatic β-cells that forms aggregates under insulin deficiency metabolic conditions, and it constitutes a pathological hallmark of type II diabetes mellitus. In type II diabetes patients, amylin is abnormally increased, self-assembled into amyloid aggregates, and ultimately contributes to the apoptotic death of β-cells by mechanisms that are not completely understood. We have screened a library of approved drugs in order to identify inhibitors of amylin aggregation that could be used as tools to investigate the role of amylin aggregation in type II diabetes or as therapeutics in order to reduce β-cell damage. Interestingly, three of the compounds analyzed—benzbromarone, quercetin, and folic acid—are able to slow down amylin fiber formation according to Thioflavin T binding, turbidimetry, and Transmission Electron Microscopy assays. In addition to the in vitro assays, we have tested the effect of these compounds in an amyloid toxicity cell culture model and we have found that one of them, quercetin, has the ability to partly protect cultured pancreatic insulinoma cells from the cytotoxic effect of amylin. Our data suggests that quercetin can contribute to reduce oxidative damage in pancreatic insulinoma β cells by modulating the aggregation propensity of amylin.

  18. Understanding curcumin-induced modulation of protein aggregation.

    Science.gov (United States)

    Ahmad, Basir; Borana, Mohanish S; Chaudhary, Ankur P

    2017-07-01

    Curcumin, a diarylheptanoid compound, found in spice turmeric is known to alter the aggregation of proteins and reduce the toxicity of the aggregates. This review looks at the molecular basis of modulating protein aggregation and toxicity of the aggregates. Foremost, we identify the interaction of curcumin and its derivatives with proteins/peptides and the effect of their interaction on the conformational stability and unfolding/folding pathway(s). The unfolding/folding processes generate partially folded/unfolded intermediate, which serve as aggregation precursor state. Secondly, we discuss the effect of curcumin binding on the kinetics parameters of the aggregation process, which give information about the mechanism of the aggregation inhibition. We describe, in addition, that curcumin can accelerate/promote fibril formation by binding to oligomeric intermediate(s) accumulated in the aggregation pathway. Finally, we discuss the correlation of curcumin-induced monomeric and/or oligomeric precursor states with aggregate structure and toxicity. On the basis of these discussions, we propose a model describing curcumin-induced inhibition/promotion of formation of amyloid-like fibrils. Copyright © 2016 Elsevier B.V. All rights reserved.

  19. Effects of Copper on Hemocyte Apoptosis, ROS Production, and Gene Expression in White Shrimp Litopenaeus vannamei.

    Science.gov (United States)

    Guo, Hui; Li, Kexu; Wang, Wei; Wang, Chenggui; Shen, Yuchun

    2017-10-01

    Copper, a common chemical contaminant in aquatic environment, is known to be toxic to aquatic life at high concentrations. In the present study, we evaluated the apoptotic cell ratio and ROS production in hemocytes of the white shrimp Litopenaeus vannamei exposed to 1 or 5 mg L -1 Cu for 0, 3, 6, 12, 24, and 48 h. The expression changes of antioxidant biomarker genes, i.e., copper-zinc superoxide dismutase (Cu-Zn SOD) and catalase (CAT), apoptosis-related genes, i.e., caspase-3 and inhibitor of apoptosis protein (IAP), and a specific biomarker gene of heavy metal pollution, i.e., metallothionein (MT), were also determined in hemocytes. Significant increases in ROS production were observed in both treatment groups at each time points. The apoptotic cell ratios were significantly increased at 6-48 h among shrimp exposed to 1 mg L -1 Cu and at each time points in 5 mg L -1 Cu group. These results indicated that Cu would induce oxidative stress and apoptosis in the hemocyte of L. vannamei. Quantitative real-time PCR analysis revealed that the relative expression levels of Cu-Zn SOD, CAT, caspase-3, IAP, and MT were upregulated in a dose-dependent and time-dependent manner, suggesting the involvement of these genes in stress response against Cu exposure.

  20. Cytotoxicity and cellular mechanisms involved in the toxicity of CdS quantum dots in hemocytes and gill cells of the mussel Mytilus galloprovincialis

    Energy Technology Data Exchange (ETDEWEB)

    Katsumiti, A. [CBET Research Group, Dept. Zoology and Animal Cell Biology, Faculty of Science and Technology and Research Centre for Experimental Marine Biology and Biotechnology PIE, University of the Basque Country UPV/EHU, Basque Country (Spain); Gilliland, D. [EU Commission–Joint Research Centre, Institute of Health and Consumer Protection, NSB Unit, Ispra (Italy); Arostegui, I. [Department of Applied Mathematics, Statistics and Operations Research, Faculty of Science and Technology, University of the Basque Country UPV/EHU, Leioa (Spain); Cajaraville, M.P., E-mail: mirenp.cajaraville@ehu.es [CBET Research Group, Dept. Zoology and Animal Cell Biology, Faculty of Science and Technology and Research Centre for Experimental Marine Biology and Biotechnology PIE, University of the Basque Country UPV/EHU, Basque Country (Spain)

    2014-08-15

    Highlights: • CdS QDs were cytotoxic for mussel hemocytes and gill cells in vitro. • Ionic Cd was the most toxic form, followed by CdS QDs and bulk CdS. • CdS QDs altered oxidative balance and caused DNA damage in mussel cells. • CdS QDs caused a particle-specific immunostimulation on phagocytosis of hemocytes. • Conceptual models for cellular handling and toxicity of CdS QDs are proposed. - Abstract: CdS quantum dots (QDs) show a great promise for treatment and diagnosis of cancer and for targeted drug delivery, due to their size-tunable fluorescence and ease of functionalization for tissue targeting. In spite of their advantages it is important to determine if CdS QDs can exert toxicity on biological systems. In the present work, cytotoxicity of CdS QDs (5 nm) at a wide range of concentrations (0.001–100 mg Cd/L) was screened using neutral red (NR) and thiazolyl blue tetrazolium bromide (MTT) assays in isolated hemocytes and gill cells of mussels (Mytilus galloprovincialis). The mechanisms of action of CdS QDs were assessed at sublethal concentrations (0.31–5 mg Cd/L) in the same cell types through a series of functional in vitro assays: production of reactive oxygen species (ROS), catalase (CAT) activity, DNA damage, lysosomal acid phosphatase (AcP) activity, multixenobiotic resistance (MXR) transport activity, Na-K-ATPase activity (only in gill cells) and phagocytic activity and damage to actin cytoskeleton (only in hemocytes). Exposures to CdS QDs lasted for 24 h and were performed in parallel with exposures to bulk CdS and ionic Cd. Ionic Cd was the most toxic form to both cell types, followed by CdS QDs and bulk CdS. ROS production, DNA damage, AcP activity and MXR transport were significantly increased in both cell types exposed to the 3 forms of Cd. CAT activity increased in hemocytes exposed to the three forms of Cd while in gill cells only in those exposed to ionic Cd. No effects were found on hemocytes cytoskeleton integrity. Effects on

  1. Ingestion of onion soup high in quercetin inhibits platelet aggregation and essential components of the collagen-stimulated platelet activation pathway in man: a pilot study.

    Science.gov (United States)

    Hubbard, Gary P; Wolffram, Siegfried; de Vos, Ric; Bovy, Arnaud; Gibbins, Jonathan M; Lovegrove, Julie A

    2006-09-01

    Epidemiological data suggest that those who consume a diet rich in quercetin-containing foods may have a reduced risk of CVD. Furthermore, in vitro and ex vivo studies have observed the inhibition of collagen-induced platelet activation by quercetin. The aim of the present study was to investigate the possible inhibitory effects of quercetin ingestion from a dietary source on collagen-stimulated platelet aggregation and signalling. A double-blind randomised cross-over pilot study was undertaken. Subjects ingested a soup containing either a high or a low amount of quercetin. Plasma quercetin concentrations and platelet aggregation and signalling were assessed after soup ingestion. The high-quercetin soup contained 69 mg total quercetin compared with the low-quercetin soup containing 5 mg total quercetin. Plasma quercetin concentrations were significantly higher after high-quercetin soup ingestion than after low-quercetin soup ingestion and peaked at 2.59 (sem 0.42) mumol/l. Collagen-stimulated (0.5 mug/ml) platelet aggregation was inhibited after ingestion of the high-quercetin soup in a time-dependent manner. Collagen-stimulated tyrosine phosphorylation of a key component of the collagen-signalling pathway via glycoprotein VI, Syk, was significantly inhibited by ingestion of the high-quercetin soup. The inhibition of Syk tyrosine phosphorylation was correlated with the area under the curve for the high-quercetin plasma profile. In conclusion, the ingestion of quercetin from a dietary source of onion soup could inhibit some aspects of collagen-stimulated platelet aggregation and signalling ex vivo. This further substantiates the epidemiological data suggesting that those who preferentially consume high amounts of quercetin-containing foods have a reduced risk of thrombosis and potential CVD risk.

  2. Shrimp hemocyte homeostasis-associated protein (PmHHAP) interacts with WSSV134 to control apoptosis in white spot syndrome virus infection.

    Science.gov (United States)

    Apitanyasai, Kantamas; Amparyup, Piti; Charoensapsri, Walaiporn; Sangsuriya, Pakkakul; Tassanakajon, Anchalee

    2018-05-01

    Hemocyte homeostasis-associated protein (PmHHAP) was first identified as a viral-responsive gene, due to a high upregulation in transcription following white spot syndrome virus (WSSV) infection. Functional studies using RNA interference have suggested that PmHHAP is involved in hemocyte homeostasis by controlling apoptosis during WSSV infection. In this study, the role of PmHHAP in host-viral interactions was further investigated. Yeast two-hybrid assay and co-immunoprecipitation revealed that PmHHAP binds to an anti-apoptosis protein, WSSV134. The viral protein WSSV134 is a late protein of WSSV, expressed 24 h post infection (hpi). Gene silencing of WSSV134 in WSSV-infected shrimp resulted in a reduction of the expression level of the viral replication marker genes VP28, wsv477, and ie-1, which suggests that WSSV134 is likely involved in viral propagation. However, co-silencing of PmHHAP and WSSV134 counteracted the effects on WSSV infection, which implies the importance of the host-pathogen interaction between PmHHAP and WSSV134 in WSSV infection. In addition, caspase 3/7 activity was noticeably induced in the PmHHAP and WSSV134 co-silenced shrimp upon WSSV infection. Moreover, PmHHAP and WSSV134 inhibited caspase-induced activation of PmCasp in vitro in a non-competitive manner. Taken together, these results suggest that PmHHAP and WSSV134 play a role in the host-pathogen interaction and work concordantly to control apoptosis in WSSV infection. Copyright © 2018 Elsevier Ltd. All rights reserved.

  3. Piperine Inhibits the Activities of Platelet Cytosolic Phospholipase A2 and Thromboxane A2 Synthase without Affecting Cyclooxygenase-1 Activity: Different Mechanisms of Action Are Involved in the Inhibition of Platelet Aggregation and Macrophage Inflammatory Response

    Directory of Open Access Journals (Sweden)

    Dong Ju Son

    2014-08-01

    Full Text Available PURPOSE: Piperine, a major alkaloid of black pepper (Piper nigrum and long pepper (Piper longum, was shown to have anti-inflammatory activity through the suppression of cyclooxygenase (COX-2 gene expression and enzyme activity. It is also reported to exhibit anti-platelet activity, but the mechanism underlying this action remains unknown. In this study, we investigated a putative anti-platelet aggregation mechanism involving arachidonic acid (AA metabolism and how this compares with the mechanism by which it inhibits macrophage inflammatory responses; METHODS: Rabbit platelets and murine macrophage RAW264.7 cells were treated with piperine, and the effect of piperine on the activity of AA-metabolizing enzymes, including cytosolic phospholipase A2 (cPLA2, COX-1, COX-2, and thromboxane A2 (TXA2 synthase, as well as its effect on AA liberation from the plasma membrane components, were assessed using isotopic labeling methods and enzyme immunoassay kit; RESULTS: Piperine significantly suppressed AA liberation by attenuating cPLA2 activity in collagen-stimulated platelets. It also significantly inhibited the activity of TXA2 synthase, but not of COX-1, in platelets. These results suggest that piperine inhibits platelet aggregation by attenuating cPLA2 and TXA2 synthase activities, rather than through the inhibition of COX-1 activity. On the other hand, piperine significantly inhibited lipopolysaccharide-induced generation of prostaglandin (PGE2 and PGD2 in RAW264.7 cells by suppressing the activity of COX-2, without effect on cPLA2; CONCLUSION: Our findings indicate that piperine inhibits platelet aggregation and macrophage inflammatory response by different mechanisms.

  4. Genotoxic and immunotoxic potential effects of selected psychotropic drugs and antibiotics on blue mussel (Mytilus edulis) hemocytes

    International Nuclear Information System (INIS)

    Lacaze, Emilie; Pédelucq, Julie; Fortier, Marlène; Brousseau, Pauline; Auffret, Michel; Budzinski, Hélène; Fournier, Michel

    2015-01-01

    The potential toxicity of pharmaceuticals towards aquatic invertebrates is still poorly understood and sometimes controversial. This study aims to document the in vitro genotoxicity and immunotoxicity of psychotropic drugs and antibiotics on Mytilus edulis. Mussel hemocytes were exposed to fluoxetine, paroxetine, venlafaxine, carbamazepine, sulfamethoxazole, trimethoprim and erythromycin, at concentrations ranging from μg/L to mg/L. Paroxetine at 1.5 μg/L led to DNA damage while the same concentration of venlafaxine caused immunomodulation. Fluoxetine exposure resulted in genotoxicity, immunotoxicity and cytotoxicity. In the case of antibiotics, trimethoprim was genotoxic at 200 μg/L and immunotoxic at 20 mg/L whereas erythromycin elicited same detrimental effects at higher concentrations. DNA metabolism seems to be a highly sensitive target for psychotropic drugs and antibiotics. Furthermore, these compounds affect the immune system of bivalves, with varying intensity. This attests the relevance of these endpoints to assess the toxic mode of action of pharmaceuticals in the aquatic environment. - Highlights: • Psychotropic drugs and antibiotics affect the immune system of Mytilus edulis. • Genotoxic and immunotoxic endpoints were relevant to assess pharmaceuticals toxicity. • DNA metabolism is a highly sensitive target for pharmaceuticals. • Fluoxetine and paroxetine were the most toxic compounds on mussel hemocytes. - Psychotropic drugs and antibiotics have the potential to cause immune toxicity and genotoxicity on Mytilus edulis hemocytes

  5. Rac1 mediates cytokine-stimulated hemocyte spreading via prostaglandin biosynthesis in the beet armyworm, Spodoptera exigua

    Science.gov (United States)

    Cell spreading is an integral component of insect hemocytic immune reactions to infections and invasions. Cell spreading is accomplished by cytoskeleton rearrangement, which is activated by three major immune mediators, biogenic monoamines, plasmatocyte-spreading peptide (PSP), and eicosanoids, part...

  6. Evaluation of radiosensitivity hemocytes of Biomphalaria glabrata exposed to gamma radiation

    International Nuclear Information System (INIS)

    Silva, L.R.S.; Amaral, A.J.; Silva, E.B.; Amancio, F.F.; Melo, A.M.M.A.

    2013-01-01

    The mollusc Biomphalaria glabrata have characteristics that allow them to be identified as an animal model ideal for monitoring areas exposed to chemical agents and physical. This study evaluated the effect of ionizing radiation from Cobalt-60 in haemocytes present in the hemolymph of Biomphalaria glabrata, with the goal of using these cells as indicators of the presence of radiation in aquatic environments. The mollusks were divided into five groups: one control and four subjected doses of 25, 35, 45 and 55 Gy of gamma radiation. After 48 hours of irradiation, the clam hemolymph was collected and slides were prepared and stained with Giemsa for analyses under a light microscope. Statistical analysis was performed using ANOVA and Tukey's test, p <0.05. The results showed that the total number of cells after irradiation reduced compared to control except at a dose of 55 Gy. During data analysis, morphological changes were observed in haemocytes of mollusks subjected to doses of 35, 45 and 55 Gy. These modifications consisted of nucleus bilobulated and nucleo plasmatic bridges. Another change was exclusively observed in the cellular exposure of 55 Gy, where hemocytes showed misshapen nuclei and cytoplasm vacuolisation, suggestive of apoptosis. It is concluded that hemocytes are sensitive to radiation and can be used as indicators of the presence of high doses of ionizing radiation in aquatic environments. (author)

  7. Ultrastructural studies of the hemocytes of Panstrongylus megistus (Hemiptera: Reduvidae Ultra-estrutura dos hemócitos de Panstrongylus megistus (Hemiptera: Reduviidae

    Directory of Open Access Journals (Sweden)

    Margherita A. Barracco

    1989-06-01

    Full Text Available Ultrastructural analyses revealed the presence of six hemocyte types in the hemolymph of Panstrogylus megistus, partially confirming our previous results obtained through light microscopy. Prohemocytes: small, round hemocytes with a thin cytoplasm layer, espcieally rich in free ribosomes and poor in membranous systems. Plasmatocytes: polymorphic cells, whose cytoplasm contains many lysosomes and a well developed rough endoplasmic reticulum (RER.They are extremely phagocytic. Sometimes, they show a large vacuolation. Granulocytes: granular hemocytes whose granules show different degrees of electrondensity. Most of them, have an internal structuration. Coagulocytes: oval or elongated hemocytes, which show pronounced perinuclear cisternae as normally observed in coagulocytes. The cytoplasm is usually electrondense, poor in membranous systems and contains many labile granules. Oenocytoids: large and very stable hemocytes, whose homogeneous cytoplasme is rich in loose ribosomes and poor in membranous systems. Adipohemocytes: large cells, containing several characteristic lipid droplets. The cytoplasm is also rich in glycogen, RER and large mitochondria. The total and differential hemocyte count (THC and DHC were also calculated for this reduviid. THC increases from 2,900 hemocytes/cubic millimeter of hemolymph in the 4th intar to 4,350 in the 5th and then, decreases to 1,950 in the adults. Plasmatocytes and coagulocytes are the predominant hemocyte types.Estudos ao microscópio eletrônico de transmissão revelaram a presença de seis tipos de hemócitos na hemolinfa de Panstrongylus megistus. Estes resultados confirmam parcialmente os obtidos anteriormente através da microscopia de luz. Pró-hemócitos: células pequenas e arredondadas, cuja delgada faixa citoplasmática é especialmente rica em ribossomos livres e pobre em sistemas membranosos. Plasmatócitos: células polimórficas, cujo citoplasma caracteriza-se por um retículo endoplasm

  8. A hemocyte gene expression signature correlated with predictive capacity of oysters to survive Vibrio infections

    Directory of Open Access Journals (Sweden)

    Rosa Rafael

    2012-06-01

    Full Text Available Abstract Background The complex balance between environmental and host factors is an important determinant of susceptibility to infection. Disturbances of this equilibrium may result in multifactorial diseases as illustrated by the summer mortality syndrome, a worldwide and complex phenomenon that affects the oysters, Crassostrea gigas. The summer mortality syndrome reveals a physiological intolerance making this oyster species susceptible to diseases. Exploration of genetic basis governing the oyster resistance or susceptibility to infections is thus a major goal for understanding field mortality events. In this context, we used high-throughput genomic approaches to identify genetic traits that may characterize inherent survival capacities in C. gigas. Results Using digital gene expression (DGE, we analyzed the transcriptomes of hemocytes (immunocompetent cells of oysters able or not able to survive infections by Vibrio species shown to be involved in summer mortalities. Hemocytes were nonlethally collected from oysters before Vibrio experimental infection, and two DGE libraries were generated from individuals that survived or did not survive. Exploration of DGE data and microfluidic qPCR analyses at individual level showed an extraordinary polymorphism in gene expressions, but also a set of hemocyte-expressed genes whose basal mRNA levels discriminate oyster capacity to survive infections by the pathogenic V. splendidus LGP32. Finally, we identified a signature of 14 genes that predicted oyster survival capacity. Their expressions are likely driven by distinct transcriptional regulation processes associated or not associated to gene copy number variation (CNV. Conclusions We provide here for the first time in oyster a gene expression survival signature that represents a useful tool for understanding mortality events and for assessing genetic traits of interest for disease resistance selection programs.

  9. Multixenobiotic resistance in Mytilus edulis: Molecular and functional characterization of an ABCG2- type transporter in hemocytes and gills.

    Science.gov (United States)

    Ben Cheikh, Yosra; Xuereb, Benoit; Boulangé-Lecomte, Céline; Le Foll, Frank

    2018-02-01

    Among the cellular protection arsenal, ABC transporters play an important role in xenobiotic efflux in marine organisms. Two pumps belonging to B and C subfamily has been identified in Mytilus edulis. In this study, we investigated the presence of the third major subtype ABCG2/BCRP protein in mussel tissues. Transcript was expressed in hemocytes and with higher level in gills. Molecular characterization revealed that mussel ABCG2 transporter shares the sequence and organizational structure with mammalian and molluscan orthologs. Overall identity of the predicted amino acid sequence with corresponding homologs from other organisms was between 49% and 98%. Moreover, protein efflux activity was demonstrated using a combination of fluorescent allocrites and specific inhibitors. The accumulation of bodipy prazosin and pheophorbide A was heterogeneous in gills and hemocytes. Most of the used blockers enhanced probe accumulation at different levels, most significantly for bodipy prazosin. Moreover, Mrp classical blocker MK571 showed a polyspecificity. In conclusion, our data demonstrate that several ABC transporters contribute to MXR phenotype in the blue mussel including ABCG2 that forms an active pump in hemocytes and gills. Efforts are needed to distinguish between the different members and to explore their single function and specificity towards allocrites and chemosensitizers. Copyright © 2017 Elsevier B.V. All rights reserved.

  10. [Inhibitory mechanism of ifenprodil tartrate on rabbit platelet aggregation].

    Science.gov (United States)

    Irino, O; Saitoh, K; Hayashi, T; Ohkubo, K

    1985-05-01

    The effects of dl-erythro-4-benzyl-alpha-(4-hydroxyphenyl)-beta-methyl-l-piperidine-eth anol tartrate (ifenprodil tartrate) on rabbit platelet aggregation in vitro and ex vivo were studied. Ifenprodil tartrate inhibited platelet aggregation in vitro induced by ADP, collagen and epinephrine. It also inhibited 5-hydroxytryptamine (5-HT) uptake into platelets and 5-HT release from platelets. Since these inhibitory effects of ifenprodil tartrate on the functions of rabbit platelets were similar to the effects of imipramine, the effects of ifenprodil tartrate may be due to the stabilizing action of ifenprodil tartrate on the platelet membrane. The platelet aggregation by ADP was significantly inhibited in rabbits after oral administration of ifenprodil tartrate, the maximal plasma level of ifenprodil being reached at 20 ng/ml ex vivo, while the maximal level was only 1/40 of the minimal concentration of ifenprodil tartrate necessary to inhibit platelet aggregation in vitro. These results indicate that factors other than ifenprodil tartrate acting directly on the platelets (e.g., PGI2 which is an endogenous inhibitor of platelet aggregation) are involved in inducing the inhibitory effects of ifenprodil tartrate on platelet aggregation ex vivo. The effects of ifenprodil tartrate on both PGI2 release from the aorta and the inhibitory effects of PGI2 on platelet aggregation in vitro were investigated: PGI2 was found to intensify the inhibitory effects of ifenprodil tartrate on platelet aggregation in vitro, but there was little effect, if any, on PGI2 release. Therefore, it is considered that the ex vivo effects of ifenprodil tartrate might be due to its interaction with endogenous PGI2 in the blood.

  11. Mediated effect of ultrasound treated Diclofenac on mussel hemocytes: First evidence for the involvement of respiratory burst enzymes in the induction of DCF-mediated unspecific mode of action.

    Science.gov (United States)

    Toufexi, Eirini; Dailianis, Stefanos; Vlastos, Dimitris; Manariotis, Ioannis D

    2016-06-01

    The present study investigates the toxic behavior of diclofenac (DCF) before and after its ultrasound (US) treatment, as well as the involvement of intracellular target molecules, such as NADPH oxidase and NO synthase, in the DCF-induced adverse effects on hemocytes of mussel Mytilus galloprovincialis. In this context, appropriate volumes (350 and 500mL) of DCF solutions (at concentrations of 2, 2.5, 5 and 10mgL(-1)) were treated under different ultrasound operating conditions (frequency at 582 and 862kHz, electric power density at 133 and 167W) for assessing US method efficiency. In parallel, DCF and US DCF-mediated cytotoxic (in terms of cell viability measured with the use of neutral red uptake/NRU method), oxidative (in terms of superoxide anions/(.)O2(-), nitric oxides such as NO2(-) and lipid peroxidation products, such as malondialdehyde/MDA content) and genotoxic (DNA damage measured by the use of Comet assay method) effects were investigated in hemocytes exposed for 1h to 5, 10 and 100ngL(-1) and 1, 10 and 20μgL(-1) of DCF. The involvement of NADPH oxidase and NO synthase to the DCF-induced toxicity was further investigated by the use of 10μΜ L-NAME, a NO synthase inhibitor and 10μΜ DPI, a NADPH oxidase inhibitor. According to the results, 350mL of 2mgL(-1) DCF showed higher degradation (>50%) under 167W electric power density and frequency at 862kHz for 120min, compared to degradation in all other cases, followed by a significant elimination of its toxicity. Specifically, US DCF-treated hemocytes showed a significant attenuation of DCF-mediated cytotoxic, oxidative and genotoxic effects, which appeared to be caused by NADPH oxidase and NO synthase activation, since their inhibition was followed by a significant elimination of (.)O2(-) and NO2(-) generation and the concomitant oxidative damage within cells. The results of the present study showed for the first time that unspecific mode of action of DCF, associated with the induction of NADPH oxidase

  12. Silkworm (Bombyx mori) hemocytes do not produce reactive oxygen metabolites as a part of defense mechanisms

    Czech Academy of Sciences Publication Activity Database

    Hyršl, P.; Číž, Milan; Kubala, Lukáš; Lojek, Antonín

    2004-01-01

    Roč. 49, č. 3 (2004), s. 315-319 ISSN 0015-5632 R&D Projects: GA AV ČR IBS5004009 Institutional research plan: CEZ:AV0Z5004920 Keywords : hemocytes * Bombyx mori * reactive oxygen species Subject RIV: BO - Biophysics Impact factor: 1.034, year: 2004

  13. Discovery of novel PDE9 inhibitors capable of inhibitingaggregation as potential candidates for the treatment of Alzheimer’s disease

    Science.gov (United States)

    Su, Tao; Zhang, Tianhua; Xie, Shishun; Yan, Jun; Wu, Yinuo; Li, Xingshu; Huang, Ling; Luo, Hai-Bin

    2016-02-01

    Recently, phosphodiesterase-9 (PDE9) inhibitors and biometal-chelators have received much attention as potential therapeutics for the treatment of Alzheimer’s disease (AD). Here, we designed, synthesized, and evaluated a novel series of PDE9 inhibitors with the ability to chelate metal ions. The bioassay results showed that most of these molecules strongly inhibited PDE9 activity. Compound 16 showed an IC50 of 34 nM against PDE9 and more than 55-fold selectivity against other PDEs. In addition, this compound displayed remarkable metal-chelating capacity and a considerable ability to halt copper redox cycling. Notably, in comparison to the reference compound clioquinol, it inhibited metal-induced Aβ1-42 aggregation more effectively and promoted greater disassembly of the highly structured Aβ fibrils generated through Cu2+-induced Aβ aggregation. These activities of 16, together with its favorable blood-brain barrier permeability, suggest that 16 may be a promising compound for treatment of AD.

  14. Effect of natural antioxidants on the aggregation and disaggregation ...

    African Journals Online (AJOL)

    Conclusion: High antioxidant activities were positively correlated with the inhibition of Aβ aggregation, although not with the disaggregation of pre-formed Aβ aggregates. Nevertheless, potent antioxidants may be helpful in treating Alzheimer's disease. Keywords: Alzheimer's disease, β-Amyloid, Aggregation, Disaggregation ...

  15. Inhibition of platelet aggregation and in vitro free radical scavenging activity of dried fruiting bodies of Pleurotus eous.

    Science.gov (United States)

    Suseem, S R; Saral, Mary

    2015-07-01

    To evaluate the ethyl acetate, methanol and aqueous extracts of dried fruiting bodies of Pleurotus eous for its anti-platelet activity on human volunteer's blood. And also to analyze the free radical scavenging property of the extracts of P.eous by using various in vitro models. Anti-platelet activity of dried fruiting bodies of P.eous was evaluated by in vitro model using blood platelets. Inhibition of platelet aggregation was monitored after pre-incubation of platelets with the crude extracts of mushroom P.eous. Antioxidant activities of extracts of P.eous were evaluated by different in vitro experiments, namely, 1, 1-diphenyl-2-picryl hydrazyl (DPPH), superoxide, hydroxyl radical and lipid peroxide radical models. Crude extracts of mushroom P.eous inhibited platelet aggregation dose-dependently which was induced by adenosine diphosphate (ADP). At a maximum concentration of 10 mg/mL, methanol extract effected 64.02% inhibition of lipid per-oxidation and 50.12% scavenging effect on superoxide anion radical. Aqueous extract of P.eous have shown 69.43% chelating ability on ferrous ions, 24.27% scavenging effect on hydroxyl radical and 49.57% scavenging effect on DPPH radical at 10 mg/mL. Increasing concentrations of the extract were found to cause progressively decreasing of the intensity of absorbance. Anti-platelet effects could be related in part to the polyphenolic compounds present in the extracts. Antioxidant activity results indicated the free radical scavenging property of the extracts of P.eous which might be due to the high content of phenolic compounds and flavonoids.

  16. Nickel aggregates produced by radiolysis

    International Nuclear Information System (INIS)

    Marignier, J.L.; Belloni, J.

    1988-01-01

    Nickel aggregates with subcolloidal size and stable in water have been synthesized by inhibiting the corrosion by the medium. The protective effect of the surfactant is discussed in relation with the characteristics of various types of polyvinyl alcohol studied. The reactivity of aggregates towards oxidizing compounds, nitro blue tetrazolium, methylene blue, silver ions, oxygen, methylviologen, enables an estimation of the redox potential of nickel aggregates (E = - 04 ± 0.05 V). It has been applied to quantitative analysis of the particles in presence of nickel ions. 55 refs [fr

  17. Purification and Characterization of BmooAi: A New Toxin from Bothrops moojeni Snake Venom That Inhibits Platelet Aggregation

    Directory of Open Access Journals (Sweden)

    Mayara Ribeiro de Queiroz

    2014-01-01

    Full Text Available In this paper, we describe the purification/characterization of BmooAi, a new toxin from Bothrops moojeni that inhibits platelet aggregation. The purification of BmooAi was carried out through three chromatographic steps (ion-exchange on a DEAE-Sephacel column, molecular exclusion on a Sephadex G-75 column, and reverse-phase HPLC chromatography on a C2/C18 column. BmooAi was homogeneous by SDS-PAGE and shown to be a single-chain protein of 15,000 Da. BmooAi was analysed by MALDI-TOF Spectrometry and revealed two major components with molecular masses 7824.4 and 7409.2 as well as a trace of protein with a molecular mass of 15,237.4 Da. Sequencing of BmooAi by Edman degradation showed two amino acid sequences: IRDFDPLTNAPENTA and ETEEGAEEGTQ, which revealed no homology to any known toxin from snake venom. BmooAi showed a rather specific inhibitory effect on platelet aggregation induced by collagen, adenosine diphosphate, or epinephrine in human platelet-rich plasma in a dose-dependent manner, whereas it had little or no effect on platelet aggregation induced by ristocetin. The effect on platelet aggregation induced by BmooAi remained active even when heated to 100°C. BmooAi could be of medical interest as a new tool for the development of novel therapeutic agents for the prevention and treatment of thrombotic disorders.

  18. Inhibition of platelet aggregation by tartrazine and a pyrazolone analogue in normal and allergic individuals.

    Science.gov (United States)

    Gallagher, J S; Splansky, G L; Bernstein, I L

    1980-11-01

    The effect of tartrazine (T) (yellow dye No. 5) and one of its metabolites an aminopyrazolone analogue (1-sulphophenyl-3-carboxy-5-hydroxypyrazole, SCHP) upon collagen-induced platelet aggregation (C-PA) was investigated in fourteen atopic patients and fourteen normal subjects. Both T and SCHP inhibited C-PA in atopic patients at significantly lower doses than in normal volunteers. The mean inhibitory concentrations of SCHP were similar to aspirin in both atopic and normal individuals. Although the precise mechanism by which these chemicals block C-PA has not been elucidated, this in vitro system may be a useful method of assessing non-immune mechanisms involved in reactions to tartrazine.

  19. Curcumin Attenuates Amyloid-β Aggregate Toxicity and Modulates Amyloid-β Aggregation Pathway.

    Science.gov (United States)

    Thapa, Arjun; Jett, Stephen D; Chi, Eva Y

    2016-01-20

    The abnormal misfolding and aggregation of amyloid-β (Aβ) peptides into β-sheet enriched insoluble deposits initiates a cascade of events leading to pathological processes and culminating in cognitive decline in Alzheimer's disease (AD). In particular, soluble oligomeric/prefibrillar Aβ have been shown to be potent neurotoxins. The naturally occurring polyphenol curcumin has been shown to exert a neuroprotective effect against age-related neurodegenerative diseases such as AD. However, its protective mechanism remains unclear. In this study, we investigated the effects of curcumin on the aggregation of Aβ40 as well as Aβ40 aggregate induced neurotoxicity. Our results show that the curcumin does not inhibit Aβ fibril formation, but rather enriches the population of "off-pathway" soluble oligomers and prefibrillar aggregates that were nontoxic. Curcumin also exerted a nonspecific neuroprotective effect, reducing toxicities induced by a range of Aβ conformers, including monomeric, oligomeric, prefibrillar, and fibrillar Aβ. The neuroprotective effect is possibly membrane-mediated, as curcumin reduced the extent of cell membrane permeabilization induced by Aβ aggregates. Taken together, our study shows that curcumin exerts its neuroprotective effect against Aβ induced toxicity through at least two concerted pathways, modifying the Aβ aggregation pathway toward the formation of nontoxic aggregates and ameliorating Aβ-induced toxicity possibly through a nonspecific pathway.

  20. Hemocytes of zebra mussels (Dreissena polymorpha are relevant cells for the monitoring of environmental genotoxicity by the comet assay.

    Directory of Open Access Journals (Sweden)

    Marc Bonnard

    2015-06-01

    Full Text Available The measure of DNA integrity by the single cell gel electrophoresis (SCGE or comet assay is especially recommended for its sensitivity and its capacity for detecting different types of damages. Therefore, it has been applied in environmental genotoxicity in a variety of organisms. It appears today necessary to define both reference and threshold levels of DNA damage, for their application in in situ biomonitoring. However, little is known about the influence of both biological (sex, reproduction status or external (temperature… confounding factors on the measure of DNA damage by the comet assay. These variables need to be taken into account if the robustness of the assay is to be established (Jha, 2008. In the zebra mussel Dreissena polymorpha (recommended as a sentinel species in the evaluation of freshwater quality the measure of DNA damage by the comet assay is mainly performed on hemocytes, which are circulating cells involved in key physiological functions such as immunity, homeostasis, detoxication…. This communication will present and discuss results from an innovative study about the variability of the baseline level of DNA damage in hemocytes of mussels encaged for one year in the canal de l’Aisne à la Marne (Reims, according to their sex and their reproductive status. The sensitivity and the suitability of hemocytes in the evaluation of environmental genotoxicity will also be discussed, referring to observations during a 6 month-exposure of mussels in mesocosms to environmentally realistic concentrations of carbamazepine.

  1. A novel thromboxane receptor antagonist, nstpbp5185, inhibits platelet aggregation and thrombus formation in animal models.

    Science.gov (United States)

    Huang, Shiu-Wen; Kuo, Heng-Lan; Hsu, Ming-Tsung; Tseng, Yufeng Jane; Lin, Shu-Wha; Kuo, Sheng-Chu; Peng, Hui-Chin; Lien, Jin-Cherng; Huang, Tur-Fu

    2016-08-01

    A novel benzimidazole derivative, nstpbp5185, was discovered through in vitro and in vivo evaluations for antiplatelet activity. Thromaboxane receptor (TP) is important in vascular physiology, haemostasis and pathophysiological thrombosis. Nstpbp5185 concentration-dependently inhibited human platelet aggregation caused by collagen, arachidonic acid and U46619. Nstpbp5185 caused a right-shift of the concentration-response curve of U46619 and competitively inhibited the binding of 3H-SQ-29548 to TP receptor expressed on HEK-293 cells, with an IC50 of 0.1 µM, indicating that nstpbp5185 is a TP antagonist. In murine thrombosis models, nstpbp5185 significantly prolonged the latent period in triggering platelet plug formation in mesenteric and FeCl3-induced thrombi formation, and increased the survival rate in pulmonary embolism model with less bleeding than aspirin. This study suggests nstpbp5185, an orally selective anti-thrombotic agent, acting through blockade of TXA2 receptor, may be efficacious for prevention or treatment of pathologic thrombosis.

  2. The antimalarial activity of Ru-chloroquine complexes against resistant Plasmodium falciparum is related to lipophilicity, basicity, and heme aggregation inhibition ability near water/n-octanol interfaces.

    Science.gov (United States)

    Martínez, Alberto; Rajapakse, Chandima S K; Jalloh, Dalanda; Dautriche, Cula; Sánchez-Delgado, Roberto A

    2009-08-01

    We have measured water/n-octanol partition coefficients, pK(a) values, heme binding constants, and heme aggregation inhibition activity of a series of ruthenium-pi-arene-chloroquine (CQ) complexes recently reported to be active against CQ-resistant strains of Plasmodium falciparum. Measurements of heme aggregation inhibition activity of the metal complexes near water/n-octanol interfaces qualitatively predict their superior antiplasmodial action against resistant parasites, in relation to CQ; we conclude that this modified method may be a better predictor of antimalarial potency than standard tests in aqueous acidic buffer. Some interesting tendencies emerge from our data, indicating that the antiplasmodial activity is related to a balance of effects associated with the lipophilicity, basicity, and structural details of the compounds studied.

  3. The antimalarial activity of Ru–chloroquine complexes against resistant Plasmodium falciparum is related to lipophilicity, basicity, and heme aggregation inhibition ability near water/n-octanol interfaces

    Science.gov (United States)

    Martínez, Alberto; Rajapakse, Chandima S. K.; Jalloh, Dalanda; Dautriche, Cula

    2012-01-01

    We have measured water/n-octanol partition coefficients, pKa values, heme binding constants, and heme aggregation inhibition activity of a series of ruthenium–πarene–chloroquine (CQ) complexes recently reported to be active against CQ-resistant strains of Plasmodium falciparum. Measurements of heme aggregation inhibition activity of the metal complexes near water/n-octanol interfaces qualitatively predict their superior antiplasmodial action against resistant parasites, in relation to CQ; we conclude that this modified method may be a better predictor of antimalarial potency than standard tests in aqueous acidic buffer. Some interesting tendencies emerge from our data, indicating that the antiplasmodial activity is related to a balance of effects associated with the lipophilicity, basicity, and structural details of the compounds studied. PMID:19343380

  4. Nematocytes: Discovery and characterization of a novel anculeate hemocyte in Drosophila falleni and Drosophila phalerata.

    Directory of Open Access Journals (Sweden)

    Julianna Bozler

    Full Text Available Immune challenges, such as parasitism, can be so pervasive and deleterious that they constitute an existential threat to a species' survival. In response to these ecological pressures, organisms have developed a wide array of novel behavioral, cellular, and molecular adaptations. Research into these immune defenses in model systems has resulted in a revolutionary understanding of evolution and functional biology. As the field has expanded beyond the limited number of model organisms our appreciation of evolutionary innovation and unique biology has widened as well. With this in mind, we have surveyed the hemolymph of several non-model species of Drosophila. Here we identify and describe a novel hemocyte, type-II nematocytes, found in larval stages of numerous Drosophila species. Examined in detail in Drosophila falleni and Drosophila phalerata, we find that these remarkable cells are distinct from previously described hemocytes due to their anucleate state (lacking a nucleus and unusual morphology. Type-II nematocytes are long, narrow cells with spindle-like projections extending from a cell body with high densities of mitochondria and microtubules, and exhibit the ability to synthesize proteins. These properties are unexpected for enucleated cells, and together with our additional characterization, we demonstrate that these type-II nematocytes represent a biological novelty. Surprisingly, despite the absence of a nucleus, we observe through live cell imaging that these cells remain motile with a highly dynamic cellular shape. Furthermore, these cells demonstrate the ability to form multicellular structures, which we suggest may be a component of the innate immune response to macro-parasites. In addition, live cell imaging points to a large nucleated hemocyte, type-I nematocyte, as the progenitor cell, leading to enucleation through a budding or asymmetrical division process rather than nuclear ejection: This study is the first to report such a

  5. Inhibition of Platelet Aggregation by the Leaf Extract of Carica papaya During Dengue Infection: An In Vitro Study.

    Science.gov (United States)

    Chinnappan, Shobia; Ramachandrappa, Vijayakumar Shettikothanuru; Tamilarasu, Kadhiravan; Krishnan, Uma Maheswari; Pillai, Agiesh Kumar Balakrishna; Rajendiran, Soundravally

    2016-04-01

    Dengue cases were reported to undergo platelet activation and thrombocytopenia by a poorly understood mechanism. Recent studies suggested that Carica papaya leaf extract could recover the platelet count in dengue cases. However, no studies have attempted to unravel the mechanism of the plant extract in platelet recovery. Since there are no available drugs to treat dengue and considering the significance of C. papaya in dengue treatment, the current study aimed to evaluate two research questions: First one is to study if the C. papaya leaf extract exerts its action directly on platelets and second one is to understand if the extract can specifically inhibit the platelet aggregation during dengue viral infection. Sixty subjects with dengue positive and 60 healthy subjects were recruited in the study. Platelet-rich plasma (PRP) and platelet-poor plasma were prepared from both the dengue-infected and healthy control blood samples. Effect of the leaf extract obtained from C. papaya leaves was assessed on plasma obtained as well as platelets collected from both healthy and dengue-infected individuals. Platelet aggregation was significantly reduced when leaf extract preincubated with dengue plasma was added into control PRP, whereas no change in aggregation when leaf extract incubated-control plasma was added into control PRP. Upon direct addition of C. papaya leaf extract, both dengue PRP and control PRP showed a significant reduction in platelet aggregation. Within the dengue group, PRP from severe and nonsevere cases showed a significant decrease in aggregation without any difference between them. From the study, it is evident that C. papaya leaf extract can directly act on platelet. The present study, the first of its kind, found that the leaf extract possesses a dengue-specific neutralizing effect on dengue viral-infected plasma that may exert a protective role on platelets.

  6. Nitric oxide production by hemocytes of larva and pharate prepupa of Galleria mellonella in response to bacterial lipopolysaccharide: cytoprotective or cytotoxic?

    Czech Academy of Sciences Publication Activity Database

    Krishnan, Natraj; Hyršl, P.; Šimek, V.

    2006-01-01

    Roč. 142, 1-2 (2006), s. 103-110 ISSN 1532-0456 Institutional research plan: CEZ:AV0Z50070508 Keywords : nitric oxide * hemocytes * lipopolysaccharide Subject RIV: ED - Physiology Impact factor: 1.991, year: 2006

  7. PE859, a novel tau aggregation inhibitor, reduces aggregated tau and prevents onset and progression of neural dysfunction in vivo.

    Directory of Open Access Journals (Sweden)

    Michiaki Okuda

    Full Text Available In tauopathies, a neural microtubule-associated protein tau (MAPT is abnormally aggregated and forms neurofibrillary tangle. Therefore, inhibition of the tau aggregation is one of the key approaches for the treatment of these diseases. Here, we have identified a novel tau aggregation inhibitor, PE859. An oral administration of PE859 resulted in the significant reduction of sarkosyl-insoluble aggregated tau along with the prevention of onset and progression of the motor dysfunction in JNPL3 P301L-mutated human tau transgenic mice. These results suggest that PE859 is useful for the treatment of tauopathies.

  8. Modulation of platelet aggregation by areca nut and betel leaf ingredients: roles of reactive oxygen species and cyclooxygenase.

    Science.gov (United States)

    Jeng, Jiiang-Huei; Chen, Shiao-Yun; Liao, Chang-Hui; Tung, Yuan-Yii; Lin, Bor-Ru; Hahn, Liang-Jiunn; Chang, Mei-Chi

    2002-05-01

    There are 2 to 6 billion betel quid (BQ) chewers in the world. Areca nut (AN), a BQ component, modulates arachidonic acid (AA) metabolism, which is crucial for platelet function. AN extract (1 and 2 mg/ml) stimulated rabbit platelet aggregation, with induction of thromboxane B2 (TXB2) production. Contrastingly, Piper betle leaf (PBL) extract inhibited AA-, collagen-, and U46619-induced platelet aggregation, and TXB2 and prostaglandin-D2 (PGD2) production. PBL extract also inhibited platelet TXB2 and PGD2 production triggered by thrombin, platelet activating factor (PAF), and adenosine diphosphate (ADP), whereas little effect on platelet aggregation was noted. Moreover, PBL is a scavenger of O2(*-) and *OH, and inhibits xanthine oxidase activity and the (*)OH-induced PUC18 DNA breaks. Deferoxamine, 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid (BAPTA) and neomycin prevented AN-induced platelet aggregation and TXB2 production. Indomethacin, genistein, and PBL extract inhibited only TXB2 production, but not platelet aggregation. Catalase, superoxide dismutase, and dimethylthiourea (DMT) showed little effect on AN-induced platelet aggregation, whereas catalase and DMT inhibited the AN-induced TXB2 production. These results suggest that AN-induced platelet aggregation is associated with iron-mediated reactive oxygen species production, calcium mobilization, phospholipase C activation, and TXB2 production. PBL inhibited platelet aggregation via both its antioxidative effects and effects on TXB2 and PGD2 production. Effects of AN and PBL on platelet aggregation and AA metabolism is crucial for platelet activation in the oral mucosa and cardiovascular system in BQ chewers.

  9. Gene expression profile of Bombyx mori hemocyte under the stress of destruxin A.

    Directory of Open Access Journals (Sweden)

    Liang Gong

    Full Text Available Destruxin A (DA is a cyclo-peptidic mycotoxin from the entomopathogenic fungus Metarhizium anisopliae. To uncover potential genes associated with its molecular mechanisms, a digital gene expression (DGE profiling analysis was used to compare differentially expressed genes in the hemocytes of silkworm larvae treated with DA. Ten DGE libraries were constructed, sequenced, and assembled, and the unigenes with least 2.0-fold difference were further analyzed. The numbers of up-regulated genes were 10, 20, 18, 74 and 8, as well as the numbers of down-regulated genes were 0, 1, 8, 13 and 3 at 1, 4, 8, 12 and 24 h post treatment, respectively. Totally, the expression of 132 genes were significantly changed, among them, 1, 3 and 12 genes were continually up-regulated at 4, 3 and 2 different time points, respectively, while 1 gene was either up or down-regulated continually at 2 different time points. Furthermore, 68 genes were assigned to one or multiple gene ontology (GO terms and 89 genes were assigned to specific Kyoto Encyclopedia of Genes and Genomes (KEGG Orthology. In-depth analysis identified that these genes putatively involved in insecticide resistance, cell apoptosis, and innate immune defense. Finally, twenty differentially expressed genes were randomly chosen and validated by quantitative real-time PCR (qRT-PCR. Our studies provide insights into the toxic effect of this microbial insecticide on silkworm's hemocytes, and are helpful to better understanding of the molecular mechanisms of DA as a biological insecticide.

  10. Novel direct factor Xa inhibitory compounds from Tenebrio molitor with anti-platelet aggregation activity.

    Science.gov (United States)

    Lee, Wonhwa; Kim, Mi-Ae; Park, InWha; Hwang, Jae Sam; Na, MinKyun; Bae, Jong-Sup

    2017-11-01

    Tenebrio molitor is an edible insect that has antimicrobial, anticancer, and antihypertensive effects. The aim of this study was to identify the unreported bioactive compounds from T. molitor larvae with inhibitory activities against factor Xa (FXa) and platelet aggregation. Isolated compounds were evaluated for their anti-FXa and anti-platelet aggregation properties by monitoring clotting time, platelet aggregation, FXa activity, and thrombus formation. A diketopiperazine (1, cyclo( L -Pro- L -Tyr)) and a phenylethanoid (2, N-acetyltyramine) were isolated and inhibited the catalytic activity of FXa in a mixed inhibition model and inhibited platelet aggregation induced by adenosine diphosphate (ADP) and U46619. They inhibited ADP- and U46619-induced phosphorylation of myristoylated alanine-rich C kinase substrate (MARCKS) and the expression of P-selectin and PAC-1 in platelets. They also improved the production of nitric oxide and inhibited the oversecretion of endothelin-1 compared to that of the ADP- or U46619-treated group. In an animal model of arterial and pulmonary thrombosis, the isolated compounds showed enhanced antithrombotic effects. They also elicited anticoagulant effects in mice. Compounds 1-2 inhibited ADP-, collagen-, or U46619-induced platelet aggregation and showed similar anti-thrombotic efficacy to rivaroxaban, a positive control. Therefore, 1-2 could serve as candidates and provide scaffolds for the development of new anti-FXa and anti-platelet drugs. Copyright © 2017 Elsevier Ltd. All rights reserved.

  11. Coronatin-2 from the entomopathogenic fungus Conidiobolus coronatus kills Galleria mellonella larvae and incapacitates hemocytes.

    Science.gov (United States)

    Boguś, M I; Wieloch, W; Ligęza-Żuber, M

    2017-02-01

    Coronatin-2, a 14.5 kDa protein, was isolated from culture filtrates of the entomopathogenic fungus Conidiobolus coronatus (Costantin) Batko (Entomophthoramycota: Entomophthorales). After LC-MS/MS (liquid chromatography tandem mass spectrometry) analysis of the tryptic peptide digest of coronatin-2 and a mass spectra database search no orthologs of this protein could be found in fungi. The highest homology was observed to the partial translation elongation factor 1a from Sphaerosporium equinum (protein sequence coverage, 21%), with only one peptide sequence, suggesting that coronatin-2 is a novel fungal protein that has not yet been described. In contrast to coronatin-1, an insecticidal 36 kDa protein, which shows both elastolytic and chitinolytic activity, coronatin-2 showed no enzymatic activity. Addition of coronatin-2 into cultures of hemocytes taken from larvae of Galleria mellonella Linnaeus (Lepidoptera: Pyralidae), resulted in progressive disintegration of nets formed by granulocytes and plasmatocytes due to rapid degranulation of granulocytes, extensive vacuolization of plasmatocytes accompanied by cytoplasm expulsion, and cell disintegration. Spherulocytes remained intact, while oenocytes rapidly disintegrated. Coronatin-2 produced 80% mortality when injected into G. mellonella at 5 µg larva-1. Further study is warranted to determine the relevance of the acute toxicity of coronatin-2 and its effects on hemocytes in vitro to virulence of C. coronatus against its hosts.

  12. Cholesterol impairment contributes to neuroserpin aggregation

    Science.gov (United States)

    Giampietro, Costanza; Lionetti, Maria Chiara; Costantini, Giulio; Mutti, Federico; Zapperi, Stefano; La Porta, Caterina A. M.

    2017-03-01

    Intraneural accumulation of misfolded proteins is a common feature of several neurodegenerative pathologies including Alzheimer’s and Parkinson’s diseases, and Familial Encephalopathy with Neuroserpin Inclusion Bodies (FENIB). FENIB is a rare disease due to a point mutation in neuroserpin which accelerates protein aggregation in the endoplasmic reticulum (ER). Here we show that cholesterol depletion induced either by prolonged exposure to statins or by inhibiting the sterol reg-ulatory binding-element protein (SREBP) pathway also enhances aggregation of neuroserpin proteins. These findings can be explained considering a computational model of protein aggregation under non-equilibrium conditions, where a decrease in the rate of protein clearance improves aggregation. Decreasing cholesterol in cell membranes affects their biophysical properties, including their ability to form the vesicles needed for protein clearance, as we illustrate by a simple mathematical model. Taken together, these results suggest that cholesterol reduction induces neuroserpin aggregation, even in absence of specific neuroserpin mutations. The new mechanism we uncover could be relevant also for other neurodegenerative diseases associated with protein aggregation.

  13. Effect of protein-surfactant interactions on aggregation of β-lactoglobulin.

    Science.gov (United States)

    Hansted, Jon G; Wejse, Peter L; Bertelsen, Hans; Otzen, Daniel E

    2011-05-01

    The milk protein β-lactoglobulin (βLG) dominates the properties of whey aggregates in food products. Here we use spectroscopic and calorimetric techniques to elucidate how anionic, cationic and non-ionic surfactants interact with bovine βLG and modulate its heat-induced aggregation. Alkyl trimethyl ammonium chlorides (xTAC) strongly promote aggregation, while sodium alkyl sulfates (SxS) and alkyl maltopyranosides (xM) reduce aggregation. Sodium dodecyl sulfate (SDS) binds to non-aggregated βLG in several steps, but reduction of aggregation was associated with the first binding step, which occurs far below the critical micelle concentration. In contrast, micellar concentrations of xMs are required to reduce aggregation. The ranking order for reduction of aggregation (normalized to their tendency to self-associate) was C10-C12>C8>C14 for SxS and C8>C10>C12>C14>C16 for xM. xTAC promote aggregation in the same ranking order as xM reduce it. We conclude that SxS reduce aggregation by stabilizing the protein's ligand-bound state (the melting temperature t(m) increases by up to 10°C) and altering its charge potential. xM monomers also stabilize the protein's ligand-bound state (increasing t(m) up to 6°C) but in the absence of charged head groups this is not sufficient by itself to prevent aggregation. Although micelles of both anionic and non-ionic surfactants destabilize βLG, they also solubilize unfolded protein monomers, leaving them unavailable for protein-protein association and thus inhibiting aggregation. Cationic surfactants promote aggregation by a combination of destabilization and charge neutralization. The food compatible surfactant sodium dodecanoate also inhibited aggregation well below the cmc, suggesting that surfactants may be a practical way to modulate whey protein properties. Copyright © 2011 Elsevier B.V. All rights reserved.

  14. De novo transcriptome sequencing of the Octopus vulgaris hemocytes using Illumina RNA-Seq technology: response to the infection by the gastrointestinal parasite Aggregata octopiana.

    Science.gov (United States)

    Castellanos-Martínez, Sheila; Arteta, David; Catarino, Susana; Gestal, Camino

    2014-01-01

    Octopus vulgaris is a highly valuable species of great commercial interest and excellent candidate for aquaculture diversification; however, the octopus' well-being is impaired by pathogens, of which the gastrointestinal coccidian parasite Aggregata octopiana is one of the most important. The knowledge of the molecular mechanisms of the immune response in cephalopods, especially in octopus is scarce. The transcriptome of the hemocytes of O. vulgaris was de novo sequenced using the high-throughput paired-end Illumina technology to identify genes involved in immune defense and to understand the molecular basis of octopus tolerance/resistance to coccidiosis. A bi-directional mRNA library was constructed from hemocytes of two groups of octopus according to the infection by A. octopiana, sick octopus, suffering coccidiosis, and healthy octopus, and reads were de novo assembled together. The differential expression of transcripts was analysed using the general assembly as a reference for mapping the reads from each condition. After sequencing, a total of 75,571,280 high quality reads were obtained from the sick octopus group and 74,731,646 from the healthy group. The general transcriptome of the O. vulgaris hemocytes was assembled in 254,506 contigs. A total of 48,225 contigs were successfully identified, and 538 transcripts exhibited differential expression between groups of infection. The general transcriptome revealed genes involved in pathways like NF-kB, TLR and Complement. Differential expression of TLR-2, PGRP, C1q and PRDX genes due to infection was validated using RT-qPCR. In sick octopuses, only TLR-2 was up-regulated in hemocytes, but all of them were up-regulated in caecum and gills. The transcriptome reported here de novo establishes the first molecular clues to understand how the octopus immune system works and interacts with a highly pathogenic coccidian. The data provided here will contribute to identification of biomarkers for octopus resistance against

  15. The Silencing of a 14-3-3ɛ Homolog in Tenebrio molitor Leads to Increased Antimicrobial Activity in Hemocyte and Reduces Larval Survivability.

    Science.gov (United States)

    Seo, Gi Won; Jo, Yong Hun; Seong, Jeong Hwan; Park, Ki Beom; Patnaik, Bharat Bhusan; Tindwa, Hamisi; Kim, Sun-Am; Lee, Yong Seok; Kim, Yu Jung; Han, Yeon Soo

    2016-08-20

    The 14-3-3 family of phosphorylated serine-binding proteins acts as signaling molecules in biological processes such as metabolism, division, differentiation, autophagy, and apoptosis. Herein, we report the requirement of 14-3-3ɛ isoform from Tenebrio molitor (Tm14-3-3ɛ) in the hemocyte antimicrobial activity. The Tm14-3-3ɛ transcript is 771 nucleotides in length and encodes a polypeptide of 256 amino acid residues. The protein has the typical 14-3-3 domain, the nuclear export signal (NES) sequence, and the peptide binding residues. The Tm14-3-3ɛ transcript shows a significant three-fold expression in the hemocyte of T. molitor larvae when infected with Escherichia coli Tm14-3-3ɛ silenced larvae show significantly lower survival rates when infected with E. coli. Under Tm14-3-3ɛ silenced condition, a strong antimicrobial activity is elicited in the hemocyte of the host inoculated with E. coli. This suggests impaired secretion of antimicrobial peptides (AMP) into the hemolymph. Furthermore, a reduction in AMP secretion under Tm14-3-3ɛ silenced condition would be responsible for loss in the capacity to kill bacteria and might explain the reduced survivability of the larvae upon E. coli challenge. This shows that Tm14-3-3ɛ is required to maintain innate immunity in T. molitor by enabling antimicrobial secretion into the hemolymph and explains the functional specialization of the isoform.

  16. The Silencing of a 14-3-3ɛ Homolog in Tenebrio molitor Leads to Increased Antimicrobial Activity in Hemocyte and Reduces Larval Survivability

    Directory of Open Access Journals (Sweden)

    Gi Won Seo

    2016-08-01

    Full Text Available The 14-3-3 family of phosphorylated serine-binding proteins acts as signaling molecules in biological processes such as metabolism, division, differentiation, autophagy, and apoptosis. Herein, we report the requirement of 14-3-3ɛ isoform from Tenebrio molitor (Tm14-3-3ɛ in the hemocyte antimicrobial activity. The Tm14-3-3ɛ transcript is 771 nucleotides in length and encodes a polypeptide of 256 amino acid residues. The protein has the typical 14-3-3 domain, the nuclear export signal (NES sequence, and the peptide binding residues. The Tm14-3-3ɛ transcript shows a significant three-fold expression in the hemocyte of T. molitor larvae when infected with Escherichia coli Tm14-3-3ɛ silenced larvae show significantly lower survival rates when infected with E. coli. Under Tm14-3-3ɛ silenced condition, a strong antimicrobial activity is elicited in the hemocyte of the host inoculated with E. coli. This suggests impaired secretion of antimicrobial peptides (AMP into the hemolymph. Furthermore, a reduction in AMP secretion under Tm14-3-3ɛ silenced condition would be responsible for loss in the capacity to kill bacteria and might explain the reduced survivability of the larvae upon E. coli challenge. This shows that Tm14-3-3ɛ is required to maintain innate immunity in T. molitor by enabling antimicrobial secretion into the hemolymph and explains the functional specialization of the isoform.

  17. Aggregation patterns of fetal rat brain cells following exposure to X-irradiation

    International Nuclear Information System (INIS)

    Shoji, R.; Suzuki, K.; Lee, I.P.

