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Sample records for cdt induces formation

  1. Clostridium difficile toxin CDT induces formation of microtubule-based protrusions and increases adherence of bacteria.

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    Carsten Schwan

    2009-10-01

    Full Text Available Clostridium difficile causes antibiotic-associated diarrhea and pseudomembranous colitis by production of the Rho GTPase-glucosylating toxins A and B. Recently emerging hypervirulent Clostridium difficile strains additionally produce the binary ADP-ribosyltransferase toxin CDT (Clostridium difficile transferase, which ADP-ribosylates actin and inhibits actin polymerization. Thus far, the role of CDT as a virulence factor is not understood. Here we report by using time-lapse- and immunofluorescence microscopy that CDT and other binary actin-ADP-ribosylating toxins, including Clostridium botulinum C2 toxin and Clostridium perfringens iota toxin, induce redistribution of microtubules and formation of long (up to >150 microm microtubule-based protrusions at the surface of intestinal epithelial cells. The toxins increase the length of decoration of microtubule plus-ends by EB1/3, CLIP-170 and CLIP-115 proteins and cause redistribution of the capture proteins CLASP2 and ACF7 from microtubules at the cell cortex into the cell interior. The CDT-induced microtubule protrusions form a dense meshwork at the cell surface, which wrap and embed bacterial cells, thereby largely increasing the adherence of Clostridia. The study describes a novel type of microtubule structure caused by less efficient microtubule capture and offers a new perspective for the pathogenetic role of CDT and other binary actin-ADP-ribosylating toxins in host-pathogen interactions.

  2. Human geminin promotes pre-RC formation and DNA replication by stabilizing CDT1 in mitosis

    DEFF Research Database (Denmark)

    Ballabeni, Andrea; Melixetian, Marina; Zamponi, Raffaella

    2004-01-01

    -mediated degradation by inhibiting its ubiquitination. In particular, Geminin ensures basal levels of CDT1 during S phase and its accumulation during mitosis. Consistently, inhibition of Geminin synthesis during M phase leads to impairment of pre-RC formation and DNA replication during the following cell cycle....... Moreover, we show that inhibition of CDK1 during mitosis, and not Geminin depletion, is sufficient for premature formation of pre-RCs, indicating that CDK activity is the major mitotic inhibitor of licensing in human cells. Taken together with recent data from our laboratory, our results demonstrate...

  3. Alteration of Homeostasis in Pre-osteoclasts Induced by Aggregatibacter actinomycetemcomitans CDT

    OpenAIRE

    Dione eKawamoto; Ellen Sayuri Ando-Sugimoto; Bruno eBueno-Silva; DiRienzo, Joseph M.; Marcia Pinto Alves Mayer

    2016-01-01

    The dysbiotic microbiota associated with aggressive periodontitis includes Aggregatibacter actinomycetemcomitans, the only oral species known to produce a cytolethal distending toxin (AaCDT). Given that CDT alters the cytokine profile in monocytic cells, we aimed to test the hypothesis that CDT plays a role in bone homeostasis by affecting the differentiation of precursor cells into osteoclasts. Recombinant AaCDT was added to murine bone marrow monocytes (BMMC) in the presence or absence of R...

  4. DTL/CDT2 is essential for both CDT1 regulation and the early G2/M checkpoint.

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    Sansam, Christopher L; Shepard, Jennifer L; Lai, Kevin; Ianari, Alessandra; Danielian, Paul S; Amsterdam, Adam; Hopkins, Nancy; Lees, Jacqueline A

    2006-11-15

    Checkpoint genes maintain genomic stability by arresting cells after DNA damage. Many of these genes also control cell cycle events in unperturbed cells. By conducting a screen for checkpoint genes in zebrafish, we found that dtl/cdt2 is an essential component of the early, radiation-induced G2/M checkpoint. We subsequently found that dtl/cdt2 is required for normal cell cycle control, primarily to prevent rereplication. Both the checkpoint and replication roles are conserved in human DTL. Our data indicate that the rereplication reflects a requirement for DTL in regulating CDT1, a protein required for prereplication complex formation. CDT1 is degraded in S phase to prevent rereplication, and following DNA damage to prevent origin firing. We show that DTL associates with the CUL4-DDB1 E3 ubiquitin ligase and is required for CDT1 down-regulation in unperturbed cells and following DNA damage. The cell cycle defects of Dtl-deficient zebrafish are suppressed by reducing Cdt1 levels. In contrast, the early G2/M checkpoint defect appears to be Cdt1-independent. Thus, DTL promotes genomic stability through two distinct mechanisms. First, it is an essential component of the CUL4-DDB1 complex that controls CDT1 levels, thereby preventing rereplication. Second, it is required for the early G2/M checkpoint.

  5. Alteration of Homeostasis in Pre-osteoclasts Induced by Aggregatibacter actinomycetemcomitans CDT

    Science.gov (United States)

    Kawamoto, Dione; Ando-Suguimoto, Ellen S.; Bueno-Silva, Bruno; DiRienzo, Joseph M.; Mayer, Marcia P. A.

    2016-01-01

    The dysbiotic microbiota associated with aggressive periodontitis includes Aggregatibacter actinomycetemcomitans, the only oral species known to produce a cytolethal distending toxin (AaCDT). Give that CDT alters the cytokine profile in monocytic cells, we aimed to test the hypothesis that CDT plays a role in bone homeostasis by affecting the differentiation of precursor cells into osteoclasts. Recombinant AaCDT was added to murine bone marrow monocytes (BMMC) in the presence or absence of RANKL and the cell viability and cytokine profile of osteoclast precursor cells were determined. Multinucleated TRAP+ cell numbers, and relative transcription of genes related to osteoclastogenesis were also evaluated. The addition of AaCDT did not lead to loss in cell viability but promoted an increase in the average number of TRAP+ cells with 1-2 nuclei in the absence or presence of RANKL (Tukey, p < 0.05). This increase was also observed for TRAP+ cells with ≥3nuclei, although this difference was not significant. Levels of TGF-β, TNF-α, and IL-6, in the supernatant fraction of cells, were higher when in AaCDT exposed cells, whereas levels of IL-1β and IL-10 were lower than controls under the same conditions. After interaction with AaCDT, transcription of the rank (encoding the receptor RANK), nfatc1 (transcription factor), and ctpK (encoding cathepsin K) genes was downregulated in pre-osteoclastic cells. The data indicated that despite the presence of RANKL and M-CSF, AaCDT may inhibit osteoclast differentiation by altering cytokine profiles and repressing transcription of genes involved in osteoclastogenesis. Therefore, the CDT may impair host defense mechanisms in periodontitis. PMID:27064424

  6. Genotoxicity of Cytolethal Distending Toxin (CDT on isogenic human colorectal cell lines: potential promoting effects for colorectal carcinogenesis

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    Vanessa eGraillot

    2016-03-01

    Full Text Available The composition of the human microbiota influences tumorigenesis, notably in colorectal cancer (CRC. Pathogenic Escherichia coli possesses a variety of virulent factors, among them the Cytolethal Distending Toxin (CDT. CDT displays dual DNase and phosphatase activities and induces DNA double strand breaks, cell cycle arrest and apoptosis in a broad range of mammalian cells. As CDT could promote malignant transformation, we investigated the cellular outcomes induced by acute and chronic exposures to E. coli CDT in normal human colon epithelial cells (HCECs. Moreover, we conducted a comparative study between isogenic derivatives cell lines of the normal HCECs in order to mimic the mutation of three major genes found in CRC genetic models: APC, KRAS and TP53. Our results demonstrate that APC and p53 deficient cells showed impaired DNA damage response after CDT exposure, whereas HCECs expressing oncogenic KRASV12 were more resistant to CDT. Compared to normal HCECs, the precancerous derivatives exhibit hallmarks of malignant transformation after a chronic exposure to CDT. HCECs defective in APC and p53 showed enhanced anchorage independent growth and genetic instability, assessed by the micronucleus formation assay. In contrast, the ability to grow independently of anchorage was not impacted by CDT chronic exposure in KRASV12 HCECs, but micronucleus formation is dramatically increased. Thus CDT does not initiate CRC by itself, but may have promoting effects in premalignant HCECs, involving different mechanisms in function of the genetic alterations associated to CRC.