    1980-01-01

    In our search for a simplified in vitro test system to assess the teratogenic effects of physical factors, we studied the effects of total maternal body X-irradiation on aggregation patterns of enzymatically isolated fetal rat brain cells and on ultrastructural aggregate changes. The fetal brain cells were derived from day 14 gestation fetuses of pregnant Sprague-Dawley (CD strain) rats exposed to X-irradiation (25 - 200 R) one hour prior to sacrifice. Notable changes in the cell aggregates following X-irradiation included a reduction in cell aggregate size and an increase in number. The frequency of cell aggregates was higher in the treated than in the control group, and the mean diameter of cell aggregates was inversely related to increasing X-irradiation doses. Transmission electron microscopy revealed in isolated cells features of degenerative process which were similar to those found in intact fetal brain lesions caused by maternal X-irradiation. Furthermore, scanning electron microscopy revealed that inhibition of cell aggregation following X-irradiation could probably be attributed to inhibition of membrane filopodia development and a consequent failure of cell aggregates to fuse into a greater cell aggregate mass. These results suggest that the membrane factors which influence cell aggregation may be a useful parameter to assess early effects of X-irradiation-induced brain deformity. Presently, the cell aggregation culture system is being further evaluated as a short term test system for environmental teratogens

  18. Effects of the gelatin plasma substitutes Haemaccel, Plasmagel and Plasmion (Geloplasma) on collagen-, ADP- and adrenaline-induced aggregation of human platelets in vitro.

    Science.gov (United States)

    Stibbe, J; van der Plas, P M; Ong, G L; ten Hoor, F; Nauta, J; de Jong, D S; Krenning-Douma, E; Gomes, M

    1981-01-01

    The effect of some gelatin plasma substitutes (Haemaccel, plasmagel and Plasmion (Geloplasma), which are widely used in Europe) on collagen-, ADP- and adrenaline-induced platelet aggregation in human PRP in vitro was studied under controlled conditions (pH, electrolyte composition). Haemaccel inhibited these aggregations, both in citrated as well as in heparinised PRP, whereas they were enhanced by both Plasmagel and Plasmion as compared to the appropriate control. Increasing teh concentration of the inducer overcame the inhibition by Haemaccel. Haemaccel inhibited, while Plasmion enhanced 14C-serotonin release induced by collagen, ADP or adrenaline. Also in the presence of indomethacin (90 muM) Haemaccel inhibited aggregation induced by high concentrations of collagen and the primary aggregation induced by ADP and adrenaline, while Plasmion enhanced these aggregations induced by ADP and adrenaline, while Plasmion enhanced these aggregations. The inhibition by Haemaccel was not caused by binding of Ca2+ to haemaccel.

  19. Entrapment of Aβ1-40 peptide in unstructured aggregates

    International Nuclear Information System (INIS)

    Corsale, C; Carrotta, R; Mangione, M R; Vilasi, S; Provenzano, A; Bulone, D; San Biagio, P L; Cavallaro, G

    2012-01-01

    Recognizing the complexity of the fibrillogenesis process provides a solid ground for the development of therapeutic strategies aimed at preventing or inhibiting protein-protein aggregation. Under this perspective, it is meaningful to identify the possible aggregation pathways and their relative products. We found that Aβ-peptide dissolved in a pH 7.4 solution at small peptide concentration and low ionic strength forms globular aggregates without typical amyloid β-conformation. ThT binding kinetics was used to monitor aggregate formation. Circular dichroism spectroscopy, AFM imaging, static and dynamic light scattering were used for structural and morphological characterization of the aggregates. They appear stable or at least metastable with respect to fiber growth, therefore appearing as an incidental product in the pathway of fibrillogenesis. (paper)

  20. Pulsed electric field (PEF)-induced aggregation between lysozyme, ovalbumin and ovotransferrin in multi-protein system.

    Science.gov (United States)

    Wu, Li; Zhao, Wei; Yang, Ruijin; Yan, Wenxu

    2015-05-15

    The aggregation of multi-proteins is of great interest in food processing and a good understanding of the formation of aggregates during PEF processing is needed for the application of the process to pasteurize protein-based foods. The aggregates formation of a multi-protein system (containing ovalbumin, ovotransferrin and lysozyme) was studied through turbidity, size exclusion chromatography and SDS-PAGE patterns for interaction studies and binding forces. Results from size exclusion chromatography indicated that there was no soluble aggregates formed during PEF processing. The existence of lysozyme was important to form insoluble aggregates in the chosen ovalbumin solution. The results of SDS-PAGE patterns indicated that lysozyme was prone to precipitate, and was relatively the higher component of aggregates. Citric acid could be effective in inhibiting lysozyme from interacting with other proteins during PEF processing. Blocking the free sulphydryl by N-ethylmaleimide (NEM) did not affect aggregation inhibition. Copyright © 2014 Elsevier Ltd. All rights reserved.

  1. Morulustatin, A Disintegrin that Inhibits ADP-Induced Platelet Aggregation, Isolated from the Mexican Tamaulipan Rock Rattlesnake (Crotalus lepidus morulus)

    Science.gov (United States)

    Borja, Miguel; Galan, Jacob Anthony; Cantu, Esteban; Zugasti-Cruz, Alejandro; Rodríguez-Acosta, Alexis; Lazcano, David; Lucena, Sara; Suntravat, Montamas; Sánchez, y Elda Eliza

    2016-01-01

    The Tamaulipan rock rattlesnake (Crotalus lepidus morulus) is a montane snake that occurs in the humid pine-oak forest and the upper cloud forest of the Sierra Madre Oriental in southwestern Tamaulipas, central Nuevo Leon, and southeastern Coahuila in Mexico. Venom from this rattlesnake was fractionated by High-Performance Liquid Chromatography for the purpose of discovering disintegrin molecules. Disintegrins are non-enzymatic, small molecular weight peptides that interfere with cell-cell and cell-matrix interactions by binding to various cell receptors. Eleven fractions were collected by anion exchange chromatography and pooled into six groups (I, II, III, IV, V, and VI). Proteins of the six groups were analyzed by SDS-PAGE and western blot using antibodies raised against a disintegrin. The antibodies recognized different protein bands in five (II, III, IV, V, and VI) of six groups in a molecular mass range of 7 to 105 kDa. Western blot analysis revealed fewer protein bands in the higher molecular mass range and two bands in the disintegrin weight range in group II compared with the other four groups. Proteins in group II were further separated into nine fractions using reverse phase C18 chromatography. Fraction 4 inhibited platelet aggregation and was named morulustatin, which exhibited a single band with a molecular mass of approximately 7 kDa. Mass spectrometry analysis of fraction 4 revealed the identification of disintegrin peptides LRPGAQCADGLCCDQCR (MH+ 2035.84) and AGEECDCGSPANCCDAATCK (MH+ 2328.82). Morulustatin inhibited ADP-induced platelet aggregation in human whole blood and was concentration-dependent with an IC50 of 89.5 nM ± 12. PMID:28713196

  2. Exploiting BSA to Inhibit the Fibrous Aggregation of Magnetic Nanoparticles under an Alternating Magnetic Field

    Directory of Open Access Journals (Sweden)

    Ning Gu

    2013-03-01

    Full Text Available The alternating magnetic field was discovered to be capable of inducing the fibrous aggregation of magnetic nanoparticles. However, this anisotropic aggregation may be unfavorable for practical applications. Here, we reported that the adsorption of BSA (bovine serum albumin on the surfaces of magnetic nanoparticles can effectively make the fibrous aggregation of γ-Fe2O3 nanoparticles turn into a more isotropic aggregation in the presence of the alternating magnetic field. Also, the heating curves with and without BSA adsorption under different pH conditions were measured to show the influence of the colloidal aggregation states on the collective calorific behavior of magnetic nanoparticles.

  3. Circulating Hemocytes from Larvae of the Japanese Rhinoceros Beetle Allomyrina dichotoma (Linnaeus) (Coleoptera: Scarabaeidae) and the Cellular Immune Response to Microorganisms.

    Science.gov (United States)

    Hwang, Sejung; Bang, Kyeongrin; Lee, Jiae; Cho, Saeyoull

    2015-01-01

    Hemocytes of the last larva of the Japanese rhinoceros beetle A. dichotoma (Linnaeus) (Coleoptera: Scarabaeidae) were classified as granulocytes, plasmatocytes, oenocytoids, spherulocytes, prohemocytes, and adipohemocytes. Among these cell types, only the granulocytes became immunologically activated with obvious morphological changes, displaying large amoeba-like, lobopodia-like, and fan-like structures. In addition, their cytoplasmic granules became larger and greatly increased in number. To explore whether these granules could be immunologically generated as phagosomes, total hemocytes were stained with LysoTracker. Greater than 90% of the granulocytes retained the LysoTracker dye at 4 h post-bacterial infection. In flow cytometry analysis, the red fluorescent signal was highly increased at 4 h post-bacterial infection (60.36%) compared to controls (5.08%), as was confirmed by fluorescent microscopy. After 12 h post-infection, these signals returned to basal levels. The uptake of pathogens by granulocytes rapidly triggered the translocation of the microtubule-associated protein 1 light chain 3 alpha (LC3) to the phagosome, which may result in enhanced pathogen killing.

  4. Circulating Hemocytes from Larvae of the Japanese Rhinoceros Beetle Allomyrina dichotoma (Linnaeus (Coleoptera: Scarabaeidae and the Cellular Immune Response to Microorganisms.

    Directory of Open Access Journals (Sweden)

    Sejung Hwang

    Full Text Available Hemocytes of the last larva of the Japanese rhinoceros beetle A. dichotoma (Linnaeus (Coleoptera: Scarabaeidae were classified as granulocytes, plasmatocytes, oenocytoids, spherulocytes, prohemocytes, and adipohemocytes. Among these cell types, only the granulocytes became immunologically activated with obvious morphological changes, displaying large amoeba-like, lobopodia-like, and fan-like structures. In addition, their cytoplasmic granules became larger and greatly increased in number. To explore whether these granules could be immunologically generated as phagosomes, total hemocytes were stained with LysoTracker. Greater than 90% of the granulocytes retained the LysoTracker dye at 4 h post-bacterial infection. In flow cytometry analysis, the red fluorescent signal was highly increased at 4 h post-bacterial infection (60.36% compared to controls (5.08%, as was confirmed by fluorescent microscopy. After 12 h post-infection, these signals returned to basal levels. The uptake of pathogens by granulocytes rapidly triggered the translocation of the microtubule-associated protein 1 light chain 3 alpha (LC3 to the phagosome, which may result in enhanced pathogen killing.

  5. Aggregation of montmorillonite and organic matter in aqueous media containing artificial seawater

    Directory of Open Access Journals (Sweden)

    Kim Jinwook

    2009-01-01

    Full Text Available Abstract Background The dispersion-aggregation behaviors of suspended colloids in rivers and estuaries are affected by the compositions of suspended materials (i.e., clay minerals vs. organic macromolecules and salinity. Laboratory experiments were conducted to investigate the dispersion and aggregation mechanisms of suspended particles under simulated river and estuarine conditions. The average hydrodynamic diameters of suspended particles (representing degree of aggregation and zeta potential (representing the electrokinetic properties of suspended colloids and aggregates were determined for systems containing suspended montmorillonite, humic acid, and/or chitin at the circumneutral pH over a range of salinity (0 – 7.2 psu. Results The montmorillonite-only system increased the degree of aggregation with salinity increase, as would be expected for suspended colloids whose dispersion-aggregation behavior is largely controlled by the surface electrostatic properties and van der Waals forces. When montmorillonite is combined with humic acid or chitin, the aggregation of montmorillonite was effectively inhibited. The surface interaction energy model calculations reveal that the steric repulsion, rather than the increase in electronegativity, is the primary cause for the inhibition of aggregation by the addition of humic acid or chitin. Conclusion These results help explain the range of dispersion-aggregation behaviors observed in natural river and estuarine systems. It is postulated that the composition of suspended particles, specifically the availability of steric polymers such as those contained in humic acid, determine whether the river suspension is rapidly aggregated and settled or remains dispersed in suspension when it encounters increasingly saline environments of estuaries and oceans.

  6. Dose-dependent platelet stimulation and inhibition induced by anti-PIA1 IgG

    International Nuclear Information System (INIS)

    Ryu, T.; Davis, J.M.; Schwartz, K.A.

    1990-01-01

    The PIA1 antibody produces several clinically distinct and severe thrombocytopenias. Investigations have demonstrated divergent effects on platelet function; prior reports demonstrated inhibition, while a conflicting publication showed platelet activation. We have resolved this conflict using anti-PIA1 IgG produced by a patient with posttransfusion purpura. Relatively low concentrations stimulated platelet aggregation and release of adenosine triphosphate (ATP) whereas high concentrations inhibited platelet function, producing a thrombasthenia-like state. The number of molecules of platelet-associated IgG necessary to initiate aggregation and ATP release (2,086 +/- 556) or produce maximum aggregation (23,420 +/- 3,706) or complete inhibition (63,582 +/- 2654) were measured with a quantitative radiometric assay for bound anti-PIA1. Preincubation of platelets with high concentrations of PIA1 antibody inhibited platelet aggregation with 10 mumol/L adenosine diphosphate and blocked 125I-labeled fibrinogen platelet binding. Platelet activation with nonfibrinogen dependent agonist, 1 U/ml thrombin, was not inhibited by this high concentration of PIA1 IgG. In conclusion, anti-PIAI IgG produces (1) stimulation of platelet aggregation and ATP release that is initiated with 2000 molecules IgG per platelet and is associated with an increase of 125I-fibrinogen binding; (2) conversely, inhibition of platelet aggregation is observed with maximum antibody binding, 63,000 molecules IgG per platelet, and is mediated via a blockade of fibrinogen binding

  7. ROCK and PRK-2 Mediate the Inhibitory Effect of Y-27632 on Polyglutamine Aggregation

    Science.gov (United States)

    Shao, Jieya; Welch, William J.; Diamond, Marc I.

    2009-01-01

    Polyglutamine expansion in huntingtin (Htt) and the androgen receptor (AR) causes untreatable neurodegenerative diseases. Y-27632, a therapeutic lead, reduces Htt and AR aggregation in cultured cells, and Htt-induced neurodegeneration in Drosophila. Y-27632 inhibits both Rho-associated kinases ROCK and PRK-2, making its precise intracellular target uncertain. Over-expression of either kinase increases Htt and AR aggregation. Three ROCK inhibitors (Y-27632, H-1077, HA-1152), and a specific ROCK inhibitory peptide reduce polyglutamine protein aggregation, as does knockdown of ROCK or PRK-2 by RNAi. RNAi also indicates that each kinase is required for the inhibitory effects of Y-27632 to manifest fully. These two actin regulatory kinases are thus involved in polyglutamine aggregation, and their simultaneous inhibition may be an important therapeutic goal. PMID:18423405

  8. Thiols in the alphaIIbbeta3 integrin are necessary for platelet aggregation.

    Science.gov (United States)

    Manickam, Nagaraj; Sun, Xiuhua; Hakala, Kevin W; Weintraub, Susan T; Essex, David W

    2008-07-01

    Sulfhydryl groups of platelet surface proteins are important in platelet aggregation. While p-chloromercuribenzene sulphonate (pCMBS) has been used in most studies on platelet surface thiols, the specific thiol-proteins that pCMBS reacts with to inhibit aggregation have not been well defined. Since the thiol-containing P2Y(12) ADP receptor is involved in most types of platelet aggregation, we used the ADP scavenger apyrase and the P2Y(12) receptor antagonist 2-MeSAMP to examine thiol-dependent reactions in the absence of contributions from this receptor. We provide evidence for a non-P2Y(12) thiol-dependent reaction near the final alphaIIbbeta3-dependent events of aggregation. We then used 3-(N-maleimidylpropionyl)biocytin (MPB) and pCMBS to study thiols in alphaIIbbeta3. As previously reported, disruption of the receptor was required to obtain labelling of thiols with MPB. Specificity of labelling for thiols in the alphaIIb and beta3 subunits was confirmed by identification of the purified proteins by mass spectrometry and by inhibition of labelling with 5,5'-dithiobis-(2-nitrobenzoic acid). In contrast to MPB, pCMBS preferentially reacted with thiols in alphaIIbbeta3 and blocked aggregation under physiological conditions. Similarly, pCMBS preferentially inhibited signalling-independent activation of alphaIIbbeta3 by Mn(2+). Our results suggest that the thiols in alphaIIbbeta3 that are blocked by pCMBS are important in the activation of this integrin.

  9. Identification of expressed genes in cDNA library of hemocytes from the RLO-challenged oyster, Crassostrea ariakensis Gould with special functional implication of three complement-related fragments (CaC1q1, CaC1q2 and CaC3).

    Science.gov (United States)

    Xu, Ting; Xie, Jiasong; Li, Jianming; Luo, Ming; Ye, Shigen; Wu, Xinzhong

    2012-06-01

    A SMARTer™ cDNA library of hemocyte from Rickettsia-like organism (RLO) challenged oyster, Crassostrea ariakensis Gould was constructed. Random clones (400) were selected and single-pass sequenced, resulted in 200 unique sequences containing 96 known genes and 104 unknown genes. The 96 known genes were categorized into 11 groups based on their biological process. Furthermore, we identified and characterized three complement-related fragments (CaC1q1, CaC1q2 and CaC3). Tissue distribution analysis revealed that all of three fragments were ubiquitously expressed in all tissues studied including hemocyte, gills, mantle, digestive glands, gonads and adductor muscle, while the highest level was seen in the hemocyte. Temporal expression profile in the hemocyte monolayers reveled that the mRNA expression levels of three fragments presented huge increase after the RLO incubation at 3 h and 6 h in post-challenge, respectively. And the maximal expression levels at 3 h in post-challenge are about 256, 104 and 64 times higher than the values detected in the control of CaC1q1, CaC1q2 and CaC3, respectively. Copyright © 2012 Elsevier Ltd. All rights reserved.

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

    International Nuclear Information System (INIS)

    Laduca, F.M.; Bell, W.R.; Bettigole, R.E.

    1987-01-01

    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 [ 3 H]serotonin, or alter the dose-responsive binding of 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

  11. The effects of ocean acidification on hemocyte of crab species in Alaska from laboratory experiment studies from 2011-07-01 to 2013-07-06 (NODC Accession 0123400)

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — This archival package contains laboratory experiment data that were collected to examine the effects of ocean acidification on hemocyte of crab species in Alaska....

  12. Light-induced aggregation of microbial exopolymeric substances.

    Science.gov (United States)

    Sun, Luni; Xu, Chen; Zhang, Saijin; Lin, Peng; Schwehr, Kathleen A; Quigg, Antonietta; Chiu, Meng-Hsuen; Chin, Wei-Chun; Santschi, Peter H

    2017-08-01

    Sunlight can inhibit or disrupt the aggregation process of marine colloids via cleavage of high molecular weight compounds into smaller, less stable fragments. In contrast, some biomolecules, such as proteins excreted from bacteria can form aggregates via cross-linking due to photo-oxidation. To examine whether light-induced aggregation can occur in the marine environment, we conducted irradiation experiments on a well-characterized protein-containing exopolymeric substance (EPS) from the marine bacterium Sagitulla stellata. Our results show that after 1 h sunlight irradiation, the turbidity level of soluble EPS was 60% higher than in the dark control. Flow cytometry also confirmed that more particles of larger sized were formed by sunlight. In addition, we determined a higher mass of aggregates collected on filter in the irradiated samples. This suggests light can induce aggregation of this bacterial EPS. Reactive oxygen species hydroxyl radical and peroxide played critical roles in the photo-oxidation process, and salts assisted the aggregation process. The observation that Sagitulla stellata EPS with relatively high protein content promoted aggregation, was in contrast to the case where no significant differences were found in the aggregation of a non-protein containing phytoplankton EPS between the dark and light conditions. This, together with the evidence that protein-to-carbohydrate ratio of aggregates formed under light condition is significantly higher than that formed under dark condition suggest that proteins are likely the important component for aggregate formation. Light-induced aggregation provides new insights into polymer assembly, marine snow formation, and the fate/transport of organic carbon and nitrogen in the ocean. Copyright © 2017 Elsevier Ltd. All rights reserved.

  13. Effects of chlorpyrifos on soil carboxylesterase activity at an aggregate-size scale.

    Science.gov (United States)

    Sanchez-Hernandez, Juan C; Sandoval, Marco

    2017-08-01

    The impact of pesticides on extracellular enzyme activity has been mostly studied on the bulk soil scale, and our understanding of the impact on an aggregate-size scale remains limited. Because microbial processes, and their extracellular enzyme production, are dependent on the size of soil aggregates, we hypothesized that the effect of pesticides on enzyme activities is aggregate-size specific. We performed three experiments using an Andisol to test the interaction between carboxylesterase (CbE) activity and the organophosphorus (OP) chlorpyrifos. First, we compared esterase activity among aggregates of different size spiked with chlorpyrifos (10mgkg -1 wet soil). Next, we examined the inhibition of CbE activity by chlorpyrifos and its metabolite chlorpyrifos-oxon in vitro to explore the aggregate size-dependent affinity of the pesticides for the active site of the enzyme. Lastly, we assessed the capability of CbEs to alleviate chlorpyrifos toxicity upon soil microorganisms. Our principal findings were: 1) CbE activity was significantly inhibited (30-67% of controls) in the microaggregates (1.0mm) compared with the corresponding controls (i.e., pesticide-free aggregates), 2) chlorpyrifos-oxon was a more potent CbE inhibitor than chlorpyrifos; however, no significant differences in the CbE inhibition were found between micro- and macroaggregates, and 3) dose-response relationships between CbE activity and chlorpyrifos concentrations revealed the capability of the enzyme to bind chlorpyrifos-oxon, which was dependent on the time of exposure. This chemical interaction resulted in a safeguarding mechanism against chlorpyrifos-oxon toxicity on soil microbial activity, as evidenced by the unchanged activity of dehydrogenase and related extracellular enzymes in the pesticide-treated aggregates. Taken together, these results suggest that environmental risk assessments of OP-polluted soils should consider the fractionation of soil in aggregates of different size to measure

  14. New Sesquiterpenoids and Anti-Platelet Aggregation Constituents from the Rhizomes of Curcuma zedoaria.

    Science.gov (United States)

    Chen, Jih-Jung; Tsai, Tung-Han; Liao, Hsiang-Ruei; Chen, Li-Chai; Kuo, Yueh-Hsiung; Sung, Ping-Jyun; Chen, Chun-Lin; Wei, Chun-Sheng

    2016-10-17

    Two new sesquiterpenoids-13-hydroxycurzerenone ( 1 ) and 1-oxocurzerenone ( 2 )-have been isolated from the rhizomes of Curcuma zedoaria , together with 13 known compounds ( 3 - 15 ). The structures of two new compounds were determined through spectroscopic and MS analyses. Among the isolated compounds, 13-hydroxycurzerenone ( 1 ), 1-oxocurzerenone ( 2 ), curzerenone ( 3 ), germacrone ( 4 ), curcolone ( 5 ), procurcumenol ( 6 ), ermanin ( 7 ), curcumin ( 8 ), and a mixture of stigmast-4-en-3,6-dione ( 12 ) and stigmasta-4,22-dien-3,6-dione ( 13 ) exhibited inhibition (with inhibition % in the range of 21.28%-67.58%) against collagen-induced platelet aggregation at 100 μM. Compounds 1 , 5 , 7 , 8 , and the mixture of 12 and 13 inhibited arachidonic acid (AA)-induced platelet aggregation at 100 μM with inhibition % in the range of 23.44%-95.36%.

  15. CELLS OVEREXPRESSING HSP27 SHOW ACCELERATED RECOVERY FROM HEAT-INDUCED NUCLEAR-PROTEIN AGGREGATION

    NARCIS (Netherlands)

    KAMPINGA, HH; BRUNSTING, JF; STEGE, GJJ; KONINGS, AWT; LANDRY, J

    1994-01-01

    Protein denaturation/aggregation upon cell exposure to heat shock is a likely cause of cell death. in the nucleus, protein aggregation has often been correlated to inhibition of nuclear located processes and heat-induced cell killing. in Chinese hamster 023 cells made thermotolerant by a prior

  16. Two-Step Amyloid Aggregation: Sequential Lag Phase Intermediates

    Science.gov (United States)

    Castello, Fabio; Paredes, Jose M.; Ruedas-Rama, Maria J.; Martin, Miguel; Roldan, Mar; Casares, Salvador; Orte, Angel

    2017-01-01

    The self-assembly of proteins into fibrillar structures called amyloid fibrils underlies the onset and symptoms of neurodegenerative diseases, such as Alzheimer’s and Parkinson’s. However, the molecular basis and mechanism of amyloid aggregation are not completely understood. For many amyloidogenic proteins, certain oligomeric intermediates that form in the early aggregation phase appear to be the principal cause of cellular toxicity. Recent computational studies have suggested the importance of nonspecific interactions for the initiation of the oligomerization process prior to the structural conversion steps and template seeding, particularly at low protein concentrations. Here, using advanced single-molecule fluorescence spectroscopy and imaging of a model SH3 domain, we obtained direct evidence that nonspecific aggregates are required in a two-step nucleation mechanism of amyloid aggregation. We identified three different oligomeric types according to their sizes and compactness and performed a full mechanistic study that revealed a mandatory rate-limiting conformational conversion step. We also identified the most cytotoxic species, which may be possible targets for inhibiting and preventing amyloid aggregation.

  17. Acetylcholinesterase triggers the aggregation of PrP 106-126

    International Nuclear Information System (INIS)

    Pera, M.; Roman, S.; Ratia, M.; Camps, P.; Munoz-Torrero, D.; Colombo, L.; Manzoni, C.; Salmona, M.; Badia, A.; Clos, M.V.

    2006-01-01

    Acetylcholinesterase (AChE), a senile plaque component, promotes amyloid-β-protein (Aβ) fibril formation in vitro. The presence of prion protein (PrP) in Alzheimer's disease (AD) senile plaques prompted us to assess if AChE could trigger the PrP peptides aggregation as well. Consequently, the efficacy of AChE on the PrP peptide spanning-residues 106-126 aggregation containing a coumarin fluorescence probe (coumarin-PrP 106-126) was studied. Kinetics of coumarin-PrP 106-126 aggregation showed a significant increase of maximum size of aggregates (MSA), which was dependent on AChE concentration. AChE-PrP 106-126 aggregates showed the tinctorial and optical amyloid properties as determined by polarized light and electronic microscopy analysis. A remarkable inhibition of MSA was obtained with propidium iodide, suggesting that AChE triggers PrP 106-126 and Aβ aggregation through a similar mechanism. Huprines (AChE inhibitors) also significantly decreased MSA induced by AChE as well, unveiling the potential interest for some AChE inhibitors as a novel class of potential anti-prion drugs

  18. Structure activity relationship study of curcumin analogues toward the amyloid-beta aggregation inhibitor.

    Science.gov (United States)

    Endo, Hitoshi; Nikaido, Yuri; Nakadate, Mamiko; Ise, Satomi; Konno, Hiroyuki

    2014-12-15

    Inhibition of the amyloid β aggregation process could possibly prevent the onset of Alzheimer's disease. In this article, we report a structure-activity relationship study of curcumin analogues for anti amyloid β aggregation activity. Compound 7, the ideal amyloid β aggregation inhibitor in vitro among synthesized curcumin analogues, has not only potent anti amyloid β aggregation effects, but also water solubility more than 160 times that of curcumin. In addition, new approaches to improve water solubility of curcumin-type compounds are proposed. Copyright © 2014 Elsevier Ltd. All rights reserved.

  19. Gold Nanoparticles and Microwave Irradiation Inhibit Beta-Amyloid Amyloidogenesis

    Directory of Open Access Journals (Sweden)

    Bastus Neus

    2008-01-01

    Full Text Available Abstract Peptide-Gold nanoparticles selectively attached to β-amyloid protein (Aβ amyloidogenic aggregates were irradiated with microwave. This treatment produces dramatic effects on the Aβ aggregates, inhibiting both the amyloidogenesis and the restoration of the amyloidogenic potential. This novel approach offers a new strategy to inhibit, locally and remotely, the amyloidogenic process, which could have application in Alzheimer’s disease therapy. We have studied the irradiation effect on the amyloidogenic process in the presence of conjugates peptide-nanoparticle by transmission electronic microscopy observations and by Thioflavine T assays to quantify the amount of fibrils in suspension. The amyloidogenic aggregates rather than the amyloid fibrils seem to be better targets for the treatment of the disease. Our results could contribute to the development of a new therapeutic strategy to inhibit the amyloidogenic process in Alzheimer’s disease.

  20. Exploring the structural diversity in inhibitors of α-synuclein amyloidogenic folding, aggregation and neurotoxicity

    Science.gov (United States)

    Das, Sukanya; Pukala, Tara L.; Smid, Scott D.

    2018-05-01

    Aggregation of α-Synuclein (αS) protein to amyloid fibrils is a neuropathological hallmark of Parkinson’s disease (PD). Growing evidence suggests that extracellular αS aggregation plays a pivotal role in neurodegeneration found in PD in addition to the intracellular αS aggregates in Lewy bodies (LB). Here, we identified and compared a diverse set of molecules capable of mitigating protein aggregation and exogenous toxicity of αSA53T, a more aggregation-prone αS mutant found in familial PD. For the first time, we investigated the αS anti-amyloid activity of semi-synthetic flavonoid 2', 3', 4' trihydroxyflavone or 2-D08, which was compared with natural flavones myricetin and transilitin, as well as such structurally diverse polyphenols as honokiol and punicalagin. Additionally, two novel synthetic compounds with a dibenzyl imidazolidine scaffold, Compound 1 and Compound 2, were also investigated as they exhibited favourable binding with αSA53T. All seven compounds inhibited αSA53T aggregation as demonstrated by Thioflavin T fluorescence assays, with modified fibril morphology observed by transmission electron microscopy. Ion mobility-mass spectrometry (IM-MS) was used to monitor the structural conversion of native αSA53T into amyloidogenic conformations and all seven compounds preserved the native unfolded conformations of αSA53T following 48 hrs incubation. The presence of each test compound in a 1:2 molar ratio was also shown to inhibit the neurotoxicity of preincubated αSA53T using phaeochromocytoma (PC12) cell viability assays. Among the seven tested compounds 2-D08, honokiol and the synthetic Compound 2 demonstrated the highest inhibition of aggregation, coupled with neuroprotection from preincubated αSA53T in vitro. Molecular docking predicted that all compounds bound near the lysine-rich region of the N-terminus of αSA53T, where the flavonoids and honokiol predominantly interacted with Lys 23. Overall, these findings highlight that i

  1. Protein Folding and Aggregation into Amyloid: The Interference by Natural Phenolic Compounds

    Directory of Open Access Journals (Sweden)

    Massimo Stefani

    2013-06-01

    Full Text Available Amyloid aggregation is a hallmark of several degenerative diseases affecting the brain or peripheral tissues, whose intermediates (oligomers, protofibrils and final mature fibrils display different toxicity. Consequently, compounds counteracting amyloid aggregation have been investigated for their ability (i to stabilize toxic amyloid precursors; (ii to prevent the growth of toxic oligomers or speed that of fibrils; (iii to inhibit fibril growth and deposition; (iv to disassemble preformed fibrils; and (v to favor amyloid clearance. Natural phenols, a wide panel of plant molecules, are one of the most actively investigated categories of potential amyloid inhibitors. They are considered responsible for the beneficial effects of several traditional diets being present in green tea, extra virgin olive oil, red wine, spices, berries and aromatic herbs. Accordingly, it has been proposed that some natural phenols could be exploited to prevent and to treat amyloid diseases, and recent studies have provided significant information on their ability to inhibit peptide/protein aggregation in various ways and to stimulate cell defenses, leading to identify shared or specific mechanisms. In the first part of this review, we will overview the significance and mechanisms of amyloid aggregation and aggregate toxicity; then, we will summarize the recent achievements on protection against amyloid diseases by many natural phenols.

  2. Inhibitory Activities of Antioxidant Flavonoids from Tamarix gallica on Amyloid Aggregation Related to Alzheimer's and Type 2 Diabetes Diseases.

    Science.gov (United States)

    Ben Hmidene, Asma; Hanaki, Mizuho; Murakami, Kazuma; Irie, Kazuhiro; Isoda, Hiroko; Shigemori, Hideyuki

    2017-01-01

    The prevention of amyloid aggregation is promising for the treatment of age-related diseases such as Alzheimer's (AD) and type 2 diabetes (T2D). Ten antioxidant flavonoids isolated from the medicinal halophyte Tamarix gallica were tested for their amyloid aggregation inhibition potential. Glucuronosylated flavonoids show relatively strong inhibitory activity of Amyloid β (Aβ) and human islet amyloid polypeptide (hIAPP) aggregation compared to their aglycone analogs. Structure-activity relationship of the flavonoids suggests that the catechol moiety is important for amyloid aggregation inhibition, while the methylation of the carboxyl group in the glucuronide moiety and of the hydroxyl group in the aglycone flavonoids decreased it.

  3. The use of lithium compounds for inhibiting alkali-aggregate reaction effects in pavement structures

    Science.gov (United States)

    Zapała-Sławeta, J.; Owsiak, Z.

    2018-05-01

    Internal corrosion of concrete caused by the reaction of reactive aggregate with sodium and potassium hydroxides from cement is a threat to the durability of concrete pavements. Traditional methods for reducing the negative effects of the reaction include the use of unreactive aggregates, low alkali cements, mineral additives or chemical admixtures, incorporated during mixing. Lowering the relative humidity of the concrete below 80% is another measure for limiting the destructive reaction. The incorporation of lithium compounds, in particular lithium nitrate and lithium hydroxide, to the concrete mix is a method of limiting alkali-silica reaction effects. The challenge is to reduce the negative effects of aggregate reactivity in members in which the reaction has occurred because the aggregate happened to be reactive. The paper presents ways of limiting the deterioration of ASR-affected concrete in road pavements and other forms of transportation infrastructure, mainly through the use of lithium compounds, i.e. lithium nitrate. Impregnation methods that allow the penetration of lithium ions into the concrete structure were characterized, as was the effectiveness of the solutions applied.

  4. Anaerobic nitrogen turnover by sinking diatom aggregates at varying ambient oxygen levels

    DEFF Research Database (Denmark)

    Stief, Peter; Kamp, Anja; Thamdrup, Bo

    2016-01-01

    nitrate supply. Sinking diatom aggregates can contribute directly to fixed-nitrogen loss in low-oxygen environments in the ocean and vastly expand the ocean volume in which anaerobic nitrogen turnover is possible, despite relatively high ambient oxygen levels. Depending on the extent of intracellular......In the world’s oceans, even relatively low oxygen levels inhibit anaerobic nitrogen cycling by free-living microbes. Sinking organic aggregates, however, might provide oxygen-depleted microbial hotspots in otherwise oxygenated surface waters. Here, we show that sinking diatom aggregates can host...

  5. NABi, a novel β-sheet breaker, inhibitsaggregation and neuronal toxicity: Therapeutic implications for Alzheimer's disease.

    Science.gov (United States)

    Jang, Ja-Young; Rhim, Hyangshuk; Kang, Seongman

    2018-01-01

    Amyloid beta (Aβ) aggregates are an important therapeutic target for Alzheimer's disease (AD), a fatal neurodegenerative disease. To date, AD still remains a big challenge due to no effective treatments. Based on the property that Aβ aggregates have the cross-β-structure, a common structural feature in amyloids, we systemically designed the Aβ-aggregation inhibitor that maintains Aβ-interacting ability but removes toxic part from SOD1 (superoxide dismutase 1)-G93A. We identified NABi (Natural Aβ Binder and Aβ-aggregation inhibitor) composed of β2-3 strands, a novel breaker of Aβ aggregation, which does not self-aggregate and has no cytotoxicity at all. The NABi blocks Aβ-fibril formation in vitro and in vivo and prevents neuronal cell death, a hallmark of AD pathogenesis. Such anti-amyloidogenic properties can provide novel strategies for treating AD. Furthermore, our study provides molecular insights into the design of amyloidogenic inhibitors to cure various neurodegenerative and amyloid-associated diseases, as NABi would regulate aggregation of other toxic β-sheet proteins other than Aβ. Copyright © 2017 Elsevier B.V. All rights reserved.

  6. New Cyclolignans from Origanumglandulosum Active Against b -amyloid Aggregation

    Directory of Open Access Journals (Sweden)

    Abdelkader Basli

    2014-05-01

    Full Text Available Origanum glandulosum Desf is an endemic flavoring herb widely distributed in North Africa that is commonly used in traditional medicine. This oregano species is rich in essential oils but little is known about its phenolic composition. In the present study, a crude extract of O. glandulosum was prepared in order to isolate and investigate its neuroprotective potential to inhibit β-amyloid peptide (Aβ aggregation. The three major compounds of the extract were isolated: rosmarinic acid and two cyclolignans in Origanum genus, globoidnan A and a new derivative named globoidnan B. Rosmarinic acid and globoidnan A showed significant anti-aggregative activity against β amyloid aggregation (IC50 7.0 and 12.0 µM, respectively. In contrast, globoidnan B was found to be less active.

  7. Morphology-Variable Aggregates Prepared from Cholesterol-Containing Amphiphilic Glycopolymers: Their Protein Recognition/Adsorption and Drug Delivery Applications

    Directory of Open Access Journals (Sweden)

    Zhao Wang

    2018-02-01

    Full Text Available In this study, a series of diblock glycopolymers, poly(6-O-methacryloyl-d-galactopyranose-b-poly(6-cholesteryloxyhexyl methacrylate (PMAgala-b-PMAChols, with cholesterol/galactose grafts were prepared through a sequential reversible addition-fragmentation chain transfer (RAFT polymerization and deprotection process. The glycopolymers could self-assemble into aggregates with various morphologies depending on cholesterol/galactose-containing block weight ratios, as determined by transmission electronic microscopy (TEM and dynamic laser light scattering (DLS. In addition, the lectin (Ricinus communis agglutinin II, RCA120 recognition and bovine serum albumin (BSA adsorption of the PMAgala-b-PMAChol aggregates were evaluated. The SK-Hep-1 tumor cell inhibition properties of the PMAgala-b-PMAChol/doxorubicin (DOX complex aggregates were further examined in vitro. Results indicate that the PMAgala-b-PMAChol aggregates with various morphologies showed different interaction/recognition features with RCA120 and BSA. Spherical aggregates (d ≈ 92 nm possessed the highest RCA120 recognition ability and lowest BSA protein adsorption. In addition, the DOX-loaded spherical complex aggregates exhibited a better tumor cell inhibition property than those of nanofibrous complex aggregates. The morphology-variable aggregates derived from the amphiphilic glycopolymers may serve as multifunctional biomaterials with biomolecular recognition and drug delivery features.

  8. Comparative transcriptomic analysis of shrimp hemocytes in response to acute hepatopancreas necrosis disease (AHPND) causing Vibrio parahemolyticus infection.

    Science.gov (United States)

    Zheng, Zhihong; Wang, Fan; Aweya, Jude Juventus; Li, Ruiwei; Yao, Defu; Zhong, Mingqi; Li, Shengkang; Zhang, Yueling

    2018-03-01

    The recent emergence of acute hepatopancreas necrosis disease (AHPND) in shrimps has posed a major challenge in the shrimp aquaculture industry. The Pir toxin proteins carried by some strains of Vibrio parahaemolyticus are believed to play essential roles in the pathogenesis of AHPND. However, few studies have so far explored how the host immune system responds to these bacteria. In this study, AHPND V. parahaemolyticus (with Pir) and non-AHPND V. parahaemolyticus (without Pir) were injected into two groups of shrimps, and the hemocytes collected for comparative transcriptomic analyses. A total of 1064 differentially expressed genes (DEGs) were identified, of which 910 were up-regulated and 154 were down-regulated. Gene Ontology (GO) annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis showed that many DEGs were involved in a number of biological processes such as cellular process, metabolic process and single-organism process in the AHPND V. parahaemolyticus injected group than the non-AHPND V. parahaemolyticus injected group. Among these, major metabolic processes such as carbohydrate metabolism, lipid metabolism and amino acid metabolism were further identified as the major responsive gene groups. We observed that genes involved in cell growth and anti-apoptosis including src, iap2, cas2, cytochrome P450, gst and cytochromecoxidase were strongly activated in the AHPND V. parahaemolyticus group than in the non-AHPND V. parahaemolyticus group. Collectively, our results unveiled that shrimp hemocytes respond to AHPND related strain of Vibrio parahaemolyticus infection at the transcriptional level, which is useful in furthering our understanding of AHPND. Copyright © 2017 Elsevier Ltd. All rights reserved.

  9. Ocean Acidification Affects the Cytoskeleton, Lysozymes, and Nitric Oxide of Hemocytes: A Possible Explanation for the Hampered Phagocytosis in Blood Clams, Tegillarca granosa.

    Science.gov (United States)

    Su, Wenhao; Rong, Jiahuan; Zha, Shanjie; Yan, Maocang; Fang, Jun; Liu, Guangxu

    2018-01-01

    An enormous amount of anthropogenic carbon dioxide (CO 2 ) has been dissolved into the ocean, leading to a lower pH and changes in the chemical properties of seawater, which has been termed ocean acidification (OA). The impacts of p CO 2 -driven acidification on immunity have been revealed recently in various marine organisms. However, the mechanism causing the reduction in phagocytosis still remains unclear. Therefore, the impacts of p CO 2 -driven OA at present and near-future levels (pH values of 8.1, 7.8, and 7.4) on the rate of phagocytosis, the abundance of cytoskeleton components, the levels of nitric oxide (NO), and the concentration and activity of lysozymes (LZM) of hemocytes were investigated in a commercial bivalve species, the blood clam ( Tegillarca granosa ). In addition, the effects of OA on the expression of genes regulating actin skeleton and nitric oxide synthesis 2 ( NOS2 ) were also analyzed. The results obtained showed that the phagocytic rate, cytoskeleton component abundance, concentration and activity of LZM of hemocytes were all significantly reduced after a 2-week exposure to the future OA scenario of a pH of 7.4. On the contrary, a remarkable increase in the concentration of NO compared to that of the control was detected in clams exposed to OA. Furthermore, the expression of genes regulating the actin cytoskeleton and NOS were significantly up-regulated after OA exposure. Though the mechanism causing phagocytosis seemed to be complicated based on the results obtained in the present study and those reported previously, our results suggested that OA may reduce the phagocytosis of hemocytes by (1) decreasing the abundance of cytoskeleton components and therefore hampering the cytoskeleton-mediated process of engulfment, (2) reducing the concentration and activity of LZM and therefore constraining the degradation of the engulfed pathogen through an oxygen-independent pathway, and (3) inducing the production of NO, which may negatively

  10. Oxidative stress and cytotoxicity elicited lipid peroxidation in hemocytes of Bombyx mori larva infested with dipteran parasitoid, Exorista bombycis.

    Science.gov (United States)

    Pooja, Makwana; Pradeep, Appukuttan Nair R; Hungund, Shambhavi P; Sagar, Chandrashekhar; Ponnuvel, Kangayam M; Awasthi, Arvind K; Trivedy, Kanika

    2017-12-20

    Parasitization of silkworm, Bombyx mori by invasive larva of dipteran parasitoid Exorista bombycis caused upto 20% revenue loss in sericulture. The parasitism was successful by suppressing host immune system however mechanism of immune suppression induced by E. bombycis is unknown which is unravelled here. The infestation induced cytotoxic symptoms in host hemocytes, such as vacuolated cytoplasm, porous plasma membrane, indented nuclei with condensed chromatin and dilated RER. One of the markers of necrosis is cell permeabilization, which can be measured as released lactate dehydrogenase (LDH). LDH level showed significantly (Pmori.

  11. Potent inhibition of tau fibrillization with a multivalent ligand

    International Nuclear Information System (INIS)

    Honson, Nicolette S.; Jensen, Jordan R.; Darby, Michael V.; Kuret, Jeff

    2007-01-01

    Small-molecule inhibitors of tau fibrillization are under investigation as tools for interrogating the tau aggregation pathway and as potential therapeutic agents for Alzheimer's disease. Established inhibitors include thiacarbocyanine dyes, which can inhibit recombinant tau fibrillization in the presence of anionic surfactant aggregation inducers. In an effort to increase inhibitory potency, a cyclic bis-thiacarbocyanine molecule containing two thiacarbocyanine moieties was synthesized and characterized with respect to tau fibrillization inhibitory activity by electron microscopy and ligand aggregation state by absorbance spectroscopy. Results showed that the inhibitory activity of the bis-thiacarbocyanine was qualitatively similar to a monomeric cyanine dye, but was more potent with 50% inhibition achieved at ∼80 nM concentration. At all concentrations tested in aqueous solution, the bis-thiacarbocyanine collapsed to form a closed clamshell structure. However, the presence of tau protein selectively stabilized the open conformation. These results suggest that the inhibitory activity of bis-thiacarbocyanine results from multivalency, and reveal a route to more potent tau aggregation inhibitors

  12. Boundary-layer diabatic processes, the virtual effect, and convective self-aggregation

    Science.gov (United States)

    Yang, D.

    2017-12-01

    The atmosphere can self-organize into long-lasting large-scale overturning circulations over an ocean surface with uniform temperature. This phenomenon is referred to as convective self-aggregation and has been argued to be important for tropical weather and climate systems. Here we use a 1D shallow water model and a 2D cloud-resolving model (CRM) to show that boundary-layer diabatic processes are essential for convective self-aggregation. We will show that boundary-layer radiative cooling, convective heating, and surface buoyancy flux help convection self-aggregate because they generate available potential energy (APE), which sustains the overturning circulation. We will also show that evaporative cooling in the boundary layer (cold pool) inhibits convective self-aggregation by reducing APE. Both the shallow water model and CRM results suggest that the enhanced virtual effect of water vapor can lead to convective self-aggregation, and this effect is mainly in the boundary layer. This study proposes new dynamical feedbacks for convective self-aggregation and complements current studies that focus on thermodynamic feedbacks.

  13. The molecular mass of dextran used to modify magnetite nanoparticles affects insulin amyloid aggregation

    International Nuclear Information System (INIS)

    Siposova, Katarina; Pospiskova, Kristyna; Bednarikova, Zuzana; Safarik, Ivo; Safarikova, Mirka; Kubovcikova, Martina; Kopcansky, Peter; Gazova, Zuzana

    2017-01-01

    Protein transformation from its soluble state into amyloid aggregates is associated with amyloid-related diseases. Amyloid deposits of insulin fibrils have been found in the sites of subcutaneous insulin application in patients with prolonged diabetes. Using atomic force microscopy and ThT fluorescence assay we have investigated the interference of insulin amyloid aggregation with superparamagnetic Fe 3 O 4 -based nanoparticles (SPIONs) coated with dextran (DEX); molecular mass of dextran was equal to 15–20, 40 or 70 kDa. The obtained data indicate that all three types of dextran coated nanoparticles (NP-FeDEXs) are able to inhibit insulin fibrillization and to destroy amyloid fibrils. The extent of anti-amyloid activities depends on the properties of NP-FeDEXs, mainly on the size of nanoparticles which is determined by molecular mass of dextran molecules. The most effective inhibiting activity was observed for the smallest nanoparticles coated with 15–20 kDa dextran. Contrary, the highest destroying activity was observed for the largest NP-FeDEX (70 kDa dextran). - Highlights: • Interference of dextran- magnetite nanoparticles with insulin amyloid aggregation. • Nanoparticles inhibited insulin fibrillization and depolymerized insulin amyloid fibrils. • Size of nanoparticles significantly influences their anti-amyloid activities. • The most effective inhibition of insulin amyloid fibrillization was detected for the smallest nanoparticles. • Contrary, DC 50 values decreased with increasing size of nanoparticles.

  14. Syntheses and characterization of novel oxoisoaporphine derivatives as dual inhibitors for cholinesterases and amyloid beta aggregation.

    Science.gov (United States)

    Li, Yan-Ping; Ning, Fang-Xian; Yang, Meng-Bi; Li, Yong-Cheng; Nie, Min-Hua; Ou, Tian-Miao; Tan, Jia-Heng; Huang, Shi-Liang; Li, Ding; Gu, Lian-Quan; Huang, Zhi-Shu

    2011-05-01

    A series of 3-substituted (5c-5f, 6c-6f) and 4-substituted (10a-10g) oxoisoaporphine derivatives were synthesized. It was found that all these synthetic compounds had IC50 values at micro or nano molar range for cholinesterase inhibition, and most of them could inhibit amyloid β (Aβ) self-induced aggregation with inhibition ratio from 31.8% to 57.6%. The structure-activity relationship studies revealed that the derivatives with higher selectivity on AChE also showed better inhibition on Aβ self-induced aggregation. The results from cell toxicity study indicated that most quaternary methiodide salts had higher IC50 values than the corresponding non-quaternary compounds. This study provided potentially important information for further development of oxoisoaporphine derivatives as lead compounds for the treatment of Alzheimer's disease. Copyright © 2011 Elsevier Masson SAS. All rights reserved.

  15. Anti-aggregation action of ultraviolet irradiation on platelet-rich plasma in the presence of antioxidants

    International Nuclear Information System (INIS)

    Roshchupkin, D.I.; Anosov, A.K.; Potapenko, A.Ya.

    1983-01-01

    UV irradiation of platelet-rich plasma (PRP) results in the inhibition of ADP-induced platelet aggregation. This is accounted for by the long-living photoproducts formed in plasma. Platelets destruct these photoproducts in the dark after irradiation. Lipid antioxidants α-tocopherol and BHT administered in PRP before irradiation reduce the anti-aggregation effect of UV light. Lipid photo-peroxidation is supposed to be responsible for the anti-aggregation effect of UV irradiation on platelet-rich plasma. (Auth.)

  16. Anti-aggregation action of ultraviolet irradiation on platelet-rich plasma in the presence of antioxidants

    International Nuclear Information System (INIS)

    Roshchupkin, D.I.; Anosov, A.K.; Potapenko, A.Ya.

    1983-01-01

    UV irradiation of platelet-rich plasma (PRP) results in the inhibition of ADP-induced platelets aggregation. This is accounted for by the long-living photoproducts formed in plasma. Platelets destruct these photoproducts in the dark after irradiation. Lipid antioxidants α-tocopherol and BHT administered in PRP before irradiation reduce the anti-aggregation effect of UV light. Lipid photo-peroxidation is supposed to be responsible for the anti-aggregation effect of UV irradiation on platelet-rich plasma. (Auth.)

  17. Understanding and Mitigating Reservoir Compaction: an Experimental Study on Sand Aggregates

    Science.gov (United States)

    Schimmel, M.; Hangx, S.; Spiers, C. J.

    2016-12-01

    Fossil fuels continue to provide a source for energy, fuels for transport and chemicals for everyday items. However, adverse effects of decades of hydrocarbons production are increasingly impacting society and the environment. Production-driven reduction in reservoir pore pressure leads to a poro-elastic response of the reservoir, and in many occasions to time-dependent compaction (creep) of the reservoir. In turn, reservoir compaction may lead to surface subsidence and could potentially result in induced (micro)seismicity. To predict and mitigate the impact of fluid extraction, we need to understand production-driven reservoir compaction in highly porous siliciclastic rocks and explore potential mitigation strategies, for example, by using compaction-inhibiting injection fluids. As a first step, we investigate the effect of chemical environment on the compaction behaviour of sand aggregates, comparable to poorly consolidated, highly porous sandstones. The sand samples consist of loose aggregates of Beaujean quartz sand, sieved into a grainsize fraction of 180-212 µm. Uniaxial compaction experiments are performed at an axial stress of 35 MPa and temperature of 80°C, mimicking conditions of reservoirs buried at three kilometres depth. The chemical environment during creep is either vacuum-dry or CO2-dry, or fluid-saturated, with fluids consisting of distilled water, acid solution (CO2-saturated water), alkaline solution (pH 9), aluminium solution (pH 3) and solution with surfactants (i.e., AMP). Preliminary results show that compaction of quartz sand aggregates is promoted in a wet environment compared to a dry environment. It is inferred that deformation is controlled by subcritical crack growth when dry and stress corrosion cracking when wet, both resulting in grain failure and subsequent grain rearrangement. Fluids inhibiting these processes, have the potential to inhibit aggregate compaction.

  18. Apyrase activity and adenosine diphosphate induced platelet aggregation inhibition by the salivary gland proteins of Culicoides variipennis, the North American vector of bluetongue viruses.

    Science.gov (United States)

    Pérez de León, A A; Tabachnick, W J

    1996-02-01

    Salivary gland homogenates of Culicoides variipennis, the primary vector of bluetongue (BLU) viruses in North America, were analyzed for apyrase activity. Apyrase (ATP diphosphohydrolase, EC 3.6.1.5) is an anti-hemostatic and anti-inflammatory salivary enzyme of most hematophagous arthropods. The enzyme activity was measured by the release of orthophosphate using ATP, ADP, and AMP as substrates with Ca2+ as the divalent cation. ATPase (11.5 +/- 1 mU/pair of glands), ADPase (7.3 +/- 0.7 mU/pair of glands), and insignificant (P < 0.05) AMPase (0.07 mU/pair of glands) activities were detected in female salivary glands. Male salivary glands contained lower amounts of ATPase and ADPase activity (P < 0.05). The ATPase and ADPase activities were greatest at pH 8.5, and were similarly activated by Mg2+. Molecular sieving HPLC of salivary gland homogenates generated a single peak which coincided with ATPase and ADPase, but no AMPase, activity; the protein has an estimated molecular mass of 35,000 Da. ATPase and ADPase activity, and total protein concentration, were reduced (P < 0.05) in the salivary glands of females after taking a blood meal from a sheep. Salivary gland homogenates also inhibited ADP-induced platelet aggregation in vitro. It is concluded that the salivary ATPase and ADPase activities of C. variipennis reside in one enzyme, and that this enzyme is likely an apyrase. The apyrase activity is thought to be responsible for the inhibition of ADP-induced platelet aggregation, as indicated by the apparent discharge of apyrase from salivary glands into the host during blood feeding. This suggests that apyrase is one of the salivary proteins present in C. variipennis acting as antigens in the development of Culicoides hypersensitivity in ruminants and horses. Apyrase may inhibit an inflammatory response at the feeding site through the subsequent degradation of its end-product, AMP, to adenosine, a potent anti-inflammatory substance, by the ecto-5' nucleotidase

  19. A Protein Aggregation Inhibitor, Leuco-Methylthioninium Bis(Hydromethanesulfonate, Decreases α-Synuclein Inclusions in a Transgenic Mouse Model of Synucleinopathy

    Directory of Open Access Journals (Sweden)

    Karima Schwab

    2018-01-01

    Full Text Available α-Synuclein (α-Syn aggregation is a pathological feature of synucleinopathies, neurodegenerative disorders that include Parkinson’s disease (PD. We have tested whether N,N,N′,N′-tetramethyl-10H-phenothiazine-3,7-diaminium bis(hydromethanesulfonate (leuco-methylthioninium bis(hydromethanesulfonate; LMTM, a tau aggregation inhibitor, affects α-Syn aggregation in vitro and in vivo. Both cellular and transgenic models in which the expression of full-length human α-Syn (h-α-Syn fused with a signal sequence peptide to promote α-Syn aggregation were used. Aggregated α-Syn was observed following differentiation of N1E-115 neuroblastoma cells transfected with h-α-Syn. The appearance of aggregated α-Syn was inhibited by LMTM, with an EC50 of 1.1 μM, with minimal effect on h-α-Syn mRNA levels being observed. Two independent lines of mice (L58 and L62 transgenic for the same fusion protein accumulated neuronal h-α-Syn that, with aging, developed into fibrillary inclusions characterized by both resistance to proteinase K (PK-cleavage and their ability to bind thiazin red. There was a significant decrease in α-Syn-positive neurons in multiple brain regions following oral treatment of male and female mice with LMTM administered daily for 6 weeks at 5 and 15 mg MT/kg. The early aggregates of α-Syn and the late-stage fibrillar inclusions were both susceptible to inhibition by LMTM, a treatment that also resulted in the rescue of movement and anxiety-related traits in these mice. The results suggest that LMTM may provide a potential disease modification therapy in PD and other synucleinopathies through the inhibition of α-Syn aggregation.

  20. Isolation and characterization of two disintegrins inhibiting ADP-induced human platelet aggregation from the venom of Crotalus scutulatus scutulatus (Mohave Rattlesnake)

    International Nuclear Information System (INIS)

    Sanchez, Elda E.; Galan, Jacob A.; Russell, William K.; Soto, Julio G.; Russell, David H.; Perez, John C.

    2006-01-01

    Disintegrins and disintegrin-like proteins are molecules found in the venom of four snake families (Atractaspididae, Elapidae, Viperidae, and Colubridae). The disintegrins are nonenzymatic proteins that inhibit cell-cell interactions, cell-matrix interactions, and signal transduction, and may have potential in the treatment of strokes, heart attacks, cancers, and osteoporosis. Prior to 1983, the venom of Crotalus scutulatus scutulatus (Mohave Rattlesnake) was known to be only neurotoxic; however, now there is evidence that these snakes can contain venom with: (1) neurotoxins; (2) hemorrhagins; and (3) both neurotoxins and hemorrhagins. In this study, two disintegrins, mojastin 1 and mojastin 2, from the venom of a Mohave rattlesnake collected in central Arizona (Pinal County), were isolated and characterized. The disintegrins in these venoms were identified by mass-analyzed laser desorption ionization/time-of-flight/time-of-flight (MALDI/TOF/TOF) mass spectrometry as having masses of 7.436 and 7.636 kDa. Their amino acid sequences are similar to crotratroxin, a disintegrin isolated from the venom of the western diamondback rattlesnake (C. atrox). The amino acid sequence of mojastin 1 was identical to the amino acid sequence of a disintegrin isolated from the venom of the Timber rattlesnake (C. horridus). The disintegrins from the Mohave rattlesnake venom were able to inhibit ADP-induced platelet aggregation in whole human blood both having IC 5 s of 13.8 nM, but were not effective in inhibiting the binding of human urinary bladder carcinoma cells (T24) to fibronectin

  1. Bifenthrin activates homotypic aggregation in human T-cell lines.

    Science.gov (United States)

    Hoffman, Nataly; Tran, Van; Daniyan, Anthony; Ojugbele, Olutosin; Pryor, Stephen C; Bonventre, Josephine A; Flynn, Katherine; Weeks, Benjamin S

    2006-03-01

    Here, we addressed the concern that, despite the lack of overt toxicity, exposure to low levels of the common household pyrethroid pesticide, bifenthrin, could cause harm to the immune system. To do this, we measure the effect of bifenthrin on phytohemagglutinin (PHA) activation of homotypic aggregation in human T-cell lines. The human CD4+ H9, and Jurkat cell lines and the human promonocyte U937 cell line, were exposed to varying concentrations of bifenthrin. Cell viability was determined using the AlmarBlue Toxicity Assay. Concentrations of bifenthrin which did not reduce cell viability were determined and these concentrations were tested for the effect of bifenthrin on PHA-mediated homotypic aggregation. Blocking antibodies to ICAM and LFA-1 were used to disrupt aggregation and a nonspecific IgG was used as a control. Bifenthrin was found to be nontoxic at concentrations ranging from 10(-4) to 10(-13) M. Bifenthrin did not inhibit PHA induced cell aggregation in all cell lines tested. However, at 10(-4) M, bifenthrin to form aggregates stimulated homotypic aggregation in the H9 and Jurkat T-cell lines. The bifenthrin-induced aggregate formation, like that seen with PHA, was blocked by treating the cells with antibodies to either LFA-1 or ICAM. The results here show that bifenthrin activates T-cell function by stimulating ICAM/LFA-1 mediated homotypic aggregation. This data suggests that exposure to bifenthrin, even at "acceptable" limits, can increase the risk for and frequency of inflammatory responses and diseases such as asthma.

  2. The molecular mass of dextran used to modify magnetite nanoparticles affects insulin amyloid aggregation

    Energy Technology Data Exchange (ETDEWEB)

    Siposova, Katarina [Department of Biophysics, Institute of Experimental Physics, Slovak Academy of Sciences, Kosice (Slovakia); Pospiskova, Kristyna [Regional Centre of Advanced Technologies and Materials, Palacky University, Olomouc (Czech Republic); Bednarikova, Zuzana [Department of Biophysics, Institute of Experimental Physics, Slovak Academy of Sciences, Kosice (Slovakia); Department of Biochemistry, Faculty of Science, Safarik University, Kosice (Slovakia); Safarik, Ivo [Regional Centre of Advanced Technologies and Materials, Palacky University, Olomouc (Czech Republic); Department of Nanobiotechnology, Biology Centre, ISB, CAS, Ceske Budejovice (Czech Republic); Safarikova, Mirka [Department of Nanobiotechnology, Biology Centre, ISB, CAS, Ceske Budejovice (Czech Republic); Kubovcikova, Martina; Kopcansky, Peter [Department of Magnetism, Institute of Experimental Physics, Slovak Academy of Sciences, Kosice (Slovakia); Gazova, Zuzana, E-mail: gazova@saske.sk [Department of Biophysics, Institute of Experimental Physics, Slovak Academy of Sciences, Kosice (Slovakia)

    2017-04-01

    Protein transformation from its soluble state into amyloid aggregates is associated with amyloid-related diseases. Amyloid deposits of insulin fibrils have been found in the sites of subcutaneous insulin application in patients with prolonged diabetes. Using atomic force microscopy and ThT fluorescence assay we have investigated the interference of insulin amyloid aggregation with superparamagnetic Fe{sub 3}O{sub 4}-based nanoparticles (SPIONs) coated with dextran (DEX); molecular mass of dextran was equal to 15–20, 40 or 70 kDa. The obtained data indicate that all three types of dextran coated nanoparticles (NP-FeDEXs) are able to inhibit insulin fibrillization and to destroy amyloid fibrils. The extent of anti-amyloid activities depends on the properties of NP-FeDEXs, mainly on the size of nanoparticles which is determined by molecular mass of dextran molecules. The most effective inhibiting activity was observed for the smallest nanoparticles coated with 15–20 kDa dextran. Contrary, the highest destroying activity was observed for the largest NP-FeDEX (70 kDa dextran). - Highlights: • Interference of dextran- magnetite nanoparticles with insulin amyloid aggregation. • Nanoparticles inhibited insulin fibrillization and depolymerized insulin amyloid fibrils. • Size of nanoparticles significantly influences their anti-amyloid activities. • The most effective inhibition of insulin amyloid fibrillization was detected for the smallest nanoparticles. • Contrary, DC{sub 50} values decreased with increasing size of nanoparticles.

  3. Interactions of cationic polystyrene nanoparticles with marine bivalve hemocytes in a physiological environment: Role of soluble hemolymph proteins

    Energy Technology Data Exchange (ETDEWEB)

    Canesi, Laura, E-mail: Laura.Canesi@unige.it [Dept. of Earth, Environmental and Life Sciences – DISTAV, University of Genoa (Italy); Ciacci, Caterina [Dept. of Biomolecular Sciences – DIBS, University of Urbino (Italy); Fabbri, Rita; Balbi, Teresa [Dept. of Earth, Environmental and Life Sciences – DISTAV, University of Genoa (Italy); Salis, Annalisa; Damonte, Gianluca [Centre of Excellence for Biomedical Research – CEBR, University of Genoa (Italy); Cortese, Katia [Department of Experimental Medicine – DIMES, University of Genoa (Italy); Caratto, Valentina [Dept. of Earth, Environmental and Life Sciences – DISTAV, University of Genoa (Italy); Monopoli, Marco P. [Centre for BioNanoInteractions, School of Chemistry and Chemical Biology, University College Dublin (Ireland); Department of Pharmaceutical and Medical Chemistry, Royal College of Surgeons, 123 St. Stephen Green, Dublin (Ireland); Dawson, Kenneth [Centre for BioNanoInteractions, School of Chemistry and Chemical Biology, University College Dublin (Ireland); Bergami, Elisa; Corsi, Ilaria [Dept. of Physical, Earth and Environmental Sciences, University of Siena (Italy)

    2016-10-15

    The bivalve Mytilus galloprovincialis has proven as a suitable model invertebrate for evaluating the potential impact of nanoparticles (NPs) in the marine environment. In particular, in mussels, the immune system represents a sensitive target for different types of NPs. In environmental conditions, both NP intrinsic properties and those of the receiving medium will affect particle behavior and consequent bioavailability/uptake/toxicity. However, the evaluation of the biological effects of NPs requires additional understanding of how, once within the organism, NPs interact at the molecular level with cells in a physiological environment. In mammalian systems, different NPs associate with serum soluble components, organized into a “protein corona”, which affects particle interactions with target cells. However, no information is available so far on the interactions of NPs with biological fluids of aquatic organisms. In this work, the influence of hemolymph serum (HS) on the in vitro effects of amino modified polystyrene NPs (PS-NH{sub 2}) on Mytilus hemocytes was investigated. Hemocytes were incubated with PS-NH{sub 2} suspensions in HS (1, 5 and 50 µg/mL) and the results were compared with those obtained in ASW medium. Cell functional parameters (lysosomal membrane stability, oxyradical production, phagocytosis) were evaluated, and morphological changes were investigated by TEM. The activation state of the signalling components involved in Mytilus immune response (p38 MAPK and PKC) was determined. The results show that in the presence of HS, PS-NH{sub 2} increased cellular damage and ROS production with respect to ASW medium. The effects were apparently mediated by disregulation of p38 MAPK signalling. The formation of a PS-NH{sub 2}-protein corona in HS was investigated by centrifugation, and 1D- gel electrophoresis and nano-HPLC-ESI-MS/MS. The results identified the Putative C1q domain containing protein (MgC1q6) as the only component of the PS-NH{sub 2} hard

  4. Interactions of cationic polystyrene nanoparticles with marine bivalve hemocytes in a physiological environment: Role of soluble hemolymph proteins

    International Nuclear Information System (INIS)

    Canesi, Laura; Ciacci, Caterina; Fabbri, Rita; Balbi, Teresa; Salis, Annalisa; Damonte, Gianluca; Cortese, Katia; Caratto, Valentina; Monopoli, Marco P.; Dawson, Kenneth; Bergami, Elisa; Corsi, Ilaria

    2016-01-01

    The bivalve Mytilus galloprovincialis has proven as a suitable model invertebrate for evaluating the potential impact of nanoparticles (NPs) in the marine environment. In particular, in mussels, the immune system represents a sensitive target for different types of NPs. In environmental conditions, both NP intrinsic properties and those of the receiving medium will affect particle behavior and consequent bioavailability/uptake/toxicity. However, the evaluation of the biological effects of NPs requires additional understanding of how, once within the organism, NPs interact at the molecular level with cells in a physiological environment. In mammalian systems, different NPs associate with serum soluble components, organized into a “protein corona”, which affects particle interactions with target cells. However, no information is available so far on the interactions of NPs with biological fluids of aquatic organisms. In this work, the influence of hemolymph serum (HS) on the in vitro effects of amino modified polystyrene NPs (PS-NH 2 ) on Mytilus hemocytes was investigated. Hemocytes were incubated with PS-NH 2 suspensions in HS (1, 5 and 50 µg/mL) and the results were compared with those obtained in ASW medium. Cell functional parameters (lysosomal membrane stability, oxyradical production, phagocytosis) were evaluated, and morphological changes were investigated by TEM. The activation state of the signalling components involved in Mytilus immune response (p38 MAPK and PKC) was determined. The results show that in the presence of HS, PS-NH 2 increased cellular damage and ROS production with respect to ASW medium. The effects were apparently mediated by disregulation of p38 MAPK signalling. The formation of a PS-NH 2 -protein corona in HS was investigated by centrifugation, and 1D- gel electrophoresis and nano-HPLC-ESI-MS/MS. The results identified the Putative C1q domain containing protein (MgC1q6) as the only component of the PS-NH 2 hard protein corona in

  5. Opposed Effects of Dityrosine Formation in Soluble and Aggregated α-Synuclein on Fibril Growth.

    Science.gov (United States)

    Wördehoff, Michael M; Shaykhalishahi, Hamed; Groß, Luca; Gremer, Lothar; Stoldt, Matthias; Buell, Alexander K; Willbold, Dieter; Hoyer, Wolfgang

    2017-10-13

    Parkinson's disease is the second most common neurodegenerative disease. It is characterized by aggregation of the protein α-synuclein (α-syn) in Lewy bodies, mitochondrial dysfunction, and increased oxidative stress in the substantia nigra. Oxidative stress leads to several modifications of biomolecules including dityrosine (DiY) crosslinking in proteins, which has recently been detected in α-syn in Lewy bodies from Parkinson's disease patients. Here we report that α-syn is highly susceptible to ultraviolet-induced DiY formation. We investigated DiY formation of α-syn and nine tyrosine-to-alanine mutants and monitored its effect on α-syn fibril formation in vitro. Ultraviolet irradiation of intrinsically disordered α-syn generates DiY-modified monomers and dimers, which inhibit fibril formation of unmodified α-syn by interfering with fibril elongation. The inhibition depends on both the DiY group and its integration into α-syn. When preformed α-syn fibrils are crosslinked by DiY formation, they gain increased resistance to denaturation. DiY-stabilized α-syn fibrils retain their high seeding efficiency even after being exposed to denaturant concentrations that completely depolymerize non-crosslinked seeds. Oxidative stress-associated DiY crosslinking of α-syn therefore entails two opposing effects: (i) inhibition of aggregation by DiY-modified monomers and dimers, and (ii) stabilization of fibrillar aggregates against potential degradation mechanisms, which can lead to promotion of aggregation, especially in the presence of secondary nucleation. Copyright © 2017 The Author(s). Published by Elsevier Ltd.. All rights reserved.

  6. Aggregation in thin-film silver: Induced by chlorine and inhibited by alloying with two dopants

    International Nuclear Information System (INIS)

    Koike, Katsuhiko; Shimada, Koichi; Fukuda, Shin

    2009-01-01

    The Ag aggregation mechanism triggered by chlorine (Cl) is discussed. The frontier orbital theory by K. Fukui is applied in order to determine the growing point in the silver (Ag) cluster. Ag in the thin-film silver would grow to Ag n Cl and stack, triggered by Cl from the outside according to the mechanism described. This would lead to an aggregate with a high Ag density. It is suggested that this would be the generating mechanism of the silver-gray aggregate consisting mostly of Ag, which is generated by exposing it to Cl. Two tactics in order to prevent restrain aggregation induced by Cl according to the mechanism are proposed. Tactic 1 is a restraining of structure change to a plane in the process of Ag 6 Cl + Ag → Ag 7 Cl. Tactic 2 is the trapping of Cl before it generates a bond to Ag. The ability of the two combined dopants with the abilities of tactics 1 and 2, such as in an Ag alloy including palladium and copper (APC), and including neodymium and gold (ANA) is expected to be very high. The aggregation resistance of an Ag alloy including two dopants is evaluated by a salt water immersion test. The APC and ANA demonstrated a very high resistance to Cl, because of the combination of the dopants working with tactic 1 (Pd, Au) and tactic 2 (Cu, Nd). The multilayer sputter coating with an ANA layer demonstrated a very interesting profile where the light transmittance and the electrical sheet resistance are almost the same as the multilayer sputter coating with a pure Ag. The multilayer sputter coating with AIS also demonstrates a very interesting profile, where the light transmittance is higher than the multilayer sputter coating with a pure Ag.

  7. Systematic development of small molecules to inhibit specific microscopic steps of Aβ42 aggregation in Alzheimer's disease.

    Science.gov (United States)

    Habchi, Johnny; Chia, Sean; Limbocker, Ryan; Mannini, Benedetta; Ahn, Minkoo; Perni, Michele; Hansson, Oskar; Arosio, Paolo; Kumita, Janet R; Challa, Pavan Kumar; Cohen, Samuel I A; Linse, Sara; Dobson, Christopher M; Knowles, Tuomas P J; Vendruscolo, Michele

    2017-01-10

    The aggregation of the 42-residue form of the amyloid-β peptide (Aβ42) is a pivotal event in Alzheimer's disease (AD). The use of chemical kinetics has recently enabled highly accurate quantifications of the effects of small molecules on specific microscopic steps in Aβ42 aggregation. Here, we exploit this approach to develop a rational drug discovery strategy against Aβ42 aggregation that uses as a read-out the changes in the nucleation and elongation rate constants caused by candidate small molecules. We thus identify a pool of compounds that target specific microscopic steps in Aβ42 aggregation. We then test further these small molecules in human cerebrospinal fluid and in a Caenorhabditis elegans model of AD. Our results show that this strategy represents a powerful approach to identify systematically small molecule lead compounds, thus offering an appealing opportunity to reduce the attrition problem in drug discovery.

  8. The molecular chaperone α-crystallin inhibits UV-induced protein aggregation

    International Nuclear Information System (INIS)

    Borkman, R.F.; Knight, Grady; Obi, Bettie

    1996-01-01

    Solutions of γ-crystallin, and various enzymes, at neutral pH and 24-26 o C, became turbid upon exposure to UV radiation at 295 or 308 nm. SDS-PAGE analysis revealed interchain cross-linking and aggregate formation compared to dark control solutions as reported previously. When α-crystallin was added to the protein solutions in stoichiometric amounts. UV irradiation resulted in significantly less turbidity than in the absence of α-crystallin. For example, addition of 0.5 mg of α-crystallin to 0.5 mg of γ-crystallin in 1.0 ml solution yielded only 25% of the turbidity seen in the absence of α-crystallin. Addition of 2.0 mg of α-crystallin resulted in 20% of the turbidity. Given the molecular weights of α- and γ-crystallin (about 800 kDa and 20 kDa, respectively), A γ/α 1:1 weight ratio corresponds to a 40:1 molar ratio, and a γ-/α 1:4 weight ratio corresponds to a 10:1 molar ratio. Hence, the molar ratio of α-crystallin needed to effectively protect γ-crystallin from photochemical opacification was γ/α = n:1, where n was in the range 10-40. In terms of subunits, this ratio is γ/α = 1:m, where m = 1-4. Thus, each γ-crystallin molecule needs 1-4 α subunits for protection. Similar stoichiometries were observed for protection of the other proteins studied. The protection stems in part from screening of UV radiation by α-crystallin but more importantly from a chaperone effect analogous to that seen in thermal aggregation experiments. (author)

  9. Serratia marcescens Suppresses Host Cellular Immunity via the Production of an Adhesion-inhibitory Factor against Immunosurveillance Cells*

    Science.gov (United States)

    Ishii, Kenichi; Adachi, Tatsuo; Hamamoto, Hiroshi; Sekimizu, Kazuhisa

    2014-01-01

    Injection of a culture supernatant of Serratia marcescens into the bloodstream of the silkworm Bombyx mori increased the number of freely circulating immunosurveillance cells (hemocytes). Using a bioassay with live silkworms, serralysin metalloprotease was purified from the culture supernatant and identified as the factor responsible for this activity. Serralysin inhibited the in vitro attachment of both silkworm hemocytes and murine peritoneal macrophages. Incubation of silkworm hemocytes or murine macrophages with serralysin resulted in degradation of the cellular immune factor BmSPH-1 or calreticulin, respectively. Furthermore, serralysin suppressed in vitro phagocytosis of bacteria by hemocytes and in vivo bacterial clearance in silkworms. Disruption of the ser gene in S. marcescens attenuated its host killing ability in silkworms and mice. These findings suggest that serralysin metalloprotease secreted by S. marcescens suppresses cellular immunity by decreasing the adhesive properties of immunosurveillance cells, thereby contributing to bacterial pathogenesis. PMID:24398686

  10. Serratia marcescens suppresses host cellular immunity via the production of an adhesion-inhibitory factor against immunosurveillance cells.

    Science.gov (United States)

    Ishii, Kenichi; Adachi, Tatsuo; Hamamoto, Hiroshi; Sekimizu, Kazuhisa

    2014-02-28

    Injection of a culture supernatant of Serratia marcescens into the bloodstream of the silkworm Bombyx mori increased the number of freely circulating immunosurveillance cells (hemocytes). Using a bioassay with live silkworms, serralysin metalloprotease was purified from the culture supernatant and identified as the factor responsible for this activity. Serralysin inhibited the in vitro attachment of both silkworm hemocytes and murine peritoneal macrophages. Incubation of silkworm hemocytes or murine macrophages with serralysin resulted in degradation of the cellular immune factor BmSPH-1 or calreticulin, respectively. Furthermore, serralysin suppressed in vitro phagocytosis of bacteria by hemocytes and in vivo bacterial clearance in silkworms. Disruption of the ser gene in S. marcescens attenuated its host killing ability in silkworms and mice. These findings suggest that serralysin metalloprotease secreted by S. marcescens suppresses cellular immunity by decreasing the adhesive properties of immunosurveillance cells, thereby contributing to bacterial pathogenesis.

  11. Shear-induced aggregation or disaggregation in edible oils: Models, computer simulation, and USAXS measurements

    Science.gov (United States)

    Townsend, B.; Peyronel, F.; Callaghan-Patrachar, N.; Quinn, B.; Marangoni, A. G.; Pink, D. A.

    2017-12-01

    The effects of shear upon the aggregation of solid objects formed from solid triacylglycerols (TAGs) immersed in liquid TAG oils were modeled using Dissipative Particle Dynamics (DPD) and the predictions compared to experimental data using Ultra-Small Angle X-ray Scattering (USAXS). The solid components were represented by spheres interacting via attractive van der Waals forces and short range repulsive forces. A velocity was applied to the liquid particles nearest to the boundary, and Lees-Edwards boundary conditions were used to transmit this motion to non-boundary layers via dissipative interactions. The shear was created through the dissipative forces acting between liquid particles. Translational diffusion was simulated, and the Stokes-Einstein equation was used to relate DPD length and time scales to SI units for comparison with USAXS results. The SI values depended on how large the spherical particles were (250 nm vs. 25 nm). Aggregation was studied by (a) computing the Structure Function and (b) quantifying the number of pairs of solid spheres formed. Solid aggregation was found to be enhanced by low shear rates. As the shear rate was increased, a transition shear region was manifested in which aggregation was inhibited and shear banding was observed. Aggregation was inhibited, and eventually eliminated, by further increases in the shear rate. The magnitude of the transition region shear, γ˙ t, depended on the size of the solid particles, which was confirmed experimentally.

  12. Modulation of invasive phenotype by interstitial pressure-driven convection in aggregates of human breast cancer cells.

    Directory of Open Access Journals (Sweden)

    Joe Tien

    Full Text Available This paper reports the effect of elevated pressure on the invasive phenotype of patterned three-dimensional (3D aggregates of MDA-MB-231 human breast cancer cells. We found that the directionality of the interstitial pressure profile altered the frequency of invasion by cells located at the surface of an aggregate. In particular, application of pressure at one end of an aggregate suppressed invasion at the opposite end. Experimental alteration of the configuration of cell aggregates and computational modeling of the resulting flow and solute concentration profiles revealed that elevated pressure inhibited invasion by altering the chemical composition of the interstitial fluid near the surface of the aggregate. Our data reveal a link between hydrostatic pressure, interstitial convection, and invasion.

  13. Star Polymers Reduce Islet Amyloid Polypeptide Toxicity via Accelerated Amyloid Aggregation.

    Science.gov (United States)

    Pilkington, Emily H; Lai, May; Ge, Xinwei; Stanley, William J; Wang, Bo; Wang, Miaoyi; Kakinen, Aleksandr; Sani, Marc-Antonie; Whittaker, Michael R; Gurzov, Esteban N; Ding, Feng; Quinn, John F; Davis, Thomas P; Ke, Pu Chun

    2017-12-11

    Protein aggregation into amyloid fibrils is a ubiquitous phenomenon across the spectrum of neurodegenerative disorders and type 2 diabetes. A common strategy against amyloidogenesis is to minimize the populations of toxic oligomers and protofibrils by inhibiting protein aggregation with small molecules or nanoparticles. However, melanin synthesis in nature is realized by accelerated protein fibrillation to circumvent accumulation of toxic intermediates. Accordingly, we designed and demonstrated the use of star-shaped poly(2-hydroxyethyl acrylate) (PHEA) nanostructures for promoting aggregation while ameliorating the toxicity of human islet amyloid polypeptide (IAPP), the peptide involved in glycemic control and the pathology of type 2 diabetes. The binding of PHEA elevated the β-sheet content in IAPP aggregates while rendering a new morphology of "stelliform" amyloids originating from the polymers. Atomistic molecular dynamics simulations revealed that the PHEA arms served as rodlike scaffolds for IAPP binding and subsequently accelerated IAPP aggregation by increased local peptide concentration. The tertiary structure of the star nanoparticles was found to be essential for driving the specific interactions required to impel the accelerated IAPP aggregation. This study sheds new light on the structure-toxicity relationship of IAPP and points to the potential of exploiting star polymers as a new class of therapeutic agents against amyloidogenesis.

  14. Evaluation of the effects of several zoanthamine-type alkaloids on the aggregation of human platelets.

    Science.gov (United States)

    Villar, Rosa M; Gil-Longo, José; Daranas, Antonio H; Souto, María L; Fernández, José J; Peixinho, Solange; Barral, Miguel A; Santafé, Gilmar; Rodríguez, Jaime; Jiménez, Carlos

    2003-05-15

    Ten zoanthamine-type alkaloids from two marine zoanthids belonging to the Zoanthus genus (Zoanthus nymphaeus and Zoanthus sp.) along with one semisynthetic derivative were evaluated for their antiplatelet activities on human platelet aggregation induced by several stimulating agents. 11-Hydroxyzoanthamine (11) and a synthetic derivative of norzoanthamine (16) showed strong inhibition against thrombin-, collagen- and arachidonic acid-induced aggregation, zoanthenol (15) displayed a selective inhibitory activity induced by collagen, while zoanthaminone (10) behaved as a potent aggregant agent. These evaluations allowed us to deduce several structure-activity relationships and suggest some mechanisms of action for this type of compounds.

  15. Platelet inhibition by nitrite is dependent on erythrocytes and deoxygenation.

    Directory of Open Access Journals (Sweden)

    Sirada Srihirun

    Full Text Available 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.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.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.

  16. Influence of Aluminium and EGCG on Fibrillation and Aggregation of Human Islet Amyloid Polypeptide

    Directory of Open Access Journals (Sweden)

    Zhi-Xue Xu

    2016-01-01

    Full Text Available The abnormal fibrillation of human islet amyloid polypeptide (hIAPP has been implicated in the development of type II diabetes. Aluminum is known to trigger the structural transformation of many amyloid proteins and induce the formation of toxic aggregate species. The (−-epigallocatechin gallate (EGCG is considered capable of binding both metal ions and amyloid proteins with inhibitory effect on the fibrillation of amyloid proteins. However, the effect of Al(III/EGCG complex on hIAPP fibrillation is unclear. In the present work, we sought to view insight into the structures and properties of Al(III and EGCG complex by using spectroscopic experiments and quantum chemical calculations and also investigated the influence of Al(III and EGCG on hIAPP fibrillation and aggregation as well as their combined interference on this process. Our studies demonstrated that Al(III could promote fibrillation and aggregation of hIAPP, while EGCG could inhibit the fibrillation of hIAPP and lead to the formation of hIAPP amorphous aggregates instead of the ordered fibrils. Furthermore, we proved that the Al(III/EGCG complex in molar ratio of 1 : 1 as Al(EGCG(H2O2 could inhibit the hIAPP fibrillation more effectively than EGCG alone. The results provide the invaluable reference for the new drug development to treat type II diabetes.

  17. Effect of cocoa products and flavanols on platelet aggregation in humans: a systematic review.

    Science.gov (United States)

    Peluso, Ilaria; Palmery, Maura; Serafini, Mauro

    2015-07-01

    Previous evidence suggested an active role of cocoa products and flavanols in modulating platelet aggregation. However, cocoa flavanols are characterized by a low bioavailability that can deeply affect their presence in biological fluids and raise questions on their biological effect in humans. We performed a systematic search on Medline, Embase, Cochrane and ProQuest databases, until April 2015, on the effect of cocoa products on platelet aggregation in human intervention studies. We identified 13 interventions, of which only five involved repeated administration. Different effects were observed on the basis of the platelet aggregation test used, whereas neither a longer duration of treatment nor a higher dose was associated with a higher inhibition of platelet aggregation. In conclusion, the reviewed results suggest that consumption of cocoa products in bolus administration positively affects platelet aggregation in both healthy subjects and diseased patients. On the other hand, more evidence is required in order to assess the effect of long-term cocoa product ingestion and to identify the bioactive components involved.

  18. Inhibition of platelet aggregation and thrombosis by indole alkaloids isolated from the edible insect Protaetia brevitarsis seulensis (Kolbe).

    Science.gov (United States)

    Lee, JungIn; Lee, Wonhwa; Kim, Mi-Ae; Hwang, Jae Sam; Na, MinKyun; Bae, Jong-Sup

    2017-06-01

    Protaetia brevitarsis seulensis (Kolbe) has been temporarily registered as a food material by the Ministry of Food and Drug Safety of Korea (MFDS). The current study aimed to discover small antithrombotic molecules from this edible insect. Five indole alkaloids, 5-hydroxyindolin-2-one (1), (1R,3S)-1-methyl-1,2,3,4-tetrahydro-β-carboline-3-carboxylic acid (2), (1S,3S)-1-methyl-1,2,3,4-tetrahydro-β-carboline-3-carboxylic acid (3), (3S)-1,2,3,4-tetrahydro-β-carboline-3-carboxylic acid (4) and L-tryptophan (5), were isolated from the insect. Among them, compounds 1 and 2 prolonged aPTT and PT and impaired thrombin and FXa generation on HUVEC surface. Moreover, these compounds inhibited platelet aggregation. Antithrombotic effects of compounds 1 and 2 were further confirmed in pre-clinical models of pulmonary embolism and arterial thrombosis. Collectively, these results demonstrated that compounds 1 and 2 could be effective antithrombotic agents and serve as new scaffolds for the development of antithrombotic drug. © 2016 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

  19. Anaerobic Nitrogen Turnover by Sinking Diatom Aggregates at Varying Ambient Oxygen Levels

    Directory of Open Access Journals (Sweden)

    Peter eStief

    2016-02-01

    Full Text Available In the world’s oceans, even relatively low oxygen (O2 levels inhibit anaerobic nitrogen cycling by free-living microbes. Sinking organic aggregates, however, might provide oxygen-depleted microbial hotspots in otherwise oxygenated surface waters. Here we show that sinking diatom aggregates can host anaerobic nitrogen cycling at ambient O2 levels well above the hypoxic threshold. Aggregates were produced from the ubiquitous diatom Skeletonema marinoi and the natural microbial community of seawater. Microsensor profiling through the center of sinking aggregates revealed internal anoxia at ambient 40% air saturation (~100 µmol O2 L-1 and below. Accordingly, anaerobic nitrate turnover inside the aggregates was evident within this range of ambient O2 levels. In incubations with 15N-labeled nitrate, individual Skeletonema aggregates produced NO2- (up to 10.7 nmol N h-1 per aggregate, N2 (up to 7.1 nmol N h-1, NH4+ (up to 2.0 nmol N h-1, and N2O (up to 0.2 nmol N h-1. Intriguingly, nitrate stored inside the diatom cells served as an additional, internal nitrate source for N2 production, which may partially uncouple anaerobic nitrate turnover by diatom aggregates from direct ambient nitrate supply. Sinking diatom aggregates can contribute directly to fixed-nitrogen loss in low-oxygen environments in the ocean and vastly expand the ocean volume in which anaerobic nitrogen turnover is possible, despite relatively high ambient O2 levels. Depending on the extent of intracellular nitrate consumption during the sinking process, diatom aggregates may also be involved in the long-distance export of nitrate to the deep ocean.

  20. Aspirin-Mediated Acetylation Protects Against Multiple Neurodegenerative Pathologies by Impeding Protein Aggregation.

    Science.gov (United States)

    Ayyadevara, Srinivas; Balasubramaniam, Meenakshisundaram; Kakraba, Samuel; Alla, Ramani; Mehta, Jawahar L; Shmookler Reis, Robert J

    2017-12-10

    Many progressive neurological disorders, including Alzheimer's disease (AD), Huntington's disease, and Parkinson's disease (PD), are characterized by accumulation of insoluble protein aggregates. In prospective trials, the cyclooxygenase inhibitor aspirin (acetylsalicylic acid) reduced the risk of AD and PD, as well as cardiovascular events and many late-onset cancers. Considering the role played by protein hyperphosphorylation in aggregation and neurodegenerative diseases, and aspirin's known ability to donate acetyl groups, we asked whether aspirin might reduce both phosphorylation and aggregation by acetylating protein targets. Aspirin was substantially more effective than salicylate in reducing or delaying aggregation in human neuroblastoma cells grown in vitro, and in Caenorhabditis elegans models of human neurodegenerative diseases in vivo. Aspirin acetylates many proteins, while reducing phosphorylation, suggesting that acetylation may oppose phosphorylation. Surprisingly, acetylated proteins were largely excluded from compact aggregates. Molecular-dynamic simulations indicate that acetylation of amyloid peptide energetically disfavors its association into dimers and octamers, and oligomers that do form are less compact and stable than those comprising unacetylated peptides. Hyperphosphorylation predisposes certain proteins to aggregate (e.g., tau, α-synuclein, and transactive response DNA-binding protein 43 [TDP-43]), and it is a critical pathogenic marker in both cardiovascular and neurodegenerative diseases. We present novel evidence that acetylated proteins are underrepresented in protein aggregates, and that aggregation varies inversely with acetylation propensity after diverse genetic and pharmacologic interventions. These results are consistent with the hypothesis that aspirin inhibits protein aggregation and the ensuing toxicity of aggregates through its acetyl-donating activity. This mechanism may contribute to the neuro-protective, cardio

  1. Vanillin restrains non-enzymatic glycation and aggregation of albumin by chemical chaperone like function.

    Science.gov (United States)

    Awasthi, Saurabh; Saraswathi, N T

    2016-06-01

    Vanillin a major component of vanilla bean extract is commonly used a natural flavoring agent. Glycation is known to induce aggregation and fibrillation of globular proteins such as albumin, hemoglobin. Here we report the inhibitory potential of vanillin toward early and advanced glycation modification and amyloid like aggregation of albumin based on the determination of both early and advanced glycation and conformational changes in albumin using circular dichroism. Inhibition of aggregation and fibrillation of albumin was determined based on amyloid specific dyes i.e., Congo red and Thioflavin T and microscopic imaging. It was evident that vanillin restrains glycation of albumin and exhibits protective effect toward its native conformation. Copyright © 2016 Elsevier B.V. All rights reserved.

  2. Platelet-derived growth factor inhibits platelet activation in heparinized whole blood.

    Science.gov (United States)

    Selheim, F; Holmsen, H; Vassbotn, F S

    1999-08-15

    We previously have demonstrated that human platelets have functionally active platelet-derived growth factor alpha-receptors. Studies with gel-filtered platelets showed that an autocrine inhibition pathway is transduced through this tyrosine kinase receptor during platelet activation. The physiological significance of this inhibitory effect of platelet-derived growth factor on gel-filtered platelets activation is, however, not known. In the present study, we investigated whether platelet-derived growth factor inhibits platelet activation under more physiological conditions in heparinized whole blood, which represents a more physiological condition than gel-filtered platelets. Using flow cytometric assays, we demonstrate here that platelet-derived growth factor inhibits thrombin-, thrombin receptor agonist peptide SFLLRN-, and collagen-induced platelet aggregation and shedding of platelet-derived microparticles from the platelet plasma membrane during platelet aggregation in stirred heparinized whole blood. The inhibitory effect of platelet-derived growth factor was dose dependent. However, under nonaggregating conditions (no stirring), we could not demonstrate any significant effect of platelet-derived growth factor on thrombin- and thrombin receptor agonist peptide-induced platelet surface expression of P-selectin. Our results demonstrate that platelet-derived growth factor appears to be a true antithrombotic agent only under aggregating conditions in heparinized whole blood.

  3. Modulation of α-synuclein fibrillization by ring-fused 2-pyridones: templation and inhibition involve oligomers with different structure.

    Science.gov (United States)

    Horvath, Istvan; Sellstedt, Magnus; Weise, Christoph; Nordvall, Lina-Maria; Krishna Prasad, G; Olofsson, Anders; Larsson, Göran; Almqvist, Fredrik; Wittung-Stafshede, Pernilla

    2013-04-15

    In a recent study we discovered that a ring-fused 2-pyridone compound triggered fibrillization of a key protein in Parkinson's disease, α-synuclein. To reveal how variations in compound structure affect protein aggregation, we now prepared a number of strategic analogs and tested their effects on α-synuclein amyloid fiber formation in vitro. We find that, in contrast to the earlier templating effect, some analogs inhibit α-synuclein fibrillization. For both templating and inhibiting compounds, the key species formed in the reactions are α-synuclein oligomers that contain compound. Despite similar macroscopic appearance, the templating and inhibiting oligomers are distinctly different in secondary structure content. When the inhibitory oligomers are added in seed amounts, they inhibit fresh α-synuclein aggregation reactions. Our study demonstrates that small chemical changes to the same central fragment can result in opposite effects on protein aggregation. Copyright © 2013 Elsevier Inc. All rights reserved.

  4. Rydberg aggregates

    Science.gov (United States)

    Wüster, S.; Rost, J.-M.

    2018-02-01

    We review Rydberg aggregates, assemblies of a few Rydberg atoms exhibiting energy transport through collective eigenstates, considering isolated atoms or assemblies embedded within clouds of cold ground-state atoms. We classify Rydberg aggregates, and provide an overview of their possible applications as quantum simulators for phenomena from chemical or biological physics. Our main focus is on flexible Rydberg aggregates, in which atomic motion is an essential feature. In these, simultaneous control over Rydberg-Rydberg interactions, external trapping and electronic energies, allows Born-Oppenheimer surfaces for the motion of the entire aggregate to be tailored as desired. This is illustrated with theory proposals towards the demonstration of joint motion and excitation transport, conical intersections and non-adiabatic effects. Additional flexibility for quantum simulations is enabled by the use of dressed dipole-dipole interactions or the embedding of the aggregate in a cold gas or Bose-Einstein condensate environment. Finally we provide some guidance regarding the parameter regimes that are most suitable for the realization of either static or flexible Rydberg aggregates based on Li or Rb atoms. The current status of experimental progress towards enabling Rydberg aggregates is also reviewed.

  5. Phage inhibit pathogen dissemination by targeting bacterial migrants in a chronic infection model

    DEFF Research Database (Denmark)

    Darch, Sophie E.; Kragh, Kasper N.; Abbott, Evelyn A.

    2017-01-01

    The microbial communities inhabiting chronic infections are often composed of spatially organized micrometer-sized, highly dense aggregates. It has recently been hypothesized that aggregates are responsible for the high tolerance of chronic infections to host immune functions and antimicrobial...... production; however, seeding of new aggregates by dispersed migrants was inhibited. We propose a model in which aggregates provide a mechanism that allows P. aeruginosa to tolerate phage therapy during chronic infection without the need for genetic mutation. IMPORTANCE Bacteria in chronic infections often...... reside in communities composed of micrometer-sized, highly dense aggregates. A primary challenge for studying aggregates has been the lack of laboratory systems that promote natural aggregate formation in relevant environments. Here, we developed a growth medium that mimics chronic lung infection...

  6. Multitarget Therapeutic Leads for Alzheimer's Disease: Quinolizidinyl Derivatives of Bi- and Tricyclic Systems as Dual Inhibitors of Cholinesterases and β-Amyloid (Aβ) Aggregation.

    Science.gov (United States)

    Tonelli, Michele; Catto, Marco; Tasso, Bruno; Novelli, Federica; Canu, Caterina; Iusco, Giovanna; Pisani, Leonardo; Stradis, Angelo De; Denora, Nunzio; Sparatore, Anna; Boido, Vito; Carotti, Angelo; Sparatore, Fabio

    2015-06-01

    Multitarget therapeutic leads for Alzheimer's disease were designed on the models of compounds capable of maintaining or restoring cell protein homeostasis and of inhibiting β-amyloid (Aβ) oligomerization. Thirty-seven thioxanthen-9-one, xanthen-9-one, naphto- and anthraquinone derivatives were tested for the direct inhibition of Aβ(1-40) aggregation and for the inhibition of electric eel acetylcholinesterase (eeAChE) and horse serum butyrylcholinesterase (hsBChE). These compounds are characterized by basic side chains, mainly quinolizidinylalkyl moieties, linked to various bi- and tri-cyclic (hetero)aromatic systems. With very few exceptions, these compounds displayed inhibitory activity on both AChE and BChE and on the spontaneous aggregation of β-amyloid. In most cases, IC50 values were in the low micromolar and sub-micromolar range, but some compounds even reached nanomolar potency. The time course of amyloid aggregation in the presence of the most active derivative (IC50 =0.84 μM) revealed that these compounds might act as destabilizers of mature fibrils rather than mere inhibitors of fibrillization. Many compounds inhibited one or both cholinesterases and Aβ aggregation with similar potency, a fundamental requisite for the possible development of therapeutics exhibiting a multitarget mechanism of action. The described compounds thus represent interesting leads for the development of multitarget AD therapeutics. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  7. The S/T-Rich Motif in the DNAJB6 Chaperone Delays Polyglutamine Aggregation and the Onset of Disease in a Mouse Model.

    Science.gov (United States)

    Kakkar, Vaishali; Månsson, Cecilia; de Mattos, Eduardo P; Bergink, Steven; van der Zwaag, Marianne; van Waarde, Maria A W H; Kloosterhuis, Niels J; Melki, Ronald; van Cruchten, Remco T P; Al-Karadaghi, Salam; Arosio, Paolo; Dobson, Christopher M; Knowles, Tuomas P J; Bates, Gillian P; van Deursen, Jan M; Linse, Sara; van de Sluis, Bart; Emanuelsson, Cecilia; Kampinga, Harm H

    2016-04-21

    Expanded CAG repeats lead to debilitating neurodegenerative disorders characterized by aggregation of proteins with expanded polyglutamine (polyQ) tracts. The mechanism of aggregation involves primary and secondary nucleation steps. We show how a noncanonical member of the DNAJ-chaperone family, DNAJB6, inhibits the conversion of soluble polyQ peptides into amyloid fibrils, in particular by suppressing primary nucleation. This inhibition is mediated by a serine/threonine-rich region that provides an array of surface-exposed hydroxyl groups that bind to polyQ peptides and may disrupt the formation of the H bonds essential for the stability of amyloid fibrils. Early prevention of polyQ aggregation by DNAJB6 occurs also in cells and leads to delayed neurite retraction even before aggregates are visible. In a mouse model, brain-specific coexpression of DNAJB6 delays polyQ aggregation, relieves symptoms, and prolongs lifespan, pointing to DNAJB6 as a potential target for disease therapy and tool for unraveling early events in the onset of polyQ diseases. Copyright © 2016 Elsevier Inc. All rights reserved.

  8. DNA sensors and aptasensors based on the hemin/G-quadruplex-controlled aggregation of Au NPs in the presence of L-cysteine.

    Science.gov (United States)

    Niazov-Elkan, Angelica; Golub, Eyal; Sharon, Etery; Balogh, Dora; Willner, Itamar

    2014-07-23

    L-cysteine induces the aggregation of Au nanoparticles (NPs), resulting in a color transition from red to blue due to interparticle plasmonic coupling in the aggregated structure. The hemin/G-quadruplex horseradish peroxidase-mimicking DNAzyme catalyzes the aerobic oxidation of L-cysteine to cystine, a process that inhibits the aggregation of the NPs. The degree of inhibition of the aggregation process is controlled by the concentration of the DNAzyme in the system. These functions are implemented to develop sensing platforms for the detection of a target DNA, for the analysis of aptamer-substrate complexes, and for the analysis of L-cysteine in human urine samples. A hairpin DNA structure that includes a recognition site for the DNA analyte and a caged G-quadruplex sequence, is opened in the presence of the target DNA. The resulting self-assembled hemin/G-quadruplex acts as catalyst that controls the aggregation of the Au NPs. Also, the thrombin-binding aptamer folds into a G-quadruplex nanostructure upon binding to thrombin. The association of hemin to the resulting G-quadruplex aptamer-thrombin complex leads to a catalytic label that controls the L-cysteine-mediated aggregation of the Au NPs. The hemin/G-qaudruplex-controlled aggregation of Au NPs process is further implemented for visual and spectroscopic detection of L-cysteine concentration in urine samples. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  9. An anticancer drug suppresses the primary nucleation reaction that initiates the production of the toxic Aβ42 aggregates linked with Alzheimer's disease

    NARCIS (Netherlands)

    Habchi, Johnny; Arosio, Paolo; Perni, Michele; Costa, Ana Rita; Yagi-Utsumi, Maho; Joshi, Priyanka; Chia, Sean; Cohen, Samuel I A; Müller, Martin B D; Linse, Sara; Nollen, Ellen A A; Dobson, Christopher M; Knowles, Tuomas P J; Vendruscolo, Michele

    2016-01-01

    The conversion of the β-amyloid (Aβ) peptide into pathogenic aggregates is linked to the onset and progression of Alzheimer's disease. Although this observation has prompted an extensive search for therapeutic agents to modulate the concentration of Aβ or inhibit its aggregation, all clinical trials

  10. Modeling the Interaction between β-Amyloid Aggregates and Choline Acetyltransferase Activity and Its Relation with Cholinergic Dysfunction through Two-Enzyme/Two-Compartment Model

    Directory of Open Access Journals (Sweden)

    Hedia Fgaier

    2015-01-01

    Full Text Available The effect of β-amyloid aggregates on activity of choline acetyltransferase (ChAT which is responsible for synthesizing acetylcholine (ACh in human brain is investigated through the two-enzyme/two-compartment (2E2C model where the presynaptic neuron is considered as compartment 1 while both the synaptic cleft and the postsynaptic neuron are considered as compartment 2 through suggesting three different kinetic mechanisms for the inhibition effect. It is found that the incorporation of ChAT inhibition by β-amyloid aggregates into the 2E2C model is able to yield dynamic solutions for concentrations of generated β-amyloid, ACh, choline, acetate, and pH in addition to the rates of ACh synthesis and ACh hydrolysis in compartments 1 and 2. It is observed that ChAT activity needs a high concentration of β-amyloid aggregates production rate. It is found that ChAT activity is reduced significantly when neurons are exposed to high levels of β-amyloid aggregates leading to reduction in levels of ACh which is one of the most significant physiological symptoms of AD. Furthermore, the system of ACh neurocycle is dominated by the oscillatory behavior when ChAT enzyme is completely inhibited by β-amyloid. It is observed that the direct inactivation of ChAT by β-amyloid aggregates may be a probable mechanism contributing to the development of AD.

  11. Mechanism for release of arachidonic acid during guinea pig platelet aggregation: a role for the diacylglycerol lipase inhibitor RHC 80267

    International Nuclear Information System (INIS)

    Amin, D.

    1986-01-01

    The mechanism of the release of arachidonic acid from phospholipids after the stimulation of guinea pig platelets with collagen, thrombin and platelet activating factor (PAF) was studied. RHC 80267, a diacylglycerol lipase inhibitor, and indomethacin, a cyclooxygenase inhibitor, were used. Various in vitro assays for enzymes involved in arachidonic acid release and metabolism were conducted. Platelet aggregation and simultaneous release of ADP from platelets were monitored using a Chrono-log Lumiaggregometer. Platelets were labeled with ( 14 C)arachidonic acid to facilitate sensitive determination of small changes in platelet phospholipids during platelet aggregation. In the present investigation it is shown that collagen, thrombin and PAF increased phospholipase C activity. It was also discovered that cyclooxygenase products were responsible for further stimulation (a positive feed-back) of phospholipase C activity, while diacylglycerol provided a negative feed-back control over receptor-stimulated phospholipase C activity and inhibited ADP release. The guinea pig platelet is an ideal model to study phospholipase C-diacylglycerol lipase pathway for the release of arachidonic acid from platelet phospholipids because it does not have any phospholipase A 2 activity. It was observed that cyclooxygenase products were responsible for collagen-induced guinea pig platelet aggregation. Indomethacin completely inhibited collagen-induced platelet aggregation, was less effective against thrombin, and had no effect on PAF-induced platelet aggregation. On the other hand, RHC 80267 was a powerful inhibitor of aggregation and ADP release induced by all three of these potent aggregating agents

  12. 17-AAG induces cytoplasmic alpha-synuclein aggregate clearance by induction of autophagy.

    Science.gov (United States)

    Riedel, Michael; Goldbaum, Olaf; Schwarz, Lisa; Schmitt, Sebastian; Richter-Landsberg, Christiane

    2010-01-18

    The accumulation and aggregation of alpha-synuclein in nerve cells and glia are characteristic features of a number of neurodegenerative diseases termed synucleinopathies. alpha-Synuclein is a highly soluble protein which in a nucleation dependent process is capable of self-aggregation. The causes underlying aggregate formation are not yet understood, impairment of the proteolytic degradation systems might be involved. In the present study the possible aggregate clearing effects of the geldanamycin analogue 17-AAG (17-(Allylamino)-17-demethoxygeldanamycin) was investigated. Towards this, an oligodendroglial cell line (OLN-93 cells), stably expressing human alpha-synuclein (A53T mutation) was used. In these cells small punctate aggregates, not staining with thioflavine S, representing prefibrillary aggregates, occur characteristically. Our data demonstrate that 17-AAG attenuated the formation of alpha-synuclein aggregates by stimulating macroautophagy. By blocking the lysosomal compartment with NH(4)Cl the aggregate clearing effects of 17-AAG were abolished and alpha-synuclein deposits were enlarged. Analysis of LC3-II immunoreactivity, which is an indicator of autophagosome formation, further revealed that 17-AAG led to the recruitment of LC3-II and to the formation of LC3 positive puncta. This effect was also observed in cultured oligodendrocytes derived from the brains of newborn rats. Inhibition of macroautophagy by 3-methyladenine prevented 17-AAG induced occurrence of LC3 positive puncta as well as the removal of alpha-synuclein aggregates in OLN-A53T cells. Our data demonstrate for the first time that 17-AAG not only causes the upregulation of heat shock proteins, but also is an effective inducer of the autophagic pathway by which alpha-synuclein can be removed. Hence geldanamycin derivatives may provide a means to modulate autophagy in neural cells, thereby ameliorating pathogenic aggregate formation and protecting the cells during disease and aging.

  13. Effects of extracts and tannins from Arbutus unedo leaves on rat platelet aggregation.

    Science.gov (United States)

    Mekhfi, Hassane; ElHaouari, Mohammed; Bnouham, Mohamed; Aziz, Mohammed; Ziyyat, Abderrahim; Legssyer, Abdelkhaleq

    2006-02-01

    Many cardiovascular diseases such as arterial hypertension are associated with an increase in blood platelet activity. Arbutus unedo (Ericaceae) is a medicinal plant reputed to treat arterial hypertension, so the present study was undertaken in order to determine the antiaggregant effect. The crude aqueous extract showed an inhibition of thrombin-induced platelet aggregation (IC50 = 1.8 +/- 0.09 g/L, n = 10). The subsequent extraction of Arbutus unedo leaves by successive solvents showed that the methanol and ethyl acetate extracts accounted for most of the antiaggregant activity (IC50 = 0.7 +/- 0.08, n = 9; 0.6 +/- 0.05; n = 9, respectively). The tannins isolated from the methanol extract exhibited a strong antiplatelet effect (% of inhibition = 75.3 +/- 1.4, n = 8) and may be the major chemical compounds responsible for this action. Our results support the traditional use of this plant in the preventive or therapeutic treatment of platelet aggregation linked to arterial hypertension. Copyright 2006 John Wiley & Sons, Ltd.

  14. Keampferol-3-O-rhamnoside abrogates amyloid beta toxicity by modulating monomers and remodeling oligomers and fibrils to non-toxic aggregates

    Directory of Open Access Journals (Sweden)

    Sharoar Md

    2012-12-01

    Full Text Available Abstract Background Aggregation of soluble, monomeric β- amyloid (Aβ to oligomeric and then insoluble fibrillar Aβ is a key pathogenic feature in development of Alzheimer’s disease (AD. Increasing evidence suggests that toxicity is linked to diffusible Aβ oligomers, rather than to insoluble fibrils. The use of naturally occurring small molecules for inhibition of Aβ aggregation has recently attracted significant interest for development of effective therapeutic strategies against the disease. A natural polyphenolic flavone, Kaempferol-3-O-rhamnoside (K-3-rh, was utilized to investigate its effects on aggregation and cytotoxic effects of Aβ42 peptide. Several biochemical techniques were used to determine the conformational changes and cytotoxic effect of the peptide in the presence and absence of K-3-rh. Results K-3-rh showed a dose-dependent effect against Aβ42 mediated cytotoxicity. Anti-amyloidogenic properties of K-3-rh were found to be efficient in inhibiting fibrilogenesis and secondary structural transformation of the peptide. The consequence of these inhibitions was the accumulation of oligomeric structural species. The accumulated aggregates were smaller, soluble, non-β-sheet and non-toxic aggregates, compared to preformed toxic Aβ oligomers. K-3-rh was also found to have the remodeling properties of preformed soluble oligomers and fibrils. Both of these conformers were found to remodel into non-toxic aggregates. The results showed that K-3-rh interacts with different Aβ conformers, which affects fibril formation, oligomeric maturation and fibrillar stabilization. Conclusion K-3-rh is an efficient molecule to hinder the self assembly and to abrogate the cytotoxic effects of Aβ42 peptide. Hence, K-3-rh and small molecules with similar structure might be considered for therapeutic development against AD.

  15. Neutrophil derived LTB4 induces macrophage aggregation in response to encapsulated Streptococcus iniae infection.

    Directory of Open Access Journals (Sweden)

    William J B Vincent

    Full Text Available Immune cells sense and react to a multitude of factors including both host and microbe-derived signals. Understanding how cells translate these cues into particular cellular behaviors is a complex yet critical area of study. We have previously shown that both neutrophils and macrophages are important for controlling the fish pathogen Streptococcus iniae. Here, we report both host and bacterial determinants leading to the formation of organized macrophage aggregates as part of the host inflammatory response in a subset of infected larvae. Streptococcal capsule was a required signal for aggregate formation. Macrophage aggregation coincided with NFκB activity, and the formation of these aggregates is mediated by leukotriene B4 (LTB4 produced by neutrophils. Depletion, inhibition, or genetic deletion of leukotriene A4 hydrolase (Lta4h, which catalyzes the last step in LTB4 synthesis, resulted in the absence of macrophage aggregation. Larvae with impaired neutrophil function also had impaired macrophage aggregation; however, aggregate formation was partially rescued with the addition of exogenous LTB4. Neutrophil-specific expression of lta4h was sufficient to rescue macrophage aggregation in Lta4h-deficient larvae and increased host survival following infection. In summary, our findings highlight a novel innate immune response to infection in which specific bacterial products drive neutrophils that modulate macrophage behavior through eicosanoid signaling.

  16. Glyceraldehyde-3-phosphate dehydrogenase aggregation inhibitor peptide: A potential therapeutic strategy against oxidative stress-induced cell death.

    Science.gov (United States)

    Itakura, Masanori; Nakajima, Hidemitsu; Semi, Yuko; Higashida, Shusaku; Azuma, Yasu-Taka; Takeuchi, Tadayoshi

    2015-11-13

    The glycolytic enzyme glyceraldehyde-3-phosphate dehydrogenase (GAPDH) has multiple functions, including mediating oxidative stress-induced neuronal cell death. This process is associated with disulfide-bonded GAPDH aggregation. Some reports suggest a link between GAPDH and the pathogenesis of several oxidative stress-related diseases. However, the pathological significance of GAPDH aggregation in disease pathogenesis remains unclear due to the lack of an effective GAPDH aggregation inhibitor. In this study, we identified a GAPDH aggregation inhibitor (GAI) peptide and evaluated its biological profile. The decapeptide GAI specifically inhibited GAPDH aggregation in a concentration-dependent manner. Additionally, the GAI peptide did not affect GAPDH glycolytic activity or cell viability. The GAI peptide also exerted a protective effect against oxidative stress-induced cell death in SH-SY5Y cells. This peptide could potentially serve as a tool to investigate GAPDH aggregation-related neurodegenerative and neuropsychiatric disorders and as a possible therapy for diseases associated with oxidative stress-induced cell death. Copyright © 2015 Elsevier Inc. All rights reserved.

  17. Inhibitory Effect of Waste Glass Powder on ASR Expansion Induced by Waste Glass Aggregate

    Directory of Open Access Journals (Sweden)

    Shuhua Liu

    2015-10-01

    Full Text Available Detailed research is carried out to ascertain the inhibitory effect of waste glass powder (WGP on alkali-silica reaction (ASR expansion induced by waste glass aggregate in this paper. The alkali reactivity of waste glass aggregate is examined by two methods in accordance with the China Test Code SL352-2006. The potential of WGP to control the ASR expansion is determined in terms of mean diameter, specific surface area, content of WGP and curing temperature. Two mathematical models are developed to estimate the inhibitory efficiency of WGP. These studies show that there is ASR risk with an ASR expansion rate over 0.2% when the sand contains more than 30% glass aggregate. However, WGP can effectively control the ASR expansion and inhibit the expansion rate induced by the glass aggregate to be under 0.1%. The two mathematical models have good simulation results, which can be used to evaluate the inhibitory effect of WGP on ASR risk.

  18. Glucose impairs aspirin inhibition in platelets through a NAD(P)H oxidase signaling pathway.

    Science.gov (United States)

    Kobzar, Gennadi; Mardla, Vilja; Samel, Nigulas

    2017-07-01

    Hyperglycemia has been suggested to play a role in the increased platelet resistance to antiplatelet therapy in patients with diabetes mellitus. Exposure to high glucose impairs platelet inhibition by aspirin. It has been found that antioxidant agents reduce the effect of glucose, confirming the involvement of reactive oxygen species (ROS) in the effect of glucose. The aim of the study was to examine the mechanism of ROS increase by high glucose in aspirin-treated platelets. Platelet aggregation was measured by the optical method, and the production of ROS was detected using luminol-dependent horseradish peroxidase-enhanced chemiluminescence. We found that glucose did not affect ADP-induced platelet aggregation. However, it reduced the effect of aspirin on platelet aggregation, which was accompanied by an increase in ROS generation. The inhibition of NAD(P)H oxidase (NOX) prevented the glucose effect and ROS generation. The same result was recorded after the inhibition of p38 mitogen-activated protein kinases (p38 MAPK), phospholipase A 2 (PLA 2 ) or 12-lipoxygenase (12-LOX). The inhibition of TxA 2 receptor did not decrease the effect of glucose indicating that the effect was not caused by activation of TxA 2 receptors. Copyright © 2017 Elsevier Inc. All rights reserved.

  19. Flavonoids and platelet aggregation: A brief review.

    Science.gov (United States)

    Faggio, Caterina; Sureda, Antoni; Morabito, Silvia; Sanches-Silva, Ana; Mocan, Andrei; Nabavi, Seyed Fazel; Nabavi, Seyed Mohammad

    2017-07-15

    Platelets are small anucleated fragments derived from a megakaryocyte precursor. Platelets play a key role in many physiological functions especially in hemostasis and wound healing processes in order to maintain the integrity of the circulatory system. In addition, activated platelets release cytokines and chemokines which modulate the immune response and, in some cases of hyperactivation, they could be associated to the pathogenesis of inflammatory diseases. Flavonoids are polyphenolic compounds ubiquosly found in plants known to be potent antioxidants with positive effects against diverse diseases such as cancer, neurodegenerative or cardiovascular disease. It has been reported that some flavonoids possess anti-platelet aggregation effects though different pathways, being the inhibition of the arachidonic acid-based pathway the most representative mechanism of action. In the present review, the main sources of flavonoids, as well as their bioavailability and metabolism are summarized. Moreover, the available data about the anti-aggregation effects of flavonoids and the different mechanisms of action that has been proposed until now are also discussed. Copyright © 2017 Elsevier B.V. All rights reserved.

  20. Marine Synechococcus Aggregation

    Science.gov (United States)

    Neuer, S.; Deng, W.; Cruz, B. N.; Monks, L.

    2016-02-01

    Cyanobacteria are considered to play an important role in the oceanic biological carbon pump, especially in oligotrophic regions. But as single cells are too small to sink, their carbon export has to be mediated by aggregate formation and possible consumption by zooplankton producing sinking fecal pellets. Here we report results on the aggregation of the ubiquitous marine pico-cyanobacterium Synechococcus as a model organism. We first investigated the mechanism behind such aggregation by studying the potential role of transparent exopolymeric particles (TEP) and the effects of nutrient (nitrogen or phosphorus) limitation on the TEP production and aggregate formation of these pico-cyanobacteria. We further studied the aggregation and subsequent settling in roller tanks and investigated the effects of the clays kaolinite and bentonite in a series of concentrations. Our results show that despite of the lowered growth rates, Synechococcus in nutrient limited cultures had larger cell-normalized TEP production, formed a greater volume of aggregates, and resulted in higher settling velocities compared to results from replete cultures. In addition, we found that despite their small size and lack of natural ballasting minerals, Synechococcus cells could still form aggregates and sink at measureable velocities in seawater. Clay minerals increased the number and reduced the size of aggregates, and their ballasting effects increased the sinking velocity and carbon export potential of aggregates. In comparison with the Synechococcus, we will also present results of the aggregation of the pico-cyanobacterium Prochlorococcus in roller tanks. These results contribute to our understanding in the physiology of marine Synechococcus as well as their role in the ecology and biogeochemistry in oligotrophic oceans.

  1. Vitamin k3 inhibits protein aggregation: Implication in the treatment of amyloid diseases

    OpenAIRE

    Parvez Alam; Sumit Kumar Chaturvedi; Mohammad Khursheed Siddiqi; Ravi Kant Rajpoot; Mohd Rehan Ajmal; Masihuz Zaman; Rizwan Hasan Khan

    2016-01-01

    Protein misfolding and aggregation have been associated with several human diseases such as Alzheimer?s, Parkinson?s and familial amyloid polyneuropathy etc. In this study, anti-fibrillation activity of vitamin k3 and its effect on the kinetics of amyloid formation of hen egg white lysozyme (HEWL) and A?-42 peptide were investigated. Here, in combination with Thioflavin T (ThT) fluorescence assay, circular dichroism (CD), transmission electron microscopy and cell cytotoxicity assay, we demons...

  2. The effect of the substituted amphetamines, 2.4-methylenedioxymethamphetamine (MDMA) and P-methoxyamphetamine (PMA), on platelet aggregation

    International Nuclear Information System (INIS)

    Sluggett, A.J.; Irvine, R.J.; Bochner, F.; Rodgers, S.; Lloyd, J.V.

    2001-01-01

    Full text: Illicit substituted amphetamines such as 3,4-methylenedioxymethamphetamine (MDMA) and p-methoxyamphetamine (PMA) can cause severe toxicity. Disruption of normal coagulation mechanisms have been observed in most fatal cases. However, the precise mechanisms underlying these events are not clearly understood. MDMA and PMA are known to inhibit serotonin transporter function in the central nervous system (Daws et al 2000) and platelet serotonin transporter sites (Rudnick and Wall 1992). Serotonin is in high concentrations in platelets and activation of 5HT 2 receptors on the platelet surface potentiates aggregation of platelets. Therefore, we postulated that MDMA and PMA may have effects on coagulation via inhibition of normal platelet function. Human citrated platelets were incubated in the presence of MDMA (43- 435μM) or PMA (49-498μM) and their aggregator y response to a critical dose of adenosine diphosphate (ADP) determined. These responses were compared to the serotonin reuptake inhibitor fluoxetine (13-130μM). All 3 compounds were found to inhibit platelet aggregation. The IC50s for % aggregation at 5 minutes were MDMA 197μM ± 63μM PMA 344μM ±76μM and fluoxetine 24μM ±1 1μM (n=4). The effect of these drugs on the uptake of 14 C-5HT (0.9 μM /ml) into platelets was also determined and the IC50s observed were MDMA 62.3 μM ±11μM , PMA 24μM ±6μM and fluoxetine 2.5μM ± 0.6μM (n=4). The in vitro effects of MDMA and PMA on aggregation and uptake observed here are close to concentrations reported to have occurred in human fatalities. Therefore it is possible that direct effects of these drugs on coagulation mechanisms may contribute to the toxicity of these compounds. Copyright (2001) Australasian Society of Clinical and Experimental Pharmacologists and Toxicologists

  3. BAG3 directly interacts with mutated alphaB-crystallin to suppress its aggregation and toxicity.

    Directory of Open Access Journals (Sweden)

    Akinori Hishiya

    Full Text Available A homozygous disruption or genetic mutation of the bag3 gene causes progressive myofibrillar myopathy in mouse and human skeletal and cardiac muscle disorder while mutations in the small heat shock protein αB-crystallin gene (CRYAB are reported to be responsible for myofibrillar myopathy. Here, we demonstrate that BAG3 directly binds to wild-type αB-crystallin and the αB-crystallin mutant R120G, via the intermediate domain of BAG3. Peptides that inhibit this interaction in an in vitro binding assay indicate that two conserved Ile-Pro-Val regions of BAG3 are involved in the interaction with αB-crystallin, which is similar to results showing BAG3 binding to HspB8 and HspB6. BAG3 overexpression increased αB-crystallin R120G solubility and inhibited its intracellular aggregation in HEK293 cells. BAG3 suppressed cell death induced by αB-crystallin R120G overexpression in differentiating C2C12 mouse myoblast cells. Our findings indicate a novel function for BAG3 in inhibiting protein aggregation caused by the genetic mutation of CRYAB responsible for human myofibrillar myopathy.