  7. Distinct Roles for CdtA and CdtC during Intoxication by Cytolethal Distending Toxins.

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    Shandee D Dixon

    Full Text Available Cytolethal distending toxins (CDTs are heterotrimeric protein exotoxins produced by a diverse array of Gram-negative pathogens. The enzymatic subunit, CdtB, possesses DNase and phosphatidylinositol 3-4-5 trisphosphate phosphatase activities that induce host cell cycle arrest, cellular distension and apoptosis. To exert cyclomodulatory and cytotoxic effects CDTs must be taken up from the host cell surface and transported intracellularly in a manner that ultimately results in localization of CdtB to the nucleus. However, the molecular details and mechanism by which CDTs bind to host cells and exploit existing uptake and transport pathways to gain access to the nucleus are poorly understood. Here, we report that CdtA and CdtC subunits of CDTs derived from Haemophilus ducreyi (Hd-CDT and enteropathogenic E. coli (Ec-CDT are independently sufficient to support intoxication by their respective CdtB subunits. CdtA supported CdtB-mediated killing of T-cells and epithelial cells that was nearly as efficient as that observed with holotoxin. In contrast, the efficiency by which CdtC supported intoxication was dependent on the source of the toxin as well as the target cell type. Further, CdtC was found to alter the subcellular trafficking of Ec-CDT as determined by sensitivity to EGA, an inhibitor of endosomal trafficking, colocalization with markers of early and late endosomes, and the kinetics of DNA damage response. Finally, host cellular cholesterol was found to influence sensitivity to intoxication mediated by Ec-CdtA, revealing a role for cholesterol or cholesterol-rich membrane domains in intoxication mediated by this subunit. In summary, data presented here support a model in which CdtA and CdtC each bind distinct receptors on host cell surfaces that direct alternate intracellular uptake and/or trafficking pathways.

  8. Distinct Roles for CdtA and CdtC during Intoxication by Cytolethal Distending Toxins

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    Tamilselvam, Batcha; Spiegelman, Lindsey M.; Son, Sophia B.; Eshraghi, Aria; Blanke, Steven R.; Bradley, Kenneth A.

    2015-01-01

    Cytolethal distending toxins (CDTs) are heterotrimeric protein exotoxins produced by a diverse array of Gram-negative pathogens. The enzymatic subunit, CdtB, possesses DNase and phosphatidylinositol 3-4-5 trisphosphate phosphatase activities that induce host cell cycle arrest, cellular distension and apoptosis. To exert cyclomodulatory and cytotoxic effects CDTs must be taken up from the host cell surface and transported intracellularly in a manner that ultimately results in localization of CdtB to the nucleus. However, the molecular details and mechanism by which CDTs bind to host cells and exploit existing uptake and transport pathways to gain access to the nucleus are poorly understood. Here, we report that CdtA and CdtC subunits of CDTs derived from Haemophilus ducreyi (Hd-CDT) and enteropathogenic E. coli (Ec-CDT) are independently sufficient to support intoxication by their respective CdtB subunits. CdtA supported CdtB-mediated killing of T-cells and epithelial cells that was nearly as efficient as that observed with holotoxin. In contrast, the efficiency by which CdtC supported intoxication was dependent on the source of the toxin as well as the target cell type. Further, CdtC was found to alter the subcellular trafficking of Ec-CDT as determined by sensitivity to EGA, an inhibitor of endosomal trafficking, colocalization with markers of early and late endosomes, and the kinetics of DNA damage response. Finally, host cellular cholesterol was found to influence sensitivity to intoxication mediated by Ec-CdtA, revealing a role for cholesterol or cholesterol-rich membrane domains in intoxication mediated by this subunit. In summary, data presented here support a model in which CdtA and CdtC each bind distinct receptors on host cell surfaces that direct alternate intracellular uptake and/or trafficking pathways. PMID:26618479

  9. Distinct Roles for CdtA and CdtC during Intoxication by Cytolethal Distending Toxins.

    Science.gov (United States)

    Dixon, Shandee D; Huynh, Melanie M; Tamilselvam, Batcha; Spiegelman, Lindsey M; Son, Sophia B; Eshraghi, Aria; Blanke, Steven R; Bradley, Kenneth A

    2015-01-01

    Cytolethal distending toxins (CDTs) are heterotrimeric protein exotoxins produced by a diverse array of Gram-negative pathogens. The enzymatic subunit, CdtB, possesses DNase and phosphatidylinositol 3-4-5 trisphosphate phosphatase activities that induce host cell cycle arrest, cellular distension and apoptosis. To exert cyclomodulatory and cytotoxic effects CDTs must be taken up from the host cell surface and transported intracellularly in a manner that ultimately results in localization of CdtB to the nucleus. However, the molecular details and mechanism by which CDTs bind to host cells and exploit existing uptake and transport pathways to gain access to the nucleus are poorly understood. Here, we report that CdtA and CdtC subunits of CDTs derived from Haemophilus ducreyi (Hd-CDT) and enteropathogenic E. coli (Ec-CDT) are independently sufficient to support intoxication by their respective CdtB subunits. CdtA supported CdtB-mediated killing of T-cells and epithelial cells that was nearly as efficient as that observed with holotoxin. In contrast, the efficiency by which CdtC supported intoxication was dependent on the source of the toxin as well as the target cell type. Further, CdtC was found to alter the subcellular trafficking of Ec-CDT as determined by sensitivity to EGA, an inhibitor of endosomal trafficking, colocalization with markers of early and late endosomes, and the kinetics of DNA damage response. Finally, host cellular cholesterol was found to influence sensitivity to intoxication mediated by Ec-CdtA, revealing a role for cholesterol or cholesterol-rich membrane domains in intoxication mediated by this subunit. In summary, data presented here support a model in which CdtA and CdtC each bind distinct receptors on host cell surfaces that direct alternate intracellular uptake and/or trafficking pathways.

  10. The Copenhagen Dependency Treebank (CDT)

    DEFF Research Database (Denmark)

    Høeg Müller, Henrik; Korzen, Iørn

    2014-01-01

    the fundamentals of how CDT is marked up with semantic relations in accordance with the dependency principles governing the annotation on the other levels of CDT. Specifically, focus will be on how Generative Lexicon (GL) theory has been incorporated into the unitary theoretical dependency framework of CDT...

  11. Clostridium difficile toxin CDT hijacks microtubule organization and reroutes vesicle traffic to increase pathogen adherence.

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    Schwan, Carsten; Kruppke, Anna S; Nölke, Thilo; Schumacher, Lucas; Koch-Nolte, Friedrich; Kudryashev, Mikhail; Stahlberg, Henning; Aktories, Klaus

    2014-02-11

    Clostridium difficile causes antibiotic-associated diarrhea and pseudomembranous colitis by the actions of Rho-glucosylating toxins A and B. Recently identified hypervirulent strains, which are associated with increased morbidity and mortality, additionally produce the actin-ADP-ribosylating toxin C. difficile transferase (CDT). CDT depolymerizes actin, causes formation of microtubule-based protrusions, and increases pathogen adherence. Here we show that CDT-induced protrusions allow vesicle traffic and contain endoplasmic reticulum tubules, connected to microtubules via the calcium sensor Stim1. The toxin reroutes Rab11-positive vesicles containing fibronectin, which is involved in bacterial adherence, from basolateral to the apical membrane sides in a microtubule- and Stim1-dependent manner. The data yield a model of C. difficile adherence regulated by actin depolymerization, microtubule restructuring, subsequent Stim1-dependent Ca(2+) signaling, vesicle rerouting, and secretion of ECM proteins to increase bacterial adherence.

  12. Detection of cdtA, cdtB, and cdtC genes in Campylobacter jejuni by multiplex PCR.

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    Martínez, Irati; Mateo, Estibaliz; Churruca, Estibaliz; Girbau, Cecilia; Alonso, Rodrigo; Fernández-Astorga, Aurora

    2006-02-01

    A multiplex PCR was developed for simultaneous detection of the cytolethal distending toxin (cdt) genes of Campylobacter jejuni. Three primer pairs targeting each one of the cdtA, cdtB and cdtC genes were designed and combined in the same PCR reaction. The assay was evaluated with 100 C. jejuni strains recovered from humans and animals and it was found to be rapid and specific. Two isolates presented several deletions affecting both cdtA and cdtB genes. High prevalence (98%) of the three cdt genes was found among isolates of different geographic origins.

  13. Excess Cdt1 inhibits nascent strand elongation by repressing the progression of replication forks in Xenopus egg extracts.

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    Nakazaki, Yuta; Tsuyama, Takashi; Seki, Masayuki; Takahashi, Mikiko; Enomoto, Takemi; Tada, Shusuke

    2016-02-01

    Cdt1 is a protein essential for initiation of DNA replication; it recruits MCM helicase, a core component of the replicative DNA helicase, onto replication origins. In our previous study, we showed that addition of excess Cdt1 inhibits nascent strand elongation during DNA replication in Xenopus egg extracts. In the present study, we investigated the mechanism behind the inhibitory effect of Cdt1. We found that addition of recombinant Cdt1 inhibited nascent DNA synthesis in a reinitiation-independent manner. To identify the mechanism by which Cdt1 inhibits nascent strand elongation, the effect of Cdt1 on loading of Mcm4 and Rpa70 onto chromatin was examined. The results showed that Cdt1 suppressed the excessive Rpa70 binding caused by extensive, aphidicolin-induced DNA unwinding; this unwinding occurs between stalled DNA polymerases and advancing replication forks. These findings suggested that excess Cdt1 suppressed the progression of replication forks.

  14. The stress phenotype makes cancer cells addicted to CDT2, a substrate receptor of the CRL4 ubiquitin ligase.

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    Olivero, Martina; Dettori, Daniela; Arena, Sabrina; Zecchin, Davide; Lantelme, Erica; Di Renzo, Maria Flavia

    2014-08-15

    CDT2/L2DTL/RAMP is one of the substrate receptors of the Cullin Ring Ubiquitin Ligase 4 that targets for ubiquitin mediated degradation a number of substrates, such as CDT1, p21 and CHK1, involved in the regulation of cell cycle and survival. Here we show that CDT2 depletion was alone able to induce the apoptotic death in 12/12 human cancer cell lines from different tissues, regardless of the mutation profile and CDT2 expression level. Cell death was associated to rereplication and to loss of CDT1 degradation. Conversely, CDT2 depletion did not affect non-transformed human cells, such as immortalized kidney, lung and breast cell lines, and primary cultures of endothelial cells and osteoblasts. The ectopic over-expression of an activated oncogene, such as the mutation-activated RAS or the amplified MET in non-transformed immortalized breast cell lines and primary human osteoblasts, respectively, made cells transformed in vitro, tumorigenic in vivo, and susceptible to CDT2 loss. The widespread effect of CDT2 depletion in different cancer cells suggests that CDT2 is not in a synthetic lethal interaction to a single specific pathway. CDT2 likely is a non-oncogene to which transformed cells become addicted because of their enhanced cellular stress, such as replicative stress and DNA damage.

  15. Recent results in CDT quantum gravity

    CERN Document Server

    Ambjorn, Jan; Gizbert-Studnicki, Jakub; Jurkiewicz, Jerzy

    2015-01-01

    We review some recent results from the causal dynamical triangulation (CDT) approach to quantum gravity. We review recent observations of dimensional reduction at a number of previously undetermined points in the parameter space of CDT, and discuss their possible relevance to the asymptotic safety scenario. We also present an updated phase diagram of CDT, discussing properties of a newly discovered phase and its possible relation to a signature change of the metric.

  16. Evidence of a critical role for cellodextrin transporte 2 (CDT-2) in both cellulose and hemicellulose degradation and utilization in Neurospora crassa.

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    Cai, Pengli; Gu, Ruimeng; Wang, Bang; Li, Jingen; Wan, Li; Tian, Chaoguang; Ma, Yanhe

    2014-01-01

    CDT-1 and CDT-2 are two cellodextrin transporters discovered in the filamentous fungus Neurospora crassa. Previous studies focused on characterizing the role of these transporters in only a few conditions, including cellulose degradation, and the function of these two transporters is not yet completely understood. In this study, we show that deletion of cdt-2, but not cdt-1, results in growth defects not only on Avicel but also on xylan. cdt-2 can be highly induced by xylan, and this mutant has a xylodextrin consumption defect. Transcriptomic analysis of the cdt-2 deletion strain on Avicel and xylan showed that major cellulase and hemicellulase genes were significantly down-regulated in the cdt-2 deletion strain and artificial over expression of cdt-2 in N. crassa increased cellulase and hemicellulase production. Together, these data clearly show that CDT-2 plays a critical role in hemicellulose sensing and utilization. This is the first time a sugar transporter has been assigned a function in the hemicellulose degradation pathway. Furthermore, we found that the transcription factor XLR-1 is the major regulator of cdt-2, while cdt-1 is primarily regulated by CLR-1. These results deepen our understanding of the functions of both cellodextrin transporters, particularly for CDT-2. Our study also provides novel insight into the mechanisms for hemicellulose sensing and utilization in N. crassa, and may be applicable to other cellulolytic filamentous fungi.

  17. Carbohydrate-deficient transferrin (CDT)--a biomarker for long-term alcohol consumption.

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    Golka, Klaus; Wiese, Andreas

    2004-01-01

    Carbohydrate-deficient transferrin (CDT) is a biomarker for chronic alcohol intake of more than 60 g ethanol/d. It has been reported to be superior to conventional markers like gamma-glutamyltransferase (GGT) and mean corpuscular volume MCV). This review covers theoretical and analytical aspects, with data from controlled drinking experiments and from different population subgroups such as subjects with different liver diseases or different drinking patterns. CDT determinations are particularly indicated in (1) cases of chronic alcohol consumption and relapses after withdrawal, (2) license reapplication after driving under alcohol influence, (3) differentiating patients with enzyme-inducing medication from those with alcohol abuse, 4) congenital disorders of glycosylation such as carbohydrate-deficient glycoprotein syndrome Ia (CDGS Ia), and (5) patients treated for galactosemia. The main advantage of CDT is its high specificity, as evidenced in combination with increased alcohol consumption. CDT values are not markedly influenced by medication except in immunosuppressed patients, who may show low CDT values. In general, CDT values appear less elevated after alcohol intake in women. The main disadvantage is the relatively low sensitivity. Hence, this parameter is not suitable for screening for subjects with alcohol abuse in the general population. As CDT, GGT, and MCV are connected with chronic alcohol consumption by different pathophysiological mechanisms, a combination of these parameters will further improve the diagnostic value.

  18. Cdt1 revisited: complex and tight regulation during the cell cycle and consequences of deregulation in mammalian cells

    Directory of Open Access Journals (Sweden)

    Fujita Masatoshi

    2006-10-01

    Full Text Available Abstract In eukaryotic cells, replication of genomic DNA initiates from multiple replication origins distributed on multiple chromosomes. To ensure that each origin is activated precisely only once during each S phase, a system has evolved which features periodic assembly and disassembly of essential pre-replication complexes (pre-RCs at replication origins. The pre-RC assembly reaction involves the loading of a presumptive replicative helicase, the MCM2-7 complexes, onto chromatin by the origin recognition complex (ORC and two essential factors, CDC6 and Cdt1. The eukaryotic cell cycle is driven by the periodic activation and inactivation of cyclin-dependent kinases (Cdks and assembly of pre-RCs can only occur during the low Cdk activity period from late mitosis through G1 phase, with inappropriate re-assembly suppressed during S, G2, and M phases. It was originally suggested that inhibition of Cdt1 function after S phase in vertebrate cells is due to geminin binding and that Cdt1 hyperfunction resulting from Cdt1-geminin imbalance induces re-replication. However, recent progress has revealed that Cdt1 activity is more strictly regulated by two other mechanisms in addition to geminin: (1 functional and SCFSkp2-mediated proteolytic regulation through phosphorylation by Cdks; and (2 replication-coupled proteolysis mediated by the Cullin4-DDB1Cdt2 ubiquitin ligase and PCNA, an eukaryotic sliding clamp stimulating replicative DNA polymerases. The tight regulation implies that Cdt1 control is especially critical for the regulation of DNA replication in mammalian cells. Indeed, Cdt1 overexpression evokes chromosomal damage even without re-replication. Furthermore, deregulated Cdt1 induces chromosomal instability in normal human cells. Since Cdt1 is overexpressed in cancer cells, this could be a new molecular mechanism leading to carcinogenesis. In this review, recent insights into Cdt1 function and regulation in mammalian cells are discussed.