  4. BAG3 Directly Interacts with Mutated alphaB-Crystallin to Suppress Its Aggregation and Toxicity

    Science.gov (United States)

    Hishiya, Akinori; Salman, Mortada Najem; Carra, Serena; Kampinga, Harm H.; Takayama, Shinichi

    2011-01-01

    A homozygous disruption or genetic mutation of the bag3 gene causes progressive myofibrillar myopathy in mouse and human skeletal and cardiac muscle disorder while mutations in the small heat shock protein αB-crystallin gene (CRYAB) are reported to be responsible for myofibrillar myopathy. Here, we demonstrate that BAG3 directly binds to wild-type αB-crystallin and the αB-crystallin mutant R120G, via the intermediate domain of BAG3. Peptides that inhibit this interaction in an in vitro binding assay indicate that two conserved Ile-Pro-Val regions of BAG3 are involved in the interaction with αB-crystallin, which is similar to results showing BAG3 binding to HspB8 and HspB6. BAG3 overexpression increased αB-crystallin R120G solubility and inhibited its intracellular aggregation in HEK293 cells. BAG3 suppressed cell death induced by αB-crystallin R120G overexpression in differentiating C2C12 mouse myoblast cells. Our findings indicate a novel function for BAG3 in inhibiting protein aggregation caused by the genetic mutation of CRYAB responsible for human myofibrillar myopathy. PMID:21423662

  5. Ellagic acid promotes A{beta}42 fibrillization and inhibits A{beta}42-induced neurotoxicity

    Energy Technology Data Exchange (ETDEWEB)

    Feng, Ying [Department of Histology and Embryology, College of Basic Medical Science, China Medical University, Shenyang 110001 (China); Tsinghua University School of Medicine, Haidian District, Beijing 100084 (China); Yang, Shi-gao; Du, Xue-ting; Zhang, Xi; Sun, Xiao-xia; Zhao, Min [Tsinghua University School of Medicine, Haidian District, Beijing 100084 (China); Sun, Gui-yuan, E-mail: sungy2004@sohu.com [Department of Histology and Embryology, College of Basic Medical Science, China Medical University, Shenyang 110001 (China); Liu, Rui-tian, E-mail: rtliu@tsinghua.edu.cn [Tsinghua University School of Medicine, Haidian District, Beijing 100084 (China)

    2009-12-25

    Smaller, soluble oligomers of {beta}-amyloid (A{beta}) play a critical role in the pathogenesis of Alzheimer's disease (AD). Selective inhibition of A{beta} oligomer formation provides an optimum target for AD therapy. Some polyphenols have potent anti-amyloidogenic activities and protect against A{beta} neurotoxicity. Here, we tested the effects of ellagic acid (EA), a polyphenolic compound, on A{beta}42 aggregation and neurotoxicity in vitro. EA promoted A{beta} fibril formation and significant oligomer loss, contrary to previous results that polyphenols inhibited A{beta} aggregation. The results of transmission electron microscopy (TEM) and Western blot displayed more fibrils in A{beta}42 samples co-incubated with EA in earlier phases of aggregation. Consistent with the hypothesis that plaque formation may represent a protective mechanism in which the body sequesters toxic A{beta} aggregates to render them harmless, our MTT results showed that EA could significantly reduce A{beta}42-induced neurotoxicity toward SH-SY5Y cells. Taken together, our results suggest that EA, an active ingredient in many fruits and nuts, may have therapeutic potential in AD.

  6. Defining and systematic analyses of aggregation indices to evaluate degree of calcium oxalate crystal aggregation

    Science.gov (United States)

    Chaiyarit, Sakdithep; Thongboonkerd, Visith

    2017-12-01

    Crystal aggregation is one of the most crucial steps in kidney stone pathogenesis. However, previous studies of crystal aggregation were rarely done and quantitative analysis of aggregation degree was handicapped by a lack of the standard measurement. We thus performed an in vitro assay to generate aggregation of calcium oxalate monohydrate (COM) crystals with various concentrations (25-800 µg/ml) in saturated aggregation buffer. The crystal aggregates were analyzed by microscopic examination, UV-visible spectrophotometry, and GraphPad Prism6 software to define a total of 12 aggregation indices (including number of aggregates, aggregated mass index, optical density, aggregation coefficient, span, number of aggregates at plateau time-point, aggregated area index, aggregated diameter index, aggregated symmetry index, time constant, half-life, and rate constant). The data showed linear correlation between crystal concentration and almost all of these indices, except only for rate constant. Among these, number of aggregates provided the greatest regression coefficient (r=0.997; pr=0.993; pr=‑0.993; pr=0.991; p<0.001 for both). These five indices are thus recommended as the most appropriate indices for quantitative analysis of COM crystal aggregation in vitro.

  7. A Novel, Multi-Target Natural Drug Candidate, Matrine, Improves Cognitive Deficits in Alzheimer's Disease Transgenic Mice by InhibitingAggregation and Blocking the RAGE/Aβ Axis.

    Science.gov (United States)

    Cui, Lili; Cai, Yujie; Cheng, Wanwen; Liu, Gen; Zhao, Jianghao; Cao, Hao; Tao, Hua; Wang, Yan; Yin, Mingkang; Liu, Tingting; Liu, Yu; Huang, Pengru; Liu, Zhou; Li, Keshen; Zhao, Bin

    2017-04-01

    The treatment of AD is a topic that has puzzled researchers for many years. Current mainstream theories still consider Aβ to be the most important target for the cure of AD. In this study, we attempted to explore multiple targets for AD treatments with the aim of identifying a qualified compound that could both inhibit the aggregation of Aβ and block the RAGE/Aβ axis. We believed that a compound that targets both Aβ and RAGE may be a feasible strategy for AD treatment. A novel and small natural compound, Matrine (Mat), was identified by high-throughput screening of the main components of traditional Chinese herbs used to treat dementia. Various experimental techniques were used to evaluate the effect of Mat on these two targets both in vitro and in AD mouse model. Mat could inhibit Aβ42-induced cytotoxicity and suppress the Aβ/RAGE signaling pathway in vitro. Additionally, the results of in vivo evaluations of the effects of Mat on the two targets were consistent with the results of our in vitro studies. Furthermore, Mat reduced proinflammatory cytokines and Aβ deposition and attenuated the memory deficits of AD transgenic mice. We believe that this novel, multi-target strategy to inhibit both Aβ and RAGE, is worthy of further exploration. Therefore, our future studies will focus on identifying even more effective multi-target compounds for the treatment of AD based on the molecular structure of Mat.

  8. Gene targeting implicates Cdc42 GTPase in GPVI and non-GPVI mediated platelet filopodia formation, secretion and aggregation.

    Directory of Open Access Journals (Sweden)

    Huzoor Akbar

    Full Text Available Cdc42 and Rac1, members of the Rho family of small GTPases, play critical roles in actin cytoskeleton regulation. We have shown previously that Rac1 is involved in regulation of platelet secretion and aggregation. However, the role of Cdc42 in platelet activation remains controversial. This study was undertaken to better understand the role of Cdc42 in platelet activation.We utilized the Mx-cre;Cdc42(lox/lox inducible mice with transient Cdc42 deletion to investigate the involvement of Cdc42 in platelet function. The Cdc42-deficient mice exhibited a significantly reduced platelet count than the matching Cdc42(+/+ mice. Platelets isolated from Cdc42(-/-, as compared to Cdc42(+/+, mice exhibited (a diminished phosphorylation of PAK1/2, an effector molecule of Cdc42, (b inhibition of filopodia formation on immobilized CRP or fibrinogen, (c inhibition of CRP- or thrombin-induced secretion of ATP and release of P-selectin, (d inhibition of CRP, collagen or thrombin induced platelet aggregation, and (e minimal phosphorylation of Akt upon stimulation with CRP or thrombin. The bleeding times were significantly prolonged in Cdc42(-/- mice compared with Cdc42(+/+ mice.Our data demonstrate that Cdc42 is required for platelet filopodia formation, secretion and aggregation and therefore plays a critical role in platelet mediated hemostasis and thrombosis.

  9. Piceatannol and Other Wine Stilbenes: A Pool of Inhibitors against α-Synuclein Aggregation and Cytotoxicity

    Directory of Open Access Journals (Sweden)

    Hamza Temsamani

    2016-06-01

    Full Text Available The aggregation of α-synuclein is one on the key pathogenic events in Parkinson’s disease. In the present study, we investigated the inhibitory capacities of stilbenes against α-synuclein aggregation and toxicity. Thioflavin T fluorescence, transmission electronic microscopy, and SDS-PAGE analysis were performed to investigate the inhibitory effects of three stilbenes against α-synuclein aggregation: piceatannol, ampelopsin A, and isohopeaphenol. Lipid vesicle permeabilization assays were performed to screen stilbenes for protection against membrane damage induced by aggregated α-synuclein. The viability of PC12 cells was examined using an MTT assay to assess the preventive effects of stilbenes against α-synuclein-induced toxicity. Piceatannol inhibited the formation of α synuclein fibrils and was able to destabilize preformed filaments. It seems to induce the formation of small soluble complexes protecting membranes against α-synuclein-induced damage. Finally, piceatannol protected cells against α-synuclein-induced toxicity. The oligomers tested (ampelopsin A and hopeaphenol were less active.

  10. Sustainable aggregates production : green applications for aggregate by-products.

    Science.gov (United States)

    2015-06-01

    Increased emphasis in the construction industry on sustainability and recycling requires production of : aggregate gradations with lower dust (cleaner aggregates) and smaller maximum sizeshence, increased : amount of quarry by-products (QBs). QBs ...

  11. β-Hairpin of Islet Amyloid Polypeptide Bound to an Aggregation Inhibitor

    Science.gov (United States)

    Mirecka, Ewa A.; Feuerstein, Sophie; Gremer, Lothar; Schröder, Gunnar F.; Stoldt, Matthias; Willbold, Dieter; Hoyer, Wolfgang

    2016-01-01

    In type 2 diabetes, the formation of islet amyloid consisting of islet amyloid polypeptide (IAPP) is associated with reduction in β-cell mass and contributes to the failure of islet cell transplantation. Rational design of inhibitors of IAPP amyloid formation has therapeutic potential, but is hampered by the lack of structural information on inhibitor complexes of the conformationally flexible, aggregation-prone IAPP. Here we characterize a β-hairpin conformation of IAPP in complex with the engineered binding protein β-wrapin HI18. The β-strands correspond to two amyloidogenic motifs, 12-LANFLVH-18 and 22-NFGAILS-28, which are connected by a turn established around Ser-20. Besides backbone hydrogen bonding, the IAPP:HI18 interaction surface is dominated by non-polar contacts involving hydrophobic side chains of the IAPP β-strands. Apart from monomers, HI18 binds oligomers and fibrils and inhibits IAPP aggregation and toxicity at low substoichiometric concentrations. The IAPP β-hairpin can serve as a molecular recognition motif enabling control of IAPP aggregation. PMID:27641459

  12. Influence of Aggregate Wettability with Different Lithology Aggregates on Concrete Drying Shrinkage

    Directory of Open Access Journals (Sweden)

    Yuanchen Guo

    2015-01-01

    Full Text Available The correlation of the wettability of different lithology aggregates and the drying shrinkage of concrete materials is studied, and some influential factors such as wettability and wetting angle are analyzed. A mercury porosimeter is used to measure the porosities of different lithology aggregates accurately, and the pore size ranges that significantly affect the drying shrinkage of different lithology aggregate concretes are confirmed. The pore distribution curve of the different coarse aggregates is also measured through a statistical method, and the contact angle of different coarse aggregates and concrete is calculated according to the linear fitting relationship. Research shows that concrete strength is determined by aggregate strength. Aggregate wettability is not directly correlated with concrete strength, but wettability significantly affects concrete drying shrinkage. In all types’ pores, the greatest impacts on wettability are capillary pores and gel pores, especially for the pores of the size locating 2.5–50 nm and 50–100 nm two ranges.

  13. RELATIONSHIPS BETWEEN SOIL MICROBIAL BIOMASS, AGGREGATE STABILITY AND AGGREGATE ASSOCIATED-C: A MECHANISTIC APPROACH

    Directory of Open Access Journals (Sweden)

    Patrizia Guidi

    2014-01-01

    Full Text Available For the identification of C pools involved in soil aggregation, a physically-based aggregate fractionation was proposed, and  additional pretreatments were used in the measurement of the 1-2 mm aggregate stability in order to elucidate the relevance of the role of soil microorganisms with respect to the different aggregate breakdown mechanisms. The study was carried out on three clay loam Regosols, developed on calcareous shales, known history of organic cultivation.Our results showed that the soil C pool controlling the process of stabilisation of aggregates was related to the microbial community. We identified the resistance to fast wetting as the major mechanism of aggregate stability driven by microorganims. The plausible hypothesis is that organic farming promotes fungi growth, improving water repellency of soil aggregates by fungal hydrophobic substances. By contrast, we failed in the identification of C pools controlling the formation of aggregates, probably because of the disturbance of mechanical tillage which contributes to the breakdown of soil aggregates.The physically-based aggregate fractionation proposed in this study resulted useful in the  mechanistically understanding of the role of microorganisms in soil aggregation and it might be suggested for studying the impact of management on C pools, aggregates properties and their relationships in agricultural soils.

  14. Comparison of effect of locally available brands of clopidogrel on platelet aggregation in patients with coronary disease

    International Nuclear Information System (INIS)

    Khan, S.B.; Hameedullah; Noor, L.; Awan, Z.A.; Din, S.U.; Muhammad Hafeezullah, M.

    2010-01-01

    Background: Anticoagulant effect of clopidogrel is of utmost importance in coronary artery disease, especially in prevention of coronary stent thrombosis. Recently, many new local brands of clopidogrel have been launched, with unknown efficacy. This study was conducted with the aim to compare two locally prepared clopidogrel brands, in terms of the effect of a loading dose of 600 mg on inhibition of platelet aggregation in patients with coronary artery disease. Methods: This was a double blind randomised study. Sample population consisting of 35 patients, were admitted at Lady Reading Hospital, Peshawar, for the management of coronary artery disease. Baseline platelet aggregation of all these patients was measured. These patients were divided in two groups randomly. Group-A consisting of 18 patients was given brand 'A' clopidogrel 600 mg, while Group-B consisting of 17 patients was give brand 'B' of clopidogrel 600 mg. The platelet aggregation of both groups was then measured at baseline, and at 2, 4, and 6 hours after taking the loading dose of 600 mg. Results: Platelet aggregation time at baseline in Group-A was 2.61+- 2.28 sec. and in Group-B it was 2.24 +- 1.52 sec. (p=0.57). After 2 hours of clopidogrel administration in Group-A the platelet aggregation time was 1.44 +- 1.58 sec. and in Group-B it was 1.53 +- 1.107 sec. (p=0.85). Platelet aggregation time after 4 hours in Group-A was 0.28 +- 0.57 sec. and in Group-B 1.06 +- 1.03 sec. (p=0.009), and after 6 hours it was 0.00 +- 0.00 sec. in Group-A and in Group-B it was 0.59 +- 0.71 sec. (p=0.001). Conclusion: The two brands of clopidogrel had a significant difference in their effect on inhibition of platelet aggregation. Different brands of clopidogrel may not be equally effective. (author)

  15. Facilitated aggregation of FG nucleoporins under molecular crowding conditions.

    Science.gov (United States)

    Milles, Sigrid; Huy Bui, Khanh; Koehler, Christine; Eltsov, Mikhail; Beck, Martin; Lemke, Edward A

    2013-02-01

    Intrinsically disordered and phenylalanine-glycine-rich nucleoporins (FG Nups) form a crowded and selective transport conduit inside the NPC that can only be transited with the help of nuclear transport receptors (NTRs). It has been shown in vitro that FG Nups can assemble into two distinct appearances, amyloids and hydrogels. If and how these phenomena are linked and if they have a physiological role still remains unclear. Using a variety of high-resolution fluorescence and electron microscopic (EM) tools, we reveal that crowding conditions mimicking the NPC environment can accelerate the aggregation and amyloid formation speed of yeast and human FG Nups by orders of magnitude. Aggregation can be inhibited by NTRs, providing a rationale on how the cell might control amyloid formation of FG Nups. The superb spatial resolving power of EM also reveals that hydrogels are enlaced amyloid fibres, and these findings have implications for existing transport models and for NPC assembly.

  16. Patterns of [PSI+] aggregation allow insights into cellular organization of yeast prion aggregates

    Science.gov (United States)

    Tyedmers, Jens

    2012-01-01

    The yeast prion phenomenon is very widespread and mounting evidence suggests that it has an impact on cellular regulatory mechanisms related to phenotypic responses to changing environments. Studying the aggregation patterns of prion amyloids during different stages of the prion life cycle is a first key step to understand major principles of how and where cells generate, organize and turn-over prion aggregates. The induction of the [PSI+] state involves the actin cytoskeleton and quality control compartments such as the Insoluble Protein Deposit (IPOD). An initially unstable transitional induction state can be visualized by overexpression of the prion determinant and displays characteristic large ring- and ribbon-shaped aggregates consisting of poorly fragmented bundles of very long prion fibrils. In the mature prion state, the aggregation pattern is characterized by highly fragmented, shorter prion fibrils that form aggregates, which can be visualized through tagging with fluorescent proteins. The number of aggregates formed varies, ranging from a single large aggregate at the IPOD to multiple smaller ones, depending on several parameters discussed. Aggregate units below the resolution of light microscopy that are detectable by fluorescence correlation spectroscopy are in equilibrium with larger aggregates in this stage and can mediate faithful inheritance of the prion state. Loss of the prion state is often characterized by reduced fragmentation of prion fibrils and fewer, larger aggregates. PMID:22449721

  17. Antiplatelet Effects of Qishen Yiqi Dropping Pill in Platelets Aggregation in Hyperlipidemic Rabbits

    Directory of Open Access Journals (Sweden)

    Yi Wang

    2012-01-01

    Full Text Available We investigated the effects of Qishen Yiqi Dropping Pill (QSYQ on platelets aggregation and its possible mechanisms. Hyperlipidemic model in rabbits was produced by a high fat/cholesterol diet for 6 weeks, the therapeutic effect of QSYQ with 2.0 g/kg, 1.0 g/kg, and 0.5 g/kg was observed. Fourteen days after drug treatment, platelet aggregation induced by adenosine diphosphate (ADP, arachidonic acid (AA, and collagen (COLL was significantly reduced in rabbits of model group. Moreover, β-thromboglobulin (β-TG level decreased obviously but no significant change in P-selectin and platelet factor 4 (PF4 level, while QSYQ significantly decreased the ratio of thromboxane B2 (TXB2 to 6-keto-prostaglandin F1α (6-Keto-PGF1α and increased cyclic adenosine monophosphate (cAMP level in rabbits. In summary, QSYQ can improve platelets aggregation and inhibit the over-release of β-TG in hyperlipidemic rabbits; and the increased cAMP level may be involved in this process. These results suggest that the antiplatelet aggregation effect of QSYQ may be due to its ability to increase cAMP level for improving cAMP metabolism.

  18. The molecular mass of dextran used to modify magnetite nanoparticles affects insulin amyloid aggregation

    Science.gov (United States)

    Siposova, Katarina; Pospiskova, Kristyna; Bednarikova, Zuzana; Safarik, Ivo; Safarikova, Mirka; Kubovcikova, Martina; Kopcansky, Peter; Gazova, Zuzana

    2017-04-01

    Protein transformation from its soluble state into amyloid aggregates is associated with amyloid-related diseases. Amyloid deposits of insulin fibrils have been found in the sites of subcutaneous insulin application in patients with prolonged diabetes. Using atomic force microscopy and ThT fluorescence assay we have investigated the interference of insulin amyloid aggregation with superparamagnetic Fe3O4-based nanoparticles (SPIONs) coated with dextran (DEX); molecular mass of dextran was equal to 15-20, 40 or 70 kDa. The obtained data indicate that all three types of dextran coated nanoparticles (NP-FeDEXs) are able to inhibit insulin fibrillization and to destroy amyloid fibrils. The extent of anti-amyloid activities depends on the properties of NP-FeDEXs, mainly on the size of nanoparticles which is determined by molecular mass of dextran molecules. The most effective inhibiting activity was observed for the smallest nanoparticles coated with 15-20 kDa dextran. Contrary, the highest destroying activity was observed for the largest NP-FeDEX (70 kDa dextran).

  19. Effect of aggregate graining compositions on skid resistance of Exposed Aggregate Concrete pavement

    Science.gov (United States)

    Wasilewska, Marta; Gardziejczyk, Wladysław; Gierasimiuk, Pawel

    2018-05-01

    The paper presents the evaluation of skid resistance of EAC (Exposed Aggregate Concrete) pavements which differ in aggregate graining compositions. The tests were carried out on concrete mixes with a maximum aggregate size of 8 mm. Three types of coarse aggregates were selected depending on their resistance to polishing which was determined on the basis of the PSV (Polished Stone Value). Basalt (PSV 48), gabbro (PSV 50) and trachybasalt (PSV 52) aggregates were chosen. For each type of aggregate three graining compositions were designed, which differed in the content of coarse aggregate > 4mm. Their content for each series was as follows: A - 38%, B - 50% and C - 68%. Evaluation of the skid resistance has been performed using the FAP (Friction After Polishing) test equipment also known as the Wehner/Schulze machine. Laboratory method enables to compare the skid resistance of different types of wearing course under specified conditions simulating polishing processes. In addition, macrotexture measurements were made on the surface of each specimen using the Elatexure laser profile. Analysis of variance showed that at significance level α = 0.05, aggregate graining compositions as well as the PSV have a significant influence on the obtained values of the friction coefficient μm of the tested EAC pavements. The highest values of the μm have been obtained for EAC with the lowest amount of coarse aggregates (compositions A). In these cases the resistance to polishing of the aggregate does not significantly affect the friction coefficients. This is related to the large areas of cement mortar between the exposed coarse grains. Based on the analysis of microscope images, it was observed that the coarse aggregates were not sufficiently exposed. It has been proved that PSV significantly affected the coefficient of friction in the case of compositions B and C. This is caused by large areas of exposed coarse aggregate. The best parameters were achieved for the EAC pavements

  20. Concrete produced with recycled aggregates

    Directory of Open Access Journals (Sweden)

    J. J. L. Tenório

    Full Text Available This paper presents the analysis of the mechanical and durable properties of recycled aggregate concrete (RAC for using in concrete. The porosity of recycled coarse aggregates is known to influence the fresh and hardened concrete properties and these properties are related to the specific mass of the recycled coarse aggregates, which directly influences the mechanical properties of the concrete. The recycled aggregates were obtained from construction and demolition wastes (CDW, which were divided into recycled sand (fine and coarse aggregates. Besides this, a recycled coarse aggregate of a specific mass with a greater density was obtained by mixing the recycled aggregates of the CDW with the recycled aggregates of concrete wastes (CW. The concrete was produced in laboratory by combining three water-cement ratios, the ratios were used in agreement with NBR 6118 for structural concretes, with each recycled coarse aggregates and recycled sand or river sand, and the reference concrete was produced with natural aggregates. It was observed that recycled aggregates can be used in concrete with properties for structural concrete. In general, the use of recycled coarse aggregate in combination with recycled sand did not provide good results; but when the less porous was used, or the recycled coarse aggregate of a specific mass with a greater density, the properties of the concrete showed better results. Some RAC reached bigger strengths than the reference concrete.

  1. Graph Aggregation

    NARCIS (Netherlands)

    Endriss, U.; Grandi, U.

    Graph aggregation is the process of computing a single output graph that constitutes a good compromise between several input graphs, each provided by a different source. One needs to perform graph aggregation in a wide variety of situations, e.g., when applying a voting rule (graphs as preference

  2. p53 Aggregates penetrate cells and induce the co-aggregation of intracellular p53.

    Directory of Open Access Journals (Sweden)

    Karolyn J Forget

    Full Text Available Prion diseases are unique pathologies in which the infectious particles are prions, a protein aggregate. The prion protein has many particular features, such as spontaneous aggregation, conformation transmission to other native PrP proteins and transmission from an individual to another. Protein aggregation is now frequently associated to many human diseases, for example Alzheimer's disease, Parkinson's disease or type 2 diabetes. A few proteins associated to these conformational diseases are part of a new category of proteins, called prionoids: proteins that share some, but not all, of the characteristics associated with prions. The p53 protein, a transcription factor that plays a major role in cancer, has recently been suggested to be a possible prionoid. The protein has been shown to accumulate in multiple cancer cell types, and its aggregation has also been reproduced in vitro by many independent groups. These observations suggest a role for p53 aggregates in cancer development. This study aims to test the «prion-like» features of p53. Our results show in vitro aggregation of the full length and N-terminally truncated protein (p53C, and penetration of these aggregates into cells. According to our findings, the aggregates enter cells using macropinocytosis, a non-specific pathway of entry. Lastly, we also show that once internalized by the cell, p53C aggregates can co-aggregate with endogenous p53 protein. Together, these findings suggest prion-like characteristics for p53 protein, based on the fact that p53 can spontaneously aggregate, these aggregates can penetrate cells and co-aggregate with cellular p53.

  3. Anti-Platelet Aggregation and Vasorelaxing Effects of the Constituents of the Rhizomes of Zingiber officinale

    Directory of Open Access Journals (Sweden)

    Tian-Shung Wu

    2012-07-01

    Full Text Available In the present study, the chemical investigation of the bioactive fractions of the rhizomes of Zingiber officinale has resulted in the identification of twenty-nine compounds including one new compound, O-methyldehydrogingerol (1. Some of the isolates were subjected into the evaluation of their antiplatelet aggregation and vasorelaxing bioactivities. Among the tested compounds, [6]-gingerol (13 and [6]-shogaol (17 exhibited potent anti-platelet aggregation bioactivity. In addition, [10]-gingerol (15 inhibited the Ca2+-dependent contractions in high K+ medium. According to the results in the present research, the bioactivity of ginger could be related to the anti-platelet aggregation and vasorelaxing mechanism.

  4. Cell Surface Binding and Internalization of Aβ Modulated by Degree of Aggregation

    Directory of Open Access Journals (Sweden)

    David A. Bateman

    2011-01-01

    Full Text Available The amyloid peptides, Aβ40 and Aβ42, are generated through endoproteolytic cleavage of the amyloid precursor protein. Here we have developed a model to investigate the interaction of living cells with various forms of aggregated Aβ40/42. After incubation at endosomal pH 6, we observed a variety of Aβ conformations after 3 (Aβ3, 24 (Aβ24, and 90 hours (Aβ90. Both Aβ4224 and Aβ4024 were observed to rapidly bind and internalize into differentiated PC12 cells, leading to accumulation in the lysosome. In contrast, Aβ40/4290 were both found to only weakly associate with cells, but were observed as the most aggregated using dynamic light scattering and thioflavin-T. Internalization of Aβ40/4224 was inhibited with treatment of monodansylcadaverine, an endocytosis inhibitor. These studies indicate that the ability of Aβ40/42 to bind and internalize into living cells increases with degree of aggregation until it reaches a maximum beyond which its ability to interact with cells diminishes drastically.

  5. Shift in aggregation, ROS generation, antioxidative defense, lysozyme and acetylcholinesterase activities in the cells of an Indian freshwater sponge exposed to washing soda (sodium carbonate).

    Science.gov (United States)

    Mukherjee, Soumalya; Ray, Mitali; Ray, Sajal

    2016-09-01

    Washing soda, chemically identified as anhydrous sodium carbonate, is a popular cleaning agent among the rural and urban populations of India which often contaminates the freshwater ponds and lakes, the natural habitat of sponge Eunapius carteri. Present investigation deals with estimation of cellular aggregation, generation of ROS and activities of antioxidant enzymes, lysozyme and acetylcholinesterase in the cells of E. carteri under the environmentally realistic concentrations of washing soda. Prolonged treatment of washing soda inhibited the degree of cellular aggregation. Experimental exposure of 8 and 16mg/l of sodium carbonate for 48h elevated the physiological level of reactive oxygen species (ROS) generation in the agranulocytes, semigranulocytes and granulocytes of E. carteri, whereas, treatment of 192h inhibited the ROS generation in three cellular morphotypes. Activities of superoxide dismutase, catalase and glutathione-S-transferase were recorded to be inhibited under prolonged exposure of washing soda. Washing soda mediated inhibition of ROS generation and depletion in the activities of antioxidant enzymes were indicative to an undesirable shift in cytotoxic status and antioxidative defense in E. carteri. Inhibition in the activity of lysozyme under the treatment of sodium carbonate was suggestive to a severe impairment of the innate immunological efficiency of E. carteri distributed in the washing soda contaminated habitat. Washing soda mediated inhibition in the activity of acetylcholinesterase indicated its neurotoxicity in E. carteri. Washing soda, a reported environmental contaminant, affected adversely the immunophysiological status of E. carteri with reference to cellular aggregation, oxidative stress, antioxidative defense, lysozyme and acetylcholinesterase activity. Copyright © 2016 Elsevier Inc. All rights reserved.

  6. Laser isotope separation using selective inhibition and encouragement of dimer formation

    International Nuclear Information System (INIS)

    Kivel, B.

    1979-01-01

    Method and apparatus for inhibiting dimer formation of molecules of a selected isotope type in a cooled flow of gas to enhance the effectiveness of mass difference isotope separation techniques are described. Molecules in the flow containing atoms of the selected isotope type are selectively excited by infrared radiation in order to inhibit the formation of dimers and larger clusters of such molecules, while the molecules not containing atoms of the selected, excited type are encouraged to form dimers and higher order aggregates by the cooling of the gaseous flow. The molecules with the excited isotope will predominate in monomers and will constitute the enriched product stream, while the aggregated group comprising molecules having the unexcited isotope will predominate in dimers and larger clusters of molecules, forming the tails stream. The difference in diffusion coefficientts between particles of the excited and unexcited isotopes is enhanced by the greater mass differences resulting from aggregation of unexcited particles into dimers and larger clusters. Prior art separation techniques which exploit differences in isotopic diffusion rates will consequently exhibit enhanced enrichment per stage by the utilization of the present invention

  7. Information Aggregation in Organizations

    OpenAIRE

    Schulte, Elisabeth

    2006-01-01

    This dissertation contributes to the analysis of information aggregation procedures within organizations. Facing uncertainty about the consequences of a collective decision, information has to be aggregated before making a choice. Two main questions are addressed. Firstly, how well is an organization suited for the aggregation of decision-relevant information? Secondly, how should an organization be designed in order to aggregate information efficiently? The main part deals with information a...

  8. An anticancer drug suppresses the primary nucleation reaction that initiates the production of the toxic Aβ42 aggregates linked with Alzheimer's disease.

    Science.gov (United States)

    Habchi, Johnny; Arosio, Paolo; Perni, Michele; Costa, Ana Rita; Yagi-Utsumi, Maho; Joshi, Priyanka; Chia, Sean; Cohen, Samuel I A; Müller, Martin B D; Linse, Sara; Nollen, Ellen A A; Dobson, Christopher M; Knowles, Tuomas P J; Vendruscolo, Michele

    2016-02-01

    The conversion of the β-amyloid (Aβ) peptide into pathogenic aggregates is linked to the onset and progression of Alzheimer's disease. Although this observation has prompted an extensive search for therapeutic agents to modulate the concentration of Aβ or inhibit its aggregation, all clinical trials with these objectives have so far failed, at least in part because of a lack of understanding of the molecular mechanisms underlying the process of aggregation and its inhibition. To address this problem, we describe a chemical kinetics approach for rational drug discovery, in which the effects of small molecules on the rates of specific microscopic steps in the self-assembly of Aβ42, the most aggregation-prone variant of Aβ, are analyzed quantitatively. By applying this approach, we report that bexarotene, an anticancer drug approved by the U.S. Food and Drug Administration, selectively targets the primary nucleation step in Aβ42 aggregation, delays the formation of toxic species in neuroblastoma cells, and completely suppresses Aβ42 deposition and its consequences in a Caenorhabditis elegans model of Aβ42-mediated toxicity. These results suggest that the prevention of the primary nucleation of Aβ42 by compounds such as bexarotene could potentially reduce the risk of onset of Alzheimer's disease and, more generally, that our strategy provides a general framework for the rational identification of a range of candidate drugs directed against neurodegenerative disorders.

  9. A Novel Method to Quantify Soil Aggregate Stability by Measuring Aggregate Bond Energies

    Science.gov (United States)

    Efrat, Rachel; Rawlins, Barry G.; Quinton, John N.; Watts, Chris W.; Whitmore, Andy P.

    2016-04-01

    Soil aggregate stability is a key indicator of soil quality because it controls physical, biological and chemical functions important in cultivated soils. Micro-aggregates are responsible for the long term sequestration of carbon in soil, therefore determine soils role in the carbon cycle. It is thus vital that techniques to measure aggregate stability are accurate, consistent and reliable, in order to appropriately manage and monitor soil quality, and to develop our understanding and estimates of soil as a carbon store to appropriately incorporate in carbon cycle models. Practices used to assess the stability of aggregates vary in sample preparation, operational technique and unit of results. They use proxies and lack quantification. Conflicting results are therefore drawn between projects that do not provide methodological or resultant comparability. Typical modern stability tests suspend aggregates in water and monitor fragmentation upon exposure to an un-quantified amount of ultrasonic energy, utilising a laser granulometer to measure the change in mean weight diameter. In this project a novel approach has been developed based on that of Zhu et al., (2009), to accurately quantify the stability of aggregates by specifically measuring their bond energies. The bond energies are measured operating a combination of calorimetry and a high powered ultrasonic probe, with computable output function. Temperature change during sonication is monitored by an array of probes which enables calculation of the energy spent heating the system (Ph). Our novel technique suspends aggregates in heavy liquid lithium heteropolytungstate, as opposed to water, to avoid exposing aggregates to an immeasurable disruptive energy source, due to cavitation, collisions and clay swelling. Mean weight diameter is measured by a laser granulometer to monitor aggregate breakdown after successive periods of calculated ultrasonic energy input (Pi), until complete dispersion is achieved and bond

  10. Comparative evaluation of antiplatelet effect of lycopene with aspirin and the effect of their combination on platelet aggregation: An in vitro study.

    Science.gov (United States)

    Sawardekar, Swapna B; Patel, Tejal C; Uchil, Dinesh

    2016-01-01

    The objective was to compare antiplatelet effect of lycopene with aspirin and to study effect of combination of the two on platelet aggregation in vitro, using platelets from healthy volunteers. Platelets were harvested; platelet count of platelet-rich plasma adjusted to 2.5 Χ 10(5)/μL. Aspirin (140 μmol/L) and lycopene (4, 6, 8, 10, and 12 μmol/L) were studied in vitro against adenosine-5'- diphosphate (ADP) (2.5 μM/L) and collagen. All the concentrations of lycopene (4-12 μmol/L) exhibited reduction in maximum platelet aggregation induced by aggregating agents ADP and collagen (P Lycopene at concentration 10 μmol/L showed maximum platelet inhibition (47.05% ± 19.56%) against ADP, whereas lycopene at concentration 8 μmol/L showed maximum platelet inhibition (54.26% ± 30.71%) against collagen. Four μmol/L of lycopene combined with 140 μmol/L and 70 μmol/L aspirin showed greater inhibition of platelets as compared to aspirin 140 μmol/L alone, against both ADP and collagen. The study favorably compares lycopene and aspirin with respect to their antiplatelet activities against ADP and collagen. Lycopene can be considered as a potential target for modifying the thrombotic and pro-inflammatory events associated with platelet activation.

  11. Pterostilbene-O-acetamidoalkylbenzylamines derivatives as novel dual inhibitors of cholinesterase with anti-β-amyloid aggregation and antioxidant properties for the treatment of Alzheimer's disease.

    Science.gov (United States)

    Li, Yuxing; Qiang, Xiaoming; Li, Yan; Yang, Xia; Luo, Li; Xiao, Ganyuan; Cao, Zhongcheng; Tan, Zhenghuai; Deng, Yong

    2016-04-15

    A series of pterostilbene-O-acetamidoalkylbenzylamines were designed, synthesized and evaluated as dual inhibitors of AChE and BuChE. To further explore the multifunctional properties of the new derivatives, their antioxidant activities and inhibitory effects on self-induced Aβ1-42 aggregation and HuAChE-induced Aβ1-40 aggregation were also tested. The results showed that most of these compounds could effectively inhibit AChE and BuChE. Particularly, compound 21d exhibited the best AChE inhibitory activity (IC50=0.06 μM) and good inhibition of BuChE (IC50=28.04 μM). Both the inhibition kinetic analysis and molecular modeling study revealed that these compounds showed mixed-type inhibition, binding simultaneously to the CAS and PAS of AChE. In addition to cholinesterase inhibitory activities, these compounds showed different levels of antioxidant activity. However, the inhibitory activities against self-induced and HuAChE-induced Aβ aggregation of these new derivatives were unsatisfied. Taking into account the results of the biological evaluation, further modifications will be designed in order to increase the potency on the different targets. The results displayed in this Letter can be a new starting point for further development of multifunctional agents for Alzheimer's disease. Copyright © 2016 Elsevier Ltd. All rights reserved.

  12. Recycled aggregates concrete: aggregate and mix properties

    Directory of Open Access Journals (Sweden)

    González-Fonteboa, B.

    2005-09-01

    Full Text Available This study of structural concrete made with recycled concrete aggregate focuses on two issues: 1. The characterization of such aggregate on the Spanish market. This involved conducting standard tests to determine density, water absorption, grading, shape, flakiness and hardness. The results obtained show that, despite the considerable differences with respect to density and water absorption between these and natural aggregates, on the whole recycled aggregate is apt for use in concrete production. 2. Testing to determine the values of basic concrete properties: mix design parameters were established for structural concrete in non-aggressive environments. These parameters were used to produce conventional concrete, and then adjusted to manufacture recycled concrete aggregate (RCA concrete, in which 50% of the coarse aggregate was replaced by the recycled material. Tests were conducted to determine the physical (density of the fresh and hardened material, water absorption and mechanical (compressive strength, splitting tensile strength and modulus of elasticity properties. The results showed that, from the standpoint of its physical and mechanical properties, concrete in which RCA accounted for 50% of the coarse aggregate compared favourably to conventional concrete.

    Se aborda el estudio de hormigones estructurales fabricados con áridos reciclados procedentes de hormigón, incidiéndose en dos aspectos: 1. Caracterización de tales áridos, procedentes del mercado español. Para ello se llevan a cabo ensayos de densidad, absorción, granulometría, coeficiente de forma, índice de lajas y dureza. Los resultados obtenidos han puesto de manifiesto que, a pesar de que existen diferencias notables (sobre todo en cuanto a densidad y absorción con los áridos naturales, las características de los áridos hacen posible la fabricación de hormigones. 2. Ensayos sobre propiedades básicas de los hormigones: se establecen parámetros de dosificaci

  13. Towards General Temporal Aggregation

    DEFF Research Database (Denmark)

    Boehlen, Michael H.; Gamper, Johann; Jensen, Christian Søndergaard

    2008-01-01

    associated with the management of temporal data. Indeed, temporal aggregation is complex and among the most difficult, and thus interesting, temporal functionality to support. This paper presents a general framework for temporal aggregation that accommodates existing kinds of aggregation, and it identifies...

  14. Strategy of ring-shaped aggregates in excitation energy transfer for removing disorder-induced shielding

    International Nuclear Information System (INIS)

    Tei, Go; Nakatani, Masatoshi; Ishihara, Hajime

    2013-01-01

    Peripheral light harvesting complex (LH2), which is found in photosynthetic antenna systems of purple photosynthetic bacteria, has important functions in the photosynthetic process, such as harvesting sunlight and transferring its energy to the photosynthetic reaction center. The key component in excitation energy transfer (EET) between LH2s is B850, which is a characteristic ring-shaped aggregate of pigments usually formed by 18 or 16 bacteriochlorophylls in LH2. We theoretically study the strategy of the ring-shaped aggregate structure, which maximizes EET efficiency, by using the standard Frenkel exciton model and the self-consistent calculation method for the Markovian quantum master equation and Maxwell equation. As a result, we have revealed a simple but ingenious strategy of the ring-shaped aggregate structure. The combination of three key properties of the ring unit system maximizes the EET efficiency, namely the large dipole moment of aggregates causes the basic improvement of EET efficiency, and the isotropic nature and the large occupying area are critically effective to remove the disorder-induced shielding that inhibits EET in the presence of the randomness of orientation and alignment of carriers of excitation energy. (paper)

  15. Strategy of ring-shaped aggregates in excitation energy transfer for removing disorder-induced shielding

    Science.gov (United States)

    Tei, Go; Nakatani, Masatoshi; Ishihara, Hajime

    2013-06-01

    Peripheral light harvesting complex (LH2), which is found in photosynthetic antenna systems of purple photosynthetic bacteria, has important functions in the photosynthetic process, such as harvesting sunlight and transferring its energy to the photosynthetic reaction center. The key component in excitation energy transfer (EET) between LH2s is B850, which is a characteristic ring-shaped aggregate of pigments usually formed by 18 or 16 bacteriochlorophylls in LH2. We theoretically study the strategy of the ring-shaped aggregate structure, which maximizes EET efficiency, by using the standard Frenkel exciton model and the self-consistent calculation method for the Markovian quantum master equation and Maxwell equation. As a result, we have revealed a simple but ingenious strategy of the ring-shaped aggregate structure. The combination of three key properties of the ring unit system maximizes the EET efficiency, namely the large dipole moment of aggregates causes the basic improvement of EET efficiency, and the isotropic nature and the large occupying area are critically effective to remove the disorder-induced shielding that inhibits EET in the presence of the randomness of orientation and alignment of carriers of excitation energy.

  16. TOTAL HEMOCYTE COUNT AND HEMOLYMPH GLUCOSE CONCENRATION RESPONSE OF SPINY LOBSTER Panulirus homarus ON RATIO OF SHELTER

    Directory of Open Access Journals (Sweden)

    Suhaiba Djai

    2017-11-01

    Full Text Available This research was conducted to assess the physiological response of the lobster Panulirus homarus for the ratio of the shelters. The method used completely randomized design with two replicates of each treatments with shelter ratio (A 1 : 5, (B 3 : 5, (C 4 : 5, (D 5 : 5. Weight average for 184 lobsters with the stocking density of 23 lobsters for each treatment was 32.64 ± 0.58 g. The experiment was conducted for 60 days. The lobster was fed with trash fish and acclimatized for 7 days before the experiment. Observations on the physiologycal of every 10 days. The physiological responses that observed were total hemocyte count (THC and hemolymph glucose concentration. The results showed that 4:5 was the best lobster shelter ratio because it could reduce stress levels. This is indicated by the stable values of THC and hemolymph glucose level during the experiment and supported by the growth of 57.28 ± 0.15 g and survival rate of 91.31 ± 2.60%. Keywords: lobster, Panulirus homarus, ratio, shelter, THC, glucose

  17. A novel role of sesamol in inhibiting NF-κB-mediated signaling in platelet activation

    Directory of Open Access Journals (Sweden)

    Chang Chao-Chien

    2011-12-01

    Full Text Available Abstract Background Platelet activation is relevant to a variety of coronary heart diseases. Our previous studies revealed that sesamol possesses potent antiplatelet activity through increasing cyclic AMP formation. Although platelets are anucleated cells, they also express the transcription factor, NF-κB, that may exert non-genomic functions in platelet activation. Therefore, we further investigated the inhibitory roles of sesamol in NF-κB-mediated platelet function. Methods Platelet aggregation, Fura 2-AM fluorescence, and immunoblotting analysis were used in this study. Results NF-κB signaling events, including IKKβ phosphorylation, IκBα degradation, and p65 phosphorylation, were markedly activated by collagen (1 μg/ml in washed human platelets, and these signaling events were attenuated by sesamol (2.5~25 μM. Furthermore, SQ22536 and ODQ, inhibitors of adenylate cyclase and guanylate cyclase, respectively, strongly reversed the sesamol (25 μM-mediated inhibitory effects of IKKβ phosphorylation, IκBα degradation, and p65 phosphorylation stimulated by collagen. The protein kinase A (PKA inhibitor, H89, also reversed sesamol-mediated inhibition of IκBα degradation. Moreover, BAY11-7082, an NF-κB inhibitor, abolished IκBα degradation, phospholipase C (PLCγ2 phosphorylation, protein kinase C (PKC activation, [Ca2+]i mobilization, and platelet aggregation stimulated by collagen. Preincubation of platelets with the inhibitors, SQ22536 and H89, both strongly reversed sesamol-mediated inhibition of platelet aggregation and [Ca2+]i mobilization. Conclusions Sesamol activates cAMP-PKA signaling, followed by inhibition of the NF-κB-PLC-PKC cascade, thereby leading to inhibition of [Ca2+]i mobilization and platelet aggregation. Because platelet activation is not only linked to hemostasis, but also has a relevant role in inflammation and metastasis, our data demonstrating that inhibition of NF-κB interferes with platelet function may

  18. Awa1p on the cell surface of sake yeast inhibits biofilm formation and the co-aggregation between sake yeasts and Lactobacillus plantarum ML11-11.

    Science.gov (United States)

    Hirayama, Satoru; Shimizu, Masashi; Tsuchiya, Noriko; Furukawa, Soichi; Watanabe, Daisuke; Shimoi, Hitoshi; Takagi, Hiroshi; Ogihara, Hirokazu; Morinaga, Yasushi

    2015-05-01

    We examined mixed-species biofilm formation between Lactobacillus plantarum ML11-11 and both foaming and non-foaming mutant strains of Saccharomyces cerevisiae sake yeasts. Wild-type strains showed significantly lower levels of biofilm formation compared with the non-foaming mutants. Awa1p, a protein involved in foam formation during sake brewing, is a glycosylphosphatidylinositol (GPI)-anchored protein and is associated with the cell wall of sake yeasts. The AWA1 gene of the non-foaming mutant strain Kyokai no. 701 (K701) has lost the C-terminal sequence that includes the GPI anchor signal. Mixed-species biofilm formation and co-aggregation of wild-type strain Kyokai no. 7 (K7) were significantly lower than K701 UT-1 (K701 ura3/ura3 trp1/trp1), while the levels of strain K701 UT-1 carrying the AWA1 on a plasmid were comparable to those of K7. The levels of biofilm formation and co-aggregation of the strain K701 UT-1 harboring AWA1 with a deleted GPI anchor signal were similar to those of K701 UT-1. These results clearly demonstrate that Awa1p present on the surface of sake yeast strain K7 inhibits adhesion between yeast cells and L. plantarum ML11-11, consequently impeding mixed-species biofilm formation. Copyright © 2014 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.

  19. Inhibition of urinary calculi -- a spectroscopic study

    Science.gov (United States)

    Manciu, Felicia; Govani, Jayesh; Durrer, William; Reza, Layra; Pinales, Luis

    2008-10-01

    Although a considerable number of investigations have already been undertaken and many causes such as life habits, metabolic disorders, and genetic factors have been noted as sources that accelerate calculi depositions and aggregations, there are still plenty of unanswered questions regarding efficient inhibition and treatment mechanisms. Thus, in an attempt to acquire more insights, we propose here a detailed scientific study of kidney stone formation and growth inhibition based on a traditional medicine approach with Rotula Aquatica Lour (RAL) herbal extracts. A simplified single diffusion gel growth technique was used for synthesizing the samples for the present study. The unexpected Zn presence in the sample with RAL inhibitor, as revealed by XPS measurements, explains the inhibition process and the dramatic reflectance of the incident light observed in the infrared transmission studies. Raman data demonstrate potential binding of the inhibitor with the oxygen of the kidney stone. Photoluminescence results corroborate to provide additional evidence of Zn-related inhibition.

  20. Proteins aggregation and human diseases

    International Nuclear Information System (INIS)

    Hu, Chin-Kun

    2015-01-01

    Many human diseases and the death of most supercentenarians are related to protein aggregation. Neurodegenerative diseases include Alzheimer's disease (AD), Huntington's disease (HD), Parkinson's disease (PD), frontotemporallobar degeneration, etc. Such diseases are due to progressive loss of structure or function of neurons caused by protein aggregation. For example, AD is considered to be related to aggregation of Aβ40 (peptide with 40 amino acids) and Aβ42 (peptide with 42 amino acids) and HD is considered to be related to aggregation of polyQ (polyglutamine) peptides. In this paper, we briefly review our recent discovery of key factors for protein aggregation. We used a lattice model to study the aggregation rates of proteins and found that the probability for a protein sequence to appear in the conformation of the aggregated state can be used to determine the temperature at which proteins can aggregate most quickly. We used molecular dynamics and simple models of polymer chains to study relaxation and aggregation of proteins under various conditions and found that when the bending-angle dependent and torsion-angle dependent interactions are zero or very small, then protein chains tend to aggregate at lower temperatures. All atom models were used to identify a key peptide chain for the aggregation of insulin chains and to find that two polyQ chains prefer anti-parallel conformation. It is pointed out that in many cases, protein aggregation does not result from protein mis-folding. A potential drug from Chinese medicine was found for Alzheimer's disease. (paper)

  1. Proteins aggregation and human diseases

    Science.gov (United States)

    Hu, Chin-Kun

    2015-04-01

    Many human diseases and the death of most supercentenarians are related to protein aggregation. Neurodegenerative diseases include Alzheimer's disease (AD), Huntington's disease (HD), Parkinson's disease (PD), frontotemporallobar degeneration, etc. Such diseases are due to progressive loss of structure or function of neurons caused by protein aggregation. For example, AD is considered to be related to aggregation of Aβ40 (peptide with 40 amino acids) and Aβ42 (peptide with 42 amino acids) and HD is considered to be related to aggregation of polyQ (polyglutamine) peptides. In this paper, we briefly review our recent discovery of key factors for protein aggregation. We used a lattice model to study the aggregation rates of proteins and found that the probability for a protein sequence to appear in the conformation of the aggregated state can be used to determine the temperature at which proteins can aggregate most quickly. We used molecular dynamics and simple models of polymer chains to study relaxation and aggregation of proteins under various conditions and found that when the bending-angle dependent and torsion-angle dependent interactions are zero or very small, then protein chains tend to aggregate at lower temperatures. All atom models were used to identify a key peptide chain for the aggregation of insulin chains and to find that two polyQ chains prefer anti-parallel conformation. It is pointed out that in many cases, protein aggregation does not result from protein mis-folding. A potential drug from Chinese medicine was found for Alzheimer's disease.

  2. Predation by feeding aggregations of Drupella spp. inhibits the recovery of reefs damaged by a mass bleaching event

    Science.gov (United States)

    Bruckner, Andrew W.; Coward, Georgia; Bimson, Kathyrn; Rattanawongwan, Tipwimon

    2017-12-01

    High densities of two corallivorous gastropods, Drupella cornus and D. rugosa, may delay the recovery of coral reefs impacted by mass bleaching events by aggregating on the remaining corals. Following severe bleaching in April/May 2016 that resulted in the loss of up to 80% of the living coral cover from reefs in South Malé, Maldives, aggregations of up to 250 Drupella per coral were recorded on surviving colonies. The distribution of snails was not random; larger aggregations were seen on reefs with fewer remaining live corals and also on the largest corals. Branching, digitate and tabular corals, especially species of Acropora and Pocillopora, sustained the highest mortality from the bleaching. Remaining colonies of these taxa exhibited the highest occurrence of snails and the most extensive snail predation, although less-preferred taxa such as Montipora, Porites, Astreopora, Cyphastrea and Pachyseris were also targeted. Drupella also concentrated on broken Acropora branches and overturned colonies; on some reefs, these were the only surviving acroporids, and many of them did not bleach. Continued predation pressure from Drupella may eliminate formerly dominant corals, including genets that are resistant to higher sea water temperatures.

  3. Engineered aggregation inhibitor fusion for production of highly amyloidogenic human islet amyloid polypeptide.

    Science.gov (United States)

    Mirecka, Ewa Agnieszka; Gremer, Lothar; Schiefer, Stephanie; Oesterhelt, Filipp; Stoldt, Matthias; Willbold, Dieter; Hoyer, Wolfgang

    2014-12-10

    Human islet amyloid polypeptide (IAPP) is the major component of pancreatic amyloid deposits in type 2 diabetes. The structural conversion of IAPP from a monomeric state into amyloid assemblies is the subject of intense research. Recombinant production of IAPP is, however, difficult due to its extreme aggregation propensity. Here we describe a novel strategy for expression of IAPP in Escherichia coli, based on an engineered protein tag, which sequesters IAPP monomers and prevents IAPP aggregation. The IAPP-binding protein HI18 was selected by phage display from a β-wrapin library. Fusion of HI18 to IAPP enabled the soluble expression of the construct. IAPP was cleaved from the fusion construct and purified to homogeneity with a yield of 3mg of isotopically labeled peptide per liter of culture. In the monomeric state, IAPP was largely disordered as evidenced by far-UV CD and liquid-state NMR spectroscopy but competent to form amyloid fibrils according to atomic force microscopy. These results demonstrate the ability of the engineered β-wrapin HI18 for shielding the hydrophobic sequence of IAPP during expression and purification. Fusion of aggregation-inhibiting β-wrapins is a suitable approach for the recombinant production of aggregation-prone proteins. Copyright © 2014 Elsevier B.V. All rights reserved.

  4. Gallic Acid Attenuates Platelet Activation and Platelet-Leukocyte Aggregation: Involving Pathways of Akt and GSK3β

    Science.gov (United States)

    Chang, Shih-Sheng; Lee, Viola S. Y.; Tseng, Yu-Lun; Chang, Kuan-Cheng; Chen, Kuen-Bao; Chen, Yuh-Lien; Li, Chi-Yuan

    2012-01-01

    Platelet activation and its interaction with leukocytes play an important role in atherothrombosis. Cardiovascular diseases resulted from atherothrombosis remain the major causes of death worldwide. Gallic acid, a major constituent of red wine and tea, has been believed to have properties of cardiovascular protection, which is likely to be related to its antioxidant effects. Nonetheless, there were few and inconsistent data regarding the effects of gallic acid on platelet function. Therefore, we designed this in vitro study to determine whether gallic acid could inhibit platelet activation and the possible mechanisms. From our results, gallic acid could concentration-dependently inhibit platelet aggregation, P-selectin expression, and platelet-leukocyte aggregation. Gallic acid prevented the elevation of intracellular calcium and attenuated phosphorylation of PKCα/p38 MAPK and Akt/GSK3β on platelets stimulated by the stimulants ADP or U46619. This is the first mechanistic explanation for the inhibitory effects on platelets from gallic acid. PMID:22811749

  5. Gallic Acid Attenuates Platelet Activation and Platelet-Leukocyte Aggregation: Involving Pathways of Akt and GSK3β

    Directory of Open Access Journals (Sweden)

    Shih-Sheng Chang

    2012-01-01

    Full Text Available Platelet activation and its interaction with leukocytes play an important role in atherothrombosis. Cardiovascular diseases resulted from atherothrombosis remain the major causes of death worldwide. Gallic acid, a major constituent of red wine and tea, has been believed to have properties of cardiovascular protection, which is likely to be related to its antioxidant effects. Nonetheless, there were few and inconsistent data regarding the effects of gallic acid on platelet function. Therefore, we designed this in vitro study to determine whether gallic acid could inhibit platelet activation and the possible mechanisms. From our results, gallic acid could concentration-dependently inhibit platelet aggregation, P-selectin expression, and platelet-leukocyte aggregation. Gallic acid prevented the elevation of intracellular calcium and attenuated phosphorylation of PKCα/p38 MAPK and Akt/GSK3β on platelets stimulated by the stimulants ADP or U46619. This is the first mechanistic explanation for the inhibitory effects on platelets from gallic acid.

  6. Denitrification in Soil Aggregate Analogues-Effect of Aggregate Size and Oxygen Diffusion

    Directory of Open Access Journals (Sweden)

    Steffen Schlüter

    2018-04-01

    Full Text Available Soil-borne nitrous oxide (N2O emissions have a high spatial and temporal variability which is commonly attributed to the occurrence of hotspots and hot moments for microbial activity in aggregated soil. Yet there is only limited information about the biophysical processes that regulate the production and consumption of N2O on microscopic scales in undisturbed soil. In this study, we introduce an experimental framework relying on simplified porous media that circumvents some of the complexities occuring in natural soils while fully accounting for physical constraints believed to control microbial activity in general and denitrification in particular. We used this framework to explore the impact of aggregate size and external oxygen concentration on the kinetics of O2 consumption, as well as CO2 and N2O production. Model aggregates of different sizes (3.5 vs. 7 mm diameter composed of porous, sintered glass were saturated with a defined growth medium containing roughly 109 cells ml−1 of the facultative anaerobic, nosZ-deficient denitrifier Agrobacterium tumefaciens with N2O as final denitrification product and incubated at five different oxygen levels (0–13 vol-%. We demonstrate that the onset of denitrification depends on the amount of external oxygen and the size of aggregates. Smaller aggregates were better supplied with oxygen due to a larger surface-to-volume ratio, which resulted in faster growth and an earlier onset of denitrification. In larger aggregates, the onset of denitrification was more gradual, but with comparably higher N2O production rates once the anoxic aggregate centers were fully developed. The normalized electron flow from the reduced carbon substrate to N-oxyanions (edenit-/etotal- ratio could be solely described as a function of initial oxygen concentration in the headspace with a simple, hyperbolic model, for which the two empirical parameters changed with aggregate size in a consistent way. These findings confirm the

  7. Effect of the Aggregate Size on Strength Properties of Recycled Aggregate Concrete

    Directory of Open Access Journals (Sweden)

    Ma Kang

    2018-01-01

    Full Text Available The study on preparation technology of recycled concrete with economical and technical feasibility has gained more serious attention in each country due to its involvement and effect on the environment protection and the sustainable development of human society. In this study, we conducted a control variable test to investigate and assess the influence of the aggregate size on the strength characteristics of concrete with different diameters of recycled aggregates. Concrete with recycled aggregates of 5∼15 mm (A, 15∼20 mm (B, 20∼30 mm (C, and their combinations were subjected to a series of unconfined pressure tests after curing for 28 days. Based on the results obtained from the tests, an effort was made to study the relationship between the mechanical characteristics of recycled aggregate concrete and aggregate particle size. Also, a regression model of recycled concrete was proposed to predict the elasticity modulus and to adjust the design of mixture proportion. It is believed that these experiment results would contribute to adjust the remediation mixture for recycling plants by considering the influence of recycled aggregate size.