  19. Impact of CDT Toxin on Human Diseases

    Directory of Open Access Journals (Sweden)

    Tiphanie Faïs

    2016-07-01

    Full Text Available Cytolethal distending toxin (CDT is found in Gram-negative bacteria, especially in certain Proteobacteria such as the Pasteurellaceae family, including Haemophilus ducreyi and Aggregatibacter (Actinobacillus actinomycetemcomitans, in the Enterobacteriaceae family and the Campylobacterales order, including the Campylobacter and Helicobacter species. In vitro and in vivo studies have clearly shown that this toxin has a strong effect on cellular physiology (inflammation, immune response modulation, tissue damage. Some works even suggest a potential involvement of CDT in cancers. In this review, we will discuss these different aspects.

  20. Impact of CDT Toxin on Human Diseases

    Science.gov (United States)

    Faïs, Tiphanie; Delmas, Julien; Serres, Arnaud; Bonnet, Richard; Dalmasso, Guillaume

    2016-01-01

    Cytolethal distending toxin (CDT) is found in Gram-negative bacteria, especially in certain Proteobacteria such as the Pasteurellaceae family, including Haemophilus ducreyi and Aggregatibacter (Actinobacillus) actinomycetemcomitans, in the Enterobacteriaceae family and the Campylobacterales order, including the Campylobacter and Helicobacter species. In vitro and in vivo studies have clearly shown that this toxin has a strong effect on cellular physiology (inflammation, immune response modulation, tissue damage). Some works even suggest a potential involvement of CDT in cancers. In this review, we will discuss these different aspects. PMID:27429000

  1. Impact of CDT Toxin on Human Diseases.

    Science.gov (United States)

    Faïs, Tiphanie; Delmas, Julien; Serres, Arnaud; Bonnet, Richard; Dalmasso, Guillaume

    2016-07-15

    Cytolethal distending toxin (CDT) is found in Gram-negative bacteria, especially in certain Proteobacteria such as the Pasteurellaceae family, including Haemophilus ducreyi and Aggregatibacter (Actinobacillus) actinomycetemcomitans, in the Enterobacteriaceae family and the Campylobacterales order, including the Campylobacter and Helicobacter species. In vitro and in vivo studies have clearly shown that this toxin has a strong effect on cellular physiology (inflammation, immune response modulation, tissue damage). Some works even suggest a potential involvement of CDT in cancers. In this review, we will discuss these different aspects.

  2. CDT6-expression can alter tumor sensitivity to chemotherapy

    NARCIS (Netherlands)

    Bouis, D; Hospers, GAP; Meijer, C; Dam, W; Mulder, NH

    2003-01-01

    Background: Cornea-derived transcript 6 (CDT6 = AngX) has been shown to have an anti-tumor effect. Materials and Methods: We transfected the murine melanoma cell line B16-F10 with the CDT6 gene and compared the sensitivity to cytostatic drugs of the resulting cell line, B16-CDT6, to that of the empt

  3. Trees and spatial topology change in CDT

    DEFF Research Database (Denmark)

    Ambjorn, Jan; Budd, Timothy George

    2013-01-01

    Generalized causal dynamical triangulations (generalized CDT) is a model of two-dimensional quantum gravity in which a limited number of spatial topology changes is allowed to occur. We solve the model at the discretized level using bijections between quadrangulations and trees. In the continuum...

  4. Characterization of null and hypomorphic alleles of the Drosophila l(2)dtl/cdt2 gene: Larval lethality and male fertility.

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    Sloan, Roketa S; Swanson, Christina I; Gavilano, Lily; Smith, Kristen N; Malek, Pamela Y; Snow-Smith, Mayronne; Duronio, Robert J; Key, S Catherine Silver

    2012-01-01

    The Drosophila lethal(2)denticleless (l(2)dtl) gene was originally reported as essential for embryogenesis and formation of the rows of tiny hairs on the larval ventral cuticle known as denticle belts. It is now well-established that l(2)dtl (also called cdt2) encodes a subunit of a Cullin 4-based E3 ubiquitin ligase complex that targets a number of key cell cycle regulatory proteins, including p21, Cdt1, E2F1 and Set8, to prevent replication defects and maintain cell cycle control. To investigate the role of l(2)dtl/cdt2 during development, we characterized existing l(2)dtl/cdt2 mutants and generated new deletion alleles, using P-element excision mutagenesis. Surprisingly, homozygous l(2)dtl/cdt2 mutant embryos developed beyond embryogenesis, had intact denticle belts, and lacked an observable embryonic replication defect. These mutants died during larval stages, affirming that loss of l(2)dtl/cdt2 function is lethal. Our data show that L(2)dtl/Cdt2 is maternally deposited, remains nuclear throughout the cell cycle, and has a previously unreported, elevated expression in the developing gonads. We also find that E2f1 regulates l(2)dtl/cdt2 expression during embryogenesis, possibly via several highly conserved putative E2f1 binding sites near the l(2)dtl/cdt2 promoter. Finally, hypomorphic allele combinations of the l(2)dtl/cdt2 gene result in a novel phenotype: viable, low-fertility males. We conclude that "denticleless" is a misnomer, but that l(2)dtl/cdt2 is an essential gene for Drosophila development.

  5. Break-induced ATR and Ddb1-Cul4(Cdt)² ubiquitin ligase-dependent nucleotide synthesis promotes homologous recombination repair in fission yeast

    DEFF Research Database (Denmark)

    Moss, Jennifer; Tinline-Purvis, Helen; Walker, Carol A

    2010-01-01

    Nucleotide synthesis is a universal response to DNA damage, but how this response facilitates DNA repair and cell survival is unclear. Here we establish a role for DNA damage-induced nucleotide synthesis in homologous recombination (HR) repair in fission yeast. Using a genetic screen, we found th...

  6. Collision Induced Galaxy Formation

    CERN Document Server

    Balland, C; Schäffer, R

    1997-01-01

    We present a semi-analytical model in which galaxy collisions and strong tidal interactions, both in the field and during the collapse phase of groups and clusters help determine galaxy morphology. From a semi-analytical analysis based on simulation results of tidal collisions (Aguilar & White 1985), we propose simple rules for energy exchanges during collisions that allow to discriminate between different Hubble types: efficient collisions result in the disruption of disks and substantial star formation, leading to the formation of elliptical galaxies; inefficient collisions allow a large gas reservoir to survive and form disks. Assuming that galaxy formation proceeds in a Omega_0=1 Cold Dark Matter universe, the model both reproduces a number of observations and makes predictions, among which are the redshifts of formation of the different Hubble types in the field. When the model is normalized to the present day abundance of X-ray clusters, the amount of energy exchange needed to produce elliptical gal...

  7. Aspects of dynamical dimensional reduction in multigraph ensembles of CDT

    CERN Document Server

    Giasemidis, Georgios; Zohren, Stefan

    2012-01-01

    We study the continuum limit of a "radially reduced" approximation of Causal Dynamical Triangulations (CDT), so-called multigraph ensembles, and explain why they serve as realistic toy models to study the dimensional reduction observed in numerical simulations of four-dimensional CDT. We present properties of this approximation in two, three and four dimensions comparing them with the numerical simulations and pointing out some common features with 2+1 dimensional Horava-Lifshitz gravity.

  8. The transfer matrix in four-dimensional CDT

    CERN Document Server

    Ambjorn, Jan; Görlich, Andrzej; Jurkiewicz, Jerzy

    2012-01-01

    The Causal Dynamical Triangulation model of quantum gravity (CDT) has a transfer matrix, relating spatial geometries at adjacent (discrete lattice) times. The transfer matrix uniquely determines the theory. We show that the measurements of the scale factor of the (CDT) universe are well described by an effective transfer matrix where the matrix elements are labeled only by the scale factor. Using computer simulations we determine the effective transfer matrix elements and show how they relate to an effective minisuperspace action at all scales.