  8. Oil-Price Shocks: Beyond Standard Aggregate Demand/Aggregate Supply Analysis.

    Science.gov (United States)

    Elwood, S. Kirk

    2001-01-01

    Explores the problems of portraying oil-price shocks using the aggregate demand/aggregate supply model. Presents a simple modification of the model that differentiates between production and absorption of goods, which enables it to better reflect the effects of oil-price shocks on open economies. (RLH)

  9. Congo red and protein aggregation in neurodegenerative diseases.

    Science.gov (United States)

    Frid, Petrea; Anisimov, Sergey V; Popovic, Natalija

    2007-01-01

    Congo red is a commonly used histological dye for amyloid detection. The specificity of this staining results from Congo red's affinity for binding to fibril proteins enriched in beta-sheet conformation. Unexpectedly, recent investigations indicate that the dye also possesses the capacity to interfere with processes of protein misfolding and aggregation, stabilizing native protein monomers or partially folded intermediates, while reducing concentration of more toxic protein oligomers. Inhibitory effects of Congo red upon amyloid toxicity may also range from blockade of channel formation and interference with glycosaminoglycans binding or immune functions, to the modulation of gene expression. Particularly, Congo red exhibits ameliorative effect in models of neurodegenerative disorders, such as Alzheimer's, Parkinson's, Huntington's and prion diseases. Another interesting application of Congo red analogues is the development of imaging probes. Based on their small molecular size and penetrability through blood-brain barrier, Congo red congeners can be used for both antemortem and in vivo visualization and quantification of brain amyloids. Therefore, understanding mechanisms involved in dye-amyloidal fibril binding and inhibition of aggregation will provide instructive guides for the design of future compounds, potentially useful for monitoring and treating neurodegenerative diseases.

  10. Fluorescence studies on the aggregation behaviors of collagen modified with NHS-activated poly(γ-glutamic acid).

    Science.gov (United States)

    Zhang, Min; Yang, Junhui; Yang, Qili; Huang, Liulian; Wu, Hui; Chen, Lihui; Ding, Cuicui

    2018-06-01

    The poly(γ-glutamic acid)-NHS (γ-PGA-NHS) esters were used to endow collagen with both of excellent water-solubility and thermal stability via cross-linking reaction between γ-PGA-NHS and collagen. In the present work, the effect of γ-PGA-NHS on the aggregation of collagen molecules was studied by fluorescence techniques. The fluorescence emission spectra of pyrene in collagen solutions and the intrinsic fluorescence emission spectra of collagen suggested different effects of γ-PGA-NHS on collagen molecules: inhibiting aggregation below critical aggregation concentration (CAC) and promoting aggregation above CAC. The two-dimensional (2D) fluorescence correlation spectra indicated that the intermolecular hydrogen bonding and cross-linking between γ-PGA-NHS and collagen would influence the aggregation of collagen molecules. By the ultra-sensitive differential scanning calorimeter (VP-DSC), it was found that the main denaturational transition temperature (T m2 ) of modified collagen increased, while its calorimetric enthalpy changes (ΔH 2 ) decreased compared to those of native collagen, further indicating that the modification of γ-PGA-NHS influenced the aggregation of collagen molecules. The study provide useful information for the utilizing and or the processing of water-soluble collagen in aqueous solution in the fields such as cosmetics, health care products, tissue engineering and biomedical materials, etc. Copyright © 2018 Elsevier B.V. All rights reserved.

  11. Photo-induced reorganization of molecular packing of amphi-PIC J-aggregates (single J-aggregate spectroscopy)

    International Nuclear Information System (INIS)

    Malyukin, Yu.V.; Sorokin, A.V.; Yefimova, S.L.; Lebedenko, A.N.

    2005-01-01

    Confocal luminescence microscopy has been used to excite and collect luminescence from single amphi-PIC J-aggregate. Two types of J-aggregates have been revealed in the luminescence image: bead-like J-aggregates, which diameter is less than 1 μm and rod-like ones, which length is about 3 μm and diameter is less than 1 μm. It has been found that single rod-like and bead-like J-aggregates exhibit different luminescence bands with different decay parameters. At the off-resonance blue tail excitation, the J-aggregate exciton luminescence disappeared within a certain time period and a new band appeared, which cannot be attributed to the monomer emission. The luminescence image shows that the J-aggregate is not destroyed. However, J-aggregate storage in darkness does not recover its exciton luminescence

  12. Studies on recycled aggregates-based concrete.

    Science.gov (United States)

    Rakshvir, Major; Barai, Sudhirkumar V

    2006-06-01

    Reduced extraction of raw materials, reduced transportation cost, improved profits, reduced environmental impact and fast-depleting reserves of conventional natural aggregates has necessitated the use of recycling, in order to be able to conserve conventional natural aggregate. In this study various physical and mechanical properties of recycled concrete aggregates were examined. Recycled concrete aggregates are different from natural aggregates and concrete made from them has specific properties. The percentages of recycled concrete aggregates were varied and it was observed that properties such as compressive strength showed a decrease of up to 10% as the percentage of recycled concrete aggregates increased. Water absorption of recycled aggregates was found to be greater than natural aggregates, and this needs to be compensated during mix design.

  13. Using Multifunctional Peptide Conjugated Au Nanorods for Monitoring β-amyloid Aggregation and Chemo-Photothermal Treatment of Alzheimer's Disease.

    Science.gov (United States)

    Li, Meng; Guan, Yijia; Zhao, Andong; Ren, Jinsong; Qu, Xiaogang

    2017-01-01

    Development of sensitive detectors of Aβ aggregates and effective inhibitors of Aβ aggregation are of diagnostic importance and therapeutic implications for Alzheimer's disease (AD) treatment. Herein, a novel strategy has been presented by self-assembly of peptide conjugated Au nanorods (AuP) as multifunctional Aβ fibrillization detectors and inhibitors. Our design combines the unique high NIR absorption property of AuNRs with two known Aβ inhibitors, Aβ15-20 and polyoxometalates (POMs). The synthesized AuP can effectively inhibitaggregation and dissociate amyloid deposits with NIR irradiation both in buffer and in mice cerebrospinal fluid (CSF), and protect cells from Aβ-related toxicity upon NIR irradiation. In addition, with the shape and size-dependent optical properties, the nanorods can also act as effective diagnostic probes to sensitively detect the Aβ aggregates. This is the first report to integrate 3 segments, an Aβ-targeting element, a reporter and inhibitors, in one drug delivery system for AD treatment.

  14. Mechanisms of the priming effect of low doses of lipopoly-saccharides on leukocyte-dependent platelet aggregation in whole blood.

    Science.gov (United States)

    Montrucchio, Giuseppe; Bosco, Ornella; Del Sorbo, Lorenzo; Fascio Pecetto, Paolo; Lupia, Enrico; Goffi, Alberto; Omedè, Paola; Emanuelli, Giorgio; Camussi, Giovanni

    2003-11-01

    Several studies focused on the ability of bacterial lipopolysac-charides (LPS) in triggering platelet and/or leukocyte activation. The aim of this study was to investigate the molecular mechanisms involved in the aggregation of platelets and in their interaction with leukocytes in whole blood after stimulation with low doses of LPS. LPS did not directly induce platelet aggregation in whole blood, but they primed the aggregation of platelets induced by epinephrine, adenosine diphosphate and arachidonic acid. As shown by cytofluorimetry, platelets neither bind FITC-LPS, nor express the LPS-receptors CD14 and toll-like receptor 4 (TLR4). On the contrary, LPS primed monocytes and to a lesser extent polymorphonuclear neutrophils to adhere to platelets. Both platelet-leukocyte interaction and platelet aggregation in whole blood were inhibited by blockade of CD14 and TLR4. Moreover, the interaction between platelets and leukocytes was inhibited by P-selectin, and by blockade of PAF and reactive oxygen species, suggesting a role of P-selectin and of leukocyte-derived mediators. In conclusion, these results elucidate the mechanisms leading to platelet activation and interaction with leukocytes triggered by LPS. They suggest that the activation of platelets by LPS is mainly dependent on leukocytes and especially monocytes as a result of CD14 and TLR4 engagement. Moreover, we found that leukocyte-platelet interaction was triggered by the synthesis of PAF and the generation of oxygen radicals that induced upregulation of surface expression of P-selectin.

  15. An exact approach for aggregated formulations

    DEFF Research Database (Denmark)

    Gamst, Mette; Spoorendonk, Simon; Røpke, Stefan

    Aggregating formulations is a powerful approach for problems to take on tractable forms. Aggregation may lead to loss of information, i.e. the aggregated formulation may be an approximation of the original problem. In branch-and-bound context, aggregation can also complicate branching, e.g. when...... optimality cannot be guaranteed by branching on aggregated variables. We present a generic exact solution method to remedy the drawbacks of aggregation. It combines the original and aggregated formulations and applies Benders' decomposition. We apply the method to the Split Delivery Vehicle Routing Problem....

  16. Properties of Concrete with Tire Derived Aggregate Partially Replacing Coarse Aggregates.

    Science.gov (United States)

    Siringi, Gideon; Abolmaali, Ali; Aswath, Pranesh B

    2015-01-01

    Tire derived aggregate (TDA) has been proposed as a possible lightweight replacement for mineral aggregate in concrete. The role played by the amount of TDA replacing coarse aggregate as well as different treatment and additives in concrete on its properties is examined. Conventional concrete (without TDA) and concrete containing TDA are compared by examining their compressive strength based on ASTM C39, workability based on ASTM C143, splitting tensile strength based on ASTM C496, modulus of rupture (flexural strength) based on ASTM C78, and bond stress based on ASTM C234. Results indicate that while replacement of coarse aggregates with TDA results in reduction in strength, it may be mitigated with addition of silica fume to obtain the desired strength. The greatest benefit of using TDA is in the development of a higher ductile product while utilizing recycled TDA.

  17. Protein aggregate turbidity: Simulation of turbidity profiles for mixed-aggregation reactions.

    Science.gov (United States)

    Hall, Damien; Zhao, Ran; Dehlsen, Ian; Bloomfield, Nathaniel; Williams, Steven R; Arisaka, Fumio; Goto, Yuji; Carver, John A

    2016-04-01

    Due to their colloidal nature, all protein aggregates scatter light in the visible wavelength region when formed in aqueous solution. This phenomenon makes solution turbidity, a quantity proportional to the relative loss in forward intensity of scattered light, a convenient method for monitoring protein aggregation in biochemical assays. Although turbidity is often taken to be a linear descriptor of the progress of aggregation reactions, this assumption is usually made without performing the necessary checks to provide it with a firm underlying basis. In this article, we outline utilitarian methods for simulating the turbidity generated by homogeneous and mixed-protein aggregation reactions containing fibrous, amorphous, and crystalline structures. The approach is based on a combination of Rayleigh-Gans-Debye theory and approximate forms of the Mie scattering equations. Crown Copyright © 2015. Published by Elsevier Inc. All rights reserved.

  18. Aggregates from mineral wastes

    Directory of Open Access Journals (Sweden)

    Baic Ireneusz

    2016-01-01

    Full Text Available The problem concerning the growing demand for natural aggregates and the need to limit costs, including transportation from remote deposits, cause the increase in growth of interest in aggregates from mineral wastes as well as in technologies of their production and recovery. The paper presents the issue related to the group of aggregates other than natural. A common name is proposed for such material: “alternative aggregates”. The name seems to be fully justified due to adequacy of this term because of this raw materials origin and role, in comparison to the meaning of natural aggregates based on gravel and sand as well as crushed stones. The paper presents characteristics of the market and basic application of aggregates produced from mineral wastes, generated in the mining, power and metallurgical industries as well as material from demolished objects.

  19. Aggregated Computational Toxicology Online Resource

    Data.gov (United States)

    U.S. Environmental Protection Agency — Aggregated Computational Toxicology Online Resource (AcTOR) is EPA's online aggregator of all the public sources of chemical toxicity data. ACToR aggregates data...

  20. Aggregation and pH-temperature phase behavior for aggregates of an IgG2 antibody.

    Science.gov (United States)

    Sahin, Erinc; Weiss, William F; Kroetsch, Andrew M; King, Kevin R; Kessler, R Kendall; Das, Tapan K; Roberts, Christopher J

    2012-05-01

    Monomer unfolding and thermally accelerated aggregation kinetics to produce soluble oligomers or insoluble macroscopic aggregates were characterized as a function of pH for an IgG2 antibody using differential scanning calorimetry (DSC) and size-exclusion chromatography (SEC). Aggregate size was quantified via laser light scattering, and aggregate solubility via turbidity and visual inspection. Interestingly, nonnative oligomers were soluble at pH 5.5 above approximately 15°C, but converted reversibly to visible/insoluble particles at lower temperatures. Lower pH values yielded only soluble aggregates, whereas higher pH resulted in insoluble aggregates, regardless of the solution temperature. Unlike the growing body of literature that supports the three-endotherm model of IgG1 unfolding in DSC, the results here also illustrate limitations of that model for other monoclonal antibodies. Comparison of DSC with monomer loss (via SEC) from samples during thermal scanning indicates that the least conformationally stable domain is not the most aggregation prone, and that a number of the domains remain intact within the constituent monomers of the resulting aggregates. This highlights continued challenges with predicting a priori which domain(s) or thermal transition(s) is(are) most relevant for product stability with respect to aggregation. Copyright © 2012 Wiley Periodicals, Inc.

  1. Slow aggregation of lysozyme in alkaline pH monitored in real time employing the fluorescence anisotropy of covalently labelled dansyl probe.

    Science.gov (United States)

    Homchaudhuri, Lopamudra; Kumar, Satish; Swaminathan, Rajaram

    2006-04-03

    The onset of hen egg white lysozyme aggregation on exposure to alkaline pH of 12.2 and subsequent slow growth of soluble lysozyme aggregates (at 298 K) was directly monitored by steady-state and time-resolved fluorescence anisotropy of covalently attached dansyl probe over a period of 24 h. The rotational correlation time accounting for tumbling of lysozyme in solution (40 microM) increased from approximately 3.6 ns (in pH 7) to approximately 40ns on exposure to pH 12.2 over a period of 6 h and remained stable thereafter. The growth of aggregates was strongly concentration dependent, irreversible after 60 min and inhibited by the presence of 0.9 M l-arginine in the medium. The day old aggregates were resistant to denaturation by 6 M guanidine.HCl. Our results reveal slow segmental motion of the dansyl probe in day old aggregates in the absence of L-arginine (0.9 M), but a much faster motion in its presence, when growth of aggregates is halted.

  2. Development of multifunctional, heterodimeric isoindoline-1,3-dione derivatives as cholinesterase and β-amyloid aggregation inhibitors with neuroprotective properties.

    Science.gov (United States)

    Guzior, Natalia; Bajda, Marek; Skrok, Mirosław; Kurpiewska, Katarzyna; Lewiński, Krzysztof; Brus, Boris; Pišlar, Anja; Kos, Janko; Gobec, Stanislav; Malawska, Barbara

    2015-03-06

    The presented study describes the synthesis, pharmacological evaluation (AChE and BuChE inhibition, beta amyloid anti-aggregation effect and neuroprotective effect), molecular modeling and crystallographic studies of a novel series of isoindoline-1,3-dione derivatives. The target compounds were designed as dual binding site acetylcholinesterase inhibitors with an arylalkylamine moiety binding at the catalytic site of the enzyme and connected via an alkyl chain to a heterocyclic fragment, capable of binding at the peripheral anionic site of AChE. Among these molecules, compound 15b was found to be the most potent and selective AChE inhibitor (IC50EeAChE = 0.034 μM). Moreover, compound 13b in addition to AChE inhibition (IC50 EeAChE = 0.219 μM) possesses additional properties, such as the ability to inhibitaggregation (65.96% at 10 μM) and a neuroprotective effect against Aβ toxicity at 1 and 3 μM. Compound 13b emerges as a promising multi-target ligand for the further development of the therapy for age-related neurodegenerative disorders. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

  3. Adsorption and desorption of Cu2+ on paddy soil aggregates pretreated with different levels of phosphate.

    Science.gov (United States)

    Dai, Jun; Wang, Wenqin; Wu, Wenchen; Gao, Jianbo; Dong, Changxun

    2017-05-01

    Interactions between anions and cations are important for understanding the behaviors of chemical pollutants and their potential risks in the environment. Here we prepared soil aggregates of a yellow paddy soil from the Taihu Lake region, and investigated the effects of phosphate (P) pretreatment on adsorption-desorption of Cu 2+ of soil aggregates, free iron oxyhydrates-removed soil aggregates, goethite, and kaolinite with batch adsorption method. The results showed that Cu 2+ adsorption was reduced on the aggregates pretreated with low concentrations of P, and promoted with high concentrations of P, showing a V-shaped change. Compared with the untreated aggregates, the adsorption capacity of Cu 2+ was reduced when P application rates were lower than 260, 220, 130 and 110mg/kg for coarse, clay, silt and fine sand fractions, respectively. On the contrary, the adsorption capacity of Cu 2+ was higher on P-pretreated soil aggregates than on the control ones when P application rates were greater than those values. However, the desorption of Cu 2+ was enhanced at low levels of P, but suppressed at high levels of P, displaying an inverted V-shaped change over P adsorption. The Cu 2+ adsorption by the aggregate particles with and without P pretreatments was well described by the Freundlich equation. Similar results were obtained on P-pretreated goethite. However, such P effects on Cu 2+ adsorption-desorption were not observed on kaolinite and free iron oxyhydrates-removed soil aggregates. The present results indicate that goethite is one of the main soil substances responsible for the P-induced promotion and inhibition of Cu 2+ adsorption. Copyright © 2016. Published by Elsevier B.V.

  4. Atick salivary protein targets cathepsin G and chymase and inhibits host inflammation and platelet aggregation

    Czech Academy of Sciences Publication Activity Database

    Chmelař, Jindřich; Oliveira, C. J.; Řezáčová, Pavlína; Francischetti, I.M.B.; Kovářová, Zuzana; Pejler, G.; Kopáček, Petr; Ribeiro, J.M.C.; Mareš, Michael; Kopecký, Jan; Kotsyfakis, Michalis

    2011-01-01

    Roč. 117, č. 2 (2011), s. 736-744 ISSN 0006-4971 R&D Projects: GA AV ČR IAA600960811; GA MŠk(CZ) LC06009; GA ČR(CZ) GAP207/10/2183 Institutional research plan: CEZ:AV0Z60220518; CEZ:AV0Z40550506 Keywords : parasite serpin * IRS-2 * tick * Ixodes ricinus * platelet aggregation * inflammation * cathepsin G * chymase Subject RIV: EC - Immunology Impact factor: 9.898, year: 2011

  5. Properties of Concrete with Tire Derived Aggregate Partially Replacing Coarse Aggregates

    Science.gov (United States)

    Siringi, Gideon; Abolmaali, Ali; Aswath, Pranesh B.

    2015-01-01

    Tire derived aggregate (TDA) has been proposed as a possible lightweight replacement for mineral aggregate in concrete. The role played by the amount of TDA replacing coarse aggregate as well as different treatment and additives in concrete on its properties is examined. Conventional concrete (without TDA) and concrete containing TDA are compared by examining their compressive strength based on ASTM C39, workability based on ASTM C143, splitting tensile strength based on ASTM C496, modulus of rupture (flexural strength) based on ASTM C78, and bond stress based on ASTM C234. Results indicate that while replacement of coarse aggregates with TDA results in reduction in strength, it may be mitigated with addition of silica fume to obtain the desired strength. The greatest benefit of using TDA is in the development of a higher ductile product while utilizing recycled TDA. PMID:26161440

  6. Properties of Concrete with Tire Derived Aggregate Partially Replacing Coarse Aggregates

    Directory of Open Access Journals (Sweden)

    Gideon Siringi

    2015-01-01

    Full Text Available Tire derived aggregate (TDA has been proposed as a possible lightweight replacement for mineral aggregate in concrete. The role played by the amount of TDA replacing coarse aggregate as well as different treatment and additives in concrete on its properties is examined. Conventional concrete (without TDA and concrete containing TDA are compared by examining their compressive strength based on ASTM C39, workability based on ASTM C143, splitting tensile strength based on ASTM C496, modulus of rupture (flexural strength based on ASTM C78, and bond stress based on ASTM C234. Results indicate that while replacement of coarse aggregates with TDA results in reduction in strength, it may be mitigated with addition of silica fume to obtain the desired strength. The greatest benefit of using TDA is in the development of a higher ductile product while utilizing recycled TDA.

  7. Characteristic and functional analysis of toll-like receptors (TLRs in the lophotrocozoan, Crassostrea gigas, reveals ancient origin of TLR-mediated innate immunity.

    Directory of Open Access Journals (Sweden)

    Yang Zhang

    Full Text Available The evolution of TLR-mediated innate immunity is a fundamental question in immunology. Here, we report the characterization and functional analysis of four TLR members in the lophotrochozoans Crassostreagigas (CgTLRs. All CgTLRs bear a conserved domain organization and have a close relationship with TLRs in ancient non-vertebrate chordates. In HEK293 cells, every CgTLR could constitutively activate NF-κB responsive reporter, but none of the PAMPs tested could stimulate CgTLR-activated NF-κB induction. Subcellular localization showed that CgTLR members have similar and dual distribution on late endosomes and plasma membranes. Moreover, CgTLRs and CgMyD88 mRNA show a consistent response to multiple PAMP challenges in oyster hemocytes. As CgTLR-mediated NF-κB activation is dependent on CgMyD88, we designed a blocking peptide for CgTLR signaling that would inhibit CgTLR-CgMyD88 dependent NF-κB activation. This was used to demonstrate that a Vibrio parahaemolyticus infection-induced enhancement of degranulation and increase of cytokines TNF mRNA in hemocytes, could be inhibited by blocking CgTLR signaling. In summary, our study characterized the primitive TLRs in the lophotrocozoan C. gigas and demonstrated a fundamental role of TLR signaling in infection-induced hemocyte activation. This provides further evidence for an ancient origin of TLR-mediated innate immunity.

  8. Hematological Analysis of the Ascidian Botrylloides leachii (Savigny, 1816) During Whole-Body Regeneration.

    Science.gov (United States)

    Blanchoud, Simon; Zondag, Lisa; Lamare, Miles D; Wilson, Megan J

    2017-06-01

    Whole-body regeneration (WBR)-the formation of an entire adult from only a small fragment of its own tissue-is extremely rare among chordates. Exceptionally, in the colonial ascidian Botrylloides leachii (Savigny, 1816) a fully functional adult is formed from their common vascular system after ablation of all adults from the colony in just 10 d, thanks to their high blastogenetic potential. While previous studies have identified key genetic markers and morphological changes, no study has yet focused on the hematological aspects of regeneration despite the major involvement of the remaining vascular system and the contained hemocytes in this process. To dissect this process, we analyzed colony blood flow patterns using time-lapse microscopy to obtain a quantitative description of the velocity, reversal pattern, and average distance traveled by hemocytes. We also observed that flows present during regeneration are powered by temporally and spatially synchronized contractions of the terminal ampullae. In addition, we revised previous studies of B. leachii hematology as well as asexual development using histological sectioning and compared the role played by hemocytes during WBR. We found that regeneration starts with a rapid healing response characterized by hemocyte aggregation and infiltration of immunocytes, followed by increased activity of hemoblasts, recruitment of macrophage-like cells for clearing the tissues of debris, and their subsequent disappearance from the circulation concomitant with the maturation of a single regenerated adult. Overall, we provide a detailed account of the hematological properties of regenerating B. leachii colonies, providing novel lines of inquiry toward the decipherment of regeneration in chordates.

  9. Ecotoxicity of CdTe quantum dots to freshwater mussels: Impacts on immune system, oxidative stress and genotoxicity

    International Nuclear Information System (INIS)

    Gagne, F.; Auclair, J.; Turcotte, P.; Fournier, M.; Gagnon, C.; Sauve, S.; Blaise, C.

    2008-01-01

    The purpose of this study was to examine the toxic effects of cadmium-telluride (CdTe) quantum dots on freshwater mussels. Elliption complanata mussels were exposed to increasing concentrations of CdTe (0, 1.6, 4 and 8 mg/L) and cadmium sulfate (CdSO 4 , 0.5 mg/L) for 24 h at 15 o C. After the exposure period, they were removed for assessments of immunocompetence, oxidative stress (lipid peroxidation) and genotoxicity (DNA strand breaks). Preliminary experiments revealed that CdTe dissolved in aquarium water tended to aggregate in the particulate phase (85%) while 15% of CdTe was found in the dissolved phase. Immunotoxicity was characterized by a significant decrease in the number of hemocytes capable of ingesting fluorescent beads, and hemocyte viability. The cytotoxic capacity of hemocytes to lyse mammalian K-562 cells was significantly increased, but the number of circulating hemocytes remained unchanged. Lipid peroxidation was significantly increased at a threshold concentration of 5.6 mg/L in gills and significantly reduced in digestive glands at a threshold concentration <1.6 mg/L CdTe. The levels of DNA strand breaks were significantly reduced in gills at <1.6 mg/L CdTe. In digestive glands, a transient but marginal increase in DNA strand breaks occurred at the lowest concentration and dropped significantly at the higher concentrations. A multivariate analysis revealed that the various response patterns differed based on the concentration of CdTe, thus permitting the identification of biomarkers associated with the form (colloidal vs. molecular) of cadmium

  10. Ecotoxicity of CdTe quantum dots to freshwater mussels: Impacts on immune system, oxidative stress and genotoxicity

    Energy Technology Data Exchange (ETDEWEB)

    Gagne, F. [Fluvial Ecosystem Research, Environment Canada, 105 McGill Street, Montreal, Quebec, H2Y 2E7 (Canada)], E-mail: francois.gagne@ec.gc.ca; Auclair, J.; Turcotte, P. [Fluvial Ecosystem Research, Environment Canada, 105 McGill Street, Montreal, Quebec, H2Y 2E7 (Canada); Fournier, M. [INRS-Institut Armand-Frappier, 245 Hymus, Pointe-Claire, Quebec, H9R 3G6 (Canada); Gagnon, C. [Fluvial Ecosystem Research, Environment Canada, 105 McGill Street, Montreal, Quebec, H2Y 2E7 (Canada); Sauve, S. [Departement de Chimie, Universite de Montreal, C.P. 6128, Succursale Centre-ville, Montreal, Quebec, H3C 3J7 (Canada); Blaise, C. [Fluvial Ecosystem Research, Environment Canada, 105 McGill Street, Montreal, Quebec, H2Y 2E7 (Canada)

    2008-02-18

    The purpose of this study was to examine the toxic effects of cadmium-telluride (CdTe) quantum dots on freshwater mussels. Elliption complanata mussels were exposed to increasing concentrations of CdTe (0, 1.6, 4 and 8 mg/L) and cadmium sulfate (CdSO{sub 4}, 0.5 mg/L) for 24 h at 15 {sup o}C. After the exposure period, they were removed for assessments of immunocompetence, oxidative stress (lipid peroxidation) and genotoxicity (DNA strand breaks). Preliminary experiments revealed that CdTe dissolved in aquarium water tended to aggregate in the particulate phase (85%) while 15% of CdTe was found in the dissolved phase. Immunotoxicity was characterized by a significant decrease in the number of hemocytes capable of ingesting fluorescent beads, and hemocyte viability. The cytotoxic capacity of hemocytes to lyse mammalian K-562 cells was significantly increased, but the number of circulating hemocytes remained unchanged. Lipid peroxidation was significantly increased at a threshold concentration of 5.6 mg/L in gills and significantly reduced in digestive glands at a threshold concentration <1.6 mg/L CdTe. The levels of DNA strand breaks were significantly reduced in gills at <1.6 mg/L CdTe. In digestive glands, a transient but marginal increase in DNA strand breaks occurred at the lowest concentration and dropped significantly at the higher concentrations. A multivariate analysis revealed that the various response patterns differed based on the concentration of CdTe, thus permitting the identification of biomarkers associated with the form (colloidal vs. molecular) of cadmium.

  11. Respiratory and Metabolic Impacts of Crustacean Immunity: Are there Implications for the Insects?

    Science.gov (United States)

    Burnett, Karen G; Burnett, Louis E

    2015-11-01

    Extensive similarities in the molecular architecture of the crustacean immune system to that of insects give credence to the current view that the Hexapoda, including Insecta, arose within the clade Pancrustacea. The crustacean immune system is mediated largely by hemocytes, relying on suites of pattern recognition receptors, effector functions, and signaling pathways that parallel those of insects. In crustaceans, as in insects, the cardiovascular system facilitates movement of hemocytes and delivery of soluble immune factors, thereby supporting immune surveillance and defense along with other physiological functions such as transport of nutrients, wastes, and hormones. Crustaceans also rely heavily on their cardiovascular systems to mediate gas exchange; insects are less reliant on internal circulation for this function. Among the largest crustaceans, the decapods have developed a condensed heart and a highly arteriolized cardiovascular system that supports the metabolic demands of their often large body size. However, recent studies indicate that mounting an immune response can impair gas exchange and metabolism in their highly developed vascular system. When circulating hemocytes detect the presence of potential pathogens, they aggregate rapidly with each other and with the pathogen. These growing aggregates can become trapped in the microvasculature of the gill where they are melanized and may be eliminated at the next molt. Prior to molting, trapped aggregates of hemocytes also can impair hemolymph flow and oxygenation at the gill. Small shifts to anaerobic metabolism only partially compensate for this decrease in oxygen uptake. The resulting metabolic depression is likely to impact other energy-expensive cellular processes and whole-animal performance. For crustaceans that often live in microbially-rich, but oxygen-poor aquatic environments, there appear to be distinct tradeoffs, based on the gill's multiple roles in respiration and immunity. Insects have

  12. Kinetics of aggregation with choice.

    Science.gov (United States)

    Ben-Naim, E; Krapivsky, P L

    2016-12-01

    We generalize the ordinary aggregation process to allow for choice. In ordinary aggregation, two random clusters merge and form a larger aggregate. In our implementation of choice, a target cluster and two candidate clusters are randomly selected and the target cluster merges with the larger of the two candidate clusters. We study the long-time asymptotic behavior and find that as in ordinary aggregation, the size density adheres to the standard scaling form. However, aggregation with choice exhibits a number of different features. First, the density of the smallest clusters exhibits anomalous scaling. Second, both the small-size and the large-size tails of the density are overpopulated, at the expense of the density of moderate-size clusters. We also study the complementary case where the smaller candidate cluster participates in the aggregation process and find an abundance of moderate clusters at the expense of small and large clusters. Additionally, we investigate aggregation processes with choice among multiple candidate clusters and a symmetric implementation where the choice is between two pairs of clusters.

  13. Kinetic Behaviors of Catalysis-Driven Growth of Three-Species Aggregates on Base of Exchange-Driven Aggregations

    International Nuclear Information System (INIS)

    Sun Yunfei; Chen Dan; Lin Zhenquan; Ke Jianhong

    2009-01-01

    We propose a solvable aggregation model to mimic the evolution of population A, asset B, and the quantifiable resource C in a society. In this system, the population and asset aggregates themselves grow through self-exchanges with the rate kernels K 1 (k, j) = K 1 kj and K 2 (k, j) = K 2 kj, respectively. The actions of the population and asset aggregations on the aggregation evolution of resource aggregates are described by the population-catalyzed monomer death of resource aggregates and asset-catalyzed monomer birth of resource aggregates with the rate kernels J 1 (k, j) = J 1 k and J 2 (k, j) = J 2 k, respectively. Meanwhile, the asset and resource aggregates conjunctly catalyze the monomer birth of population aggregates with the rate kernel I 1 (k, i, j) = I 1 ki μ j η , and population and resource aggregates conjunctly catalyze the monomer birth of asset aggregates with the rate kernel I 2 (k, i, j) = I 2 ki v j η . The kinetic behaviors of species A, B, and C are investigated by means of the mean-field rate equation approach. The effects of the population-catalyzed death and asset-catalyzed birth on the evolution of resource aggregates based on the self-exchanges of population and asset appear in effective forms. The coefficients of the effective population-catalyzed death and the asset-catalyzed birth are expressed as J 1e = J 1 /K 1 and J 2e = J 2 /K 2 , respectively. The aggregate size distribution of C species is found to be crucially dominated by the competition between the effective death and the effective birth. It satisfies the conventional scaling form, generalized scaling form, and modified scaling form in the cases of J 1e 2e , J 1e = J 2e , and J 1e > J 2e , respectively. Meanwhile, we also find the aggregate size distributions of populations and assets both fall into two distinct categories for different parameters μ, ν, and η: (i) When μ = ν = η = 0 and μ = ν = 0, η = 1, the population and asset aggregates obey the generalized

  14. Research on Judgment Aggregation Based on Logic

    Directory of Open Access Journals (Sweden)

    Li Dai

    2014-05-01

    Full Text Available Preference aggregation and judgment aggregation are two basic research models of group decision making. And preference aggregation has been deeply studied in social choice theory. However, researches of social choice theory gradually focus on judgment aggregation which appears recently. Judgment aggregation focuses on how to aggregate many consistent logical formulas into one, from the perspective of logic. We try to start with judgment aggregation model based on logic and then explore different solutions to problem of judgment aggregation.

  15. Volcanic Aggregates from Azores and Madeira Archipelagos (Portugal): An Overview Regarding the Alkali Silica Reactions

    Science.gov (United States)

    Medeiros, Sara; Ramos, Violeta; Fernandes, Isabel; Nunes, João Carlos; Fournier, Benoit; Santos Silva, António; Soares, Dora

    2017-12-01

    Alkali-silica reaction (ASR) is a type of deterioration that has been causing serious expansion, cracking and durability/operational issues in concrete structures worldwide. The presence of sufficient moisture, high alkali content in the cement paste and reactive forms of silica in the aggregates are the required conditions for this reaction to occur. Reactive aggregates of volcanic nature have been reported in different countries such as Japan, Iceland and Turkey, among others. The presence of silica minerals and SiO2-rich volcanic glass is regarded as the main cause for the reactivity of volcanic rocks. In Portugal, volcanic aggregates are mainly present in Azores and Madeira Archipelagos and, for several years, there was no information regarding the potential alkali-reactivity of these rocks. Since the beginning of this decade some data was obtained by the work of Medeiros (2011) and Ramos (2013) and by the national research projects ReAVA, (Characterization of potential reactivity of the volcanic aggregates from the Azores Archipelago: implications on the durability of concrete structures) and IMPROVE (Improvement of performance of aggregates in the inhibition of alkali-aggregate reactions in concrete), respectively. In order to investigate the potential alkali-reactivity of aggregates from both archipelagos, a total of sixteen aggregates were examined under the optical microscope and, some of them, also under the Scanning Electron Microscope with Energy Dispersive X-ray Spectroscopy. A set of geochemical analyses and laboratory expansion tests were also performed on those volcanic aggregates. The main results showed that the presence of volcanic glass is rare in both archipelagos and that the samples of Madeira Archipelago contain clay minerals (mainly from scoria/tuff formations inter-layered with the lava flows), which can play a role in concrete expansion. The results of the laboratory tests showed that one of the samples performed as potentially reactive

  16. Molecular characterization of shrimp harbinger transposase derived 1 (HARBI1)-like and its role in white spot syndrome virus and Vibrio alginolyticus infection.

    Science.gov (United States)

    Sun, Baozhen; Qian, Xiyi; Zhu, Fei

    2018-07-01

    The role of the nuclease, HARBI1-like protein (mjHARBI1-like) in the innate immunity of Marsupenaeus japonicus was explored in this study. The 1361 bp cDNA sequence of mjHARBI1-like was cloned from M. japonicus using RACE. RT-qPCR analysis results showed that the gills and hepatopancreas of M. japonicus were the main tissues where mjHARBI1-like is expressed. In addition, it was also found that white spot syndrome virus (WSSV) or Vibrio alginolyticus challenge could stimulate mjHARBI1-like expression. After mjHARBI1-likewas inhibited, expression of immune genes such as toll, p53, myosin, and proPO were significantly downregulated (P shrimp hemocytes, hemocyanin and tumor necrosis factor-α (TNF-α) were up-regulated significantly (P shrimp was significantly advanced by double-strand RNA interference (dsRNAi) of mjHARBI1-like. Apoptosis studies indicated that mjHARBI1-dsRNA treatment caused a reduction in hemocyte apoptosis in bacterial and viral groups. In addition, phagocytosis experiments illustrated that mjHARBI1-dsRNA treatment led to a lower phagocytosis rate in hemocytes of V. alginolyticus-challenged shrimp. It was also found that knockdown of mjHARBI1-like inhibited shrimp phenoloxidase (PO) activity, superoxide dismutase (SOD) activity, and total hemocyte count (THC) after WSSV or V. alginolyticus infection. These data indicate a regulative role of mjHARBI1-likein the immunity of shrimp in response to pathogen infection. Resultantly, it was concluded that mjHARBI1-like might have a positive effect on the anti-WSSV immune response of shrimp by regulating apoptosis, THC, PO activity, and SOD activity. Additionally, mjHARBI1-like might promote anti-V. alginolyticus infection by participating in regulating phagocytosis, apoptosis, SOD activity, PO activity, and THC. Copyright © 2018 Elsevier Ltd. All rights reserved.

  17. Heating of Porous Icy Dust Aggregates

    Energy Technology Data Exchange (ETDEWEB)

    Sirono, Sin-iti [Earth and Environmental Sciences, Nagoya University, Tikusa-ku, Furo-cho, Nagoya 464-8601 (Japan)

    2017-06-10

    At the beginning of planetary formation, highly porous dust aggregates are formed through coagulation of dust grains. Outside the snowline, the main component of an aggregate is H{sub 2}O ice. Because H{sub 2}O ice is formed in amorphous form, its thermal conductivity is extremely small. Therefore, the thermal conductivity of an icy dust aggregate is low. There is a possibility of heating inside an aggregate owing to the decay of radionuclides. It is shown that the temperature increases substantially inside an aggregate, leading to crystallization of amorphous ice. During the crystallization, the temperature further increases sufficiently to continue sintering. The mechanical properties of icy dust aggregates change, and the collisional evolution of dust aggregates is affected by the sintering.

  18. Interactions of cationic polystyrene nanoparticles with marine bivalve hemocytes in a physiological environment: Role of soluble hemolymph proteins.

    Science.gov (United States)

    Canesi, Laura; Ciacci, Caterina; Fabbri, Rita; Balbi, Teresa; Salis, Annalisa; Damonte, Gianluca; Cortese, Katia; Caratto, Valentina; Monopoli, Marco P; Dawson, Kenneth; Bergami, Elisa; Corsi, Ilaria

    2016-10-01

    The bivalve Mytilus galloprovincialis has proven as a suitable model invertebrate for evaluating the potential impact of nanoparticles (NPs) in the marine environment. In particular, in mussels, the immune system represents a sensitive target for different types of NPs. In environmental conditions, both NP intrinsic properties and those of the receiving medium will affect particle behavior and consequent bioavailability/uptake/toxicity. However, the evaluation of the biological effects of NPs requires additional understanding of how, once within the organism, NPs interact at the molecular level with cells in a physiological environment. In mammalian systems, different NPs associate with serum soluble components, organized into a "protein corona", which affects particle interactions with target cells. However, no information is available so far on the interactions of NPs with biological fluids of aquatic organisms. In this work, the influence of hemolymph serum (HS) on the in vitro effects of amino modified polystyrene NPs (PS-NH2) on Mytilus hemocytes was investigated. Hemocytes were incubated with PS-NH2 suspensions in HS (1, 5 and 50µg/mL) and the results were compared with those obtained in ASW medium. Cell functional parameters (lysosomal membrane stability, oxyradical production, phagocytosis) were evaluated, and morphological changes were investigated by TEM. The activation state of the signalling components involved in Mytilus immune response (p38 MAPK and PKC) was determined. The results show that in the presence of HS, PS-NH2 increased cellular damage and ROS production with respect to ASW medium. The effects were apparently mediated by disregulation of p38 MAPK signalling. The formation of a PS-NH2-protein corona in HS was investigated by centrifugation, and 1D- gel electrophoresis and nano-HPLC-ESI-MS/MS. The results identified the Putative C1q domain containing protein (MgC1q6) as the only component of the PS-NH2 hard protein corona in Mytilus

  19. Antiplatelet effect of phloroglucinol is related to inhibition of cyclooxygenase, reactive oxygen species, ERK/p38 signaling and thromboxane A2 production

    International Nuclear Information System (INIS)

    Chang, Mei-Chi; Chang, Hsiao-Hua; Chan, Chiu-Po; Chou, Han-Yi; Chang, Bei-En; Yeung, Sin-Yuet; Wang, Tong-Mei; Jeng, Jiiang-Huei

    2012-01-01

    Platelet dysfunction is a major risk factor of cardiovascular diseases such as atherosclerosis, stroke and myocardial infarction. Many antiplatelet agents are used for prevention and treatment of these diseases. In this study, phloroglucinol (2.5–25 μM) suppressed AA-induced platelet aggregation and thromboxane B 2 (TXB 2 ) production, but not U46619-induced platelet aggregation. Phloroglucinol (100–250 μM) showed little cytotoxicity to platelets. Phloroglucinol inhibited the COX-1 and COX-2 activities by 45–74% and 49–72% respectively at concentrations of 10–50 μM. At concentrations of 1 and 5 μM, phloroglucinol attenuated the AA-induced ROS production in platelets by 30% and 53%, with an IC 50 of 13.8 μM. Phloroglucinol also inhibited the PMA-stimulated ROS production in PMN. Preincubation of platelets by phloroglucinol (10–25 μM) markedly attenuated the AA-induced ERK and p38 phosphorylation. Intravenous administration of phloroglucinol (2.5 and 5 μmol/mouse) suppressed the ex vivo AA-induced platelet aggregation by 57–71%. Phloroglucinol administration also elevated the mice tail bleeding time. Moreover, phloroglucinol inhibited the IL-1β-induced PGE 2 production in pulp fibroblasts. These results indicate that antiplatelet and anti-inflammatory effects of phloroglucinol are related to inhibition of COX, ROS and TXA2 production as well as ERK/p38 phosphorylation in platelets. Phloroglucinol further suppress PMA-induced ROS production in PMN. The antiplatelet effect of phloroglucinol was confirmed by ex vivo study. Clinically, the consumption of phloroglucinol-containing food/natural products as nutritional supplement may be helpful to cardiovascular health. Phloroglucinol has potential pharmacological use. -- Highlights: ► Phloroglucinol suppressed AA-induced platelet aggregation and thromboxane production. ► Phloroglucinol inhibited COX activity and IL-1b-induced PGE2 production in fibroblast. ► Phloroglucinol declined platelet and

  20. GENERAL: Kinetic Behaviors of Catalysis-Driven Growth of Three-Species Aggregates on Base of Exchange-Driven Aggregations

    Science.gov (United States)

    Sun, Yun-Fei; Chen, Dan; Lin, Zhen-Quan; Ke, Jian-Hong

    2009-06-01

    We propose a solvable aggregation model to mimic the evolution of population A, asset B, and the quantifiable resource C in a society. In this system, the population and asset aggregates themselves grow through self-exchanges with the rate kernels K1(k, j) = K1kj and K2(k, j) = K2kj, respectively. The actions of the population and asset aggregations on the aggregation evolution of resource aggregates are described by the population-catalyzed monomer death of resource aggregates and asset-catalyzed monomer birth of resource aggregates with the rate kernels J1(k, j) = J1k and J2(k, j) = J2k, respectively. Meanwhile, the asset and resource aggregates conjunctly catalyze the monomer birth of population aggregates with the rate kernel I1(k, i, j) = I1kiμjη, and population and resource aggregates conjunctly catalyze the monomer birth of asset aggregates with the rate kernel I2(k, i, j) = I2kivjη. The kinetic behaviors of species A, B, and C are investigated by means of the mean-field rate equation approach. The effects of the population-catalyzed death and asset-catalyzed birth on the evolution of resource aggregates based on the self-exchanges of population and asset appear in effective forms. The coefficients of the effective population-catalyzed death and the asset-catalyzed birth are expressed as J1e = J1/K1 and J2e = J2/K2, respectively. The aggregate size distribution of C species is found to be crucially dominated by the competition between the effective death and the effective birth. It satisfies the conventional scaling form, generalized scaling form, and modified scaling form in the cases of J1e J2e, respectively. Meanwhile, we also find the aggregate size distributions of populations and assets both fall into two distinct categories for different parameters μ, ν, and η: (i) When μ = ν = η = 0 and μ = ν = 0, η = 1, the population and asset aggregates obey the generalized scaling forms; and (ii) When μ = ν = 1, η = 0, and μ = ν = η = 1, the

  1. Rosuvastatin ameliorates cognitive impairment in rats fed with high-salt and cholesterol diet via inhibiting acetylcholinesterase activity and amyloid beta peptide aggregation.

    Science.gov (United States)

    Husain, I; Akhtar, M; Abdin, M Zainul; Islamuddin, M; Shaharyar, M; Najmi, A K

    2018-04-01

    Amyloid beta (Aβ) peptide aggregation and cholinergic neurodegeneration are involved in the development of cognitive impairment. Therefore, in this article, we examined rosuvastatin (RSV), an oral hypolipidemic drug, to determine its potential as a dual inhibitor of acetylcholinesterase (AChE) and Aβ peptide aggregation for the treatment of cognitive impairment. Molecular docking study was done to examine the affinity of RSV with Aβ 1-42 and AChE in silico. We also employed neurobehavioral activity tests, biochemical estimation, and histopathology to study the anti-Aβ 1-42 aggregation capability of RSV in vivo. Molecular docking study provided evidence that RSV has the best binding conformer at its receptor site or active site of an enzyme. The cognitive impairment in female Wistar rats was induced by high-salt and cholesterol diet (HSCD) ad libitum for 8 weeks. RSV ameliorated serum cholesterol level, AChE activity, and Aβ 1-42 peptide aggregations in HSCD induced cognitive impairment. In addition, RSV-treated rats showed greater scores in the open field (locomotor activity) test. Moreover, the histopathological studies in the hippocampus and cortex of rat brain also supported that RSV markedly reduced the cognitive impairment and preserved the normal histoarchitectural pattern of the hippocampus and cortex. Taken together, these data indicate that RSV may act as a dual inhibitor of AChE and Aβ 1-42 peptide aggregation, therefore suggesting a therapeutic strategy for cognitive impairment treatment.

  2. Model for amorphous aggregation processes

    Science.gov (United States)

    Stranks, Samuel D.; Ecroyd, Heath; van Sluyter, Steven; Waters, Elizabeth J.; Carver, John A.; von Smekal, Lorenz

    2009-11-01

    The amorphous aggregation of proteins is associated with many phenomena, ranging from the formation of protein wine haze to the development of cataract in the eye lens and the precipitation of recombinant proteins during their expression and purification. While much literature exists describing models for linear protein aggregation, such as amyloid fibril formation, there are few reports of models which address amorphous aggregation. Here, we propose a model to describe the amorphous aggregation of proteins which is also more widely applicable to other situations where a similar process occurs, such as in the formation of colloids and nanoclusters. As first applications of the model, we have tested it against experimental turbidimetry data of three proteins relevant to the wine industry and biochemistry, namely, thaumatin, a thaumatinlike protein, and α -lactalbumin. The model is very robust and describes amorphous experimental data to a high degree of accuracy. Details about the aggregation process, such as shape parameters of the aggregates and rate constants, can also be extracted.

  3. A comparative study on the aggregating effects of guanidine thiocyanate, guanidine hydrochloride and urea on lysozyme aggregation

    Energy Technology Data Exchange (ETDEWEB)

    Emadi, Saeed, E-mail: emadi@iasbs.ac.ir; Behzadi, Maliheh

    2014-08-08

    Highlights: • Lysozyme aggregated in guanidine thiocyanate (1.0 and 2.0 M). • Lysozyme aggregated in guanidine hydrochloride (4 and 5 M). • Lysozyme did not aggregated at any concentration (0.5–5 M) of urea. • Unfolding pathway is more important than unfolding per se in aggregation. - Abstract: Protein aggregation and its subsequent deposition in different tissues culminate in a diverse range of diseases collectively known as amyloidoses. Aggregation of hen or human lysozyme depends on certain conditions, namely acidic pH or the presence of additives. In the present study, the effects on the aggregation of hen egg-white lysozyme via incubation in concentrated solutions of three different chaotropic agents namely guanidine thiocyanate, guanidine hydrochloride and urea were investigated. Here we used three different methods for the detection of the aggregates, thioflavin T fluorescence, circular dichroism spectroscopy and atomic force microscopy. Our results showed that upon incubation with different concentrations (0.5, 1.0, 2.0, 3.0, 4.0, 5.0 M) of the chemical denaturants, lysozyme was aggregated at low concentrations of guanidine thiocyanate (1.0 and 2.0 M) and at high concentrations of guanidine hydrochloride (4 and 5 M), although no fibril formation was detected. In the case of urea, no aggregation was observed at any concentration.

  4. [Design, synthesis and evaluation of bis-nicotine derivatives as inhibitors of cholinesterases and beta-amyloid aggregation].

    Science.gov (United States)

    Luo, Wen; Zhao, Yong-mei; Tian, Run-guo; Su, Ya-bin; Hong, Chen

    2013-11-01

    A novel series of bis-nicotine derivatives (3a-3i) were designed, synthesized and evaluated as bivalent anti-Alzheimer's disease agents. The pharmacological results indicated that compounds 3e-3i inhibited both acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) in the micromolar range (IC50, 2.28-117.86 micromol x L(-1) for AChE and 1.67-125 micromol x L(-1) for BChE), which was at the same potency as rivastigmine. A Lineweaver-Burk plot and molecular modeling study showed that these derivatives targeted both the catalytic active site (CAS) and the peripheral anionic site (PAS) of AChE. Besides, these compounds could significantly inhibit the self-induced Abeta aggregation with inhibition activity (11.85%-62.14%) at the concentration of 20 micromol x L(-1).

  5. Influence of granitic aggregates from Northeast Brazil on the alkali-aggregate reaction

    Energy Technology Data Exchange (ETDEWEB)

    Gomes Neto, David de Paiva; Santana, Rodrigo Soares de; Barreto, Ledjane Silva, E-mail: pvgomes@uol.com.br [Universidade Federal de Sergipe (UFS), Sao Cristovao, SE (Brazil). Dept. de Ciencias dos Materiais e Engenharia; Conceicao, Herbert; Lisboa, Vinicios Anselmo Carvalho [Universidade Federal de Sergipe (UFS), Sao Cristovao, SE (Brazil). Dept. de Geologia

    2014-08-15

    The alkali-aggregate reaction (AAR) in concrete structures is a problem that has concerned engineers and researchers for decades. This reaction occurs when silicates in the aggregates react with the alkalis, forming an expanded gel that can cause cracks in the concrete and reduce its lifespan. The aim of this study was to characterize three coarse granitic aggregates employed in concrete production in northeastern Brazil, correlating petrographic analysis with the kinetics of silica dissolution and the evolution of expansions in mortar bars, assisted by SEM/EDS, XRD, and EDX. The presence of grains showing recrystallization into individual microcrystalline quartz subgrains was associated with faster dissolution of silica and greater expansion in mortar bars. Aggregates showing substantial deformation, such as stretched grains of quartz with strong undulatory extinction, experienced slower dissolution, with reaction and expansion occurring over longer periods that could not be detected using accelerated tests with mortar bars. (author)

  6. Fractal Aggregates in Tennis Ball Systems

    Science.gov (United States)

    Sabin, J.; Bandin, M.; Prieto, G.; Sarmiento, F.

    2009-01-01

    We present a new practical exercise to explain the mechanisms of aggregation of some colloids which are otherwise not easy to understand. We have used tennis balls to simulate, in a visual way, the aggregation of colloids under reaction-limited colloid aggregation (RLCA) and diffusion-limited colloid aggregation (DLCA) regimes. We have used the…

  7. A Functional Reference Architecture for Aggregators

    DEFF Research Database (Denmark)

    Bondy, Daniel Esteban Morales; Heussen, Kai; Gehrke, Oliver

    2015-01-01

    Aggregators are considered to be a key enabling technology for harvesting power system services from distributed energy resources (DER). As a precondition for more widespread use of aggregators in power systems, methods for comparing and validating aggregator designs must be established. This paper...... proposes a functional reference architecture for aggregators to address this requirement....

  8. Aggregation server for grid-integrated vehicles

    Science.gov (United States)

    Kempton, Willett

    2015-05-26

    Methods, systems, and apparatus for aggregating electric power flow between an electric grid and electric vehicles are disclosed. An apparatus for aggregating power flow may include a memory and a processor coupled to the memory to receive electric vehicle equipment (EVE) attributes from a plurality of EVEs, aggregate EVE attributes, predict total available capacity based on the EVE attributes, and dispatch at least a portion of the total available capacity to the grid. Power flow may be aggregated by receiving EVE operational parameters from each EVE, aggregating the received EVE operational parameters, predicting total available capacity based on the aggregated EVE operational parameters, and dispatching at least a portion of the total available capacity to the grid.

  9. Sand Cement Brick Containing Recycled Concrete Aggregate as Fine-Aggregate Replacement

    Directory of Open Access Journals (Sweden)

    Sheikh Khalid Faisal

    2017-01-01

    Full Text Available Nowadays, the usage amount of the concrete is increasing drastically. The construction industry is a huge consumer of natural consumer. It is also producing the huge wastage products. The usage of concrete has been charged to be not environmentally friendly due to depletion of reserve natural resources, high energy consumption and disposal issues. The conservation of natural resources and reduction of disposal site by reuse and recycling waste material was interest possibilites. The aim of this study is to determine the physical and mechanical properties of sand cement brick containing recycled concrete aggregate and to determine the optimum mix ratio containing recycled concrete aggregate. An experiment done by comparing the result of control specimen using 100% natural sand with recycled concrete aggregate replacement specimen by weight for 55%, 65%, and 75%. The sample was tested under density, compressive strength, flexural strength and water absorption to study the effect of using recycled concrete aggregate on the physical and mechanical properties of bricks. The result shows that the replacement of natural sand by recycled concrete aggregate at the level of 55% provide the highest compressive and flexural strength compared to other percentage and control specimen. However, if the replacement higher than 55%, the strength of brick was decreased for compressive and flexural strength, respectively. The relationship of compressive-flexural strength is determined from statistical analysis and the predicted result can be obtained by using equation ff,RCA = 0.5375 (fc0.3272.

  10. Antioxidant Treatment and Induction of Autophagy Cooperate to Reduce Desmin Aggregation in a Cellular Model of Desminopathy.

    Directory of Open Access Journals (Sweden)

    Eva Cabet

    Full Text Available Desminopathies, a subgroup of myofibrillar myopathies (MFMs, the progressive muscular diseases characterized by the accumulation of granulofilamentous desmin-positive aggregates, result from mutations in the desmin gene (DES, encoding a muscle-specific intermediate filament. Desminopathies often lead to severe disability and premature death from cardiac and/or respiratory failure; no specific treatment is currently available. To identify drug-targetable pathophysiological pathways, we performed pharmacological studies in C2C12 myoblastic cells expressing mutant DES. We found that inhibition of the Rac1 pathway (a G protein signaling pathway involved in diverse cellular processes, antioxidant treatment, and stimulation of macroautophagy reduced protein aggregation by up to 75% in this model. Further, a combination of two or three of these treatments was more effective than any of them alone. These results pave the way towards the development of the first treatments for desminopathies and are potentially applicable to other muscle or brain diseases associated with abnormal protein aggregation.

  11. A Fragment-Based Method of Creating Small-Molecule Libraries to Target the Aggregation of Intrinsically Disordered Proteins.

    Science.gov (United States)

    Joshi, Priyanka; Chia, Sean; Habchi, Johnny; Knowles, Tuomas P J; Dobson, Christopher M; Vendruscolo, Michele

    2016-03-14

    The aggregation process of intrinsically disordered proteins (IDPs) has been associated with a wide range of neurodegenerative disorders, including Alzheimer's and Parkinson's diseases. Currently, however, no drug in clinical use targets IDP aggregation. To facilitate drug discovery programs in this important and challenging area, we describe a fragment-based approach of generating small-molecule libraries that target specific IDPs. The method is based on the use of molecular fragments extracted from compounds reported in the literature to inhibit of the aggregation of IDPs. These fragments are used to screen existing large generic libraries of small molecules to form smaller libraries specific for given IDPs. We illustrate this approach by describing three distinct small-molecule libraries to target, Aβ, tau, and α-synuclein, which are three IDPs implicated in Alzheimer's and Parkinson's diseases. The strategy described here offers novel opportunities for the identification of effective molecular scaffolds for drug discovery for neurodegenerative disorders and to provide insights into the mechanism of small-molecule binding to IDPs.

  12. Observing Convective Aggregation

    Science.gov (United States)

    Holloway, Christopher E.; Wing, Allison A.; Bony, Sandrine; Muller, Caroline; Masunaga, Hirohiko; L'Ecuyer, Tristan S.; Turner, David D.; Zuidema, Paquita

    2017-11-01

    Convective self-aggregation, the spontaneous organization of initially scattered convection into isolated convective clusters despite spatially homogeneous boundary conditions and forcing, was first recognized and studied in idealized numerical simulations. While there is a rich history of observational work on convective clustering and organization, there have been only a few studies that have analyzed observations to look specifically for processes related to self-aggregation in models. Here we review observational work in both of these categories and motivate the need for more of this work. We acknowledge that self-aggregation may appear to be far-removed from observed convective organization in terms of time scales, initial conditions, initiation processes, and mean state extremes, but we argue that these differences vary greatly across the diverse range of model simulations in the literature and that these comparisons are already offering important insights into real tropical phenomena. Some preliminary new findings are presented, including results showing that a self-aggregation simulation with square geometry has too broad distribution of humidity and is too dry in the driest regions when compared with radiosonde records from Nauru, while an elongated channel simulation has realistic representations of atmospheric humidity and its variability. We discuss recent work increasing our understanding of how organized convection and climate change may interact, and how model discrepancies related to this question are prompting interest in observational comparisons. We also propose possible future directions for observational work related to convective aggregation, including novel satellite approaches and a ground-based observational network.

  13. What favors convective aggregation and why?

    Science.gov (United States)

    Muller, Caroline; Bony, Sandrine

    2015-07-01

    The organization of convection is ubiquitous, but its physical understanding remains limited. One particular type of organization is the spatial self-aggregation of convection, taking the form of cloud clusters, or tropical cyclones in the presence of rotation. We show that several physical processes can give rise to self-aggregation and highlight the key features responsible for it, using idealized simulations. Longwave radiative feedbacks yield a "radiative aggregation." In that case, sufficient spatial variability of radiative cooling rates yields a low-level circulation, which induces the upgradient energy transport and radiative-convective instability. Not only do vertically integrated radiative budgets matter but the vertical profile of cooling is also crucial. Convective aggregation is facilitated when downdrafts below clouds are weak ("moisture-memory aggregation"), and this is sufficient to trigger aggregation in the absence of longwave radiative feedbacks. These results shed some light on the sensitivity of self-aggregation to various parameters, including resolution or domain size.

  14. Coconut (Cocos nucifera) Ethanolic Leaf Extract Reduces Amyloid-β (1-42) Aggregation and Paralysis Prevalence in Transgenic Caenorhabditis elegans Independently of Free Radical Scavenging and Acetylcholinesterase Inhibition.

    Science.gov (United States)

    Manalo, Rafael Vincent; Silvestre, Maries Ann; Barbosa, Aza Lea Anne; Medina, Paul Mark

    2017-04-21

    Virgin coconut oil (VCO) has been the subject of several studies which have aimed to alleviate Alzheimer's disease (AD) pathology, focusing on in vitro antioxidant and acetylcholinesterase (AChE) inhibitory activities. Here, we studied an underutilized and lesser-valued part of the coconut tree, specifically the leaves, using in vitro and in vivo approaches. Coconut leaf extract (CLE) was screened for antioxidant and AChE inhibitory properties in vitro and therapeutic effects in two strains of transgenic Caenorhabditis elegans expressing amyloid-β 1-42 (Aβ 1-42 ) in muscle cells. CLE demonstrated free radical scavenging activity with an EC 50 that is 79-fold less compared to ascorbic acid, and an AChE inhibitory activity that is 131-fold less compared to Rivastigmine. Surprisingly, in spite of its low antioxidant activity and AChE inhibition, CLE reduced Aβ deposits by 30.31% in CL2006 in a dose-independent manner, and reduced the percentage of paralyzed nematodes at the lowest concentration of CLE (159.38 μg/mL), compared to dH₂O/vehicle (control). Phytochemical analysis detected glycosides, anthocyanins, and hydrolyzable tannins in CLE, some of which are known to be anti-amyloidogenic. Taken together, these findings suggest that CLE metabolites alternatively decrease AB 1-42 aggregation and paralysis prevalence independently of free radical scavenging and AChE inhibition, and this warrants further investigation on the bioactive compounds of CLE.