  9. Outer membrane vesicle-mediated release of cytolethal distending toxin (CDT from Campylobacter jejuni

    Directory of Open Access Journals (Sweden)

    Uhlin Bernt

    2009-10-01

    Full Text Available Abstract Background Background: Cytolethal distending toxin (CDT is one of the well-characterized virulence factors of Campylobacter jejuni, but it is unknown how CDT becomes surface-exposed or is released from the bacterium to the surrounding environment. Results Our data suggest that CDT is secreted to the bacterial culture supernatant via outer membrane vesicles (OMVs released from the bacteria. All three subunits (the CdtA, CdtB, and CdtC proteins were detected by immunogold labeling and electron microscopy of OMVs. Subcellular fractionation of the bacteria indicated that, apart from the majority of CDT detected in the cytoplasmic compartment, appreciable amounts (20-50% of the cellular pool of CDT proteins were present in the periplasmic compartment. In the bacterial culture supernatant, we found that a majority of the extracellular CDT was tightly associated with the OMVs. Isolated OMVs could exert the cell distending effects typical of CDT on a human intestinal cell line, indicating that CDT is present there in a biologically active form. Conclusion Our results strongly suggest that the release of outer membrane vesicles is functioning as a route of C. jejuni to deliver all the subunits of CDT toxin (CdtA, CdtB, and CdtC to the surrounding environment, including infected host tissue.

  10. Characteristics of the new phase in CDT

    CERN Document Server

    Ambjørn, J; Görlich, A; Jurkiewicz, J; Klitgaard, N; Loll, R

    2016-01-01

    Causal Dynamical Triangulations (CDT), a candidate theory of nonperturbative quantum gravity in 4D, turns out to have a rich phase structure. We investigate the recently discovered bifurcation phase $C_b$ and relate some of its characteristics to the presence of singular vertices of very high order. The transition lines separating this phase from the "time-collapsed" $B$-phase and the de Sitter phase $C_{dS}$ are of great interest when searching for physical scaling limits. The work presented here sheds light on the mechanisms behind these transitions. First, we study how the $B$-$C_b$ transition signal depends on the volume-fixing implemented in the simulations, and find results compatible with the previously determined second-order character of the transition. The transition persists in a transfer matrix formulation, where the system's time extension is taken to be minimal. Second, we relate the new $C_b$-$C_{dS}$ transition to the appearance of singular vertices, which leads to a direct physical interpreta...

  11. Distribution of the cytolethal distending toxin A gene (cdtA) among species of Shigella and Vibrio, and cloning and sequencing of the cdt gene from Shigella dysenteriae.

    Science.gov (United States)

    Okuda, J; Kurazono, H; Takeda, Y

    1995-03-01

    We investigated the distribution of the cytolethal distending toxin A gene (cdtA) among S. dysenteriae, Vibrio cholerae 01 and Vibrio parahaemolyticus by polymerase chain reaction (PCR) using primers constructed from the nucleotide sequences of Escherichia coli cdtA gene reported independently by Scott and Kaper (Infect Immun 1994; 62: 244-51) and by Pickett et al. (Infect Immun 1994; 62: 1046-51). The cdtA gene reported by Scott and Kaper was found to occur among eight of the 35 strains of S. dysenteriae but was not found among V. cholerae O1 and V. parahaemolyticus. The cdtA gene reported by Pickett et al. was not found among S. dysenteriae, V. cholerae O1 and V. parahaemolyticus. To further investigate the distribution of the cdtA gene among a large number of Shigella spp. (S. dysenteriae, S. flexneri, S. boydii and S. sonnei), and among Vibrio spp. (Vibrio cholerae O1, V. cholerae O139 and V. parahaemolyticus) by colony hybridization test, we constructed a cdtA gene specific DNA probe by amplifying the cdtA gene by PCR with primers designed from the nucleotide sequence of the cdtA gene reported by Scott and Kaper. The cdtA gene reported by Scott and Kaper was found to occur among eight of the 35 strains of S. dysenteriae and one of the 100 strains of S. sonnei, but was not found among other species of Shigella or among the Vibrio species examined. From one cdtA gene-positive S. dysenteriae strain that showed cytolethal distending toxin (CDT) activity on Chinese hamster ovary cells, we cloned and sequenced the entire cdt gene comprising cdtA, cdtB and cdtC genes.(ABSTRACT TRUNCATED AT 250 WORDS)

  12. Adsorption-induced step formation

    DEFF Research Database (Denmark)

    Thostrup, P.; Christoffersen, Ebbe; Lorensen, Henrik Qvist

    2001-01-01

    Through an interplay between density functional calculations, Monte Carlo simulations and scanning tunneling microscopy experiments, we show that an intermediate coverage of CO on the Pt(110) surface gives rise to a new rough equilibrium structure with more than 50% step atoms. CO is shown to bin...... so strongly to low-coordinated Pt atoms that it can break Pt-Pt bonds and spontaneously form steps on the surface. It is argued that adsorption-induced step formation may be a general effect, in particular at high gas pressures and temperatures....

  13. Crystallization of Escherichia coli CdtB, the biologically active subunit of cytolethal distending toxin

    Science.gov (United States)

    Hontz, Jill S.; Villar-Lecumberri, Maria T.; Dreyfus, Lawrence A.; Yoder, Marilyn D.

    2006-01-01

    Cytolethal distending toxin (CDT) is a secreted protein toxin produced by several bacterial pathogens. The biologically active CDT subunit CdtB is an active homolog of mammalian type I DNase. Internalization of CdtB and subsequent translocation into the nucleus of target cells results in DNA-strand breaks, leading to cell-cycle arrest and apoptosis. CdtB crystals were grown using microbatch methods with polyethylene glycol 8000 as the precipitant. The CdtB crystals contain one molecule of MW 30.5 kDa per asymmetric unit, belong to space group P212121 and diffract to 1.72 Å. PMID:16511299

  14. Pressure induced polymerization of Formates

    Science.gov (United States)

    Tschauner, Oliver

    2004-03-01

    The discovery of pressure induced polymerization of CO2 inspired us to search for C-O based chain structures forming at high pressure. We used salts of carboxylic acids as starting materials and exposed them to pressures between 10 and 30 GPa. Upon heating to temperatures above 1800 K we observed deprotonation and significant changes in the Raman shifts of C-O streching modes. Structure analysis based on powder diffraction patterns collected at sector 16 of the APS showed formation of extended C-O chain structures with the cations of the salts residing in the interchain spaces. These new high pressure polymers are interesting by their mechanical strength and provide basic molecular patterns of organic metallic conductors.

  15. Analytical approaches to 2D CDT coupled to matter

    CERN Document Server

    Atkin, Max R

    2013-01-01

    We review some recent results by Ambjorn et al. (1202.4435) and the authors (1202.4322,1203.5034) in which multicritical points of the CDT matrix model were found and in a particular example identified with a hard dimer model. This identification requires solving the combinatorial problem of counting configurations of dimers on CDTs.

  16. Searching for a Continuum Limit in CDT Quantum Gravity

    CERN Document Server

    Ambjorn, Jan; Gizbert-Studnicki, Jakub; Jurkiewicz, Jerzy

    2016-01-01

    We search for a continuum limit in the causal dynamical triangulation (CDT) approach to quantum gravity by determining the change in lattice spacing using two independent methods. The two methods yield similar results that may indicate how to tune the relevant couplings in the theory in order to take a continuum limit.