  15. 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...

  16. A shell-formation related carbonic anhydrase in Crassostrea gigas modulates intracellular calcium against CO2 exposure: Implication for impacts of ocean acidification on mollusk calcification.

    Science.gov (United States)

    Wang, Xiudan; Wang, Mengqiang; Jia, Zhihao; Song, Xiaorui; Wang, Lingling; Song, Linsheng

    2017-08-01

    Ocean acidification (OA) could decrease the shells and skeletons formation of mollusk by reducing the availability of carbonate ions at calcification sites. Carbonic anhydrases (CAs) convert CO 2 to HCO 3 - and play important roles in biomineralization process from invertebrate to vertebrate. In the present study, a CA (designated as CgCA) was identified and characterized in Pacific oyster C. gigas. The cDNA of CgCA was of 927bp encoding a predicted polypeptide of 308 amino acids with a signal peptide and a CA catalytic function domain. The mRNA transcripts of CgCA were constitutively expressed in all tested tissues with the highest levels in mantle and hemocytes. During the early development period, the mRNA transcripts of CgCA could be detected in all the stages with the highest level in D-veliger larvae. Elevated CO 2 increased the mRNA transcripts of CgCA in muscle, mantle, hepatopancreas, gill and hemocytes significantly (p<0.05) and induced the translocation of CgCA in hemocytes and mantle. Moreover, elevated CO 2 also caused the decrease of intracellular Ca 2+ in hemocytes (p<0.05). The inhibition of CA by acetazolamide and suppression of CgCA gene via RNA interference could increase the intracellular Ca 2+ in hemocytes (p<0.05). Besides, the decrease of intracellular Ca 2+ content caused by Ca 2+ reagent ionomycin could affect localization of CgCA in mantle tissue. The results indicated CgCA played essential roles in calcification and elevated CO 2 accelerated the mutual modulation between calcium and CgCA, implying reduced calcification rate and dissolved shells under OA. Copyright © 2017 Elsevier B.V. All rights reserved.

  17. Role of Multicellular Aggregates in Biofilm Formation

    Directory of Open Access Journals (Sweden)

    Kasper N. Kragh

    2016-03-01

    Full Text Available In traditional models of in vitro biofilm development, individual bacterial cells seed a surface, multiply, and mature into multicellular, three-dimensional structures. Much research has been devoted to elucidating the mechanisms governing the initial attachment of single cells to surfaces. However, in natural environments and during infection, bacterial cells tend to clump as multicellular aggregates, and biofilms can also slough off aggregates as a part of the dispersal process. This makes it likely that biofilms are often seeded by aggregates and single cells, yet how these aggregates impact biofilm initiation and development is not known. Here we use a combination of experimental and computational approaches to determine the relative fitness of single cells and preformed aggregates during early development of Pseudomonas aeruginosa biofilms. We find that the relative fitness of aggregates depends markedly on the density of surrounding single cells, i.e., the level of competition for growth resources. When competition between aggregates and single cells is low, an aggregate has a growth disadvantage because the aggregate interior has poor access to growth resources. However, if competition is high, aggregates exhibit higher fitness, because extending vertically above the surface gives cells at the top of aggregates better access to growth resources. Other advantages of seeding by aggregates, such as earlier switching to a biofilm-like phenotype and enhanced resilience toward antibiotics and immune response, may add to this ecological benefit. Our findings suggest that current models of biofilm formation should be reconsidered to incorporate the role of aggregates in biofilm initiation.

  18. Pre-aggregation for Probability Distributions

    DEFF Research Database (Denmark)

    Timko, Igor; Dyreson, Curtis E.; Pedersen, Torben Bach

    Motivated by the increasing need to analyze complex uncertain multidimensional data (e.g., in order to optimize and personalize location-based services), this paper proposes novel types of {\\em probabilistic} OLAP queries that operate on aggregate values that are probability distributions...... and the techniques to process these queries. The paper also presents the methods for computing the probability distributions, which enables pre-aggregation, and for using the pre-aggregated distributions for further aggregation. In order to achieve good time and space efficiency, the methods perform approximate...... multidimensional data analysis that is considered in this paper (i.e., approximate processing of probabilistic OLAP queries over probability distributions)....

  19. Discrete stochastic charging of aggregate grains

    Science.gov (United States)

    Matthews, Lorin S.; Shotorban, Babak; Hyde, Truell W.

    2018-05-01

    Dust particles immersed in a plasma environment become charged through the collection of electrons and ions at random times, causing the dust charge to fluctuate about an equilibrium value. Small grains (with radii less than 1 μm) or grains in a tenuous plasma environment are sensitive to single additions of electrons or ions. Here we present a numerical model that allows examination of discrete stochastic charge fluctuations on the surface of aggregate grains and determines the effect of these fluctuations on the dynamics of grain aggregation. We show that the mean and standard deviation of charge on aggregate grains follow the same trends as those predicted for spheres having an equivalent radius, though aggregates exhibit larger variations from the predicted values. In some plasma environments, these charge fluctuations occur on timescales which are relevant for dynamics of aggregate growth. Coupled dynamics and charging models show that charge fluctuations tend to produce aggregates which are much more linear or filamentary than aggregates formed in an environment where the charge is stationary.

  20. HSP70 gene expression in Mytilus galloprovincialis hemocytes is triggered by moderate heat shock and Vibrio anguillarum, but not by V. splendidus or Micrococcus lysodeikticus.

    Science.gov (United States)

    Cellura, Cinzia; Toubiana, Mylène; Parrinello, Nicolo; Roch, Philippe

    2006-01-01

    Complete sequence of HSP70 cDNA from the mussel, Mytilus galloprovincialis was established before quantifying its expression following moderate heat shock or injection of heat-killed bacteria. HSP70 cDNA is comprised of 2378 bp including one ORF of 654 aa, with a predicted 70 bp 5'-UTR and a 343 bp 3'-UTR (GenBank, 18 Jan 05, AY861684). Alignment identity ranged from 89% for Crassostrea ariakensis to 72% for C. virginica. Curiously, HSP70 gene and cDNA sequences from M. galloprovincialis, deposited later (03 and 27 May), show only 73% identity with the present sequence. Meanwhile, characteristic motifs of the HSP70 family were located in conserved positions. Expression of HSP70 gene was quantified on circulating hemocyte mRNA using Q-PCR after RT using random hexaprimers. Housekeeping gene was 28S rRNA. Four stresses were applied: heat shock that consisted of immersing mussels for 90 min at 30 degrees C and returning them to 20 degrees C sea water, one injection of heat-killed Gram-negative bacteria, Vibrio splendidus LGP32, one injection of heat-killed Gram-negative bacteria Vibrio anguillarum, one injection of heat-killed Gram-positive bacteria Micrococcus lysodeikticus. We found no significant modification of 28S rRNA gene expression. Significant increase of 5.2 +/- 0.4 fold the ratio HSP70/28S rRNA was observed 6 h after heat shock and was maximum at 15 h (6.1 +/- 1.1), and still significant after 24 h (1.7 +/- 0.03). Similarly, injecting V. anguillarum resulted in a significant increase of 2.7 +/- 0.1 after 12 h. Expression was maximum after 48 h (5.2 +/- 0.05) and returned to baseline after 72 h. In contrast, injecting V. splendidus or M. lysodeikticus failed to significantly modulate HSP70 gene expression at least during the first 3 days post-injection. Consequently, mussel hemocytes appeared to discriminate between pathogenic and non-pathogenic Vibrios, as well as between Gram-negative and Gram-positive bacteria.

  1. Prediction of the aggregation propensity of proteins from the primary sequence: aggregation properties of proteomes.

    Science.gov (United States)

    Castillo, Virginia; Graña-Montes, Ricardo; Sabate, Raimon; Ventura, Salvador

    2011-06-01

    In the cell, protein folding into stable globular conformations is in competition with aggregation into non-functional and usually toxic structures, since the biophysical properties that promote folding also tend to favor intermolecular contacts, leading to the formation of β-sheet-enriched insoluble assemblies. The formation of protein deposits is linked to at least 20 different human disorders, ranging from dementia to diabetes. Furthermore, protein deposition inside cells represents a major obstacle for the biotechnological production of polypeptides. Importantly, the aggregation behavior of polypeptides appears to be strongly influenced by the intrinsic properties encoded in their sequences and specifically by the presence of selective short regions with high aggregation propensity. This allows computational methods to be used to analyze the aggregation properties of proteins without the previous requirement for structural information. Applications range from the identification of individual amyloidogenic regions in disease-linked polypeptides to the analysis of the aggregation properties of complete proteomes. Herein, we review these theoretical approaches and illustrate how they have become important and useful tools in understanding the molecular mechanisms underlying protein aggregation. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  2. Customer Aggregation: An Opportunity for Green Power?

    Energy Technology Data Exchange (ETDEWEB)

    Holt, E.; Bird, L.

    2001-02-26

    We undertook research into the experience of aggregation groups to determine whether customer aggregation offers an opportunity to bring green power choices to more customers. The objectives of this report, therefore, are to (1) identify the different types of aggregation that are occurring today, (2) learn whether aggregation offers an opportunity to advance sales of green power, and (3) share these concepts and approaches with potential aggregators and green power advocates.

  3. Transportation and utilization of aggregates for road construction

    Science.gov (United States)

    Fladvad, Marit; Wigum, Børge Johannes; Aurstad, Joralf

    2017-04-01

    Road construction relies on non-renewable aggregate resources as the main construction material. Sources for high-quality aggregate resources are scattered, and requirements for aggregate quality can cause long transport distances between quarry and road construction site. In European countries, the average aggregate consumption per capita is 5 tonnes per year (European Aggregates Association, 2016), while the corresponding figure for Norway is 11 tonnes (Neeb, 2015). Half the Norwegian aggregate production (sand, gravel and crushed rock) is used for road construction. In Norway, aggregate resources have been considered abundant. However, stricter requirement for aggregate quality, and increased concern for sustainability and environmental issues have spurred focus on reduction of transport lengths through better utilization of local aggregate materials. In this research project, information about pavement design and aggregate quality requirements were gathered from a questionnaire sent to selected experts from the World Road Organization (PIARC), European Committee for Standardization (CEN), and Nordic Road Association (NVF). The gathered data was compared to identify differences and similarities for aggregate use in the participating countries. Further, the data was compared to known data from Norway regarding: - amount of aggregates required for a road structure - aggregate transport lengths and related costs A total of 18 countries participated in the survey, represented by either road authorities, research institutions, or contractors. There are large variations in practice for aggregate use among the represented countries, and the selection of countries is sufficient to illustrate a variety in pavement designs, aggregate sizes, and quality requirements for road construction. There are considerable differences in both pavement thickness and aggregate sizes used in the studied countries. Total thicknesses for pavement structures varies from 220 mm to 2400 mm

  4. Reusing recycled aggregates in structural concrete

    Science.gov (United States)

    Kou, Shicong

    The utilization of recycled aggregates in concrete can minimize environmental impact and reduce the consumption of natural resources in concrete applications. The aim of this thesis is to provide a scientific basis for the possible use of recycled aggregates in structure concrete by conducting a comprehensive programme of laboratory study to gain a better understanding of the mechanical, microstructure and durability properties of concrete produced with recycled aggregates. The study also explored possible techniques to of improve the properties of recycled aggregate concrete that is produced with high percentages (≧ 50%) of recycled aggregates. These techniques included: (a) using lower water-to-cement ratios in the concrete mix design; (b) using fly ash as a cement replacement or as an additional mineral admixture in the concrete mixes, and (c) precasting recycled aggregate concrete with steam curing regimes. The characteristics of the recycled aggregates produced both from laboratory and a commercially operated pilot construction and demolition (C&D) waste recycling plant were first studied. A mix proportioning procedure was then established to produce six series of concrete mixtures using different percentages of recycled coarse aggregates with and without the use of fly ash. The water-to-cement (binder) ratios of 0.55, 0.50, 0.45 and 0.40 were used. The fresh properties (including slump and bleeding) of recycled aggregate concrete (RAC) were then quantified. The effects of fly ash on the fresh and hardened properties of RAC were then studied and compared with those RAC prepared with no fly ash addition. Furthermore, the effects of steam curing on the hardened properties of RAC were investigated. For micro-structural properties, the interfacial transition zones of the aggregates and the mortar/cement paste were analyzed by SEM and EDX-mapping. Moreover, a detailed set of results on the fracture properties for RAC were obtained. Based on the experimental

  5. Cellular Immune Reactions of the Sunn Pest, Eurygaster integriceps, to the Entomopathogenic Fungus, Beauveria bassiana and Its Secondary Metabolites

    Science.gov (United States)

    Zibaee, Arash; Bandani, Ali Reza; Talaei-Hassanlouei, Reza; Malagoli, Davide

    2011-01-01

    In this study, five morphological types of circulating hemocytes were recognized in the hemolymph of the adult sunn pest, Eurygaster integriceps Puton (Hemiptera: Scutelleridae), namely prohemocytes, plasmatocytes, granulocytes, adipohemocytes, and oenocytoids. The effects of the secondary metabolites of the entomopathogenic fungus Beauveria bassiana on cellular immune defenses of Eurygaster integriceps were investigated. The results showed that the fungal secondary metabolites inhibited phagocytic activity of E. integriceps hemocytes and hampered nodule formation. A reduction of phenoloxidase activity was also observed. The data suggest that B. bassiana produce secondary metabolites that disable several immune mechanisms allowing the fungus to overcome and then kill its host. This characteristic makes B. bassiana a promising model for biological control of insect pests such as E. integriceps. PMID:22233481

  6. Aggregated particles caused by instrument artifact

    Science.gov (United States)

    Pierce, Ashley M.; Loría-Salazar, S. Marcela; Arnott, W. Patrick; Edwards, Grant C.; Miller, Matthieu B.; Gustin, Mae S.

    2018-04-01

    Previous studies have indicated that superaggregates, clusters of aggregates of soot primary particles, can be formed in large-scale turbulent fires. Due to lower effective densities, higher porosity, and lower aerodynamic diameters, superaggregates may pass through inlets designed to remove particles 2.5 µm in aerodynamic diameter were collected on 36 out of 158 sample days. On preliminary analysis, it was thought that these aggregated particles were superaggregates, depositing past PM10 (particles wind speeds, as well as the use of generators on site. Samples with aggregated particles, referred to as aggregates, were analyzed using a scanning electron microscope for size and shape and energy dispersive X-ray spectroscopy was used for elemental analysis. It was determined, based on the high amounts of aluminum present in the aggregate samples, that a sampling artifact associated with the sample inlet and prolonged, high wind events was the probable reason for the observed aggregates.

  7. The alkali–aggregate reaction for various aggregates used in concrete

    Directory of Open Access Journals (Sweden)

    Calderón, V.

    2010-09-01

    Full Text Available The aim of this work is to contribute to the knowledge of the interactions between aggregates and the components of the interstitial phase of concrete and to determine whether those aggregates that are subsequently used in the manufacture of concrete are reagents and are therefore likely to undergo a progressive deterioration of their initial properties. An initial petrographic study of each aggregate is performed in order to be able to determine its subsequent behaviour and reactivity under the influence of various factors. The potential reactivity of different silicaceous aggregates (slates, gneiss, hornfels, granites, quartzite and serpentine is then determined by a chemical method for evaluating the potential reactivity of aggregates and an accelerated method in mortar specimens, and finally the surface reactivity is investigated. The results of these studies suggest that some aggregates are able to react with the components of the interstitial phase of concrete. The existence of this kind of interaction is confirmed by the results of the surface investigations before and after the basic reaction.

    Este trabajo pretende contribuir al conocimiento de las reacciones de interacción entre los áridos y los componentes de la fase intersticial del hormigón y determinar si estos áridos, empleados posteriormente en la fabricación del hormigón, son reactivos y por tanto susceptibles de provocar una disminución progresiva de sus propiedades iniciales. Para la caracterización de cada árido se ha realizado un estudio petrográfico, fundamental a la hora de determinar su posterior comportamiento en términos de reactividad frente a diversos factores. Seguidamente, se ha analizado la reactividad potencial de diferentes áridos silicatados (pizarras, gneis, corneanas, granitos, cuarcita y serpentina mediante los dos métodos normalizados existentes: el método químico para la determinación de la reactividad potencial de áridos y

  8. New pyridine derivatives as inhibitors of acetylcholinesterase and amyloid aggregation.

    Science.gov (United States)

    Pandolfi, Fabiana; De Vita, Daniela; Bortolami, Martina; Coluccia, Antonio; Di Santo, Roberto; Costi, Roberta; Andrisano, Vincenza; Alabiso, Francesco; Bergamini, Christian; Fato, Romana; Bartolini, Manuela; Scipione, Luigi

    2017-12-01

    A new series of pyridine derivatives with carbamic or amidic function has been designed and synthesized to act as cholinesterase inhibitors. The synthesized compounds were tested toward EeAChE and hAChE and toward eqBChE and hBChE. The carbamate 8 was the most potent hAChE inhibitor (IC 50  = 0.153 ± 0.016 μM) while the carbamate 11 was the most potent inhibitor of hBChE (IC 50  = 0.828 ± 0.067 μM). A molecular docking study indicated that the carbamate 8 was able to bind AChE by interacting with both CAS and PAS, in agreement with the mixed inhibition mechanism. Furthermore, the carbamates 8, 9 and 11 were able to inhibit Aβ 42 self-aggregation and possessed quite low toxicity against human astrocytoma T67 and HeLa cell lines, being the carbamate 8 the less toxic compound on both cell lines. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  9. Influence of hirudin and cobra venom factor on the release of 14C-serotonin and 51chromium from human platelets induced by thrombin, collagen, aggregate gammaglobulin and HLA antibody

    International Nuclear Information System (INIS)

    Hagemeyer, G.M.

    1982-01-01

    The present work investigates the influence of hirudin and cobra venom factor on thrombin, collagen, aggregate gammaglobulin and HLA-antibody-induced release of 14 C-serotonin and 51 chromium from human platelets. Besides the platelet-specific release reaction ( 14 C-serotonin) the extent of platelet lysis was determined by measurement of the loss of 51 chromium from the platelets. The results showed the thrombin, collagen and aggregate-gammaglobulin-induced platelet alteration to be a non-complement-dependent reaction of the platelets with release of 14 C-serotonin. Following long-term incubation small quantities of 51 chromium are also released. As this release of 51 chromium cannot be inhibited using cobra venom factor and does not occur in washed platelets either, it is most probably a non-complement-dependent reaction. The HLA-antibody-induced, specific platelet alteration is both complement-dependent and complement-independent. Differentiation is possible by inhibition of the complement-dependent lysis. On the other hand thrombin is of no relevance to the collagen, aggregate gammaglobulin, and HLA-antibody-induced platelet alteration as the interactions of these substances with platelets are not inhibited by hirudin. The above results are confirmed by investigation of the 51 chromium uptake capacity of washed platelets treated previously with thrombin, collagen and HLA antibody. (orig./MG) [de

  10. Information Aggregation and Investment Decisions

    OpenAIRE

    Christian Hellwig; Aleh Tsyvinski; Elias Albagli

    2010-01-01

    This paper studies an environment in which information aggregation interacts with investment decisions. The first contribution of the paper is to develop a tractable model of such interactions. The second contribution is to solve the model in closed form and derive a series of implications that result from the interplay between information aggregation and the value of market information for the firms' decision problem. We show that the model generates an information aggregation wedge between ...

  11. Platelet activation, adhesion, inflammation, and aggregation potential are altered in the presence of electronic cigarette extracts of variable nicotine concentrations.

    Science.gov (United States)

    Hom, Sarah; Chen, Li; Wang, Tony; Ghebrehiwet, Berhane; Yin, Wei; Rubenstein, David A

    2016-11-01

    Tobacco smoke extracts prepared from both mainstream and sidestream smoking have been associated with heightened platelet activation, aggregation, adhesion, and inflammation. Conversely, it has been shown that pure nicotine inhibits similar platelet functions. In this work, we 1) evaluated the effects of e-cigarette extracts on platelet activities and 2) elucidated the differences between the nicotine-dependent and non-nicotine dependent (e.g. fine particulate matter or toxic compounds) effects of tobacco and e-cigarette products on platelet activities. To accomplish these goals, platelets from healthy volunteers (n = 50) were exposed to tobacco smoke extracts, e-cigarette vapor extracts, and pure nicotine and changes in platelet activation, adhesion, aggregation, and inflammation were evaluated, using optical aggregation, flow cytometry, and ELISA methods. Interestingly, the exposure of platelets to e-vapor extracts induced a significant up-regulation in the expression of the pro-inflammatory gC1qR and cC1qR and induced a marked increase in the deposition of C3b as compared with traditional tobacco smoke extracts. Similarly, platelet activation, as measured by a prothrombinase based assay, and platelet aggregation were also significantly enhanced after exposure to e-vapor extracts. Finally, platelet adhesion potential toward fibrinogen, von Willebrand factor, and other platelets was also enhanced after exposure to e-cigarette vapor extracts. In the presence of pure nicotine, platelet functions were observed to be inhibited, which further suggests that other constituents of tobacco smoke and electronic vapor can antagonize platelet functions, however, the presence of nicotine in extracts somewhat perpetuated the platelet functional changes in a dose-dependent manner.

  12. Formation of nucleoplasmic protein aggregates impairs nuclear function in response to SiO2 nanoparticles

    International Nuclear Information System (INIS)

    Chen Min; Mikecz, Anna von

    2005-01-01

    Despite of their exponentially growing use, little is known about cell biological effects of nanoparticles. Here, we report uptake of silica (SiO 2 ) nanoparticles to the cell nucleus where they induce aberrant clusters of topoisomerase I (topo I) in the nucleoplasm that additionally contain signature proteins of nuclear domains, and protein aggregation such as ubiquitin, proteasomes, cellular glutamine repeat (polyQ) proteins, and huntingtin. Formation of intranuclear protein aggregates (1) inhibits replication, transcription, and cell proliferation; (2) does not significantly alter proteasomal activity or cell viability; and (3) is reversible by Congo red and trehalose. Since SiO 2 nanoparticles trigger a subnuclear pathology resembling the one occurring in expanded polyglutamine neurodegenerative disorders, we suggest that integrity of the functional architecture of the cell nucleus should be used as a read out for cytotoxicity and considered in the development of safe nanotechnology

  13. Production of lightweight aggregates from washing aggregate sludge and fly ash

    Science.gov (United States)

    González-Corrochano, Beatriz; Alonso-Azcárate, Jacinto; Rodas, Magdalena

    2010-05-01

    Increasing generation of wastes is one of the main environmental problems in industrialised countries. Heat treatment at high temperatures can convert some types of wastes into ceramic products with a wide range of microstructural features and properties (Bethanis et al., 2004). A lightweight aggregate (LWA) is a granular material with a bulk density (bd) not exceeding 1.20 g/cm3 or with a particle density not exceeding 2.00 g/cm3 (UNE-EN-13055-1, 2003). They have become a focus of interest because the low particle density and the low bulk density entail a decrease in the load transmitted to the ground, and less work and effort are required to transport them (De' Gennaro et al., 2004). The benefits associated with these low densities, which are due to the formation of voids and pores, are very good thermal and acoustic insulation and materials with a good resistance to fire (Benbow, 1987; Fakhfakh et al., 2007). The objective was to recycle fly ash, used motor oil from cars and mineral wastes from washing aggregate sludge, in order to obtain a usable material such as lightweight aggregates, and also to ensure that they are of good quality for different applications. Raw materials have been physically, chemically and mineralogically characterized. On the basis of the results obtained, they were mixed, milled to a grain size of less than 200 μm (Yasuda, 1991), formed into pellets, pre-heated for 5 min and sintered in a rotary kiln at 1150°C, 1175°C, 1200°C and 1225°C for 10 and 15 min at each temperature (Theating). Effects of raw material characteristics, heating temperature and dwell time on the following LWAs properties were determined: loss on ignition (LOI), bloating index (BI), loose bulk density (bd), apparent and dry particle density (ad, dd), voids (H), water absorption (WA24h) and compressive strength (S). The products obtained were lightweight aggregates in accordance with norm UNE-EN-13055-1 (bd ≤1.20 g/cm3 or particle density ≤2.00 g/cm3). LWAs

  14. Internal water curing with Liapor aggregates

    DEFF Research Database (Denmark)

    Lura, Pietro

    2005-01-01

    Internal water curing is a very efficient way to counteract self-desiccation and autogenous shrinkage in high performance concrete, thereby reducing the likelihood of early-age cracking. This paper deals with early-age volume changes and moisture transport in lightweight aggregate concrete realized...... with wet lightweight aggregates. Lightweight aggregate concrete mixtures with different degree of saturation and different particle size of the lightweight aggregates were studied and compared to normal weight concrete. Autogenous deformations, selfinduced stresses in fully restrained conditions, elastic...

  15. Fly ash aggregates. Vliegaskunstgrind

    Energy Technology Data Exchange (ETDEWEB)

    1983-03-01

    A study has been carried out into artificial aggregates made from fly ash, 'fly ash aggregates'. Attention has been drawn to the production of fly ash aggregates in the Netherlands as a way to obviate the need of disposal of fly ash. Typical process steps for the manufacturing of fly ash aggregates are the agglomeration and the bonding of fly ash particles. Agglomeration techniques are subdivided into agitation and compaction, bonding methods into sintering, hydrothermal and 'cold' bonding. In sintering no bonding agent is used. The fly ash particles are more or less welded together. Sintering in general is performed at a temperature higher than 900 deg C. In hydrothermal processes lime reacts with fly ash to a crystalline hydrate at temperatures between 100 and 250 deg C at saturated steam pressure. As a lime source not only lime as such, but also portland cement can be used. Cold bonding processes rely on reaction of fly ash with lime or cement at temperatures between 0 and 100 deg C. The pozzolanic properties of fly ash are used. Where cement is applied, this bonding agent itself contributes also to the strength development of the artificial aggregate. Besides the use of lime and cement, several processes are known which make use of lime containing wastes such as spray dry absorption desulfurization residues or fluid bed coal combustion residues. (In Dutch)

  16. Non-Watson–Crick interactions between PNA and DNA inhibit the ATPase activity of bacteriophage T4 Dda helicase

    Science.gov (United States)

    Tackett, Alan J.; Corey, David R.; Raney, Kevin D.

    2002-01-01

    Peptide nucleic acid (PNA) is a DNA mimic in which the nucleobases are linked by an N-(2-aminoethyl) glycine backbone. Here we report that PNA can interact with single-stranded DNA (ssDNA) in a non-sequence-specific fashion. We observed that a 15mer PNA inhibited the ssDNA-stimulated ATPase activity of a bacteriophage T4 helicase, Dda. Surprisingly, when a fluorescein-labeled 15mer PNA was used in binding studies no interaction was observed between PNA and Dda. However, fluorescence polarization did reveal non-sequence-specific interactions between PNA and ssDNA. Thus, the inhibition of ATPase activity of Dda appears to result from depletion of the available ssDNA due to non-Watson–Crick binding of PNA to ssDNA. Inhibition of the ssDNA-stimulated ATPase activity was observed for several PNAs of varying length and sequence. To study the basis for this phenomenon, we examined self-aggregation by PNAs. The 15mer PNA readily self-aggregates to the point of precipitation. Since PNAs are hydrophobic, they aggregate more than DNA or RNA, making the study of this phenomenon essential for understanding the properties of PNA. Non-sequence-specific interactions between PNA and ssDNA were observed at moderate concentrations of PNA, suggesting that such interactions should be considered for antisense and antigene applications. PMID:11842106

  17. Macrophage triggering by aggregated immunoglobulins. II. Comparison of IgE and IgG aggregates or immune complexes.

    Science.gov (United States)

    Pestel, J; Dessaint, J P; Joseph, M; Bazin, H; Capron, A

    1984-01-01

    Macrophages incubated with complexed or aggregated IgE released beta-glucuronidase (beta-G) within 30 min. In contrast in the presence of aggregated or complexed IgG, macrophages liberated equivalent amount of beta-G only after 6 h incubation. In addition the rapid macrophage stimulation induced by aggregated IgE was also followed by a faster 3H-glucosamine incorporation when compared to the delayed activation caused by aggregated IgG. However, macrophages stimulated either by IgG or by IgE oligomers produced the same percentage of plasminogen activator at 24 h. In contrast, while the interaction between macrophages and aggregated IgE was only followed by a peak of cyclic GMP and a beta-G release during the first 30 min of incubation, the interaction between macrophages and IgG oligomers was accompanied by a simultaneous increase of cyclic GMP and AMP nucleotides and by an absence of beta-G exocytosis. Moreover, the beta-G release induced by aggregated IgE was increased when macrophages were preincubated with aggregated IgG. This additive effect was not observed in the reverse situation. Finally macrophages activated by IgG oligomers were demonstrated to exert a cytotoxic effect on tumour cells and to kill schistosomula in the presence of a low level of complement. Taken together these results underline the peculiar ability of aggregated or complexed IgE to trigger rapidly the macrophage activation compared to aggregated IgG and can explain the important role of complexed IgE in some macrophage dependent cytotoxicity mechanisms (i.e. in parasitic diseases). PMID:6088135

  18. Microfluidic magnetic switching valves based on aggregates of magnetic nanoparticles: Effects of aggregate length and nanoparticle sizes

    Energy Technology Data Exchange (ETDEWEB)

    Jiemsakul, Thanakorn [National Nanotechnology Center (NANOTEC), National Science and Technology Development Agency (NSTDA), 111 Thailand Science Park, Thanon Phahonyothin, Tambon Khlong Nueng, Amphoe Khlong Luang, Pathum Thani 12120 (Thailand); Manakasettharn, Supone, E-mail: supone@nanotec.or.th [National Nanotechnology Center (NANOTEC), National Science and Technology Development Agency (NSTDA), 111 Thailand Science Park, Thanon Phahonyothin, Tambon Khlong Nueng, Amphoe Khlong Luang, Pathum Thani 12120 (Thailand); Kanharattanachai, Sivakorn; Wanna, Yongyuth [College of Nanotechnology, King Mongkut' s Institute of Technology Ladkrabang, Chalongkrung Road, Bangkok 10520 (Thailand); Wangsuya, Sujint [College of Nanotechnology, King Mongkut' s Institute of Technology Ladkrabang, Chalongkrung Road, Bangkok 10520 (Thailand); Faculty of Science, Mahidol University, 272 Rama VI Road, Ratchathewi District, Bangkok 10400 (Thailand); Pratontep, Sirapat [College of Nanotechnology, King Mongkut' s Institute of Technology Ladkrabang, Chalongkrung Road, Bangkok 10520 (Thailand)

    2017-01-15

    We demonstrate microfluidic switching valves using magnetic nanoparticles blended within the working fluid as an alternative microfluidic flow control in microchannels. Y-shaped microchannels have been fabricated by using a CO{sub 2} laser cutter to pattern microchannels on transparent poly(methyl methacrylate) (PMMA) sheets covered with thermally bonded transparent polyvinyl chloride (PVC) sheets. To examine the performance of the microfluidic magnetic switching valves, an aqueous magnetic nanoparticle suspension was injected into the microchannels by a syringe pump. Neodymium magnets were then employed to attract magnetic nanoparticles and form an aggregate that blocked the microchannels at a required position. We have found that the maximum volumetric flow rate of the syringe pump that the magnetic nanoparticle aggregate can withstand scales with the square of the external magnetic flux density. The viscosity of the fluid exhibits dependent on the aggregate length and the size of the magnetic nanoparticles. This microfluidic switching valve based on aggregates of magnetic nanoparticles has strong potentials as an on-demand flow control, which may help simplifying microfluidic channel designs. - Highlights: • We demonstrate microfluidic switching valves based on aggregates of magnetic particles. • Maximum flow rate that the aggregate can withstand scales with the square of the external magnetic flux density. • Aggregates with smaller magnetic nanoparticle size can withstand higher flow rate. • Aggregate length exhibits a linear dependence with flow resistance of a viscous fluid.

  19. Macroeconomic susceptibility, inflation, and aggregate supply

    Science.gov (United States)

    Hawkins, Raymond J.

    2017-03-01

    We unify aggregate-supply dynamics as a time-dependent susceptibility-mediated relationship between inflation and aggregate economic output. In addition to representing well various observations of inflation-output dynamics this parsimonious formalism provides a straightforward derivation of popular representations of aggregate-supply dynamics and a natural basis for economic-agent expectations as an element of inflation formation. Our formalism also illuminates questions of causality and time-correlation that challenge central banks for whom aggregate-supply dynamics is a key constraint in their goal of achieving macroeconomic stability.

  20. Aggregated recommendation through random forests.

    Science.gov (United States)

    Zhang, Heng-Ru; Min, Fan; He, Xu

    2014-01-01

    Aggregated recommendation refers to the process of suggesting one kind of items to a group of users. Compared to user-oriented or item-oriented approaches, it is more general and, therefore, more appropriate for cold-start recommendation. In this paper, we propose a random forest approach to create aggregated recommender systems. The approach is used to predict the rating of a group of users to a kind of items. In the preprocessing stage, we merge user, item, and rating information to construct an aggregated decision table, where rating information serves as the decision attribute. We also model the data conversion process corresponding to the new user, new item, and both new problems. In the training stage, a forest is built for the aggregated training set, where each leaf is assigned a distribution of discrete rating. In the testing stage, we present four predicting approaches to compute evaluation values based on the distribution of each tree. Experiments results on the well-known MovieLens dataset show that the aggregated approach maintains an acceptable level of accuracy.

  1. Microbial properties of soil aggregates created by earthworms and other factors: spherical and prismatic soil aggregates from unreclaimed post-mining sites

    Energy Technology Data Exchange (ETDEWEB)

    Frouz, J.; Kristufek, V.; Liveckova, M.; van Loo, D.; Jacobs, P.; Van Hoorebeke, L. [Charles University of Prague, Prague (Czech Republic). Inst. of Environmental Studies

    2011-01-15

    Soil aggregates between 2 and 5 mm from 35- and 45-year-old unreclaimed post-mining sites near Sokolov (Czech Republic) were divided into two groups: spherical and prismatic. X-ray tomography indicated that prismatic aggregates consisted of fragments of claystone bonded together by amorphous clay and roots while spherical aggregates consisted of a clay matrix and organic fragments of various sizes. Prismatic aggregates were presumed to be formed by plant roots and physical processes during weathering of Tertiary mudstone, while earthworms were presumed to contribute to the formation of spherical aggregates. The effects of drying and rewetting and glucose addition on microbial respiration, microbial biomass, and counts of bacteria in these aggregates were determined. Spherical aggregates contained a greater percentage of C and N and a higher C-to-N ratio than prismatic ones. The C content of the particulate organic matter was also higher in the spherical than in the prismatic aggregates. Although spherical aggregates had a higher microbial respiration and biomass, the growth of microbial biomass in spherical aggregates was negatively correlated with initial microbial biomass, indicating competition between bacteria. Specific respiration was negatively correlated with microbial biomass. Direct counts of bacteria were higher in spherical than in prismatic aggregates. Bacterial numbers were more stable in the center than in the surface layers of the aggregates. Transmission electron microscopy indicated that bacteria often occurred as individual cells in prismatic aggregates but as small clusters of cells in spherical aggregates. Ratios of colony forming units (cultivatable bacteria) to direct counts were higher in spherical than in prismatic aggregates. Spherical aggregates also contained faster growing bacteria.

  2. S-Mercuration of rat sorbitol dehydrogenase by methylmercury causes its aggregation and the release of the zinc ion from the active site.

    Science.gov (United States)

    Kanda, Hironori; Toyama, Takashi; Shinohara-Kanda, Azusa; Iwamatsu, Akihiro; Shinkai, Yasuhiro; Kaji, Toshiyuki; Kikushima, Makoto; Kumagai, Yoshito

    2012-11-01

    We previously developed a screening method to identify proteins that undergo aggregation through S-mercuration by methylmercury (MeHg) and found that rat arginase I is a target protein for MeHg (Kanda et al. in Arch Toxicol 82:803-808, 2008). In the present study, we characterized another S-mercurated protein from a rat hepatic preparation that has a subunit mass of 42 kDa, thereby facilitating its aggregation. Two-dimensional SDS-polyacrylamide gel electrophoresis and subsequent peptide mass fingerprinting using matrix-assisted laser desorption and ionization time-of-flight mass spectrometry revealed that the 42 kDa protein was NAD-dependent sorbitol dehydrogenase (SDH). With recombinant rat SDH, we found that MeHg is covalently bound to SDH through Cys44, Cys119, Cys129 and Cys164, resulting in the inhibition of its catalytic activity, release of zinc ions and facilitates protein aggregation. Mutation analysis indicated that Cys44, which ligates the active site zinc atom, and Cys129 play a crucial role in the MeHg-mediated aggregation of SDH. Pretreatment with the cofactor NAD, but not NADP or FAD, markedly prevented aggregation of SDH. Such a protective effect of NAD on the aggregation of SDH caused by MeHg is discussed.

  3. Glycation precedes lens crystallin aggregation

    International Nuclear Information System (INIS)

    Swamy, M.S.; Perry, R.E.; Abraham, E.C.

    1987-01-01

    Non-enzymatic glycosylation (glycation) seems to have the potential to alter the structure of crystallins and make them susceptible to thiol oxidation leading to disulfide-linked high molecular weight (HMW) aggregate formation. They used streptozotocin diabetic rats during precataract and cataract stages and long-term cell-free glycation of bovine lens crystallins to study the relationship between glycation and lens crystallin aggregation. HMW aggregates and other protein components of the water-soluble (WS) and urea-soluble (US) fractions were separated by molecular sieve high performance liquid chromatography. Glycation was estimated by both [ 3 H]NaBH 4 reduction and phenylboronate agarose affinity chromatography. Levels of total glycated protein (GP) in the US fractions were about 2-fold higher than in the WS fractions and there was a linear increase in GP in both WS and US fractions. This increase was parallelled by a corresponding increase in HMW aggregates. Total GP extracted by the affinity method from the US fraction showed a predominance of HMW aggregates and vice versa. Cell-free glycation studies with bovine crystallins confirmed the results of the animals studies. Increasing glycation caused a corresponding increase in protein insolubilization and the insoluble fraction thus formed also contained more glycated protein. It appears that lens protein glycation, HMW aggregate formation, and protein insolubilization are interrelated

  4. Intravenous immunglobulin binds beta amyloid and modifies its aggregation, neurotoxicity and microglial phagocytosis in vitro.

    Directory of Open Access Journals (Sweden)

    Susann Cattepoel

    Full Text Available Intravenous Immunoglobulin (IVIG has been proposed as a potential therapeutic for Alzheimer's disease (AD and its efficacy is currently being tested in mild-to-moderate AD. Earlier studies reported the presence of anti-amyloid beta (Aβ antibodies in IVIG. These observations led to clinical studies investigating the potential role of IVIG as a therapeutic agent in AD. Also, IVIG is known to mediate beneficial effects in chronic inflammatory and autoimmune conditions by interfering with various pathological processes. Therefore, we investigated the effects of IVIG and purified polyclonal Aβ-specific antibodies (pAbs-Aβ on aggregation, toxicity and phagocytosis of Aβ in vitro, thus elucidating some of the potential mechanisms of action of IVIG in AD patients. We report that both IVIG and pAbs-Aβ specifically bound to Aβ and inhibited its aggregation in a dose-dependent manner as measured by Thioflavin T assay. Additionally, IVIG and the purified pAbs-Aβ inhibited Aβ-induced neurotoxicity in the SH-SY5Y human neuroblastoma cell line and prevented Aβ binding to rat primary cortical neurons. Interestingly, IVIG and pAbs-Aβ also increased the number of phagocytosing cells as well as the amount of phagocytosed fibrillar Aβ by BV-2 microglia. Phagocytosis of Aβ depended on receptor-mediated endocytosis and was accompanied by upregulation of CD11b expression. Importantly, we could also show that Privigen dose-dependently reversed Aβ-mediated LTP inhibition in mouse hippocampal slices. Therefore, our in vitro results suggest that IVIG may have an impact on different processes involved in AD pathogenesis, thereby promoting further understanding of the effects of IVIG observed in clinical studies.

  5. Reuse of industrial sludge as construction aggregates.

    Science.gov (United States)

    Tay, J H; Show, K Y; Hong, S Y

    2001-01-01

    Industrial wastewater sludge and dredged marine clay are high volume wastes that needed enormous space at landfill disposal sites. Due to the limitation of land space, there is an urgent need for alternative disposal methods for these two wastes. This study investigates the possibility of using the industrial sludge in combination with marine clay as construction aggregates. Different proportions of sludge and clay were made into round and angular aggregates. It was found that certain mix proportions could provide aggregates of adequate strength, comparable to that of conventional aggregates. Concrete samples cast from the sludge-clay aggregates yield compressive strengths in the range of 31.0 to 39.0 N/mm2. The results showed that the round aggregates of 100% sludge and the crush aggregates of sludge with up to 20% clay produced concrete of compressive strengths which are superior to that of 38.0 N/mm2 for conventional aggregate. The study indicates that the conversion of high volume wastes into construction materials is a potential option for waste management.

  6. Silt-clay aggregates on Mars

    International Nuclear Information System (INIS)

    Greeley, R.

    1979-01-01

    Viking observations suggest abundant silt and clay particles on Mars. It is proposed that some of these particles agglomerate to form sand size aggregates that are redeposited as sandlike features such as drifts and dunes. Although the binding for the aggregates could include salt cementation or other mechanisms, electrostatic bonding is considered to be a primary force holding the aggregates together. Various laboratory experiments conducted since the 19th century, and as reported here for simulated Martian conditions, show that both the magnitude and sign of electrical charges on windblown particles are functions of particle velocity, shape and composition, atmospheric pressure, atmospheric composition, and other factors. Electrical charges have been measured for saltating particles in the wind tunnel and in the field, on the surfaces of sand dunes, and within dust clouds on earth. Similar, and perhaps even greater, charges are proposed to occur on Mars, which could form aggregates of silt and clay size particles. Electrification is proposed to occur within Martian dust clouds, generating silt-clay aggregates which would settle to the surface where they may be deposited in the form of sandlike structures. By analog, silt-clay dunes are known in many parts of the earth where silt-clay aggregated were transported by saltation and deposited as 'sand.' In these structures the binding forces were later destroyed, and the particles reassumed the physical properties of silt and clay, but the sandlike bedding structure within the 'dunes' was preserved. The bedding observed in drifts at the Viking landing site is suggested to result from a similar process involving silt-clay aggregates on Mars

  7. Selective and rapid monitoring of dual platelet inhibition by aspirin and P2Y12 antagonists by using multiple electrode aggregometry

    Directory of Open Access Journals (Sweden)

    Lorenz Reinhard

    2010-05-01

    Full Text Available Abstract Background Poor platelet inhibition by aspirin or clopidogrel has been associated with adverse outcomes in patients with cardiovascular diseases. A reliable and facile assay to measure platelet inhibition after treatment with aspirin and a P2Y12 antagonist is lacking. Multiple electrode aggregometry (MEA, which is being increasingly used in clinical studies, is sensitive to platelet inhibition by aspirin and clopidogrel, but a critical evaluation of MEA monitoring of dual anti-platelet therapy with aspirin and P2Y12 antagonists is missing. Design and Methods By performing in vitro and ex vivo experiments, we evaluated in healthy subjects the feasibility of using MEA to monitor platelet inhibition of P2Y12 antagonists (clopidogrel in vivo, cangrelor in vitro and aspirin (100 mg per day in vivo, and 1 mM or 5.4 mM in vitro alone, and in combination. Statistical analyses were performed by the Mann-Whitney rank sum test, student' t-test, analysis of variance followed by the Holm-Sidak test, where appropriate. Results ADP-induced platelet aggregation in hirudin-anticoagulated blood was inhibited by 99.3 ± 1.4% by in vitro addition of cangrelor (100 nM; p 95% and 100 ± 3.2%, respectively (p in vitro or ex vivo. Oral intake of clopidogrel did not significantly reduce AA-induced aggregation, but P2Y12 blockade by cangrelor (100 nM in vitro diminished AA-stimulated aggregation by 53 ± 26% (p Conclusions Selective platelet inhibition by aspirin and P2Y12 antagonists alone and in combination can be rapidly measured by MEA. We suggest that dual anti-platelet therapy with these two types of anti-platelet drugs can be optimized individually by measuring platelet responsiveness to ADP and AA with MEA before and after drug intake.

  8. Aggregating and Disaggregating Flexibility Objects

    DEFF Research Database (Denmark)

    Siksnys, Laurynas; Valsomatzis, Emmanouil; Hose, Katja

    2015-01-01

    In many scientific and commercial domains we encounter flexibility objects, i.e., objects with explicit flexibilities in a time and an amount dimension (e.g., energy or product amount). Applications of flexibility objects require novel and efficient techniques capable of handling large amounts...... and aiming at energy balancing during aggregation. In more detail, this paper considers the complete life cycle of flex-objects: aggregation, disaggregation, associated requirements, efficient incremental computation, and balance aggregation techniques. Extensive experiments based on real-world data from...

  9. CPAD, Curated Protein Aggregation Database: A Repository of Manually Curated Experimental Data on Protein and Peptide Aggregation.

    Science.gov (United States)

    Thangakani, A Mary; Nagarajan, R; Kumar, Sandeep; Sakthivel, R; Velmurugan, D; Gromiha, M Michael

    2016-01-01

    Accurate distinction between peptide sequences that can form amyloid-fibrils or amorphous β-aggregates, identification of potential aggregation prone regions in proteins, and prediction of change in aggregation rate of a protein upon mutation(s) are critical to research on protein misfolding diseases, such as Alzheimer's and Parkinson's, as well as biotechnological production of protein based therapeutics. We have developed a Curated Protein Aggregation Database (CPAD), which has collected results from experimental studies performed by scientific community aimed at understanding protein/peptide aggregation. CPAD contains more than 2300 experimentally observed aggregation rates upon mutations in known amyloidogenic proteins. Each entry includes numerical values for the following parameters: change in rate of aggregation as measured by fluorescence intensity or turbidity, name and source of the protein, Uniprot and Protein Data Bank codes, single point as well as multiple mutations, and literature citation. The data in CPAD has been supplemented with five different types of additional information: (i) Amyloid fibril forming hexa-peptides, (ii) Amorphous β-aggregating hexa-peptides, (iii) Amyloid fibril forming peptides of different lengths, (iv) Amyloid fibril forming hexa-peptides whose crystal structures are available in the Protein Data Bank (PDB) and (v) Experimentally validated aggregation prone regions found in amyloidogenic proteins. Furthermore, CPAD is linked to other related databases and resources, such as Uniprot, Protein Data Bank, PUBMED, GAP, TANGO, WALTZ etc. We have set up a web interface with different search and display options so that users have the ability to get the data in multiple ways. CPAD is freely available at http://www.iitm.ac.in/bioinfo/CPAD/. The potential applications of CPAD have also been discussed.

  10. Contrasting self-aggregation over land and ocean surfaces

    Science.gov (United States)

    Inda Diaz, H. A.; O'Brien, T. A.

    2017-12-01

    The spontaneous organization of convection into clusters, or self-aggregation, demonstrably changes the nature and statistics of precipitation. While there has been much recent progress in this area, the processes that control self-aggregation are still poorly understood. Most of the work to date has focused on self-aggregation over ocean-like surfaces, but it is particularly pressing to understand what controls convective aggregation over land, since the associated change in precipitation statistics—between non-aggregated and aggregated convection—could have huge impacts on society and infrastructure. Radiative-convective equilibrium (RCE), has been extensively used as an idealized framework to study the tropical atmosphere. Self-aggregation manifests in numerous numerical models of RCE, nevertheless, there is still a lack of understanding in how it relates to convective organization in the observed world. Numerous studies have examined self-aggregation using idealized Cloud Resolving Models (CRMs) and General Circulation Models over the ocean, however very little work has been done on RCE and self-aggregation over land. Idealized models of RCE over ocean have shown that aggregation is sensitive to sea surface temperature (SST), more intense precipitation occurs in aggregated systems, and a variety of feedbacks—such as surface flux, cloud radiative, and upgradient moisture transport— contribute to the maintenance of aggregation, however it is not clear if these results apply over land. Progress in this area could help relate understanding of self-aggregation in idealized simulations to observations. In order to explore the behavior of self-aggregation over land, we use a CRM to simulate idealized RCE over land. In particular, we examine the aggregation of convection and how it compares with aggregation over ocean. Based on previous studies, where a variety of different CRMs exhibit a SST threshold below which self-aggregation does not occur, we hypothesize

  11. MicroRNA-100 is involved in shrimp immune response to white spot syndrome virus (WSSV) and Vibrio alginolyticus infection.

    Science.gov (United States)

    Wang, Zhi; Zhu, Fei

    2017-02-09

    In this study, we discovered that shrimp miR-100 was up-regulated at 24 h after WSSV or Vibrio alginolyticus infection, confirming its participation in the innate immune system of shrimp. The anti-miRNA oligonucleotide (AMO-miR-100) was applied to inhibit the expression of miR-100. After AMO-miR-100 treatment, the shrimp was challenged with WSSV or V. alginolyticus. The knockdown of miR-100 expression decreased the mortality of WSSV-infected shrimp from 24 h to 72 h post-infection and enhanced the mortality of V. alginolyticus-infected shrimp significantly. The knockdown of miR-100 affected phenoloxidase (PO) activity, superoxide dismutase (SOD) activity and total hemocyte count (THC) after the infection with WSSV or V. alginolyticus, indicating a regulative role of miR-100 in the immune potential of shrimp in the response to WSSV or V. alginolyticus infection. The knockdown of miR-100 induced the apoptosis of shrimp hemocytes, and V. alginolyticus + AMO-miR-100 treatment caused more hemocyte apoptosis than V. alginolyticus treatment. The miR-100 influenced also the morphology of shrimp hemocytes and regulated the phagocytosis of WSSV or V. alginolyticus. Thus, we concluded that miR-100 may promote the anti-Vibrio immune response of shrimp through regulating apoptosis, phagocytosis and PO activity and affects the progression of WSSV infection at a certain level.

  12. The effect of electrolytes on the aggregation kinetics of titanium dioxide nanoparticle aggregates

    International Nuclear Information System (INIS)

    Shih Yanghsin; Zhuang Chengming; Tso Chihping; Lin Chenghan

    2012-01-01

    Metal oxide nanoparticles (NPs) are receiving increasing attention due to their increased industrial production and potential hazardous effect. The process of aggregation plays a key role in the fate of NPs in the environment and the resultant health risk. The aggregation of commercial titanium dioxide NP powder (25 nm) was investigated with various environmentally relevant solution chemistries containing different concentrations of monovalent (Na + , K + ) and divalent (Ca 2+ ) electrolytes. Titanium dioxide particle size increased with the increase in ion concentration. The stability of titanium dioxide also depended on the ionic composition. Titanium dioxide aggregated to a higher degree in the presence of divalent cations than monovalent ones. The attachment efficiency of NPs was constructed through aggregation kinetics data, from which the critical coagulation concentrations for the various electrolytes are determined (80, 19, and 1 meq/L for Na + , K + , and Ca 2+ , respectively). Our results suggest that titanium dioxide NP powders are relatively unstable in water and could easily be removed by adding multivalent cations so hazardous potentials decrease in aquatic environment.

  13. Aggregated particles caused by instrument artifact

    Directory of Open Access Journals (Sweden)

    A. M. Pierce

    2018-04-01

    Full Text Available Previous studies have indicated that superaggregates, clusters of aggregates of soot primary particles, can be formed in large-scale turbulent fires. Due to lower effective densities, higher porosity, and lower aerodynamic diameters, superaggregates may pass through inlets designed to remove particles  <  2.5 µm in aerodynamic diameter (PM2.5. Ambient particulate matter samples were collected at Peavine Peak, NV, USA (2515 m northwest of Reno, NV, USA from June to November 2014. The Teledyne Advanced Pollution Instrumentation (TAPI 602 BetaPlus particulate monitor was used to collect PM2.5 on two filter types. During this time, aggregated particles  >  2.5 µm in aerodynamic diameter were collected on 36 out of 158 sample days. On preliminary analysis, it was thought that these aggregated particles were superaggregates, depositing past PM10 (particles  <  10 µm in aerodynamic diameter pre-impactors and PM2.5 cyclones. However, further analysis revealed that these aggregated particles were dissimilar to superaggregates observed in previous studies, both in morphology and in elemental composition. To determine if the aggregated particles were superaggregates or an instrument artifact, samples were investigated for the presence of certain elements, the occurrence of fires, high relative humidity and wind speeds, as well as the use of generators on site. Samples with aggregated particles, referred to as aggregates, were analyzed using a scanning electron microscope for size and shape and energy dispersive X-ray spectroscopy was used for elemental analysis. It was determined, based on the high amounts of aluminum present in the aggregate samples, that a sampling artifact associated with the sample inlet and prolonged, high wind events was the probable reason for the observed aggregates.

  14. Concrete Waste Recycling Process for High Quality Aggregate

    International Nuclear Information System (INIS)

    Ishikura, Takeshi; Fujii, Shin-ichi

    2008-01-01

    Large amount of concrete waste generates during nuclear power plant (NPP) dismantling. Non-contaminated concrete waste is assumed to be disposed in a landfill site, but that will not be the solution especially in the future, because of decreasing tendency of the site availability and natural resources. Concerning concrete recycling, demand for roadbeds and backfill tends to be less than the amount of dismantled concrete generated in a single rural site, and conventional recycled aggregate is limited of its use to non-structural concrete, because of its inferior quality to ordinary natural aggregate. Therefore, it is vital to develop high quality recycled aggregate for general uses of dismantled concrete. If recycled aggregate is available for high structural concrete, the dismantling concrete is recyclable as aggregate for industry including nuclear field. Authors developed techniques on high quality aggregate reclamation for large amount of concrete generated during NPP decommissioning. Concrete of NPP buildings has good features for recycling aggregate; large quantity of high quality aggregate from same origin, record keeping of the aggregate origin, and little impurities in dismantled concrete such as wood and plastics. The target of recycled aggregate in this development is to meet the quality criteria for NPP concrete as prescribed in JASS 5N 'Specification for Nuclear Power Facility Reinforced Concrete' and JASS 5 'Specification for Reinforced Concrete Work'. The target of recycled aggregate concrete is to be comparable performance with ordinary aggregate concrete. The high quality recycled aggregate production techniques are assumed to apply for recycling for large amount of non-contaminated concrete. These techniques can also be applied for slightly contaminated concrete dismantled from radiological control area (RCA), together with free release survey. In conclusion: a technology on dismantled concrete recycling for high quality aggregate was developed

  15. Mechanical properties of recycled concrete with demolished waste concrete aggregate and clay brick aggregate

    Science.gov (United States)

    Zheng, Chaocan; Lou, Cong; Du, Geng; Li, Xiaozhen; Liu, Zhiwu; Li, Liqin

    2018-06-01

    This paper presents an experimental investigation on the effect of the replacement of natural coarse aggregate (NCA) with either recycled concrete aggregate (RCA) or recycled clay brick aggregate (RBA) on the compressive strengths of the hardened concrete. Two grades (C25 and C50) of concrete were investigated, which were achieved by using different water-to-cement ratios. In each grade concrete five different replacement rates, 0%, 25%, 50%, 75% and 100% were considered. In order to improve the performance of the recycled aggregates in the concrete mixes, the RCA and RBA were carefully sieved by using the optimal degradation. In this way the largest reduction in the 28-day compressive strength was found to be only 7.2% and 9.6% for C25 and C50 recycled concrete when the NCA was replaced 100% by RCA, and 11% and 13% for C25 and C50 recycled concrete when the NCA was replaced 100% by RBA. In general, the concrete with RCA has better performance than the concrete with RBA. The comparison of the present experimental results with those reported in literature for hardened concrete with either RCA or RBA demonstrates the effectiveness in improving the compressive strength by using the optimal gradation of recycled aggregates.

  16. Compressive strength improvement for recycled concrete aggregate

    Directory of Open Access Journals (Sweden)

    Mohammed Dhiyaa

    2018-01-01

    Full Text Available Increasing amount of construction waste and, concrete remnants, in particular pose a serious problem. Concrete waste exist in large amounts, do not decay and need long time for disintegration. Therefore, in this work old demolished concrete is crashed and recycled to produce recycled concrete aggregate which can be reused in new concrete production. The effect of using recycled aggregate on concrete compressive strength has been experimentally investigated; silica fume admixture also is used to improve recycled concrete aggregate compressive strength. The main parameters in this study are recycled aggregate and silica fume admixture. The percent of recycled aggregate ranged from (0-100 %. While the silica fume ranged from (0-10 %. The experimental results show that the average concrete compressive strength decreases from 30.85 MPa to 17.58 MPa when the recycled aggregate percentage increased from 0% to 100%. While, when silica fume is used the concrete compressive strength increase again to 29.2 MPa for samples with 100% of recycled aggregate.

  17. Pore structure of natural and regenerated soil aggregates

    DEFF Research Database (Denmark)

    Naveed, Muhammad; Arthur, Emmanuel; de Jonge, Lis Wollesen

    2014-01-01

    Quantitative characterization of aggregate pore structure can reveal the evolution of aggregates under different land use and management practices and their effects on soil processes and functions. Advances in X-ray Computed Tomography (CT) provide powerful means to conduct such characterization....... This study examined aggregate pore structure of three differently managed same textured Danish soils (mixed forage cropping, MFC; mixed cash cropping, MCC; cereal cash cropping, CCC) for (i) natural aggregates, and (ii) aggregates regenerated after 20 months of incubation. In total, 27 aggregates (8-16 mm...... pore diameter of 200 and 170 Hm, respectively. Pore shape analysis indicated that CCC and MFC aggregates had an abundance of rounded and elongated pores, respectively, and those of MCC were in-between CCC and MFC. Aggregate pore structure development in the lysimeters was nearly similar irrespective...

  18. DL-3-n-butylphthalide-Edaravone hybrids as novel dual inhibitors of amyloid-β aggregation and monoamine oxidases with high antioxidant potency for Alzheimer's therapy.

    Science.gov (United States)

    Qiang, Xiaoming; Li, Yan; Yang, Xia; Luo, Li; Xu, Rui; Zheng, Yunxiaozhu; Cao, Zhongcheng; Tan, Zhenghuai; Deng, Yong

    2017-02-15

    Considering the complex etiology of Alzheimer's disease (AD), multifunctional agents may be beneficial for the treatment of this disease. A series of DL-3-n-butylphthalide-Edaravone hybrids were designed, synthesized and evaluated as novel dual inhibitors of amyloid-β aggregation and monoamine oxidases. Among them, compounds 9a-d exhibited good inhibition of self-induced Aβ 1-42 aggregation with inhibition ratio 57.7-71.5%. For MAO, these new hybrids exhibited good balance of inhibition for MAO-A and MAO-B. In addition, all target compounds retained the antioxidant activity of edaravone, showed equal or better antioxidant activity than edaravone. The results of the parallel artificial membrane permeability assay for blood-brain barrier indicated that compounds 9a-d would be able to cross the blood-brain barrier and reach their biological targets in the central nervous system. The promising results in all assays demonstrated that the strategy behind the designing of compounds was rational and favourable. Taken together, these preliminary findings suggested that the compounds with the strongest bioactivity deserves further investigated for pharmacological development in AD therapy. Copyright © 2017 Elsevier Ltd. All rights reserved.