  17. CdtR Regulates TcdA and TcdB Production in Clostridium difficile.

    Directory of Open Access Journals (Sweden)

    Shelley A Lyon

    2016-07-01

    Full Text Available Clostridium difficile is a global health burden and the leading cause of antibiotic-associated diarrhoea worldwide, causing severe gastrointestinal disease and death. Three well characterised toxins are encoded by this bacterium in two genetic loci, specifically, TcdB (toxin B and TcdA (toxin A in the Pathogenicity Locus (PaLoc and binary toxin (CDT in the genomically distinct CDT locus (CdtLoc. Toxin production is controlled by regulators specific to each locus. The orphan response regulator, CdtR, encoded within the CdtLoc, up-regulates CDT production. Until now there has been no suggestion that CdtR influences TcdA and TcdB production since it is not carried by all PaLoc-containing strains and CdtLoc is not linked genetically to PaLoc. Here we show that, in addition to CDT, CdtR regulates TcdA and TcdB production but that this effect is strain dependent. Of clinical relevance, CdtR increased the production of TcdA, TcdB and CDT in two epidemic ribotype 027 human strains, modulating their virulence in a mouse infection model. Strains traditionally from animal lineages, notably ribotype 078 strains, are increasingly being isolated from humans and their genetic and phenotypic analysis is critical for future studies on this important pathogen. Here we show that CdtR-mediated toxin regulation did not occur in other strain backgrounds, including a ribotype 078 animal strain. The finding that toxin gene regulation is strain dependent highlights the regulatory diversity between C. difficile isolates and the importance of studying virulence regulation in diverse lineages and clinically relevant strains. Our work provides the first evidence that TcdA, TcdB and CDT production is linked by a common regulatory mechanism and that CdtR may act as a global regulator of virulence in epidemic 027 strains.

  18. Toward standardization of carbohydrate-deficient transferrin (CDT) measurements: III. Performance of native serum and serum spiked with disialotransferrin proves that harmonization of CDT assays is possible.

    Science.gov (United States)

    Weykamp, Cas; Wielders, Jos P M; Helander, Anders; Anton, Raymond F; Bianchi, Vincenza; Jeppsson, Jan-Olof; Siebelder, Carla; Whitfield, John B; Schellenberg, François

    2013-05-01

    Carbohydrate-deficient transferrin (CDT) is a generic term that refers to the transferrin glycoforms whose concentration in blood is temporarily increased by sustained alcohol consumption. Due to high clinical specificity, CDT was proposed as a biomarker of heavy alcohol use and has been available for about 20 years. A number of methods have been developed for CDT measurement based on different analytical techniques and principles and without any harmonization or calibration to a reference method. As a consequence, neither the reference limits nor the cut-off values have been similar across assays, hampering understanding of the diagnostic value of CDT and its routine use. This prompted the International Federation of Clinical Chemistry and Laboratory Medicine (IFCC) to initiate a Working Group on Standardization of CDT (WG-CDT). This third publication of the WG-CDT is devoted to testing the commutability of native and disialotransferrin-spiked serum panels as candidate secondary reference materials, in order to prove the harmonization potential of commercial CDT methods. The results showed that assay harmonization reduced the inter-laboratory imprecision in a network of reference laboratories running the HPLC candidate reference method. In the seven commercial methods evaluated in this study, the use of multi-level secondary calibrators of human serum origin significantly reduced the between-method imprecision. Thus, harmonization of CDT measurements by different methods can be achieved using this calibration system, opening the way for a full standardization of commercial methods against a reference method by use of certified reference materials.

  19. Crystallization of Escherichia coli CdtB, the biologically active subunit of cytolethal distending toxin

    Energy Technology Data Exchange (ETDEWEB)

    Hontz, Jill S.; Villar-Lecumberri, Maria T.; Dreyfus, Lawrence A.; Yoder, Marilyn D., E-mail: yoderm@umkc.edu [Division of Cell Biology and Biophysics, School of Biological Sciences, University of Missouri-Kansas City, 5007 Rockhill Road, Kansas City, MO 64110-2499 (United States)

    2006-03-01

    Cytolethal distending toxin subunit CdtB from E. coli strain 9142-88 was purified and crystallized. Crystals belonging to space group P2{sub 1}2{sub 1}2{sub 1} diffract to a resolution of 1.72 Å. Cytolethal distending toxin (CDT) is a secreted protein toxin produced by several bacterial pathogens. The biologically active CDT subunit CdtB is an active homolog of mammalian type I DNase. Internalization of CdtB and subsequent translocation into the nucleus of target cells results in DNA-strand breaks, leading to cell-cycle arrest and apoptosis. CdtB crystals were grown using microbatch methods with polyethylene glycol 8000 as the precipitant. The CdtB crystals contain one molecule of MW 30.5 kDa per asymmetric unit, belong to space group P2{sub 1}2{sub 1}2{sub 1} and diffract to 1.72 Å.

  20. Geminin deploys multiple mechanisms to regulate Cdt1 before cell division thus ensuring the proper execution of DNA replication

    DEFF Research Database (Denmark)

    Ballabeni, Andrea; Zamponi, Raffaella; Moore, Jodene K

    2013-01-01

    the accumulation of Cdt1 in mitosis, because decreasing the Geminin levels prevents Cdt1 accumulation and impairs DNA replication. Geminin is known to inhibit Cdt1 function; its depletion during G2 leads to DNA rereplication and checkpoint activation. Here we show that, despite rapid Cdt1 protein turnover in G2...

  1. Second- and First-Order Phase Transitions in CDT

    CERN Document Server

    Ambjorn, J; Jurkiewicz, J; Loll, R

    2012-01-01

    Causal Dynamical Triangulations (CDT) is a proposal for a theory of quantum gravity, which implements a path-integral quantization of gravity as the continuum limit of a sum over piecewise flat spacetime geometries. We use Monte Carlo simulations to analyse the phase transition lines bordering the physically interesting de Sitter phase of the four-dimensional CDT model. Using a range of numerical criteria, we present strong evidence that the so-called A-C transition is first order, while the B-C transition is second order. The presence of a second-order transition may be related to an ultraviolet fixed point of quantum gravity and thus provide the key to probing physics at and possibly beyond the Planck scale.

  2. On the Quantum Geometry of Multi-critical CDT

    CERN Document Server

    Atkin, Max R

    2012-01-01

    We extend a recently introduced model of multi-critical CDT to higher multi-critical points. It is observed that the continuum limit can be taken on the level of the action and that the resulting continuum surface model is again described by a matrix model. The resolvent, a simple observable of the quantum geometry which is accessible from the matrix model is calculated for arbitrary multi-critical points. We go beyond the matrix model by determining the propagator using the peeling procedure which is used to extract the effective quantum Hamiltonian and the Hausdorff dimension. With this at hand a string field theory formalism for multi-critical CDT is introduced and it is shown that the Dyson-Schwinger equations match the loop equations of the matrix model. We conclude by commenting on how to formally obtain the sum over topologies and a relation to stochastic quantisation.

  3. A new functional site W115 in CdtA is critical for Aggregatibacter actinomycetemcomitans cytolethal distending toxin.

    Directory of Open Access Journals (Sweden)

    Lu Li

    Full Text Available Aggregatibacter actinomycetemcomitans, a specific pathogen of localized aggressive periodontitis, produces a cytolethal distending toxin (CDT that arrests eukaryotic cells irreversibly in G0/G1 or G2/M phase of the cell cycle. Although structural studies show that the aromatic patch region of CdtA plays an important role in its biological activity, the functional sites of CdtA have not been firmly established. In this study, site-specific mutagenesis strategy was employed for cdtA point mutations construction so as to examine the contributions of individual amino acids to receptor binding and the biological activity of holotoxin. The binding ability was reduced in CdtA(Y181ABC holotoxin and the biological function of CDT was not weaken in CdtA(Y105ABC, CdtA(Y125ABC, CdtA(F109ABC and CdtA(S106NBC holotoxin suggesting that these sites were not critical to CDT. But the binding activity and cell cycle arrest ability of holotoxin complexes were inhibited in CdtA(W115GBC. And this site did not affect the holotoxin assembly by size exclusion chromatography. Therefore, W115 might be a critical site of CdtA binding ability. These findings suggest that the functional sites of CdtA are not only in the aromatic patch region. W115, the new functional site is critical for receptor binding and cell cycle arrest, which provides potential targets for pharmacological disruption of CDT activity.

  4. 2d CDT is 2d Horava-Lifshitz quantum gravity

    DEFF Research Database (Denmark)

    Ambjørn, J.; Glaser, L.; Sato, Y.;

    2013-01-01

    Causal Dynamical Triangulations (CDT) is a lattice theory where aspects of quantum gravity can be studied. Two-dimensional CDT can be solved analytically and the continuum (quantum) Hamiltonian obtained. In this Letter we show that this continuum Hamiltonian is the one obtained by quantizing two......-dimensional projectable Horava-Lifshitz gravity. © 2013....

  5. USP37 deubiquitinates Cdt1 and contributes to regulate DNA replication.

    Science.gov (United States)

    Hernández-Pérez, Santiago; Cabrera, Elisa; Amoedo, Hugo; Rodríguez-Acebes, Sara; Koundrioukoff, Stephane; Debatisse, Michelle; Méndez, Juan; Freire, Raimundo

    2016-10-01

    DNA replication control is a key process in maintaining genomic integrity. Monitoring DNA replication initiation is particularly important as it needs to be coordinated with other cellular events and should occur only once per cell cycle. Crucial players in the initiation of DNA replication are the ORC protein complex, marking the origin of replication, and the Cdt1 and Cdc6 proteins, that license these origins to replicate by recruiting the MCM2-7 helicase. To accurately achieve its functions, Cdt1 is tightly regulated. Cdt1 levels are high from metaphase and during G1 and low in S/G2 phases of the cell cycle. This control is achieved, among other processes, by ubiquitination and proteasomal degradation. In an overexpression screen for Cdt1 deubiquitinating enzymes, we isolated USP37, to date the first ubiquitin hydrolase controlling Cdt1. USP37 overexpression stabilizes Cdt1, most likely a phosphorylated form of the protein. In contrast, USP37 knock down destabilizes Cdt1, predominantly during G1 and G1/S phases of the cell cycle. USP37 interacts with Cdt1 and is able to de-ubiquitinate Cdt1 in vivo and, USP37 is able to regulate the loading of MCM complexes onto the chromatin. In addition, downregulation of USP37 reduces DNA replication fork speed. Taken together, here we show that the deubiquitinase USP37 plays an important role in the regulation of DNA replication. Whether this is achieved via Cdt1, a central protein in this process, which we have shown to be stabilized by USP37, or via additional factors, remains to be tested.

  6. Broadband Visible Light Induced NO Formation

    Science.gov (United States)

    Lubart, Rachel; Eichler, Maor; Friedmann, Harry; Savion, N.; Breitbart, Haim; Ankri, Rinat

    2009-06-01

    Nitric oxide formation is a potential mechanism for photobiomodulation because it is synthesized in cells by nitric oxide synthase (NOS), which contains both flavin and heme, and thus absorbs visible light. The purpose of this work was to study broadband visible light induced NO formation in various cells. Cardiac, endothelial, sperm cells and RAW 264.7 macrophages were illuminated with broadband visible light, 40-130 mW/cm2, 2.4-39 J/cm2, and nitric oxide production was quantified by using the Griess reagent. The results showed that visible light illumination increased NO concentration both in sperm and endothelial cells, but not in cardiac cells. Activation of RAW 264.7 macrophages was very small. It thus appears that NO is involved in photobiomodulation, though different light parameters and illumination protocols are needed to induce NO in various cells.

  7. The effective action in four-dimensional CDT

    CERN Document Server

    Gizbert-Studnicki, Jakub

    2015-01-01

    We present recent results concerning the measurement and analysis of the effective action in four-dimensional Causal Dynamical Triangulations. The action describes quantum fluctuations of the spatial volume of the CDT universe (or alternatively the scale factor) after integrating out other degrees of freedom. We use the covariance of volume fluctuations to measure and parametrize the effective action inside the de Sitter phase, also called the C phase. We show that the action is consistent with a simple discretization of the minisuperspace action (with a reversed overall sign). We discuss possible subleading corrections and show how to construct a more complicated effective action comprising both integer and half-integer discrete proper time layers. We introduce a new method of the effective action measurement based on the transfer matrix. We show that the results of the new method are fully consistent with the covariance matrix method inside the de Sitter phase. We use the new method to measure the effective...

  8. Carbohydrate-deficient transferrin (CDT) as a biomarker in persons suspected of alcohol abuse.

    Science.gov (United States)

    Golka, Klaus; Sondermann, Rolf; Reich, Susanne E; Wiese, Andreas

    2004-06-15

    The coherence of carbohydrate-deficient transferrin (CDT) as a biomarker of alcohol abuse was investigated with 15 conventional laboratory parameters, with the self-reported medical history and with clinical findings, all previously reported to be associated with chronic alcohol intake. In total, 100 male persons who were at least suspected of abusing alcohol were assessed. Medical history, clinical picture and physical examination were taken, and laboratory parameters regarding blood count, liver enzymes, serum lipids, iron balance, Ig A and uric acid were determined. These data were correlated with the CDT values, the daily ethanol intakes reported, and several findings from medical history and clinical examination. The mean CDT level (mean+/-S.D.) of the entire group was 29.4+/-19.7 U/l. Eighty-one patients admitted a daily ethanol intake of 60 g or more. The ratio AST/ALT (de Ritis ratio) appeared as the best conventional parameter correlated with both CDT and ethanol intake. Mean corpuscular volume (MCV), serum iron, AST and red blood cell count also correlated significantly with CDT. CDT, AST and ferritin correlated significantly with the reported daily ethanol intake. It is concluded that CDT provides a reliable estimate of long-term alcohol intake.

  9. Laser filament-induced aerosol formation

    Directory of Open Access Journals (Sweden)

    H. Saathoff

    2012-11-01

    Full Text Available Using the aerosol and cloud simulation chamber AIDA we investigated the laser filament induced particle formation in ambient air, humid synthetic air, humid nitrogen, argon-oxygen mixture, and pure argon in order to simulate the particle formation under realistic atmospheric conditions as well as to investigate the influence of typical gas-phase atmospheric constituents on the particle formation. Terawatt laser plasma filaments generated new particles in the size range 3 to 130 nm with particle production rates ranging from 1 × 107 to 5 × 109 cm−3 plasma s−1. In all cases the particle formation rates increased exponentially with the water content of the gas mixture. Furthermore, the presence of a few ppb of trace gases like SO2 and α-pinene clearly enhanced the particle yield by number, the latter also by mass. Our findings suggest that new particle formation is efficiently supported by acids generated by the photo-ionization of both major and minor components of the air, including N2, NH3, SO2 and organics.

  10. Nanodot formation induced by femtosecond laser irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Abere, M. J.; Kang, M.; Goldman, R. S.; Yalisove, S. M. [Department of Materials Science and Engineering, University of Michigan, Ann Arbor, Michigan 48109 (United States); Chen, C. [Applied Physics Program, University of Michigan, Ann Arbor, Michigan 48109 (United States); Rittman, D. R. [Department of Nuclear Engineering and Radiological Sciences, University of Michigan, Ann Arbor, Michigan 48109 (United States); Phillips, J. D. [Department of Electrical Engineering and Computer Science, University of Michigan, Ann Arbor, Michigan 48109 (United States); Torralva, B. [Department of Atmospheric, Oceanic, and Space Sciences, University of Michigan, Ann Arbor, Michigan 48109 (United States)

    2014-10-20

    The femtosecond laser generation of ZnSe nanoscale features on ZnSe surfaces was studied. Irradiation with multiple exposures produces 10–100 nm agglomerations of nanocrystalline ZnSe while retaining the original single crystal structure of the underlying material. The structure of these nanodots was verified using a combination of scanning transmission electron microscopy, scanning electron microscopy, and atomic force microscopy. The nanodots continue to grow hours after irradiation through a combination of bulk and surface diffusion. We suggest that in nanodot formation the result of ultrafast laser induced point defect formation is more than an order of magnitude below the ZnSe ultrafast melt threshold fluence. This unique mechanism of point defect injection will be discussed.

  11. Development of stapled helical peptides to perturb the Cdt1-Mcm6 interaction.

    Science.gov (United States)

    Lee, Jonghan Peter; Liu, Changdong; Li, Tianlu; Zhu, Guang; Li, Xuechen

    2015-07-01

    Six all-hydrocarbon-stapled Cdt1 MBD-derived peptides have been designed and synthesized to perturb the Cdt1-Mcm6 interaction, which is involved in DNA replication. Inconsistency between the helicity of the obtained peptidomimetics and their binding affinity has been observed. The helicity of 13-amino acid stapled peptides increased, while their binding to Mcm6 was decreased. On the other hand, the 30-amino acid stapled peptides exhibited decreased helicity but increased binding affinity.