  19. Effects of an angelica extract on human erythrocyte aggregation, deformation and osmotic fragility.

    Science.gov (United States)

    Wang, X; Wei, L; Ouyang, J P; Muller, S; Gentils, M; Cauchois, G; Stoltz, J F

    2001-01-01

    In Chinese traditional medicine, angelica is widely used for its known clinical effects of ameliorating blood microcirculation. But the mechanism of these beneficial effects still remains unclear. In this work the rheological behaviour of human erythrocytes treated by angelica was studied in vitro. Normal RBCs incubated with an angelica extract at different concentrations (5, 10 or 20 mg/ml) for 60 min at 37 degrees C and then their aggregation, deformation and osmotic fragility were measured with different recently developed optical techniques, namely Erythroaggregometer (Regulest, Florange, France), LORCA (Mechatronics, Amsterdam) and Fragilimeter (Regulest, Florange, France). Experimental results show that angelica (20 mg/ml) significantly decreased normal RBCs' aggregation speed (p<0.01) and could inhibit the hyperaggregability caused by dextran 500. However, the strength of normal RBCs aggregates were not influenced by angelica. When a calcium ionophore A23187 (1.9 microM) was used to harden cell membrane, angelica (20 mg/ml) could significantly (p<0.01) protect erythrocytes against the loss of their deformability even it had no effects on normal RBCs deformation. Finally angelica (5 and 10 mg/ml) decreased significantly (p<0.01) normal RBCs osmotic fragility. In conclusion angelica plays a rheologically active role on human erythrocytes, and this study suggests a possible mechanism for angelica's positive effects against certain cardiovascular diseases.

  20. Ratio-Based Gradual Aggregation of Data

    DEFF Research Database (Denmark)

    Iftikhar, Nadeem

    2012-01-01

    cause data management and data storage issues. However, non-flexible and ineffective means of data aggregation not only reduce performance of database queries but also lead to erroneous reporting. This paper presents flexible and effective ratio-based methods for gradual data aggregation in databases....... Gradual data aggregation is a process that reduces data volume by converting the detailed data into multiple levels of summarized data as the data gets older. This paper also describes implementation strategies of the proposed methods based on standard database technology.......Majority of databases contain large amounts of data, gathered over long intervals of time. In most cases, the data is aggregated so that it can be used for analysis and reporting purposes. The other reason of data aggregation is to reduce data volume in order to avoid over-sized databases that may...

  1. Aggregation of flexible polyelectrolytes: Phase diagram and dynamics.

    Science.gov (United States)

    Tom, Anvy Moly; Rajesh, R; Vemparala, Satyavani

    2017-10-14

    Similarly charged polymers in solution, known as polyelectrolytes, are known to form aggregated structures in the presence of oppositely charged counterions. Understanding the dependence of the equilibrium phases and the dynamics of the process of aggregation on parameters such as backbone flexibility and charge density of such polymers is crucial for insights into various biological processes which involve biological polyelectrolytes such as protein, DNA, etc. Here, we use large-scale coarse-grained molecular dynamics simulations to obtain the phase diagram of the aggregated structures of flexible charged polymers and characterize the morphology of the aggregates as well as the aggregation dynamics, in the presence of trivalent counterions. Three different phases are observed depending on the charge density: no aggregation, a finite bundle phase where multiple small aggregates coexist with a large aggregate and a fully phase separated phase. We show that the flexibility of the polymer backbone causes strong entanglement between charged polymers leading to additional time scales in the aggregation process. Such slowing down of the aggregation dynamics results in the exponent, characterizing the power law decay of the number of aggregates with time, to be dependent on the charge density of the polymers. These results are contrary to those obtained for rigid polyelectrolytes, emphasizing the role of backbone flexibility.

  2. Sepsis and Hemocyte Loss in Honey Bees (Apis mellifera) Infected with Serratia marcescens Strain Sicaria.

    Science.gov (United States)

    Burritt, Nancy L; Foss, Nicole J; Neeno-Eckwall, Eric C; Church, James O; Hilger, Anna M; Hildebrand, Jacob A; Warshauer, David M; Perna, Nicole T; Burritt, James B

    2016-01-01

    Global loss of honey bee colonies is threatening the human food supply. Diverse pathogens reduce honey bee hardiness needed to sustain colonies, especially in winter. We isolated a free-living Gram negative bacillus from hemolymph of worker honey bees (Apis mellifera) found separated from winter clusters. In some hives, greater than 90% of the dying bees detached from the winter cluster were found to contain this bacterium in their hemolymph. Throughout the year, the same organism was rarely found in bees engaged in normal hive activities, but was detected in about half of Varroa destructor mites obtained from colonies that housed the septic bees. Flow cytometry of hemolymph from septic bees showed a significant reduction of plasmatocytes and other types of hemocytes. Interpretation of the16S rRNA sequence of the bacterium indicated that it belongs to the Serratia genus of Gram-negative Gammaproteobacteria, which has not previously been implicated as a pathogen of adult honey bees. Complete genome sequence analysis of the bacterium supported its classification as a novel strain of Serratia marcescens, which was designated as S. marcescens strain sicaria (Ss1). When compared with other strains of S. marcescens, Ss1 demonstrated several phenotypic and genetic differences, including 65 genes not previously found in other Serratia genomes. Some of the unique genes we identified in Ss1 were related to those from bacterial insect pathogens and commensals. Recovery of this organism extends a complex pathosphere of agents which may contribute to failure of honey bee colonies.

  3. Sepsis and Hemocyte Loss in Honey Bees (Apis mellifera) Infected with Serratia marcescens Strain Sicaria

    Science.gov (United States)

    Burritt, Nancy L.; Foss, Nicole J.; Neeno-Eckwall, Eric C.; Church, James O.; Hildebrand, Jacob A.; Warshauer, David M.; Perna, Nicole T.; Burritt, James B.

    2016-01-01

    Global loss of honey bee colonies is threatening the human food supply. Diverse pathogens reduce honey bee hardiness needed to sustain colonies, especially in winter. We isolated a free-living Gram negative bacillus from hemolymph of worker honey bees (Apis mellifera) found separated from winter clusters. In some hives, greater than 90% of the dying bees detached from the winter cluster were found to contain this bacterium in their hemolymph. Throughout the year, the same organism was rarely found in bees engaged in normal hive activities, but was detected in about half of Varroa destructor mites obtained from colonies that housed the septic bees. Flow cytometry of hemolymph from septic bees showed a significant reduction of plasmatocytes and other types of hemocytes. Interpretation of the16S rRNA sequence of the bacterium indicated that it belongs to the Serratia genus of Gram-negative Gammaproteobacteria, which has not previously been implicated as a pathogen of adult honey bees. Complete genome sequence analysis of the bacterium supported its classification as a novel strain of Serratia marcescens, which was designated as S. marcescens strain sicaria (Ss1). When compared with other strains of S. marcescens, Ss1 demonstrated several phenotypic and genetic differences, including 65 genes not previously found in other Serratia genomes. Some of the unique genes we identified in Ss1 were related to those from bacterial insect pathogens and commensals. Recovery of this organism extends a complex pathosphere of agents which may contribute to failure of honey bee colonies. PMID:28002470

  4. Aqueous Extract of Paeonia lactiflora and Paeoniflorin as Aggregation Reducers Targeting Chaperones in Cell Models of Spinocerebellar Ataxia 3

    Directory of Open Access Journals (Sweden)

    Kuo-Hsuan Chang

    2013-01-01

    Full Text Available Spinocerebellar ataxia (SCA types 1, 2, 3, 6, 7, and 17 as well as Huntington’s disease are a group of neurodegenerative disorders caused by expanded CAG repeats encoding a long polyglutamine (polyQ tract in the respective proteins. Evidence has shown that the accumulation of intranuclear and cytoplasmic misfolded polyQ proteins leads to apoptosis and cell death. Thus suppression of aggregate formation is expected to inhibit a wide range of downstream pathogenic events in polyQ diseases. In this study, we established a high-throughput aggregation screening system using 293 ATXN3/Q75-GFP cells and applied this system to test the aqueous extract of Paeonia lactiflora (P. lactiflora and its constituents. We found that the aggregation can be significantly prohibited by P. lactiflora and its active compound paeoniflorin. Meanwhile, P. lactiflora and paeoniflorin upregulated HSF1 and HSP70 chaperones in the same cell models. Both of them further reduced the aggregation in neuronal differentiated SH-SY5Y ATXN3/Q75-GFP cells. Our results demonstrate how P. lactiflora and paeoniflorin are likely to work on polyQ-aggregation reduction and provide insight into the possible working mechanism of P. lactiflora in SCA3. We anticipate our paper to be a starting point for screening more potential herbs for the treatment of SCA3 and other polyQ diseases.

  5. CD147 and CD98 complex-mediated homotypic aggregation attenuates the CypA-induced chemotactic effect on Jurkat T cells.

    Science.gov (United States)

    Guo, Na; Zhang, Kui; Lv, Minghua; Miao, Jinlin; Chen, Zhinan; Zhu, Ping

    2015-02-01

    Homotypic cell aggregation plays important roles in physiological and pathological processes, including embryogenesis, immune responses, angiogenesis, tumor cell invasion and metastasis. CD147 has been implicated in most of these phenomena, and it was identified as a T cell activation-associated antigen due to its obvious up-regulation in activated T cells. However, the explicit function and mechanism of CD147 in T cells have not been fully elucidated. In this study, large and compact aggregates were observed in Jurkat T cells after treatment with the specific CD147 monoclonal antibody HAb18 or after the expression of CD147 was silenced by RNA interference, which indicated an inhibitory effect of CD147 in T cell homotypic aggregation. Knocking down CD147 expression resulted in a significant decrease in CD98, along with prominent cell aggregation, similar to that treated by CD98 and CD147 monoclonal antibodies. Furthermore, decreased cell chemotactic activity was observed following CD147- and CD98-mediated cell aggregation, and increased aggregation was correlated with a decrease in the chemotactic ability of the Jurkat T cells, suggesting that CD147- and CD98-mediated homotypic cell aggregation plays a negative role in T cell chemotaxis. Our data also showed that p-ERK, p-ZAP70, p-CD3ζ and p-LCK were significantly decreased in the CD147- and CD98-knocked down Jurkat T cells, which suggested that decreased CD147- and/or CD98-induced homotypic T cell aggregation and aggregation-inhibited chemotaxis might be associated with these signaling pathways. A role for CD147 in cell aggregation and chemotaxis was further indicated in primary CD4(+) T cells. Similarly, low expression of CD147 in primary T cells induced prominent cell aggregation and this aggregation attenuated primary T cell chemotactic ability in response to CypA. Our results have demonstrated the correlation between homotypic cell aggregation and the chemotactic response of T cells to CypA, and these data

  6. Aggregation Algorithms in Heterogeneous Tables

    Directory of Open Access Journals (Sweden)

    Titus Felix FURTUNA

    2006-01-01

    Full Text Available The heterogeneous tables are most used in the problem of aggregation. A solution for this problem is to standardize these tables of figures. In this paper, we proposed some methods of aggregation based on the hierarchical algorithms.

  7. Small file aggregation in a parallel computing system

    Science.gov (United States)

    Faibish, Sorin; Bent, John M.; Tzelnic, Percy; Grider, Gary; Zhang, Jingwang

    2014-09-02

    Techniques are provided for small file aggregation in a parallel computing system. An exemplary method for storing a plurality of files generated by a plurality of processes in a parallel computing system comprises aggregating the plurality of files into a single aggregated file; and generating metadata for the single aggregated file. The metadata comprises an offset and a length of each of the plurality of files in the single aggregated file. The metadata can be used to unpack one or more of the files from the single aggregated file.

  8. ALPHA-SYNUCLEIN STRUCTURE, AGGREGATION AND MODULATORS

    Directory of Open Access Journals (Sweden)

    Pinakin K. Makwana

    2016-06-01

    Full Text Available Alpha-synuclein is an intrinsically unstructured protein, involved in various neurodegenerative disorders. In vitro/in vivo experiments, as well as genetic mutation studies establish a direct link between alphasynuclein and synucleinopathies. Due to its natively unfolded state, alpha synuclein can adopt numerous conformations upon interaction with its partners and cellular factors, offering explanation for its diverse interactions. Aggregated form of alpha-synuclein has been observed in the brain of patients with synucleinopathies, a hallmark of neurodegeneration, and cell death has been attributed to aggregation induced toxicity. The process of aggregation involves nucleation, followed by intermediate oligomeric states, and finally the fibrillar amyloids. Of the various conformations/species that alpha-synuclein assumes before it transforms into mature amyloid fibrils, the oligomeric species is the most toxic. Thus, an effective way to limit disease progression is by modifying/slowing down protein aggregation/deposition in the brain. Various small natural products, synthetic chemicals, peptides and antibodies specific to alpha-synuclein have been designed/identified to reduce its rate of aggregation. Unfortunately, not even a handful of the molecules have cleared the clinical trials. Even today, medications available for Parkinson’s patients are mostly the drugs that adjust for loss of dopamine in the brain, and hence do not stop the progression of the disease or cure the symptoms. Thus, more molecular level studies are warranted to fully elucidate the process of alpha-synuclein aggregation, which in turn could help in identifying novel therapeutics and preventives. The present review summarizes the insights gained into the structure, in vitro aggregation and inhibitors/modulators of alpha-synuclein aggregation, that can be used to design better and effective inhibitors against the diseases.

  9. Mechanical Dissociation of Platelet Aggregates in Blood Stream

    Science.gov (United States)

    Hoore, Masoud; Fedosov, Dmitry A.; Gompper, Gerhard; Complex; Biological Fluids Group Team

    2017-11-01

    von Willebrand factor (VWF) and platelet aggregation is a key phenomenon in blood clotting. These aggregates form critically in high shear rates and dissolve reversibly in low shear rates. The emergence of a critical shear rate, beyond which aggregates form and below which they dissolve, has an interesting impact on aggregation in blood flow. As red blood cells (RBCs) migrate to the center of the vessel in blood flow, a RBC free layer (RBC-FL) is left close to the walls into which the platelets and VWFs are pushed back from the bulk flow. This margination process provides maximal VWF-platelet aggregation probability in the RBC-FL. Using mesoscale hydrodynamic simulations of aggregate dynamics in blood flow, it is shown that the aggregates form and grow in RBC-FL wherein shear rate is high for VWF stretching. By growing, the aggregates penetrate to the bulk flow and get under order of magnitude lower shear rates. Consequently, they dissolve and get back into the RBC-FL. This mechanical limitation for aggregates prohibits undesired thrombosis and vessel blockage by aggregates, while letting the VWFs and platelets to aggregate close to the walls where they are actually needed. The support by the DFG Research Unit FOR 1543 SHENC and CPU time Grant by the Julich Supercomputing Center are acknowledged.

  10. Learning about individuals' health from aggregate data.

    Science.gov (United States)

    Colbaugh, Rich; Glass, Kristin

    2017-07-01

    There is growing awareness that user-generated social media content contains valuable health-related information and is more convenient to collect than typical health data. For example, Twitter has been employed to predict aggregate-level outcomes, such as regional rates of diabetes and child poverty, and to identify individual cases of depression and food poisoning. Models which make aggregate-level inferences can be induced from aggregate data, and consequently are straightforward to build. In contrast, learning models that produce individual-level (IL) predictions, which are more informative, usually requires a large number of difficult-to-acquire labeled IL examples. This paper presents a new machine learning method which achieves the best of both worlds, enabling IL models to be learned from aggregate labels. The algorithm makes predictions by combining unsupervised feature extraction, aggregate-based modeling, and optimal integration of aggregate-level and IL information. Two case studies illustrate how to learn health-relevant IL prediction models using only aggregate labels, and show that these models perform as well as state-of-the-art models trained on hundreds or thousands of labeled individuals.

  11. Efficient clustering aggregation based on data fragments.

    Science.gov (United States)

    Wu, Ou; Hu, Weiming; Maybank, Stephen J; Zhu, Mingliang; Li, Bing

    2012-06-01

    Clustering aggregation, known as clustering ensembles, has emerged as a powerful technique for combining different clustering results to obtain a single better clustering. Existing clustering aggregation algorithms are applied directly to data points, in what is referred to as the point-based approach. The algorithms are inefficient if the number of data points is large. We define an efficient approach for clustering aggregation based on data fragments. In this fragment-based approach, a data fragment is any subset of the data that is not split by any of the clustering results. To establish the theoretical bases of the proposed approach, we prove that clustering aggregation can be performed directly on data fragments under two widely used goodness measures for clustering aggregation taken from the literature. Three new clustering aggregation algorithms are described. The experimental results obtained using several public data sets show that the new algorithms have lower computational complexity than three well-known existing point-based clustering aggregation algorithms (Agglomerative, Furthest, and LocalSearch); nevertheless, the new algorithms do not sacrifice the accuracy.

  12. C-type lectin B (SpCTL-B) regulates the expression of antimicrobial peptides and promotes phagocytosis in mud crab Scylla paramamosain.

    Science.gov (United States)

    Wei, Xiaoyuan; Wang, Limin; Sun, Wanwei; Zhang, Ming; Ma, Hongyu; Zhang, Yueling; Zhang, Xinxu; Li, Shengkang

    2018-07-01

    As pattern recognition receptors, C-type lectins (CTLs) play important roles in immune system of crustaceans through identifying and binding to the conservative pathogen-associated molecular patterns (PAMPs) on pathogen surfaces. In this study, a new CTL, SpCTL-B, was identified from the hemocytes of mud crab Scylla paramamosain. The full-length of SpCTL-B cDNA was 1278 bp with an open reading frame (ORF) of 348 bp. The predicted SpCTL-B protein contains a single carbohydrate-recognition domain (CRD). SpCTL-B transcripts were distributed in all examined tissues with the highest levels in hepatopancreas. After challenged with Vibrio parahaemolyticus, LPS, polyI:C and white spot syndrome virus (WSSV), the mRNA levels of SpCTL-B in hemocytes and hepatopancreas were up-regulated. The recombinant SpCTL-B (rSpCTL-B) purified by Ni-affinity chromatography showed stronger binding activities with Staphylococcus aureus, β-hemolytic Streptococcus, Escherichia coli, Aeromonas hydrophila, Vibrio alginolyticus than those with V. parahaemolyticus and Saccharomyces cerevisiae. rSpCTL-B exhibited a broad spectrum of microorganism-agglutination activities against Gram-positive bacteria (S. aureus, β-hemolytic Streptococcus) and Gram-negative bacteria (E. coli, V. parahaemolyticus, A. hydrophila, V. alginolyticus) in a Ca 2+ -dependent manner. The agglutination activities of rSpCTL-B could be inhibited by D-mannose and LPS, but not by d-fructose and galactose. The antimicrobial assay showed that rSpCTL-B exhibited the growth inhibition against all examined gram-positive bacteria and gram-negative bacteria. When SpCTL-B was silenced by RNAi, the bacterial clearance ability in mud crab was decreased and the transcript levels of five antimicrobial peptides (AMPs) (SpCrustin, SpHistin, SpALF4 (anti-lipopolysaccharide factor), SpALF5 and SpALF6) were significantly decreased in hemocytes. In our study, knockdown of SpCTL-B could down-regulate the expression of SpSTAT at m

  13. Customer Aggregation: An Opportunity for Green Power?; TOPICAL

    International Nuclear Information System (INIS)

    Holt, E.; Bird, L.

    2001-01-01

    We undertook research into the experience of aggregation groups to determine whether customer aggregation offers an opportunity to bring green power choices to more customers. The objectives of this report, therefore, are to (1) identify the different types of aggregation that are occurring today, (2) learn whether aggregation offers an opportunity to advance sales of green power, and (3) share these concepts and approaches with potential aggregators and green power advocates

  14. Concrete manufacture with un-graded recycled aggregates

    OpenAIRE

    Richardson, Alan; Coventry, Kathryn; Graham, Sue

    2009-01-01

    Purpose – The purpose of this paper is to investigate whether concrete that includes un-graded recycled aggregates can be manufactured to a comparable strength to concrete manufactured from virgin aggregates. \\ud \\ud Design/methodology/approach – A paired comparison test was used to evaluate the difference between concrete made with virgin aggregates (plain control) and concrete including recycled waste. Un-graded construction demolition waste and un-graded ground glass were used as aggregate...

  15. Coupling of aggregation and immunogenicity in biotherapeutics: T- and B-cell immune epitopes may contain aggregation-prone regions.

    Science.gov (United States)

    Kumar, Sandeep; Singh, Satish K; Wang, Xiaoling; Rup, Bonita; Gill, Davinder

    2011-05-01

    Biotherapeutics, including recombinant or plasma-derived human proteins and antibody-based molecules, have emerged as an important class of pharmaceuticals. Aggregation and immunogenicity are among the major bottlenecks during discovery and development of biotherapeutics. Computational tools that can predict aggregation prone regions as well as T- and B-cell immune epitopes from protein sequence and structure have become available recently. Here, we describe a potential coupling between aggregation and immunogenicity: T-cell and B-cell immune epitopes in therapeutic proteins may contain aggregation-prone regions. The details of biological mechanisms behind this observation remain to be understood. However, our observation opens up an exciting potential for rational design of de-immunized novel, as well as follow on biotherapeutics with reduced aggregation propensity.

  16. Detection of ubiquitinated huntingtin species in intracellular aggregates

    Directory of Open Access Journals (Sweden)

    Katrin eJuenemann

    2015-01-01

    Full Text Available Protein conformation diseases, including polyglutamine diseases, result from the accumulation and aggregation of misfolded proteins. Huntington’s disease is one of nine diseases caused by an expanded polyglutamine repeat within the affected protein and is hallmarked by intracellular inclusion bodies composed of aggregated N-terminal huntingtin fragments and other sequestered proteins. Fluorescence microscopy and filter trap assay are conventional methods to study protein aggregates, but cannot be used to analyze the presence and levels of post-translational modifications of aggregated huntingtin such as ubiquitination. Ubiquitination of proteins can be a signal for degradation and intracellular localization, but also affects protein activity and protein-protein interactions. The function of ubiquitination relies on its mono- and polymeric isoforms attached to protein substrates. Studying the ubiquitination pattern of aggregated huntingtin fragments offers an important possibility to understand huntingtin degradation and aggregation processes within the cell. For the identification of aggregated huntingtin and its ubiquitinated species, solubilization of the cellular aggregates is mandatory. Here we describe methods to identify post-translational modifications such as ubiquitination of aggregated mutant huntingtin. This approach is specifically described for use with mammalian cell culture and is suitable to study other disease-related proteins prone to aggregate.

  17. Microstructural characterization of concrete prepared with recycled aggregates.

    Science.gov (United States)

    Guedes, Mafalda; Evangelista, Luís; de Brito, Jorge; Ferro, Alberto C

    2013-10-01

    Several authors have reported the workability, mechanical properties, and durability of concrete produced with construction waste replacing the natural aggregate. However, a systematic microstructural characterization of recycled aggregate concrete has not been reported. This work studies the use of fine recycled aggregate to replace fine natural aggregate in the production of concrete and reports the resulting microstructures. The used raw materials were natural aggregate, recycled aggregate obtained from a standard concrete, and Portland cement. The substitution extent was 0, 10, 50, and 100 vol%; hydration was stopped at 9, 24, and 96 h and 28 days. Microscopy was focused on the cement/aggregate interfacial transition zone, enlightening the effect of incorporating recycled aggregate on the formation and morphology of the different concrete hydration products. The results show that concretes with recycled aggregates exhibit typical microstructural features of the transition zone in normal strength concrete. Although overall porosity increases with increasing replacement, the interfacial bond is apparently stronger when recycled aggregates are used. An addition of 10 vol% results in a decrease in porosity at the interface with a corresponding increase of the material hardness. This provides an opportunity for development of increased strength Portland cement concretes using controlled amounts of concrete waste.

  18. The alkali-aggregate reaction - concrete microstructure evolution

    International Nuclear Information System (INIS)

    Regourd, M.; Hornain, H.; Poitevin, P.

    1981-01-01

    The alkali-aggregate reaction has been studied by scanning electron microscopy and energy dispersive X-ray analysis, electron probe microanalysis, and X-ray diffraction in concretes containing glass aggregates or hornfels and greywacke aggregates. The surface reaction of the natural aggregates in alkaline solutions has been analysed by X-ray photo-electron spectrometry. The study of concretes with glass aggregates stored at 20 degrees Celcius and 100 percent relative humidity has revealed, irrespective of alkali content and type of cement, the formation of a gel containing SiO 2 , Na 2 O, CaO, MgO and Al 2 O 3 . Under heat and pressure (210 degrees Celcius at MPa for 48 hours), the gel crystallizes and yields silicates not very different from tobermorite found in autoclaved normal concretes but cotaining Na and K in solid solutions. The alkali reaction in two natural aggregate concretes, is also shown by the formation of gels and silicate crystals. The progressive structuring of the gels in silicate crystals is promoted by an increase in temperature. Ettringite and Ca(OH) 2 reinforce the alkali-aggregate reaction which may be looked upon as a hydration reaction, partially of the pozzolanic type

  19. Collective Rationality in Graph Aggregation

    NARCIS (Netherlands)

    Endriss, U.; Grandi, U.; Schaub, T.; Friedrich, G.; O'Sullivan, B.

    2014-01-01

    Suppose a number of agents each provide us with a directed graph over a common set of vertices. Graph aggregation is the problem of computing a single “collective” graph that best represents the information inherent in this profile of individual graphs. We consider this aggregation problem from the

  20. Sequence dependent aggregation of peptides and fibril formation

    Science.gov (United States)

    Hung, Nguyen Ba; Le, Duy-Manh; Hoang, Trinh X.

    2017-09-01

    Deciphering the links between amino acid sequence and amyloid fibril formation is key for understanding protein misfolding diseases. Here we use Monte Carlo simulations to study the aggregation of short peptides in a coarse-grained model with hydrophobic-polar (HP) amino acid sequences and correlated side chain orientations for hydrophobic contacts. A significant heterogeneity is observed in the aggregate structures and in the thermodynamics of aggregation for systems of different HP sequences and different numbers of peptides. Fibril-like ordered aggregates are found for several sequences that contain the common HPH pattern, while other sequences may form helix bundles or disordered aggregates. A wide variation of the aggregation transition temperatures among sequences, even among those of the same hydrophobic fraction, indicates that not all sequences undergo aggregation at a presumable physiological temperature. The transition is found to be the most cooperative for sequences forming fibril-like structures. For a fibril-prone sequence, it is shown that fibril formation follows the nucleation and growth mechanism. Interestingly, a binary mixture of peptides of an aggregation-prone and a non-aggregation-prone sequence shows the association and conversion of the latter to the fibrillar structure. Our study highlights the role of a sequence in selecting fibril-like aggregates and also the impact of a structural template on fibril formation by peptides of unrelated sequences.

  1. 21 CFR 1303.11 - Aggregate production quotas.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 9 2010-04-01 2010-04-01 false Aggregate production quotas. 1303.11 Section 1303.11 Food and Drugs DRUG ENFORCEMENT ADMINISTRATION, DEPARTMENT OF JUSTICE QUOTAS Aggregate Production and Procurement Quotas § 1303.11 Aggregate production quotas. (a) The Administrator shall determine...

  2. Inhibition of translation in liver polyribosomes by a new substituted thiopseudourea with antitumour action

    Science.gov (United States)

    González-Cadavid, Néstor F.; Quijada, Flor Herrera

    1974-01-01

    A new thiopseudourea, S-(10-undecen-1-yl)isothiouronium iodide (compound AHR-1911), was tested for antitumour action and shown to inhibit considerably the growth of the Walker carcinoma in rats. The mechanism of its effect on protein and nucleic acid synthesis was then studied with systems in vitro from rat liver. In incubations of liver slices, 1.4mm-compound AHR-1911 decreased by 96% the incorporation of [14C]leucine into microsomal proteins, and mitochondrial protein synthesis measured in the presence of cycloheximide was decreased by 44%. At lower doses, translation, as well as the incorporation of [3H]uridine into RNA, was also considerably impaired, compound AHR-1911 being the most active of all the thiopseudoureas tested whereas undecylenic acid and thiourea by themselves showed practically no inhibition. Protein synthesis by cytoplasmic ribosomes (microsomes and C-polyribosomes) was inhibited by compound AHR-1911 at different concentrations (72% at 0.42mm), and again the other related compounds were much less effective, with the exception of one antileukaemic thiopseudourea. The same occurred with the poly(U)-stimulated incorporation of phenylalanine. The puromycin reaction with pulse-labelled C-ribosomes was strongly inhibited, particularly when preincubation with compound AHR-1911 preceded the addition of puromycin, with no release of nascent chains by the thiopseudourea alone. In the presence of GTP and pH5 fraction, to induce translocation and transform all the ribosomes to the donor state, the percentage inhibition remained the same. The ribosomes incubated with the drug are aggregated, as shown by the polyribosome profile, but, when excess of inhibitor was removed, the activity in protein synthesis and the puromycin reaction was restored, indicating that the inhibition is not due to the polyribosomal aggregation. These results suggest that the effect on translation with both 55S and 80S ribosomes is derived from inhibition of chain elongation at the

  3. Generation of Aggregates of Mouse Embryonic Stem Cells that Show Symmetry Breaking, Polarization and Emergent Collective Behaviour In Vitro.

    Science.gov (United States)

    Baillie-Johnson, Peter; van den Brink, Susanne Carina; Balayo, Tina; Turner, David Andrew; Martinez Arias, Alfonso

    2015-11-24

    We have developed a protocol improving current Embryoid Body (EB) culture which allows the study of self-organization, symmetry breaking, axial elongation and cell fate specification using aggregates of mouse embryonic stem cells (mESCs) in suspension culture. Small numbers of mESCs are aggregated in basal medium for 48 hr in non-tissue-culture-treated, U-bottomed 96-well plates, after which they are competent to respond to experimental signals. Following treatment, these aggregates begin to show signs of polarized gene expression and gradually alter their morphology from a spherical mass of cells to an elongated, well organized structure in the absence of external asymmetry cues. These structures are not only able to display markers of the three germ layers, but actively display gastrulation-like movements, evidenced by a directional dislodgement of individual cells from the aggregate, which crucially occurs at one region of the elongated structure. This protocol provides a detailed method for the reproducible formation of these aggregates, their stimulation with signals such as Wnt/β-Catenin activation and BMP inhibition and their analysis by single time-point or time-lapse fluorescent microscopy. In addition, we describe modifications to current whole-mount mouse embryo staining procedures for immunocytochemical analysis of specific markers within fixed aggregates. The changes in morphology, gene expression and length of the aggregates can be quantitatively measured, providing information on how signals can alter axial fates. It is envisaged that this system can be applied both to the study of early developmental events such as axial development and organization, and more broadly, the processes of self-organization and cellular decision-making. It may also provide a suitable niche for the generation of cell types present in the embryo that are unobtainable from conventional adherent culture such as spinal cord and motor neurones.

  4. Heavy metals and metalloids as a cause for protein misfolding and aggregation.

    Science.gov (United States)

    Tamás, Markus J; Sharma, Sandeep K; Ibstedt, Sebastian; Jacobson, Therese; Christen, Philipp

    2014-02-25

    While the toxicity of metals and metalloids, like arsenic, cadmium, mercury, lead and chromium, is undisputed, the underlying molecular mechanisms are not entirely clear. General consensus holds that proteins are the prime targets; heavy metals interfere with the physiological activity of specific, particularly susceptible proteins, either by forming a complex with functional side chain groups or by displacing essential metal ions in metalloproteins. Recent studies have revealed an additional mode of metal action targeted at proteins in a non-native state; certain heavy metals and metalloids have been found to inhibit the in vitro refolding of chemically denatured proteins, to interfere with protein folding in vivo and to cause aggregation of nascent proteins in living cells. Apparently, unfolded proteins with motile backbone and side chains are considerably more prone to engage in stable, pluridentate metal complexes than native proteins with their well-defined 3D structure. By interfering with the folding process, heavy metal ions and metalloids profoundly affect protein homeostasis and cell viability. This review describes how heavy metals impede protein folding and promote protein aggregation, how cells regulate quality control systems to protect themselves from metal toxicity and how metals might contribute to protein misfolding disorders.

  5. The inhibition of the Human Immunodeficiency Virus type 1 activity by crude and purified human pregnancy plug mucus and mucins in an inhibition assay

    Directory of Open Access Journals (Sweden)

    Schoeman Leann

    2008-05-01

    Full Text Available Abstract Background The female reproductive tract is amongst the main routes for Human Immunodeficiency Virus (HIV transmission. Cervical mucus however is known to protect the female reproductive tract from bacterial invasion and fluid loss and regulates and facilitates sperm transport to the upper reproductive tract. The purpose of this study was to purify and characterize pregnancy plug mucins and determine their anti-HIV-1 activity in an HIV inhibition assay. Methods Pregnancy plug mucins were purified by caesium chloride density-gradient ultra-centrifugation and characterized by Western blotting analysis. The anti-HIV-1 activities of the crude pregnancy plug mucus and purified pregnancy plug mucins was determined by incubating them with HIV-1 prior to infection of the human T lymphoblastoid cell line (CEM SS cells. Results The pregnancy plug mucus had MUC1, MUC2, MUC5AC and MUC5B. The HIV inhibition assay revealed that while the purified pregnancy plug mucins inhibit HIV-1 activity by approximately 97.5%, the crude pregnancy plug mucus failed to inhibit HIV-1 activity. Conclusion Although it is not clear why the crude sample did not inhibit HIV-1 activity, it may be that the amount of mucins in the crude pregnancy plug mucus (which contains water, mucins, lipids, nucleic acids, lactoferrin, lysozyme, immunoglobulins and ions, is insufficient to cause viral inhibition or aggregation.

  6. Mechanical properties of concrete containing recycled concrete aggregate (RCA) and ceramic waste as coarse aggregate replacement

    Science.gov (United States)

    Khalid, Faisal Sheikh; Azmi, Nurul Bazilah; Sumandi, Khairul Azwa Syafiq Mohd; Mazenan, Puteri Natasya

    2017-10-01

    Many construction and development activities today consume large amounts of concrete. The amount of construction waste is also increasing because of the demolition process. Much of this waste can be recycled to produce new products and increase the sustainability of construction projects. As recyclable construction wastes, concrete and ceramic can replace the natural aggregate in concrete because of their hard and strong physical properties. This research used 25%, 35%, and 45% recycled concrete aggregate (RCA) and ceramic waste as coarse aggregate in producing concrete. Several tests, such as concrete cube compression and splitting tensile tests, were also performed to determine and compare the mechanical properties of the recycled concrete with those of the normal concrete that contains 100% natural aggregate. The concrete containing 35% RCA and 35% ceramic waste showed the best properties compared with the normal concrete.

  7. Logic-based aggregation methods for ranking student applicants

    Directory of Open Access Journals (Sweden)

    Milošević Pavle

    2017-01-01

    Full Text Available In this paper, we present logic-based aggregation models used for ranking student applicants and we compare them with a number of existing aggregation methods, each more complex than the previous one. The proposed models aim to include depen- dencies in the data using Logical aggregation (LA. LA is a aggregation method based on interpolative Boolean algebra (IBA, a consistent multi-valued realization of Boolean algebra. This technique is used for a Boolean consistent aggregation of attributes that are logically dependent. The comparison is performed in the case of student applicants for master programs at the University of Belgrade. We have shown that LA has some advantages over other presented aggregation methods. The software realization of all applied aggregation methods is also provided. This paper may be of interest not only for student ranking, but also for similar problems of ranking people e.g. employees, team members, etc.

  8. Topics in Probabilistic Judgment Aggregation

    Science.gov (United States)

    Wang, Guanchun

    2011-01-01

    This dissertation is a compilation of several studies that are united by their relevance to probabilistic judgment aggregation. In the face of complex and uncertain events, panels of judges are frequently consulted to provide probabilistic forecasts, and aggregation of such estimates in groups often yield better results than could have been made…

  9. Thermophoretic aggregation of particles in a protoplanetary disc

    Science.gov (United States)

    Smith, Francis J.

    2018-04-01

    Thermophoresis causes particles to move down a temperature gradient to a cooler region of a neutral gas. An example is the temperature gradient in the gas around a large cold object, such as an aggregate of particles, cooled by radiation in a protoplanetary disc. Particles near this aggregate move down the temperature gradient to the aggregate, equivalent to the particles being attracted to it by an inter-particle thermophoretic force. This force is proportional to the temperature difference between gas and aggregate, to the gas density and to the cross-section of the aggregate. The force can be large. For example, calculations based on the equations of motion of the interacting particles show that it can be large enough in an optically thin environment to increase the rate of aggregation by up to six orders of magnitude when an aggregate radius lies between 0.1 μm and 1 mm. From 1 mm to about 10 cm aggregates drift inwards through the gas too quickly for the thermophoretic attraction to increase aggregation significantly; so they grow slowly, causing an observed accumulation of particles at these sizes. Particles above 10 cm move more quickly, causing aggregation due to collisions, but also causing fragmentation. However, calculations show that fragmenting particles and bouncing particles in inelastic collisions often have low enough relative velocities that thermophoresis brings them together again. This allows particles to grow above 1 m, which is otherwise difficult to explain.

  10. Aggregates in monoclonal antibody manufacturing processes.

    Science.gov (United States)

    Vázquez-Rey, María; Lang, Dietmar A

    2011-07-01

    Monoclonal antibodies have proved to be a highly successful class of therapeutic products. Large-scale manufacturing of pharmaceutical antibodies is a complex activity that requires considerable effort in both process and analytical development. If a therapeutic protein cannot be stabilized adequately, it will lose partially or totally its therapeutic properties or even cause immunogenic reactions thus potentially further endangering the patients' health. The phenomenon of protein aggregation is a common issue that compromises the quality, safety, and efficacy of antibodies and can happen at different steps of the manufacturing process, including fermentation, purification, final formulation, and storage. Aggregate levels in drug substance and final drug product are a key factor when assessing quality attributes of the molecule, since aggregation might impact biological activity of the biopharmaceutical. In this review it is analyzed how aggregates are formed during monoclonal antibody industrial production, why they have to be removed and the manufacturing process steps that are designed to either minimize or remove aggregates in the final product. Copyright © 2011 Wiley Periodicals, Inc.

  11. Towards constraint-based aggregation of energy flexibilities

    DEFF Research Database (Denmark)

    Valsomatzis, Emmanouil; Pedersen, Torben Bach; Abello, Alberto

    2016-01-01

    present the problem of aggregating energy flexibilities taking into account grid capacity limitations and introduce a heuristic aggregation technique. We show through an experimental setup that our proposed technique, compared to a baseline approach, not only leads to a valid unit commitment result......The aggregation of energy flexibilities enables individual producers and/or consumers with small loads to directly participate in the emerging energy markets. On the other hand, aggregation of such flexibilities might also create problems to the operation of the electrical grid. In this paper, we...

  12. Aspects Concerning the Use of Recycled Concrete Aggregates

    Science.gov (United States)

    Robu, I.; Mazilu, C.; Deju, R.

    2016-11-01

    Natural aggregates (gravel and crushed) are essential non-renewable resources which are used for infrastructure works and civil engineering. Using recycled concrete aggregates (RCA) is a matter of high priority in the construction industry worldwide. This paper presents a study on the use of recycled aggregates, from a concrete of specified class, to acquire new cement concrete with different percentages of recycled aggregates.

  13. Sustainable normal and high strength recycled aggregate concretes using crushed tested cylinders as coarse aggregates

    Directory of Open Access Journals (Sweden)

    Bilal S. Hamad

    2017-12-01

    Full Text Available The paper reports on a research program that was designed at the American University of Beirut (AUB to investigate the fresh and hardened mechanical properties of a high performance concrete mix produced with partial or full substitution of crushed natural lime-stone aggregates with recycled aggregates from crushed tested cylinders in batching plants. Choosing crushed cylinders as source of recycling would result in reusing portion of the waste products of the concrete production industry. An extensive concrete batching and testing program was conducted to achieve two optimum normal and high strength concrete mixes. The variables were the nominal concrete strength (28 or 60 MPa and the percentage replacement of natural coarse aggregates with recycled aggregates from crushed tested cylinders (0, 20, 40, 60, 80, or 100%. Normal strength tested cylinders were used as source of the recycled aggregates for the normal strength concrete (NSC mix and high strength tested cylinders were used for the high strength concrete (HSC mix. Tests on the trial batches included plastic state slump and hardened state mechanical properties including cylinder compressive strength, cylinder splitting tensile strength, modulus of elasticity, and standard beams flexural strength. The results indicated no significant effect on the slump and around 10% average reduction in the hardened mechanical properties for both investigated levels of concrete compressive strength.

  14. Molecular cloning and characterization of autophagy-related gene TmATG8 in Listeria-invaded hemocytes of Tenebrio molitor.

    Science.gov (United States)

    Tindwa, Hamisi; Jo, Yong Hun; Patnaik, Bharat Bhusan; Lee, Yong Seok; Kang, Sang Sun; Han, Yeon Soo

    2015-07-01

    Macroautophagy (hereinafter called autophagy) is a highly regulated process used by eukaryotic cells to digest portions of the cytoplasm that remodels and recycles nutrients and disposes of unwanted cytoplasmic constituents. Currently 36 autophagy-related genes (ATG) and their homologs have been characterized in yeast and higher eukaryotes, including insects. In the present study, we identified and functionally characterized the immune function of an ATG8 homolog in a coleopteran insect, Tenebrio molitor (TmATG8). The cDNA of TmATG8 comprises of an ORF of 363 bp that encodes a protein of 120 amino acid residues. TmATG8 transcripts are detected in all the developmental stages analyzed. TmAtg8 protein contains a highly conserved C-terminal glycine residue (Gly116) and shows high amino acid sequence identity (98%) to its Tribolium castaneum homolog, TcAtg8. Loss of function of TmATG8 by RNAi led to a significant increase in the mortality rates of T. molitor larvae against Listeria monocytogenes. Unlike dsEGFP-treated control larvae, TmATG8-silenced larvae failed to turn-on autophagy in hemocytes after injection with L. monocytogenes. These data suggest that TmATG8 play a role in mediating autophagy-based clearance of Listeria in T. molitor. Copyright © 2015 Elsevier Ltd. All rights reserved.

  15. SHAPE CHARACTERIZATION OF CONCRETE AGGREGATE

    Directory of Open Access Journals (Sweden)

    Jing Hu

    2011-05-01

    Full Text Available As a composite material, the performance of concrete materials can be expected to depend on the properties of the interfaces between its two major components, aggregate and cement paste. The microstructure at the interfacial transition zone (ITZ is assumed to be different from the bulk material. In general, properties of conventional concrete have been found favoured by optimum packing density of the aggregate. Particle size is a common denominator in such studies. Size segregation in the ITZ among the binder particles in the fresh state, observed in simulation studies by concurrent algorithm-based SPACE system, additionally governs density as well as physical bonding capacity inside these shell-like zones around aggregate particles. These characteristics have been demonstrated qualitatively pertaining also after maturation of the concrete. Such properties of the ITZs have direct impact on composite properties. Despite experimental approaches revealed effects of aggregate grain shape on different features of material structure (among which density, and as a consequence on mechanical properties, it is still an underrated factor in laboratory studies, probably due to the general feeling that a suitable methodology for shape characterization is not available. A scientific argument hindering progress is the interconnected nature of size and shape. Presently, a practical problem preventing shape effects to be emphasized is the limitation of most computer simulation systems in concrete technology to spherical particles. New developments at Delft University of Technology will make it possible in the near future to generate jammed states, or other high-density fresh particle mixtures of non-spherical particles, which thereupon can be subjected to hydration algorithms. This paper will sketch the outlines of a methodological approach for shape assessment of loose (non-embedded aggregate grains, and demonstrate its use for two types of aggregate, allowing

  16. An exact approach for aggregated formulations

    DEFF Research Database (Denmark)

    Gamst, Mette; Spoorendonk, Simon

    Aggregating formulations is a powerful approach for transforming problems into taking more tractable forms. Aggregated formulations can, though, have drawbacks: some information may get lost in the aggregation and { put in a branch-and-bound context { branching may become very di_cult and even....... The paper includes general considerations on types of problems for which the method is of particular interest. Furthermore, we prove the correctness of the procedure and consider how to include extensions such as cutting planes and advanced branching strategies....

  17. Single particle detection and characterization of synuclein co-aggregation

    International Nuclear Information System (INIS)

    Giese, Armin; Bader, Benedikt; Bieschke, Jan; Schaffar, Gregor; Odoy, Sabine; Kahle, Philipp J.; Haass, Christian; Kretzschmar, Hans

    2005-01-01

    Protein aggregation is the key event in a number of human diseases such as Alzheimer's and Parkinson's disease. We present a general method to quantify and characterize protein aggregates by dual-colour scanning for intensely fluorescent targets (SIFT). In addition to high sensitivity, this approach offers a unique opportunity to study co-aggregation processes. As the ratio of two fluorescently labelled components can be analysed for each aggregate separately in a homogeneous assay, the molecular composition of aggregates can be studied even in samples containing a mixture of different types of aggregates. Using this method, we could show that wild-type α-synuclein forms co-aggregates with a mutant variant found in familial Parkinson's disease. Moreover, we found a striking increase in aggregate formation at non-equimolar mixing ratios, which may have important therapeutic implications, as lowering the relative amount of aberrant protein may cause an increase of protein aggregation leading to adverse effects

  18. Live Cell Characterization of DNA Aggregation Delivered through Lipofection.

    Science.gov (United States)

    Mieruszynski, Stephen; Briggs, Candida; Digman, Michelle A; Gratton, Enrico; Jones, Mark R

    2015-05-27

    DNA trafficking phenomena, such as information on where and to what extent DNA aggregation occurs, have yet to be fully characterised in the live cell. Here we characterise the aggregation of DNA when delivered through lipofection by applying the Number and Brightness (N&B) approach. The N&B analysis demonstrates extensive aggregation throughout the live cell with DNA clusters in the extremity of the cell and peri-nuclear areas. Once within the nucleus aggregation had decreased 3-fold. In addition, we show that increasing serum concentration of cell media results in greater cytoplasmic aggregation. Further, the effects of the DNA fragment size on aggregation was explored, where larger DNA constructs exhibited less aggregation. This study demonstrates the first quantification of DNA aggregation when delivered through lipofection in live cells. In addition, this study has presents a model for alternative uses of this imaging approach, which was originally developed to study protein oligomerization and aggregation.

  19. Divergent modes of enzyme inhibition in a homologous structure-activity series.

    Science.gov (United States)

    Ferreira, Rafaela S; Bryant, Clifford; Ang, Kenny K H; McKerrow, James H; Shoichet, Brian K; Renslo, Adam R

    2009-08-27

    A docking screen identified reversible, noncovalent inhibitors (e.g., 1) of the parasite cysteine protease cruzain. Chemical optimization of 1 led to a series of oxadiazoles possessing interpretable SAR and potencies as much as 500-fold greater than 1. Detailed investigation of the SAR series subsequently revealed that many members of the oxadiazole class (and surprisingly also 1) act via divergent modes of inhibition (competitive or via colloidal aggregation) depending on the assay conditions employed.

  20. Retiring the Short-Run Aggregate Supply Curve

    Science.gov (United States)

    Elwood, S. Kirk

    2010-01-01

    The author argues that the aggregate demand/aggregate supply (AD/AS) model is significantly improved--although certainly not perfected--by trimming it of the short-run aggregate supply (SRAS) curve. Problems with the SRAS curve are shown first for the AD/AS model that casts the AD curve as identifying the equilibrium level of output associated…

  1. Inhibition of amyloid oligomerization into different supramolecular architectures by small molecules: mechanistic insights and design rules.

    Science.gov (United States)

    Brahmachari, Sayanti; Paul, Ashim; Segal, Daniel; Gazit, Ehud

    2017-05-01

    Protein misfolding and aggregation have been associated with several human disorders, including Alzheimer's, Parkinson's and Huntington's diseases, as well as senile systemic amyloidosis and Type II diabetes. However, there is no current disease-modifying therapy available for the treatment of these disorders. In spite of extensive academic, pharmaceutical, medicinal and clinical research, a complete mechanistic model for this family of diseases is still lacking. In this review, we primarily discuss the different types of small molecular entities which have been used for the inhibition of the aggregation process of different amyloidogenic proteins under diseased conditions. These include small peptides, polyphenols, inositols, quinones and their derivatives, and metal chelator molecules. In recent years, these groups of molecules have been extensively studied using in vitro, in vivo and computational models to understand their mechanism of action and common structural features underlying the process of inhibition. A salient feature found to be instrumental in the process of inhibition is the balance between the aromatic unit that functions as the amyloid recognition unit and the hydrophilic amyloid breaker unit. The establishment of structure-function relationship for amyloid-modifying therapies by the various functional entities should serve as an important step toward the development of efficient therapeutics.

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

    DEFF Research Database (Denmark)

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

    2017-01-01

    with collagen-related peptide). Platelet aggregation had a negative predictive value of 100% for a bleeding tendency among patients. Conclusion The established platelet aggregation assay was applicable for thrombocytopenic patients, and improved the identification of bleeding risk.......Essentials •Platelet function may influence bleeding risk in thrombocytopenia, but useful tests are needed. •A flow cytometric platelet aggregation test independent of the patient platelet count was made. •Platelet aggregation was reduced in thrombocytopenic patients with hematological cancer....... •High 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...

  3. Effect of guinea pig or monkey colonic mucus on Shigella aggregation and invasion of HeLa cells by Shigella flexneri 1b and 2a.

    OpenAIRE

    Dinari, G; Hale, T L; Washington, O; Formal, S B

    1986-01-01

    The effects of guinea pig and rhesus monkey colonic mucus preparations on Shigella aggregation and invasion of HeLa cell monolayers by Shigella flexneri serotype 1b, 2a, and 5 strains were investigated. Guinea pig mucus caused agglutination of S. flexneri serotype 1b but not of S. flexneri serotype 2a or 5. Guinea pig mucus also inhibited HeLa cell invasion by S. flexneri serotypes 1b and 2a. Monkey mucus neither agglutinated any Shigella strain nor inhibited HeLa cell invasion.

  4. Environmentalism and natural aggregate mining

    Science.gov (United States)

    Drew, L.J.; Langer, W.H.; Sachs, J.S.

    2002-01-01

    Sustaining a developed economy and expanding a developing one require the use of large volumes of natural aggregate. Almost all human activity (commercial, recreational, or leisure) is transacted in or on facilities constructed from natural aggregate. In our urban and suburban worlds, we are almost totally dependent on supplies of water collected behind dams and transported through aqueducts made from concrete. Natural aggregate is essential to the facilities that produce energy-hydroelectric dams and coal-fired powerplants. Ironically, the utility created for mankind by the use of natural aggregate is rarely compared favorably with the environmental impacts of mining it. Instead, the empty quarries and pits are seen as large negative environmental consequences. At the root of this disassociation is the philosophy of environmentalism, which flavors our perceptions of the excavation, processing, and distribution of natural aggregate. The two end-member ideas in this philosophy are ecocentrism and anthropocentrism. Ecocentrism takes the position that the natural world is a organism whose arteries are the rivers-their flow must not be altered. The soil is another vital organ and must not be covered with concrete and asphalt. The motto of the ecocentrist is "man must live more lightly on the land." The anthropocentrist wants clean water and air and an uncluttered landscape for human use. Mining is allowed and even encouraged, but dust and noise from quarry and pit operations must be minimized. The large volume of truck traffic is viewed as a real menace to human life and should be regulated and isolated. The environmental problems that the producers of natural aggregate (crushed stone and sand and gravel) face today are mostly difficult social and political concerns associated with the large holes dug in the ground and the large volume of heavy truck traffic associated with quarry and pit operations. These concerns have increased in recent years as society's demand for

  5. Protein carbonylation, protein aggregation and neuronal cell death in a murine model of multiple sclerosis

    Science.gov (United States)

    Dasgupta, Anushka

    /spatial relationship between carbonylation, protein aggregation and cellular apoptosis. Furthermore, the effectiveness of the carbonyl scavenger hydralazine, histidine hydrazide and methoxylamine at preventing cell death identifies protein carbonyls as the toxic species. Experiments using well-characterized apoptosis inhibitors place protein carbonylation downstream of the mitochondrial transition pore opening and upstream of caspase activation. These in vitro studies demonstrate for the first time a causal relationship between carbonylation, protein aggregation and apoptosis of neurons undergoing oxidative damage. This relationship was further strengthened with the experiments carried out in chapter 4, which show that inhibition of protein aggregation with congo red (CR) or 2-hydroxypropyl beta-cyclodextrin (HPCD) significantly reduced neuronal cell death without affecting the levels of oxidized proteins. Interestingly, large, juxta-nuclear aggregates are not formed upon GSH depletion, suggesting that the small protein aggregates are the cytotoxic species. Together, our data suggest that protein carbonylation causes protein aggregation to mediate neuronal apoptosis in vitro and that a similar mechanism might be contributing to neuronal/glial apoptosis in EAE. These studies provide the basis for testing protein carbonylation scavengers and protein aggregation inhibitors for the treatment of inflammatory demyelinating disorders.

  6. Evaluation of Colemanite Waste as Aggregate Hot Mix Asphalt Concrete

    Directory of Open Access Journals (Sweden)

    Nihat MOROVA

    2015-09-01

    Full Text Available In this study usability of waste colemanite which is obtained after cutting block colemanite for giving proper shape to blocks as an aggregate in hot mix asphalt. For this aim asphalt concrete samples were prepared with four different aggregate groups and optimum bitumen content was determined. First of all only limestone was used as an aggregate. After that, only colemanite aggregate was used with same aggregate gradation. Then, the next step of the study, Marshall samples were produced by changing coarse and fine aggregate gradation as limestone and colemanite and Marshall test were conducted. When evaluated the results samples which produced with only limestone aggregate gave the maximum Marshall Stability value. When handled other mixture groups (Only colemanite, colemanite as coarse aggregate-limestone as fine aggregate, colemanite as fine aggregate-limestone as coarse aggregate all groups were verified specification limits. As a result, especially in areas where there is widespread colemanite waste, if transportation costs did not exceed the cost of limestone, colemanite stone waste could be used instead of limestone in asphalt concrete mixtures as fine aggregate

  7. Effects of vegetation restoration on the aggregate stability and distribution of aggregate-associated organic carbon in a typical karst gorge region

    Science.gov (United States)

    Tang, F. K.; Cui, M.; Lu, Q.; Liu, Y. G.; Guo, H. Y.; Zhou, J. X.

    2015-08-01

    Changes in soil utilization significantly affect aggregate stability and aggregate-associated soil organic carbon (SOC). A field investigation and indoor analysis were conducted in order to study the soil aggregate stability and organic carbon distribution in the water-stable aggregates (WSA) of the bare land (BL), grassland (GL), shrubland (SL), and woodland (WL) in a typical karst gorge region. The results indicated that the BL, GL, SL, and WL were dominated by particles with sizes > 5 mm under dry sieving treatment, and that the soil aggregate contents of various sizes decreased as the particle size decreased. In addition, the BL, GL, SL, and WL were predominantly comprised of WSA sieving treatment, and that the WSA contents initially increased, then decreased, and then increased again as the particle size decreased. Furthermore, at a soil depth of 0-60 cm, the mean weight diameter (MWD), geometrical mean diameter (GMD), and fractal dimensions (D) of the dry aggregates and water-stable aggregates in the different types of land were ranked, in descending order, as WL > GL > SL > BL. The contents of WSA > 0.25 mm, MWD and GMD increased significantly, in that order, and the percentage of aggregate destruction (PAD) and fractal dimensions decreased significantly as the soil aggregate stability improved. The results of this study indicated that, as the SOC contents increased after vegetation restoration, the average SOC content of WL was 2.35, 1.37, and 1.26 times greater than that in the BL, GL, and SL, respectively. The total SOC and SOC associated in WSA of various sizes were the highest at a soil depth of 0-20 cm. In addition, the SOC contents of the WSA increased as the soil aggregate sizes decreased. The SOC contents of the WSA aggregates aggregate SOC contents. The woodland and grassland facilitated WSA stability and SOC protection, thus, promoting the natural restoration of vegetation by reducing artificial disturbances could effectively restore the ecology

  8. The Mechanisms of Aberrant Protein Aggregation

    Science.gov (United States)

    Cohen, Samuel; Vendruscolo, Michele; Dobson, Chris; Knowles, Tuomas

    2012-02-01

    We discuss the development of a kinetic theory for understanding the aberrant loss of solubility of proteins. The failure to maintain protein solubility results often in the assembly of organized linear structures, commonly known as amyloid fibrils, the formation of which is associated with over 50 clinical disorders including Alzheimer's and Parkinson's diseases. A true microscopic understanding of the mechanisms that drive these aggregation processes has proved difficult to achieve. To address this challenge, we apply the methodologies of chemical kinetics to the biomolecular self-assembly pathways related to protein aggregation. We discuss the relevant master equation and analytical approaches to studying it. In particular, we derive the underlying rate laws in closed-form using a self-consistent solution scheme; the solutions that we obtain reveal scaling behaviors that are very generally present in systems of growing linear aggregates, and, moreover, provide a general route through which to relate experimental measurements to mechanistic information. We conclude by outlining a study of the aggregation of the Alzheimer's amyloid-beta peptide. The study identifies the dominant microscopic mechanism of aggregation and reveals previously unidentified therapeutic strategies.

  9. Salt-induced aggregation of stiff polyelectrolytes

    International Nuclear Information System (INIS)

    Fazli, Hossein; Mohammadinejad, Sarah; Golestanian, Ramin

    2009-01-01

    Molecular dynamics simulation techniques are used to study the process of aggregation of highly charged stiff polyelectrolytes due to the presence of multivalent salt. The dominant kinetic mode of aggregation is found to be the case of one end of one polyelectrolyte meeting others at right angles, and the kinetic pathway to bundle formation is found to be similar to that of flocculation dynamics of colloids as described by Smoluchowski. The aggregation process is found to favor the formation of finite bundles of 10-11 filaments at long times. Comparing the distribution of the cluster sizes with the Smoluchowski formula suggests that the energy barrier for the aggregation process is negligible. Also, the formation of long-lived metastable structures with similarities to the raft-like structures of actin filaments is observed within a range of salt concentration.

  10. Suspensions of colloidal particles and aggregates

    CERN Document Server

    Babick, Frank

    2016-01-01

    This book addresses the properties of particles in colloidal suspensions. It has a focus on particle aggregates and the dependency of their physical behaviour on morphological parameters. For this purpose, relevant theories and methodological tools are reviewed and applied to selected examples. The book is divided into four main chapters. The first of them introduces important measurement techniques for the determination of particle size and interfacial properties in colloidal suspensions. A further chapter is devoted to the physico-chemical properties of colloidal particles—highlighting the interfacial phenomena and the corresponding interactions between particles. The book’s central chapter examines the structure-property relations of colloidal aggregates. This comprises concepts to quantify size and structure of aggregates, models and numerical tools for calculating the (light) scattering and hydrodynamic properties of aggregates, and a discussion on van-der-Waals and double layer interactions between ...

  11. Path coupling and aggregate path coupling

    CERN Document Server

    Kovchegov, Yevgeniy

    2018-01-01

    This book describes and characterizes an extension to the classical path coupling method applied to statistical mechanical models, referred to as aggregate path coupling. In conjunction with large deviations estimates, the aggregate path coupling method is used to prove rapid mixing of Glauber dynamics for a large class of statistical mechanical models, including models that exhibit discontinuous phase transitions which have traditionally been more difficult to analyze rigorously. The book shows how the parameter regions for rapid mixing for several classes of statistical mechanical models are derived using the aggregate path coupling method.

  12. Entanglement dynamics of J-aggregate systems

    Energy Technology Data Exchange (ETDEWEB)

    Thilagam, A, E-mail: Thilagam.Lohe@unisa.edu.au [Information Technology, Engineering and the Environment, Mawson Institute, University of South Australia, South Australia 5095 (Australia)

    2011-04-01

    The entanglement dynamics of one-dimensional J-aggregate systems are examined using entanglement measures such as the von Neumann entropy and Wootters concurrence. The effect of dispersion and resonance terms associated with the exciton-phonon interaction are analyzed using Green's function formalism. A probability propagator term, derived using the Markovian approximation, presents J-aggregate systems as potential channels for large scale energy propagation for a select range of parameters. We highlight the role of a critical number of coherently coupled monomer sites and two-exciton states in determining superradiance in J-aggregate systems.

  13. Strain-dependent profile of misfolded prion protein aggregates.

    Science.gov (United States)

    Morales, Rodrigo; Hu, Ping Ping; Duran-Aniotz, Claudia; Moda, Fabio; Diaz-Espinoza, Rodrigo; Chen, Baian; Bravo-Alegria, Javiera; Makarava, Natallia; Baskakov, Ilia V; Soto, Claudio

    2016-02-15

    Prions are composed of the misfolded prion protein (PrP(Sc)) organized in a variety of aggregates. An important question in the prion field has been to determine the identity of functional PrP(Sc) aggregates. In this study, we used equilibrium sedimentation in sucrose density gradients to separate PrP(Sc) aggregates from three hamster prion strains (Hyper, Drowsy, SSLOW) subjected to minimal manipulations. We show that PrP(Sc) aggregates distribute in a wide range of arrangements and the relative proportion of each species depends on the prion strain. We observed a direct correlation between the density of the predominant PrP(Sc) aggregates and the incubation periods for the strains studied. The relative presence of PrP(Sc) in fractions of different sucrose densities was indicative of the protein deposits present in the brain as analyzed by histology. Interestingly, no association was found between sensitivity to proteolytic degradation and aggregation profiles. Therefore, the organization of PrP molecules in terms of the density of aggregates generated may determine some of the particular strain properties, whereas others are independent from it. Our findings may contribute to understand the mechanisms of strain variation and the role of PrP(Sc) aggregates in prion-induced neurodegeneration.

  14. Balancing energy flexibilities through aggregation

    DEFF Research Database (Denmark)

    Valsomatzis, Emmanouil; Hose, Katja; Pedersen, Torben Bach

    2014-01-01

    One of the main goals of recent developments in the Smart Grid area is to increase the use of renewable energy sources. These sources are characterized by energy fluctuations that might lead to energy imbalances and congestions in the electricity grid. Exploiting inherent flexibilities, which exist...... in both energy production and consumption, is the key to solving these problems. Flexibilities can be expressed as flex-offers, which due to their high number need to be aggregated to reduce the complexity of energy scheduling. In this paper, we discuss balance aggregation techniques that already during...... aggregation aim at balancing flexibilities in production and consumption to reduce the probability of congestions and reduce the complexity of scheduling. We present results of our extensive experiments....

  15. Recycled Concrete as Aggregate for Structural Concrete Production

    Directory of Open Access Journals (Sweden)

    Mirjana Malešev

    2010-04-01

    Full Text Available A comparative analysis of the experimental results of the properties of fresh and hardened concrete with different replacement ratios of natural with recycled coarse aggregate is presented in the paper. Recycled aggregate was made by crushing the waste concrete of laboratory test cubes and precast concrete columns. Three types of concrete mixtures were tested: concrete made entirely with natural aggregate (NAC as a control concrete and two types of concrete made with natural fine and recycled coarse aggregate (50% and 100% replacement of coarse recycled aggregate. Ninety-nine specimens were made for the testing of the basic properties of hardened concrete. Load testing of reinforced concrete beams made of the investigated concrete types is also presented in the paper. Regardless of the replacement ratio, recycled aggregate concrete (RAC had a satisfactory performance, which did not differ significantly from the performance of control concrete in this experimental research. However, for this to be fulfilled, it is necessary to use quality recycled concrete coarse aggregate and to follow the specific rules for design and production of this new concrete type.

  16. SHAPE ANALYSIS OF FINE AGGREGATES USED FOR CONCRETE

    Directory of Open Access Journals (Sweden)

    Huan He

    2016-12-01

    Full Text Available Fine aggregate is one of the essential components in concrete and significantly influences the material properties. As parts of natures, physical characteristics of fine aggregate are highly relevant to its behaviors in concrete. The most of previous studies are mainly focused on the physical properties of coarse aggregate due to the equipment limitations. In this paper, two typical fine aggregates, i.e. river sand and crushed rock, are selected for shape characterization. The new developed digital image analysis systems are employed as the main approaches for the purpose. Some other technical methods, e.g. sieve test, laser diffraction method are also used for the comparable references. Shape characteristics of fine aggregates with different origins but in similar size ranges are revealed by this study. Compared with coarse aggregate, fine grains of different origins generally have similar shape differences. These differences are more significant in surface texture properties, which can be easily identified by an advanced shape parameter: bluntness. The new image analysis method is then approved to be efficient for the shape characterization of fine aggregate in concrete.

  17. Self-aggregation of magnetic semiconductor EuS nanocrystals

    International Nuclear Information System (INIS)

    Tanaka, Atsushi; Hasegawa, Yasuchika; Kamikubo, Hironari; Kataoka, Mikio; Kawai, Tsuyoshi

    2009-01-01

    Controlled formation of aggregates having organized structure of cube-shaped EuS nanocrystals is reported. The EuS aggregates in liquid media (methanol) were obtained by means of van der Waals interaction between EuS nanocrystals. The packing structure of the EuS aggregates is characterized with transmission electron microscopy (TEM) and small angle X-ray scattering measurements (SAXS). TEM image indicates the EuS nanocrystals form self-aggregated 2D orthogonal lattice structure. The diffraction peak of (111) of SAXS profile shows that the cube-shaped EuS form 3D cubic superlattice. We successfully demonstrated that the aggregates of cube-shaped EuS nanocrystals formed cubic stacking structure.

  18. Modelling The Effects of Aggregate Size on Alkali Aggregate Reaction Expansion

    Directory of Open Access Journals (Sweden)

    N. Z. Sekrane

    2014-06-01

    Full Text Available This work aims at developing models to predict the potential expansion of concrete containing alkali-reactive aggregates. The paper gives measurements in order to provide experimental data concerning the effect of particle size of an alkali-reactive siliceous limestone on mortar expansion. Results show that no expansion was measured on the mortars using small particles (0.5-1.0 mm while the particles (1.0–2.0 mm gave the largest expansions (0.217%. Two models are proposed, the first one studies the correlations between the measured expansions and the size of aggregates, the second one calculates the thickness of the porous zone necessary to take again all the volume of the gel created.

  19. Contact between the β1 and β2 Segments of α-Synuclein that Inhibits Amyloid Formation.

    Science.gov (United States)

    Shaykhalishahi, Hamed; Gauhar, Aziz; Wördehoff, Michael M; Grüning, Clara S R; Klein, Antonia N; Bannach, Oliver; Stoldt, Matthias; Willbold, Dieter; Härd, Torleif; Hoyer, Wolfgang

    2015-07-20

    Conversion of the intrinsically disordered protein α-synuclein (α-syn) into amyloid aggregates is a key process in Parkinson's disease. The sequence region 35-59 contains β-strand segments β1 and β2 of α-syn amyloid fibril models and most disease-related mutations. β1 and β2 frequently engage in transient interactions in monomeric α-syn. The consequences of β1-β2 contacts are evaluated by disulfide engineering, biophysical techniques, and cell viability assays. The double-cysteine mutant α-synCC, with a disulfide linking β1 and β2, is aggregation-incompetent and inhibits aggregation and toxicity of wild-type α-syn. We show that α-syn delays the aggregation of amyloid-β peptide and islet amyloid polypeptide involved in Alzheimer's disease and type 2 diabetes, an effect enhanced in the α-synCC mutant. Tertiary interactions in the β1-β2 region of α-syn interfere with the nucleation of amyloid formation, suggesting promotion of such interactions as a potential therapeutic approach. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  20. Model of fractal aggregates induced by shear

    Directory of Open Access Journals (Sweden)

    Wan Zhanhong

    2013-01-01

    Full Text Available It is an undoubted fact that particle aggregates from marine, aerosol, and engineering systems have fractal structures. In this study, fractal geometry is used to describe the morphology of irregular aggregates. The mean-field theory is employed to solve coagulation kinetic equation of aggregates. The Taylor-expansion method of moments in conjunction with the self-similar fractal characteristics is used to represent the particulate field. The effect of the target fractal dimensions on zeroth-order moment, second-order moment, and geometric standard deviation of the aggregates is explored. Results show that the developed moment method is an efficient and powerful approach to solving such evolution equations.

  1. Purification and characterization of a platelet aggregation inhibitor and anticoagulant Cc 5_NTase, CD 73-like, from Cerastes cerastes venom.

    Science.gov (United States)

    Saoud, Samah; Chérifi, Fatah; Benhassine, Traki; Laraba-Djebari, Fatima

    2017-05-01

    The present study is the first attempt to report the characterization of a nucleotidase from Cerastes cerastes venom. A 70 kDa 5'-nucleotidase (Cc-5'NTase) was purified to homogeneity. The amino acid sequence of Cc-5'NTase displayed high homology with many nucleotidases. Its activity was optimal at pH 7 with a specific hydrolytic activity toward mono-, di-, and triphosphate adenylated nucleotides. Cc-5'NTase preferentially hydrolyzed ADP and obeyed Michaelis-Menten kinetics. Among the metals and inhibitors tested, Ni 2+ and Mg 2+ completely potentiated enzyme activity, whereas EGTA, PMSF, iodoacetamide, vanillic acid, vanillyl mandelic acid, and 1,10-phenanthroline partially abolished its activity. Cc-5'NTase was not lethal for mice at 5 mg/kg and exhibited in vivo anticoagulant effect. It also dose-dependently inhibited adenosine diphosphate-induced platelet aggregation by converting adenosine diphosphate to adenosine and prohibited arachidonic acid-induced aggregation but was not effective on fibrinogen-induced aggregation. Cc-5'NTase could be a good tool as pharmacological molecule in thrombosis diagnostic and/or therapy. © 2016 Wiley Periodicals, Inc.

  2. Towards Better Understanding of Concrete Containing Recycled Concrete Aggregate

    Directory of Open Access Journals (Sweden)

    Hisham Qasrawi

    2013-01-01

    Full Text Available The effect of using recycled concrete aggregates (RCA on the basic properties of normal concrete is studied. First, recycled aggregate properties have been determined and compared to those of normal aggregates. Except for absorption, there was not a significant difference between the two. Later, recycled aggregates were introduced in concrete mixes. In these mixes, natural coarse aggregate was partly or totally replaced by recycled aggregates. Results show that the use of recycled aggregates has an adverse effect on the workability and air content of fresh concrete. Depending on the water/cement ratio and on the percent of the normal aggregate replaced by RCA, the concrete strength is reduced by 5% to 25%, while the tensile strength is reduced by 4% to 14%. All results are compared with previous research. As new in this research, the paper introduces a simple formula for the prediction of the modulus of elasticity of RCA concrete. Furthermore, the paper shows the variation of the air content of RAC.

  3. Novel Aggregation Properties of Candida albicans Secreted Aspartyl Proteinase Sap6 Mediate Virulence in Oral Candidiasis.

    Science.gov (United States)

    Kumar, Rohitashw; Saraswat, Darpan; Tati, Swetha; Edgerton, Mira

    2015-07-01

    Candida albicans, a commensal fungus of the oral microbiome, causes oral candidiasis in humans with localized or systemic immune deficiencies. Secreted aspartic proteinases (Saps) are a family of 10 related proteases and are virulence factors due to their proteolytic activity, as well as their roles in adherence and colonization of host tissues. We found that mice infected sublingually with C. albicans cells overexpressing Sap6 (SAP6 OE and a Δsap8 strain) had thicker fungal plaques and more severe oral infection, while infection with the Δsap6 strain was attenuated. These hypervirulent strains had highly aggregative colony structure in vitro and higher secreted proteinase activity; however, the levels of proteinase activity of C. albicans Saps did not uniformly match their abilities to damage cultured oral epithelial cells (SCC-15 cells). Hyphal induction in cells overexpressing Sap6 (SAP6 OE and Δsap8 cells) resulted in formation of large cell-cell aggregates. These aggregates could be produced in germinated wild-type cells by addition of native or heat-inactivated Sap6. Sap6 bound only to germinated cells and increased C. albicans adhesion to oral epithelial cells. The adhesion properties of Sap6 were lost upon deletion of its integrin-binding motif (RGD) and could be inhibited by addition of RGD peptide or anti-integrin antibodies. Thus, Sap6 (but not Sap5) has an alternative novel function in cell-cell aggregation, independent of its proteinase activity, to promote infection and virulence in oral candidiasis.

  4. A Carbonic Anhydrase Serves as an Important Acid-Base Regulator in Pacific Oyster Crassostrea gigas Exposed to Elevated CO2: Implication for Physiological Responses of Mollusk to Ocean Acidification.

    Science.gov (United States)

    Wang, Xiudan; Wang, Mengqiang; Jia, Zhihao; Qiu, Limei; Wang, Lingling; Zhang, Anguo; Song, Linsheng

    2017-02-01

    Carbonic anhydrases (CAs) have been demonstrated to play an important role in acid-base regulation in vertebrates. However, the classification and modulatory function of CAs in marine invertebrates, especially their responses to ocean acidification remain largely unknown. Here, a cytosolic α-CA (designated as CgCAII-1) was characterized from Pacific oyster Crassostrea gigas and its molecular activities against CO 2 exposure were investigated. CgCAII-1 possessed a conserved CA catalytic domain, with high similarity to invertebrate cytoplasmic or mitochondrial α-CAs. Recombinant CgCAII-1 could convert CO 2 to HCO 3 - with calculated activity as 0.54 × 10 3  U/mg, which could be inhibited by acetazolamide (AZ). The mRNA transcripts of CgCAII-1 in muscle, mantle, hepatopancreas, gill, and hemocytes increased significantly after exposure to elevated CO 2 . CgCAII-1 could interact with the hemocyte membrane proteins and the distribution of CgCAII-1 protein became more concentrated and dense in gill and mantle under CO 2 exposure. The intracellular pH (pHi) of hemocytes under CO 2 exposure increased significantly (p ocean acidification and participate in acid-base regulation. Such cytoplasmic CA-based physiological regulation mechanism might explain other physiological responses of marine organisms to OA.

  5. Microbial Ecology of Soil Aggregation in Agroecosystems

    Science.gov (United States)

    Hofmockel, K. S.; Bell, S.; Tfailly, M.; Thompson, A.; Callister, S.

    2017-12-01

    Crop selection and soil texture influence the physicochemical attributes of the soil, which structures microbial communities and influences soil C cycling storage. At the molecular scale, microbial metabolites and necromass alter the soil environment, which creates feedbacks that influence ecosystem functions, including soil C accumulation. By integrating lab to field studies we aim to identify the molecules, organisms and metabolic pathways that control carbon cycling and stabilization in bioenergy soils. We investigated the relative influence of plants, microbes, and minerals on soil aggregate ecology at the Great Lakes Bioenergy Research experiment. Sites in WI and MI, USA have been in corn and switchgrass cropping systems for a decade. By comparing soil aggregate ecology across sites and cropping systems we are able to test the relative importance of plant, microbe, mineral influences on soil aggregate dynamics. Soil microbial communities (16S) differ in diversity and phylogeny among sites and cropping systems. FT-ICR MS revealed differences in the molecular composition of water-soluble fraction of soil organic matter for cropping systems and soil origin for both relative abundance of assigned formulas and biogeochemical classes of compounds. We found the degree of aggregation, measured by mean weighted diameter of aggregate fractions, is influenced by plant-soil interactions. Similarly, the proportion of soil aggregate fractions varied by both soil and plant factors. Differences in aggregation were reflected in differences in bacterial, but not fungal community composition across aggregate fractions, within each soil. Scanning electron microscopy revealed stark differences in mineral-organic interactions that influence the microbial niche and the accessibility of substrates within the soil. The clay soils show greater surface heterogeneity, enabling interactions with organic fraction of the soil. This is consistent with molecular data that reveal differences

  6. Design, synthesis and biological evaluation of benzo[e][1,2,4]triazin-7(1H)-one and [1,2,4]-triazino[5,6,1-jk]carbazol-6-one derivatives as dual inhibitors of beta-amyloid aggregation and acetyl/butyryl cholinesterase.

    Science.gov (United States)

    Catto, Marco; Berezin, Andrey A; Lo Re, Daniele; Loizou, Georgia; Demetriades, Marina; De Stradis, Angelo; Campagna, Francesco; Koutentis, Panayiotis A; Carotti, Angelo

    2012-12-01

    Alzheimer's disease (AD) onset and progression are associated with the dysregulation of multiple and complex physiological processes and a successful therapeutic approach should therefore address more than one target. Two new chemical entities, the easily accessible heterocyclic scaffolds 1,3-diphenylbenzo[e][1,2,4]triazin-7(1H)-one (benzotriazinone I) and 2-phenyl-6H-[1,2,4]triazino[5,6,1-jk]carbazol-6-one (triazafluoranthenone II), were explored for their multitarget-directed inhibition of beta-amyloid (Aβ) fibrillization and acetyl- (AChE) and/or butyryl- (BChE) cholinesterase, three valuable targets for AD therapy. Introduction of appropriate amine substituents at positions 6 and 5 on scaffold I and II, respectively, allowed the preparation of a series of compounds that were tested as Aβ(1-40) aggregation and cholinesterase inhibitors. Potent inhibitors of Aβ self-aggregation were discovered and among them benzotriazinone 7 exhibited an outstanding IC(50) equal to 0.37 μM. Compounds bearing a basic amine linked to the heterocyclic scaffold through a linear alkyl chain of varying length also afforded good ChE inhibitors. In particular, benzotriazinone 24 and triazafluoranthenone 38 were endowed with an interesting multiple activity, the former displaying IC(50) values of 1.4, 1.5 and 1.9 μM on Aβ aggregation and AChE and BChE inhibition, respectively, and the latter showing IC(50) values of 1.4 and an outstanding 0.025 μM in the Aβ aggregation and BChE inhibition, respectively. Benzotriazinone 24 and triazafluoranthenone 29, selected owing to their suitable aqueous solubility and Aβ aggregation inhibition, were submitted to a time course kinetic assay followed with thioflavin T (ThT) spectrofluorimetry, circular dichroism (CD) and transmission electron microscopy (TEM). Experimental data indicated that 24 acted at a low concentration ratio (10 μM 24 vs. 50 μM Aβ), stabilizing the unstructured Aβ peptide and inhibiting fibrillogenesis, and that 29

  7. Cooperative structural transitions in amyloid-like aggregation

    Science.gov (United States)

    Steckmann, Timothy; Bhandari, Yuba R.; Chapagain, Prem P.; Gerstman, Bernard S.

    2017-04-01

    Amyloid fibril aggregation is associated with several horrific diseases such as Alzheimer's, Creutzfeld-Jacob, diabetes, Parkinson's, and others. Although proteins that undergo aggregation vary widely in their primary structure, they all produce a cross-β motif with the proteins in β-strand conformations perpendicular to the fibril axis. The process of amyloid aggregation involves forming myriad different metastable intermediate aggregates. To better understand the molecular basis of the protein structural transitions and aggregation, we report on molecular dynamics (MD) computational studies on the formation of amyloid protofibrillar structures in the small model protein ccβ, which undergoes many of the structural transitions of the larger, naturally occurring amyloid forming proteins. Two different structural transition processes involving hydrogen bonds are observed for aggregation into fibrils: the breaking of intrachain hydrogen bonds to allow β-hairpin proteins to straighten, and the subsequent formation of interchain H-bonds during aggregation into amyloid fibrils. For our MD simulations, we found that the temperature dependence of these two different structural transition processes results in the existence of a temperature window that the ccβ protein experiences during the process of forming protofibrillar structures. This temperature dependence allows us to investigate the dynamics on a molecular level. We report on the thermodynamics and cooperativity of the transformations. The structural transitions that occurred in a specific temperature window for ccβ in our investigations may also occur in other amyloid forming proteins but with biochemical parameters controlling the dynamics rather than temperature.

  8. Aggregate formation in 3D turbulent-like flows

    NARCIS (Netherlands)

    Dominguez, A.; Aartrijk, van M.; Castello, Del L.; Clercx, H.J.H.; Geurts, B.; Clercx, H

    2006-01-01

    Aggregate formation is an important process in industrial and environ mental turbulent flows. Two examples in the environmental area, where turbulent aggregate formation takes place, are raindrop formation in clouds and Marine Snow (aggregate) formation in the upper layer in the oceans. The

  9. Engineering Performance of Polyurethane Bonded Aggregates

    Directory of Open Access Journals (Sweden)

    Haimin WU

    2017-08-01

    Full Text Available In this paper the engineering performance of polyurethane (PUR bonded aggregate were studied. The engineering performance, including compressive and flexural mechanical properties, void ratio, and coefficient of permeability were determined through laboratory tests. Moreover, the effects of two different curing conditions on the compressive strength properties of a PUR bonded aggregate were also evaluated. The compressive strengths of PUR bonded aggregates were found to be lower than that of conventional porous concrete, which is a commonly used cushion material. However, experimental results indicated a higher void ratio and coefficient of permeability, lower elasticity modulus, better toughness, and stronger adaptability to flexural deformation compared to porous concrete. Consequently, PUR bonded aggregate is a better solution than porous concrete when used as the cushion material of a geomembrane surface barrier for a high rock-fill dam.DOI: http://dx.doi.org/10.5755/j01.ms.23.2.15798

  10. SHAPE ANALYSIS OF FINE AGGREGATES USED FOR CONCRETE

    OpenAIRE

    HE, Huan; Courard, Luc; Pirard, Eric; Michel, Frédéric

    2016-01-01

    Fine aggregate is one of the essential components in concrete and significantly influences the material properties. As parts of natures, physical characteristics of fine aggregate are highly relevant to its behaviors in concrete. The most of previous studies are mainly focused on the physical properties of coarse aggregate due to the equipment limitations. In this paper, two typical fine aggregates, i.e. river sand and crushed rock, are selected for shape characterization. The new developed d...

  11. Probabilistic Analysis of Structural Member from Recycled Aggregate Concrete

    Science.gov (United States)

    Broukalová, I.; Šeps, K.

    2017-09-01

    The paper aims at the topic of sustainable building concerning recycling of waste rubble concrete from demolition. Considering demands of maximising recycled aggregate use and minimising of cement consumption, composite from recycled concrete aggregate was proposed. The objective of the presented investigations was to verify feasibility of the recycled aggregate cement based fibre reinforced composite in a structural member. Reliability of wall from recycled aggregate fibre reinforced composite was assessed in a probabilistic analysis of a load-bearing capacity of the wall. The applicability of recycled aggregate fibre reinforced concrete in structural applications was demonstrated. The outcomes refer to issue of high scatter of material parameters of recycled aggregate concretes.

  12. Liver tissue engineering based on aggregate assembly: efficient formation of endothelialized rat hepatocyte aggregates and their immobilization with biodegradable fibres

    International Nuclear Information System (INIS)

    Pang, Y; Shinohara, M; Komori, K; Sakai, Y; Montagne, K

    2012-01-01

    To realize long-term in vitro culture of hepatocytes at a high density while maintaining a high hepatic function for aggregate-based liver tissue engineering, we report here a novel culture method whereby endothelialized rat hepatocyte aggregates were formed using a PDMS microwell device and cultured in a perfusion bioreactor by introducing spacers between aggregates to improve oxygen and nutrient supply. Primary rat hepatocyte aggregates around 100 µm in diameter coated with human umbilical vein endothelial cells were spontaneously and quickly formed after 12 h of incubation, thanks to the continuous supply of oxygen by diffusion through the PDMS honeycomb microwell device. Then, the recovered endothelialized rat hepatocyte aggregates were mixed with biodegradable poly-l-lactic acid fibres in suspension and packed into a PDMS-based bioreactor. Perfusion culture of 7 days was successfully achieved with more than 73.8% cells retained in the bioreactor. As expected, the fibres acted as spacers between aggregates, which was evidenced from the enhanced albumin production and more spherical morphology compared with fibre-free packing. In summary, this study shows the advantages of using PDMS-based microwells to form heterotypic aggregates and also demonstrates the feasibility of spacing tissue elements for improving oxygen and nutrient supply to tissue engineering based on modular assembly. (paper)

  13. Aggregate formation in 3D turbulent-like flows

    NARCIS (Netherlands)

    Dominguez, A.; Clercx, H.J.H.

    2006-01-01

    Aggregate formation is an important process in industrial and environmental turbulent flows. In oceans turbulence play an important role on Marine Snow (aggregate) formation. For a proper description, the study of aggregate formation in turbulent flows requires a particle based model i.e. following

  14. The proteome of neurofilament-containing protein aggregates in blood

    Directory of Open Access Journals (Sweden)

    Rocco Adiutori

    2018-07-01

    Full Text Available Protein aggregation in biofluids is a poorly understood phenomenon. Under normal physiological conditions, fluid-borne aggregates may contain plasma or cell proteins prone to aggregation. Recent observations suggest that neurofilaments (Nf, the building blocks of neurons and a biomarker of neurodegeneration, are included in high molecular weight complexes in circulation. The composition of these Nf-containing hetero-aggregates (NCH may change in systemic or organ-specific pathologies, providing the basis to develop novel disease biomarkers. We have tested ultracentrifugation (UC and a commercially available protein aggregate binder, Seprion PAD-Beads (SEP, for the enrichment of NCH from plasma of healthy individuals, and then characterised the Nf content of the aggregate fractions using gel electrophoresis and their proteome by mass spectrometry (MS. Western blot analysis of fractions obtained by UC showed that among Nf isoforms, neurofilament heavy chain (NfH was found within SDS-stable high molecular weight aggregates. Shotgun proteomics of aggregates obtained with both extraction techniques identified mostly cell structural and to a lesser extent extra-cellular matrix proteins, while functional analysis revealed pathways involved in inflammatory response, phagosome and prion-like protein behaviour. UC aggregates were specifically enriched with proteins involved in endocrine, metabolic and cell-signalling regulation. We describe the proteome of neurofilament-containing aggregates isolated from healthy individuals biofluids using different extraction methods.

  15. A Novel Role of Eruca sativa Mill. (Rocket Extract: Antiplatelet (NF-κB Inhibition and Antithrombotic Activities

    Directory of Open Access Journals (Sweden)

    Eduardo Fuentes

    2014-12-01

    Full Text Available Background: Epidemiological studies have shown the prevention of cardiovascular diseases through the regular consumption of vegetables. Eruca sativa Mill., commonly known as rocket, is a leafy vegetable that has anti-inflammatory activity. However, its antiplatelet and antithrombotic activities have not been described. Methods: Eruca sativa Mill. aqueous extract (0.1 to 1 mg/mL, was evaluated on human platelets: (i P-selectin expression by flow cytometry; (ii platelet aggregation induced by ADP, collagen and arachidonic acid; (iii IL-1β, TGF-β1, CCL5 and thromboxane B2 release; and (iv activation of NF-κB and PKA by western blot. Furthermore, (v antithrombotic activity (200 mg/kg and (vi bleeding time in murine models were evaluated. Results: Eruca sativa Mill. aqueous extract (0.1 to 1 mg/mL inhibited P-selectin expression and platelet aggregation induced by ADP. The release of platelet inflammatory mediators (IL-1β, TGF-β1, CCL5 and thromboxane B2 induced by ADP was inhibited by Eruca sativa Mill. aqueous extract. Furthermore, Eruca sativa Mill. aqueous extract inhibited NF-κB activation. Finally, in murine models, Eruca sativa Mill. aqueous extract showed significant antithrombotic activity and a slight effect on bleeding time. Conclusion: Eruca sativa Mill. presents antiplatelet and antithrombotic activity.

  16. Influence of velocity gradient on optimisation of the aggregation process and properties of formed aggregates. Part 2. Quantification of the influence of agitation intensity and time on the properties of formed aggregates

    Czech Academy of Sciences Publication Activity Database

    Polášek, Pavel

    2011-01-01

    Roč. 59, č. 3 (2011), s. 196-205 ISSN 0042-790X R&D Projects: GA ČR GA103/07/1016 Institutional research plan: CEZ:AV0Z20600510 Keywords : inline high density suspension (IHDS) formation process * aggregation phases * aggregate properties * compactness * relative density of aggregates Subject RIV: BK - Fluid Dynamics Impact factor: 0.340, year: 2011

  17. Soil aggregation under different management systems

    Directory of Open Access Journals (Sweden)

    Cibele Mascioli Rebello Portella

    2012-12-01

    Full Text Available Considering that the soil aggregation reflects the interaction of chemical, physical and biological soil factors, the aim of this study was evaluate alterations in aggregation, in an Oxisol under no-tillage (NT and conventional tillage (CT, since over 20 years, using as reference a native forest soil in natural state. After analysis of the soil profile (cultural profile in areas under forest management, samples were collected from the layers 0-5, 5-10, 10-20 and 20-40 cm, with six repetitions. These samples were analyzed for the aggregate stability index (ASI, mean weighted diameter (MWD, mean geometric diameter (MGD in the classes > 8, 8-4, 4-2, 2-1, 1-0.5, 0.5-0.25, and < 0.25 mm, and for physical properties (soil texture, water dispersible clay (WDC, flocculation index (FI and bulk density (Bd and chemical properties (total organic carbon - COT, total nitrogen - N, exchangeable calcium - Ca2+, and pH. The results indicated that more intense soil preparation (M < NT < PC resulted in a decrease in soil stability, confirmed by all stability indicators analyzed: MWD, MGD, ASI, aggregate class distribution, WDC and FI, indicating the validity of these indicators in aggregation analyses of the studied soil.

  18. Aggregation of natively folded proteins: a theoretical approach

    International Nuclear Information System (INIS)

    Trovato, Antonio; Maritan, Amos; Seno, Flavio

    2007-01-01

    The reliable identification of β-aggregating stretches in protein sequences is essential for the development of therapeutic agents for Alzheimer's and Parkinson's diseases, as well as other pathological conditions associated with protein deposition. While the list of aggregation related diseases is growing, it has also been shown that many proteins that are normally well behaved can be induced to aggregate in vitro. This fact suggests the existence of a unified framework that could explain both folding and aggregation. By assuming this universal behaviour, we have recently introduced an algorithm (PASTA: prediction of amyloid structure aggregation), which is based on a sequence-specific energy function derived from the propensity of two residue types to be found paired in neighbouring strands within β-sheets in globular proteins. The algorithm is able to predict the most aggregation-prone portions of several proteins initially unfolded, in excellent agreement with experimental results. Here, we apply the method to a set of proteins which are known to aggregate, but which are natively folded. The quality of the prediction is again very high, corroborating the hypothesis that the amyloid structure is stabilized by the same physico-chemical determinants as those operating in folded proteins

  19. Protein aggregation and misfolding: good or evil?

    Science.gov (United States)

    Pastore, Annalisa; Temussi, Pierandrea

    2012-06-01

    Protein aggregation and misfolding have important implications in an increasing number of fields ranging from medicine to biology to nanotechnology and material science. The interest in understanding this field has accordingly increased steadily over the last two decades. During this time the number of publications that have been dedicated to protein aggregation has increased exponentially, tackling the problem from several different and sometime contradictory perspectives. This review is meant to summarize some of the highlights that come from these studies and introduce this topical issue on the subject. The factors that make a protein aggregate and the cellular strategies that defend from aggregation are discussed together with the perspectives that the accumulated knowledge may open.

  20. Protein aggregation and misfolding: good or evil?

    International Nuclear Information System (INIS)

    Pastore, Annalisa; Temussi, Pierandrea

    2012-01-01

    Protein aggregation and misfolding have important implications in an increasing number of fields ranging from medicine to biology to nanotechnology and material science. The interest in understanding this field has accordingly increased steadily over the last two decades. During this time the number of publications that have been dedicated to protein aggregation has increased exponentially, tackling the problem from several different and sometime contradictory perspectives. This review is meant to summarize some of the highlights that come from these studies and introduce this topical issue on the subject. The factors that make a protein aggregate and the cellular strategies that defend from aggregation are discussed together with the perspectives that the accumulated knowledge may open. (topical review)

  1. Characterization of fine aggregates in concrete by different experimental approaches

    OpenAIRE

    He, Huan; Courard, Luc; Pirard, Eric; Michel, Frédéric

    2011-01-01

    Being its major component, aggregate can occupy up to three-quarter of the volume of concrete. The structure of aggregate formed in hardened state impacts largely on mechanical and durability properties of concrete. On another hand, physical characteristics of aggregate are primarily assumed to be relevant to granular behavior of aggregate. Therefore, characterization of aggregate is of high relevance to concrete studies. In this study, different types of fine aggregate used in concrete, name...

  2. Efficient external memory structures for range-aggregate queries

    DEFF Research Database (Denmark)

    Agarwal, P.K.; Yang, J.; Arge, L.

    2013-01-01

    We present external memory data structures for efficiently answering range-aggregate queries. The range-aggregate problem is defined as follows: Given a set of weighted points in Rd, compute the aggregate of the weights of the points that lie inside a d-dimensional orthogonal query rectangle. The...

  3. Effect of fly ash on the strength of porous concrete using recycled coarse aggregate to replace low-quality natural coarse aggregate

    Science.gov (United States)

    Arifi, Eva; Cahya, Evi Nur; Christin Remayanti, N.

    2017-09-01

    The performance of porous concrete made of recycled coarse aggregate was investigated. Fly ash was used as cement partial replacement. In this study, the strength of recycled aggregate was coMPared to low quality natural coarse aggregate which has high water absorption. Compression strength and tensile splitting strength test were conducted to evaluate the performance of porous concrete using fly ash as cement replacement. Results have shown that the utilization of recycled coarse aggregate up to 75% to replace low quality natural coarse aggregate with high water absorption increases compressive strength and splitting tensile strength of porous concrete. Using fly ash up to 25% as cement replacement improves compressive strength and splitting tensile strength of porous concrete.

  4. Cellular Handling of Protein Aggregates by Disaggregation Machines.

    Science.gov (United States)

    Mogk, Axel; Bukau, Bernd; Kampinga, Harm H

    2018-01-18

    Both acute proteotoxic stresses that unfold proteins and expression of disease-causing mutant proteins that expose aggregation-prone regions can promote protein aggregation. Protein aggregates can interfere with cellular processes and deplete factors crucial for protein homeostasis. To cope with these challenges, cells are equipped with diverse folding and degradation activities to rescue or eliminate aggregated proteins. Here, we review the different chaperone disaggregation machines and their mechanisms of action. In all these machines, the coating of protein aggregates by Hsp70 chaperones represents the conserved, initializing step. In bacteria, fungi, and plants, Hsp70 recruits and activates Hsp100 disaggregases to extract aggregated proteins. In the cytosol of metazoa, Hsp70 is empowered by a specific cast of J-protein and Hsp110 co-chaperones allowing for standalone disaggregation activity. Both types of disaggregation machines are supported by small Hsps that sequester misfolded proteins. Copyright © 2018 Elsevier Inc. All rights reserved.

  5. Signature of an aggregation-prone conformation of tau

    Science.gov (United States)

    Eschmann, Neil A.; Georgieva, Elka R.; Ganguly, Pritam; Borbat, Peter P.; Rappaport, Maxime D.; Akdogan, Yasar; Freed, Jack H.; Shea, Joan-Emma; Han, Songi

    2017-03-01

    The self-assembly of the microtubule associated tau protein into fibrillar cell inclusions is linked to a number of devastating neurodegenerative disorders collectively known as tauopathies. The mechanism by which tau self-assembles into pathological entities is a matter of much debate, largely due to the lack of direct experimental insights into the earliest stages of aggregation. We present pulsed double electron-electron resonance measurements of two key fibril-forming regions of tau, PHF6 and PHF6*, in transient as aggregation happens. By monitoring the end-to-end distance distribution of these segments as a function of aggregation time, we show that the PHF6(*) regions dramatically extend to distances commensurate with extended β-strand structures within the earliest stages of aggregation, well before fibril formation. Combined with simulations, our experiments show that the extended β-strand conformational state of PHF6(*) is readily populated under aggregating conditions, constituting a defining signature of aggregation-prone tau, and as such, a possible target for therapeutic interventions.

  6. Growth hormone aggregates in the rat adenohypophysis

    Science.gov (United States)

    Farrington, M.; Hymer, W. C.

    1990-01-01

    Although it has been known for some time that GH aggregates are contained within the rat anterior pituitary gland, the role that they might play in pituitary function is unknown. The present study examines this issue using the technique of Western blotting, which permitted visualization of 11 GH variants with apparent mol wt ranging from 14-88K. Electroelution of the higher mol wt variants from gels followed by their chemical reduction with beta-mercaptoethanol increased GH immunoassayability by about 5-fold. With the blot procedure we found 1) that GH aggregates greater than 44K were associated with a 40,000 x g sedimentable fraction; 2) that GH aggregates were not present in glands from thyroidectomized rats, but were in glands from the thyroidectomized rats injected with T4; 3) that GH aggregates were uniquely associated with a heavily granulated somatotroph subpopulation isolated by density gradient centrifugation; and 4) that high mol wt GH forms were released from the dense somatotrophs in culture, since treatment of the culture medium with beta-mercaptoethanol increased GH immunoassayability by about 5-fold. Taken together, the results show that high mol wt GH aggregates are contained in secretory granules of certain somatotrophs and are also released in aggregate form from these cells in vitro.

  7. Aggregate Supply and Potential Output

    OpenAIRE

    Razin, Assaf

    2004-01-01

    The New-Keynesian aggregate supply derives from micro-foundations an inflation-dynamics model very much like the tradition in the monetary literature. Inflation is primarily affected by: (i) economic slack; (ii) expectations; (iii) supply shocks; and (iv) inflation persistence. This paper extends the New Keynesian aggregate supply relationship to include also fluctuations in potential output, as an additional determinant of the relationship. Implications for monetary rules and to the estimati...

  8. Targeting Protein Aggregation for the Treatment of Degenerative Diseases

    Science.gov (United States)

    Eisele, Yvonne S.; Monteiro, Cecilia; Fearns, Colleen; Encalada, Sandra E.; Wiseman, R. Luke; Powers, Evan T.; Kelly, Jeffery W.

    2015-01-01

    The aggregation of specific proteins is hypothesized to underlie several degenerative diseases, collectively called amyloid disorders. However, the mechanistic connection between the process of protein aggregation and tissue degeneration is not yet fully understood. Here, we review current and emerging strategies to ameliorate aggregation-associated degenerative disorders, with a focus on disease-modifying strategies that prevent the formation of and/or eliminate protein aggregates. Persuasive pharmacologic and genetic evidence now support protein aggregation as the cause of post-mitotic tissue dysfunction or loss. However, a more detailed understanding of the factors that trigger and sustain aggregate formation, as well as the structure-activity relationships underlying proteotoxicity are needed to develop future disease-modifying therapies. PMID:26338154

  9. Extending Practical Pre-Aggregation in On-Line Analytical Processing

    DEFF Research Database (Denmark)

    Pedersen, Torben Bach; Jensen, Christian Søndergaard; Dyreson, Curtis E.

    On-Line Analytical Processing (OLAP) based on a dimensional view of data is being used increasingly in traditional business applications as well as in applications such as health care for the purpose of analyzing very large amounts of data. Pre-aggregation, the prior materialization of aggregate...... select combinations of aggregates and then re-use these for efficiently computing other aggregates. However, this re-use of aggregates is contingent on the dimension hierarchies and the relationships between facts and dimensions satisfying stringent constraints. This severely limits the scope...

  10. Proteotoxic stress induces phosphorylation of p62/SQSTM1 by ULK1 to regulate selective autophagic clearance of protein aggregates.

    Directory of Open Access Journals (Sweden)

    Junghyun Lim

    Full Text Available Disruption of proteostasis, or protein homeostasis, is often associated with aberrant accumulation of misfolded proteins or protein aggregates. Autophagy offers protection to cells by removing toxic protein aggregates and injured organelles in response to proteotoxic stress. However, the exact mechanism whereby autophagy recognizes and degrades misfolded or aggregated proteins has yet to be elucidated. Mounting evidence demonstrates the selectivity of autophagy, which is mediated through autophagy receptor proteins (e.g. p62/SQSTM1 linking autophagy cargos and autophagosomes. Here we report that proteotoxic stress imposed by the proteasome inhibition or expression of polyglutamine expanded huntingtin (polyQ-Htt induces p62 phosphorylation at its ubiquitin-association (UBA domain that regulates its binding to ubiquitinated proteins. We find that autophagy-related kinase ULK1 phosphorylates p62 at a novel phosphorylation site S409 in UBA domain. Interestingly, phosphorylation of p62 by ULK1 does not occur upon nutrient starvation, in spite of its role in canonical autophagy signaling. ULK1 also phosphorylates S405, while S409 phosphorylation critically regulates S405 phosphorylation. We find that S409 phosphorylation destabilizes the UBA dimer interface, and increases binding affinity of p62 to ubiquitin. Furthermore, lack of S409 phosphorylation causes accumulation of p62, aberrant localization of autophagy proteins and inhibition of the clearance of ubiquitinated proteins or polyQ-Htt. Therefore, our data provide mechanistic insights into the regulation of selective autophagy by ULK1 and p62 upon proteotoxic stress. Our study suggests a potential novel drug target in developing autophagy-based therapeutics for the treatment of proteinopathies including Huntington's disease.

  11. Aggregate assessments support improved operational decision making

    International Nuclear Information System (INIS)

    Bauer, R.

    2003-01-01

    At Darlington Nuclear aggregate assessment of plant conditions is carried out in support of Operational Decision Making. This paper discusses how aggregate assessments have been applied to Operator Workarounds leading to improved prioritisation and alignment of work programs in different departments. As well, aggregate assessment of plant and human performance factors has been carried out to identify criteria which support conservative decision making in the main control room during unit transients. (author)

  12. Aggregated nanoplatelets: optical properties and optically induced deaggregation

    International Nuclear Information System (INIS)

    Jayabalan, J; Singh, Asha; Chari, Rama; Srivastava, Himanshu; Srivastava, A K; Mukhopadhyay, P K; Oak, S M

    2008-01-01

    A study of aggregation and laser-induced deaggregation of silver nanospheres and nanoplatelets in colloidal form is presented. Changes in the extinction spectrum caused by aggregation are explained using a two-particle approximation. In the case of platelets, controlled laser irradiation is shown to reverse the aggregation process.

  13. Aggregated nanoplatelets: optical properties and optically induced deaggregation

    Energy Technology Data Exchange (ETDEWEB)

    Jayabalan, J; Singh, Asha; Chari, Rama [Laser Physics Application Division, Raja Ramanna Centre for Advanced Technology, Indore 452013 (India); Srivastava, Himanshu; Srivastava, A K [Indus Synchrotrons Utilization Division, Raja Ramanna Centre for Advanced Technology, Indore 452013 (India); Mukhopadhyay, P K; Oak, S M [Solid State Laser Division, Raja Ramanna Centre for Advanced Technology, Indore 452013 (India)], E-mail: jjaya@cat.ernet.in

    2008-11-05

    A study of aggregation and laser-induced deaggregation of silver nanospheres and nanoplatelets in colloidal form is presented. Changes in the extinction spectrum caused by aggregation are explained using a two-particle approximation. In the case of platelets, controlled laser irradiation is shown to reverse the aggregation process.

  14. Viral Aggregation: Impact on Virus Behavior in the Environment.

    Science.gov (United States)

    Gerba, Charles P; Betancourt, Walter Q

    2017-07-05

    Aggregates of viruses can have a significant impact on quantification and behavior of viruses in the environment. Viral aggregates may be formed in numerous ways. Viruses may form crystal like structures and aggregates in the host cell during replication or may form due to changes in environmental conditions after virus particles are released from the host cells. Aggregates tend to form near the isoelectric point of the virus, under the influence of certain salts and salt concentrations in solution, cationic polymers, and suspended organic matter. The given conditions under which aggregates form in the environment are highly dependent on the type of virus, type of salts in solution (cation, anion. monovalent, divalent) and pH. However, virus type greatly influences the conditions when aggregation/disaggregation will occur, making predictions difficult under any given set of water quality conditions. Most studies have shown that viral aggregates increase the survival of viruses in the environment and resistance to disinfectants, especially with more reactive disinfectants. The presence of viral aggregates may also result in overestimation of removal by filtration processes. Virus aggregation-disaggregation is a complex process and predicting the behavior of any individual virus is difficult under a given set of environmental circumstances without actual experimental data.

  15. A brief review of the construction aggregates market

    Science.gov (United States)

    Willett, Jason Christopher

    2012-01-01

    The U.S. Geological Survey defines the construction aggregates industry as those companies that mine and process crushed stone and/or construction sand and gravel. Aggregates have been used from the earliest times of our civilization for a variety of purposes - construction being the major use. As construction aggregates, crushed stone and construction sand and gravel are the basic raw materials used to build the foundation for modern society. The widespread use of construction aggregates is the result of their general availability throughout the country and around the world along with their relatively low cost. Although construction aggregates have a low unit value, their widespread use makes them major contributors to, and indicators of, the economic well-being of the nation.

  16. Strength of masonry blocks made with recycled concrete aggregates

    Science.gov (United States)

    Matar, Pierre; Dalati, Rouba El

    The idea of recycling concrete of demolished buildings aims at preserving the environment. Indeed, the reuse of concrete as aggregate in new concrete mixes helped to reduce the expenses related to construction and demolition (C&D) waste management and, especially, to protect the environment by reducing the development rate of new quarries. This paper presents the results of an experimental study conducted on masonry blocks containing aggregates resulting from concrete recycling. The purpose of this study is to investigate the effect of recycled aggregates on compressive strength of concrete blocks. Tests were performed on series of concrete blocks: five series each made of different proportions of recycled aggregates, and one series of reference blocks exclusively composed of natural aggregates. Tests showed that using recycled aggregates with addition of cement allows the production of concrete blocks with compressive strengths comparable to those obtained on concrete blocks made exclusively of natural aggregates.

  17. Do chemical gradients within soil aggregates reflect plant/soil interactions?

    Science.gov (United States)

    Krüger, Jaane; Hallas, Till; Kinsch, Lena; Stahr, Simon; Prietzel, Jörg; Lang, Friederike

    2016-04-01

    As roots and hyphae often accumulate at the surface of soil aggregates, their formation and turnover might be related to the bioavailability especially of immobile nutrients like phosphorus. Several methods have been developed to obtain specific samples from aggregate surfaces and aggregate cores and thus to investigate differences between aggregate shell and core. However, these methods are often complex and time-consuming; therefore most common methods of soil analysis neglect the distribution of nutrients within aggregates and yield bulk soil concentrations. We developed a new sequential aggregate peeling method to analyze the distribution of different nutrients within soil aggregates (4-20 mm) from four forest sites (Germany) differing in concentrations of easily available mineral P. Aggregates from three soil depths (Ah, BwAh, Bw) were isolated, air-dried, and peeled with a sieving machine performing four sieving levels with increasing sieving intensity. This procedure was repeated in quadruplicate, and fractions of the same sample and sieving level were pooled. Carbon and N concentration, citric acid-extractable PO4 and P, as well as total element concentrations (P, K, Mg, Ca, Al, Fe) were analyzed. Additionally, synchrotron-based P K-edge XANES spectroscopy was applied on selected samples to detect P speciation changes within the aggregates. The results reveal for most samples a significantly higher C and N concentration at the surface compared to the interior of the aggregates. Carbon and N gradients get more pronounced with increasing soil depth and decreasing P status of study sites. This might be explained by lower aggregate turnover rates of subsoil horizons and intense bioturbation on P-rich sites. This assumption is also confirmed by concentrations of citric acid-extractable PO4 and P: gradients within aggregates are getting more pronounced with increasing soil depth and decreasing P status. However, the direction of these gradients is site

  18. Procedure for Validation of Aggregators Providing Demand Response

    DEFF Research Database (Denmark)

    Bondy, Daniel Esteban Morales; Gehrke, Oliver; Thavlov, Anders

    2016-01-01

    of small heterogeneous resources that are geographically distributed. Therefore, a new test procedure must be designed for the aggregator validation. This work proposes such a procedure and exemplifies is with a study case. The validation of aggregators is essential if aggregators are to be integrated...... succesfully into the power system....

  19. Morusinol extracted from Morus alba inhibits arterial thrombosis and modulates platelet activation for the treatment of cardiovascular disease.

    Science.gov (United States)

    Lee, Jung-Jin; Yang, Hyun; Yoo, Yeong-Min; Hong, Seong Su; Lee, Dongho; Lee, Hyun-Jung; Lee, Hak-Ju; Myung, Chang-Seon; Choi, Kyung-Chul; Jeung, Eui-Bae

    2012-01-01

    Morus alba (white mulberry) has been used in traditional Chinese medicine as an anti-headache, diuretic, expectorant, and anti-diabetic agent. In previous studies, extracts of Morus alba demonstrated favorable biological properties, such as antioxidant activity, suppression of lipoxygenase (LOX)-1, cytotoxicity against cancer cells, and inhibition of the invasion and migration of cancer cells. This study further evaluated the effects of morusinol, a flavonoid derived from Morus alba root bark, on platelet aggregation and thromboxane B(2) (TXB(2) formation in vitro and thrombus formation in vivo. The antiplatelet potential of morusinol was measured using in vitro rabbit platelet aggregation and TXB(2) formation assays. Arterial thrombus formation was investigated using an in vivo ferric chloride (FeCl(3)-induced thrombosis model. Morusinol significantly inhibited collagen- and arachidonic acid-induced platelet aggregation and TXB(2) formation in cultured platelets in a concentration-dependent manner. Thrombus formation was reduced by 32.1, 42.0, and 99.0% for collagen-induced TXB(2) formation, and 8.0, 24.1, and 29.2% for arachadonic acid-induced TXB(2) formation, with 5, 10, and 30 µg/mL morusinol, respectively. Moreover, oral morusinol (20 mg/kg) or aspirin (20 mg/kg) for three days significantly increased the time to occlusion in vivo by 20.3±5.0 or 6.8±2.9 min, respectively, compared with the control (1% CMC, carboxymethyl cellulose). Taken together, these results indicate that morusinol may significantly inhibit arterial thrombosis in vivo due to antiplatelet activity. Thus, morusinol may exert beneficial effects on transient ischemic attacks or stroke via the modulation of platelet activation.

  20. Functional characterization of recombinant snake venom rhodocytin: rhodocytin mutant blocks CLEC-2/podoplanin-dependent platelet aggregation and lung metastasis.

    Science.gov (United States)

    Sasaki, T; Shirai, T; Tsukiji, N; Otake, S; Tamura, S; Ichikawa, J; Osada, M; Satoh, K; Ozaki, Y; Suzuki-Inoue, K

    2018-02-28

    Essentials We generated recombinant rhodocytin that could aggregate platelets via CLEC-2. Recombinant wild-type rhodocytin formed heterooctamer with four α- and β-subunits. Asp 4 in α-subunit of rhodocytin was required for binding to CLEC-2. Inhibitory mutant of rhodocytin blocked podoplanin-dependent hematogenous metastasis. Background Rhodocytin, a disulfide-linked heterodimeric C-type lectin from Calloselasma rhodostoma consisting of α-subunits and β-subunits, induces platelet aggregation through C-type lectin-like receptor 2 (CLEC-2). CLEC-2 is a physiological binding partner of podoplanin (PDPN), which is expressed on some tumor cell types, and is involved in tumor cell-induced platelet aggregation and tumor metastasis. Thus, modified rhodocytin may be a possible source of anti-CLEC-2 drugs for both antiplatelet and antimetastasis therapy. However, its molecular function has not been well characterized, because of the lack of recombinant rhodocytin that induces platelet aggregation. Objective To produce recombinant rhodocytin, in order to verify its function with mutagenesis, and to develop an anti-CLEC-2 drug based on the findings. Methods We used Chinese hamster ovary cells to express recombinant rhodocytin (wild-type [WT] and mutant), which was analyzed for induction/inhibition of platelet aggregation with light transmission aggregometry, the formation of multimers with blue native PAGE, and binding to CLEC-2 with flow cytometry. Finally, we investigated whether mutant rhodocytin could suppress PDPN-induced metastasis in an experimental lung metastasis mouse model. Results Functional WT] rhodocytin (αWTβWT) was obtained by coexpression of both subunits. Asp4 in α-subunits of rhodocytin was required for CLEC-2 binding. αWTβWT formed a heterooctamer similarly to native rhodocytin. Moreover, an inhibitory mutant of rhodocytin (αWTβK53A/R56A), forming a heterotetramer, bound to CLEC-2 without inducing platelet aggregation, and blocked CLEC-2-PDPN

  1. Compressive strength performance of OPS lightweight aggregate concrete containing coal bottom ash as partial fine aggregate replacement

    Science.gov (United States)

    Muthusamy, K.; Mohamad Hafizuddin, R.; Mat Yahaya, F.; Sulaiman, M. A.; Syed Mohsin, S. M.; Tukimat, N. N.; Omar, R.; Chin, S. C.

    2018-04-01

    Concerns regarding the negative impact towards environment due to the increasing use of natural sand in construction industry and dumping of industrial solid wastes namely coal bottom ash (CBA) and oil palm shell (OPS) has resulted in the development of environmental friendly lightweight concrete. The present study investigates the effect of coal bottom ash as partial fine aggregate replacement towards workability and compressive strength of oil palm shell lightweight aggregate concrete (OPS LWAC). The fresh and mechanical properties of this concrete containing various percentage of coal bottom ash as partial fine aggregate replacement were investigated. The result was compared to OPS LWAC with 100 % sand as a control specimen. The concrete workability investigated by conducting slump test. All specimens were cast in form of cubes and water cured until the testing age. The compressive strength test was carried out at 7 and 28 days. The finding shows that integration of coal bottom ash at suitable proportion enhances the strength of oil palm shell lightweight aggregate concrete.

  2. Turbulent breakage of ductile aggregates.

    Science.gov (United States)

    Marchioli, Cristian; Soldati, Alfredo

    2015-05-01

    In this paper we study breakage rate statistics of small colloidal aggregates in nonhomogeneous anisotropic turbulence. We use pseudospectral direct numerical simulation of turbulent channel flow and Lagrangian tracking to follow the motion of the aggregates, modeled as sub-Kolmogorov massless particles. We focus specifically on the effects produced by ductile rupture: This rupture is initially activated when fluctuating hydrodynamic stresses exceed a critical value, σ>σ(cr), and is brought to completion when the energy absorbed by the aggregate meets the critical breakage value. We show that ductile rupture breakage rates are significantly reduced with respect to the case of instantaneous brittle rupture (i.e., breakage occurs as soon as σ>σ(cr)). These discrepancies are due to the different energy values at play as well as to the statistical features of energy distribution in the anisotropic turbulence case examined.

  3. Temporal aggregation in first order cointegrated vector autoregressive

    DEFF Research Database (Denmark)

    la Cour, Lisbeth Funding; Milhøj, Anders

    2006-01-01

    We study aggregation - or sample frequencies - of time series, e.g. aggregation from weekly to monthly or quarterly time series. Aggregation usually gives shorter time series but spurious phenomena, in e.g. daily observations, can on the other hand be avoided. An important issue is the effect of ...... of aggregation on the adjustment coefficient in cointegrated systems. We study only first order vector autoregressive processes for n dimensional time series Xt, and we illustrate the theory by a two dimensional and a four dimensional model for prices of various grades of gasoline....

  4. The fate of silver nanoparticles in soil solution--Sorption of solutes and aggregation.

    Science.gov (United States)

    Klitzke, Sondra; Metreveli, George; Peters, Andre; Schaumann, Gabriele E; Lang, Friederike

    2015-12-01

    Nanoparticles enter soils through various pathways. In the soil, they undergo various interactions with the solution and the solid phase. We tested the following hypotheses using batch experiments: i) the colloidal stability of Ag NP increases through sorption of soil-borne dissolved organic matter (DOM) and thus inhibits aggregation; ii) the presence of DOM suppresses Ag oxidation; iii) the surface charge of Ag NP governs sorption onto soil particles. Citrate-stabilized and bare Ag NPs were equilibrated with (colloid-free) soil solution extracted from a floodplain soil for 24h. Nanoparticles were removed through centrifugation. Concentrations of free Ag ions and DOC, the specific UV absorbance at a wavelength of 254 nm, and the absorption ratio α254/α410 were determined in the supernatant. Nanoparticle aggregation was studied using time-resolved dynamic light scattering (DLS) measurement following the addition of soil solution and 1.5mM Ca(2+) solution. To study the effect of surface charge on the adsorption of Ag NP onto soil particles, bare and citrate-stabilized Ag NP, differing in the zeta potential, were equilibrated with silt at a solid-to-solution ratio of 1:10 and an initial Ag concentration range of 30 to 320 μg/L. Results showed that bare Ag NPs sorb organic matter, with short-chained organic matter being preferentially adsorbed over long-chained, aromatic organic matter. Stabilizing effects of organic matter only come into play at higher Ag NP concentrations. Soil solution inhibits the release of Ag(+) ions, presumably due to organic matter coatings. Sorption to silt particles was very similar for the two particle types, suggesting that the surface charge does not control Ag NP sorption. Besides, sorption was much lower than in comparable studies with sand and glass surfaces. Copyright © 2014. Published by Elsevier B.V.

  5. Recycled aggregates in concrete production: engineering properties and environmental impact

    Directory of Open Access Journals (Sweden)

    Seddik Meddah Mohammed

    2017-01-01

    Full Text Available Recycled concrete aggregate is considered as the most abundant and used secondary aggregate in concrete production, other types of solid waste are also being used in concrete for specific purposes and to achieve some desired properties. Recycled aggregates and particularly, recycled concrete aggregate substantially affect the properties and mix design of concrete both at fresh and hardened states since it is known by high porosity due to the adhered layer of old mortar on the aggregate which results in a high water absorption of the recycled secondary aggregate. This leads to lower density and strength, and other durability related properties. The use of most recycled aggregate in concrete structures is still limited to low strength and non-structural applications due to important drop in strength and durability performances generated. Embedding recycled aggregates in concrete is now a current practice in many countries to enhance sustainability of concrete industry and reduce its environmental impacts. The present paper discusses the various possible recycled aggregates used in concrete production, their effect on both fresh and hardened properties as well as durability performances. The economic and environmental impacts of partially or fully substituting natural aggregates by secondary recycled aggregates are also discussed.

  6. Partitioning of red blood cell aggregates in bifurcating microscale flows

    Science.gov (United States)

    Kaliviotis, E.; Sherwood, J. M.; Balabani, S.

    2017-03-01

    Microvascular flows are often considered to be free of red blood cell aggregates, however, recent studies have demonstrated that aggregates are present throughout the microvasculature, affecting cell distribution and blood perfusion. This work reports on the spatial distribution of red blood cell aggregates in a T-shaped bifurcation on the scale of a large microvessel. Non-aggregating and aggregating human red blood cell suspensions were studied for a range of flow splits in the daughter branches of the bifurcation. Aggregate sizes were determined using image processing. The mean aggregate size was marginally increased in the daughter branches for a range of flow rates, mainly due to the lower shear conditions and the close cell and aggregate proximity therein. A counterintuitive decrease in the mean aggregate size was apparent in the lower flow rate branches. This was attributed to the existence of regions depleted by aggregates of certain sizes in the parent branch, and to the change in the exact flow split location in the T-junction with flow ratio. The findings of the present investigation may have significant implications for microvascular flows and may help explain why the effects of physiological RBC aggregation are not deleterious in terms of in vivo vascular resistance.

  7. Molecular origin of polyglutamine aggregation in neurodegenerative diseases.

    Directory of Open Access Journals (Sweden)

    2005-08-01

    Full Text Available Expansion of polyglutamine (polyQ tracts in proteins results in protein aggregation and is associated with cell death in at least nine neurodegenerative diseases. Disease age of onset is correlated with the polyQ insert length above a critical value of 35-40 glutamines. The aggregation kinetics of isolated polyQ peptides in vitro also shows a similar critical-length dependence. While recent experimental work has provided considerable insights into polyQ aggregation, the molecular mechanism of aggregation is not well understood. Here, using computer simulations of isolated polyQ peptides, we show that a mechanism of aggregation is the conformational transition in a single polyQ peptide chain from random coil to a parallel beta-helix. This transition occurs selectively in peptides longer than 37 glutamines. In the beta-helices observed in simulations, all residues adopt beta-strand backbone dihedral angles, and the polypeptide chain coils around a central helical axis with 18.5 +/- 2 residues per turn. We also find that mutant polyQ peptides with proline-glycine inserts show formation of antiparallel beta-hairpins in their ground state, in agreement with experiments. The lower stability of mutant beta-helices explains their lower aggregation rates compared to wild type. Our results provide a molecular mechanism for polyQ-mediated aggregation.

  8. Acid resistance of quaternary blended recycled aggregate concrete

    Directory of Open Access Journals (Sweden)

    K Jagannadha Rao

    2018-06-01