  12. Rescuing loading induced bone formation at senescence.

    Directory of Open Access Journals (Sweden)

    Sundar Srinivasan

    Full Text Available The increasing incidence of osteoporosis worldwide requires anabolic treatments that are safe, effective, and, critically, inexpensive given the prevailing overburdened health care systems. While vigorous skeletal loading is anabolic and holds promise, deficits in mechanotransduction accrued with age markedly diminish the efficacy of readily complied, exercise-based strategies to combat osteoporosis in the elderly. Our approach to explore and counteract these age-related deficits was guided by cellular signaling patterns across hierarchical scales and by the insight that cell responses initiated during transient, rare events hold potential to exert high-fidelity control over temporally and spatially distant tissue adaptation. Here, we present an agent-based model of real-time Ca(2+/NFAT signaling amongst bone cells that fully described periosteal bone formation induced by a wide variety of loading stimuli in young and aged animals. The model predicted age-related pathway alterations underlying the diminished bone formation at senescence, and hence identified critical deficits that were promising targets for therapy. Based upon model predictions, we implemented an in vivo intervention and show for the first time that supplementing mechanical stimuli with low-dose Cyclosporin A can completely rescue loading induced bone formation in the senescent skeleton. These pre-clinical data provide the rationale to consider this approved pharmaceutical alongside mild physical exercise as an inexpensive, yet potent therapy to augment bone mass in the elderly. Our analyses suggested that real-time cellular signaling strongly influences downstream bone adaptation to mechanical stimuli, and quantification of these otherwise inaccessible, transient events in silico yielded a novel intervention with clinical potential.

  13. The impact of topology in CDT quantum gravity

    CERN Document Server

    Ambjorn, Jan; Gizbert-Studnicki, Jakub; Goerlich, Andrzej; Jurkiewicz, Jerzy; Nemeth, Daniel

    2016-01-01

    We investigate the impact of spatial topology in 3+1 dimensional Causal Dynamical Triangulations (CDT) by performing numerical simulations with toroidal spatial topology instead of the previously used spherical topology. In the case of spherical spatial topology we observed in the so-called phase C an average spatial volume distribution n(t) which after a suitable time redefinition could be identified as the spatial volume distribution of the four-sphere. Imposing toroidal spatial topology we find that the average spatial volume distribution n(t) is constant. By measuring the covariance matrix of spatial volume fluctuations we determine the form of the effective action. The difference compared to the spherical case is that the effective potential has changed such that it allows a constant average n(t). This is what we observe and this is what one would expect from a minisuperspace GR action where only the scale factor is kept as dynamical variable. Although no background geometry is put in by hand, the full q...

  14. Toxic activity of the CdtB component of Haemophilus ducreyi cytolethal distending toxin expressed from an adenovirus 5 vector.

    Science.gov (United States)

    Wising, Catharina; Magnusson, Maria; Ahlman, Karin; Lindholm, Leif; Lagergård, Teresa

    2010-02-01

    The Haemophilus ducreyi cytolethal distending toxin (HdCDT) catalytic subunit CdtB has DNase-like activity and mediates DNA damage after its delivery into target cells. We constructed a replication-deficient adenovirus type 5 (Ad5) vector expressing CdtB and investigated the toxic properties of this vector on HeLa cells. Ad5CdtB caused loss of cell viability, morphologic changes, and cell cycle arrest, findings similar to HdCDT intoxication. This confirmed that CdtB is responsible for the toxicity of the holotoxin when expressed in cells following transduction by an adenoviral vector, and indicated a possible potential of this novel strategy in studies of activity of intracellular products and in gene therapy of cancer.

  15. REVISITING JOVIAN-RESONANCE INDUCED CHONDRULE FORMATION

    Energy Technology Data Exchange (ETDEWEB)

    Nagasawa, M. [Interactive Research Center of Science, Tokyo Institute of Technology, 2-12-1 Ookayama, Meguro-ku, Tokyo 152-8551 (Japan); Tanaka, K. K.; Tanaka, H. [Institute of Low Temperature Science, Hokkaido University, Kita-19, Nishi-8, Kita-ku, Sapporo 060-0819 (Japan); Nakamoto, T. [Department of Earth and Planetary Sciences, Tokyo Institute of Technology, 2-12-1 Ookayama, Meguro-ku, Tokyo 152-8551 (Japan); Miura, H. [Graduate School of Natural Sciences, Nagoya City University, 1 Yamanohata, Mizuho-cho, Mizuho-ku, Nagoya 467-8501 (Japan); Yamamoto, T., E-mail: nagasawa.m.ad@m.titech.ac.jp [Center for Planetary Science, Kobe University, 7-1-48 Minamimachi, Minatojima, Chuo-ku, Kobe 650-0047 (Japan)

    2014-10-10

    It is proposed that planetesimals perturbed by Jovian mean-motion resonances are the source of shock waves that form chondrules. It is considered that this shock-induced chondrule formation requires the velocity of the planetesimal relative to the gas disk to be on the order of ≳ 7 km s{sup –1} at 1 AU. In previous studies on planetesimal excitation, the effects of Jovian mean-motion resonance together with the gas drag were investigated, but the velocities obtained were at most 8 km s{sup –1} in the asteroid belt, which is insufficient to account for the ubiquitous existence of chondrules. In this paper, we reexamine the effect of Jovian resonances and take into account the secular resonance in the asteroid belt caused by the gravity of the gas disk. We find that the velocities relative to the gas disk of planetesimals a few hundred kilometers in size exceed 12 km s{sup –1}, and that this is achieved around the 3:1 mean-motion resonance. The heating region is restricted to a relatively narrowband between 1.5 AU and 3.5 AU. Our results suggest that chondrules were produced effectively in the asteroid region after Jovian formation. We also find that many planetesimals are scattered far beyond Neptune. Our findings can explain the presence of crystalline silicate in comets if the scattered planetesimals include silicate dust processed by shock heating.

  16. The cytolethal distending toxin-IV cdt coding region in an avian pathogenic Escherichia coli (APEC) strain shows instability and irregular excision pattern.

    Science.gov (United States)

    Tóth, István; Schneider, György

    2015-12-01

    Cytolethal distending toxins (CDT) represent an emerging toxin family, widely distributed among pathogenic bacteria. The cdtABC genes in E. coli are either part of the genome of prophages, plasmid or pathogenicity island. In order to investigate the stability and the transfer potential of cdt-IV genes cdtB gene was replaced by chloramphenicol (Cm) resistance encoding cat gene in the avian pathogenic E. coli (APEC) strain E250. After consecutive passages in non-selective medium at 37 °C 7.6% (219/2900) of the investigated colonies of E250::cat strain became Cm-sensitive (Cm(S)). To reveal deletion mechanism 177 Cm(S) colonies were investigated for presence of cdtA, cdtC and cdtC associated gene by PCR. One hundred and sixteen colonies of the Cm(S) colonies (65.5%) showed partial or complete deletion in the cdt-IV region. Progressive loss of the upstream genes of the cdt cluster in E250 compared to other CDT-IV producing APEC strains and the fact that all the potential deletion patterns were identified, suggests the presence of an unstable hitherto unknown genomic region. The failure of in vitro transfer of cdt genes into a porcine EPEC E. coli strain suggests that the deletion of cdt-IV flanking genes alone do not promote the spread of cdt-IV.

  17. A FAST SEAMLESS HANDOVER SCHEME AND ITS CDT OPTIMIZATION FOR PING-PONG TYPE OF MOVEMENT

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    In mobile IPv6 networks, the ping-pong type of movement brings about frequent handovers andthus increases signaling burden. This letter proposes a fast seamless handover scheme where the access routerkeeps the mobile node's old reservation till the offline Count Down Timer (CDT) expires in order to reducehandover signaling and delay while the mobile node returns in a very short period of time. Based upon a pois-son mobility model, an simple expression for CDT optimization is given out for the scheme to achieve the bestcost performance of resource reservation.

  18. An Analytical Analysis of CDT Coupled to Dimer-like Matter

    CERN Document Server

    Atkin, Max R

    2012-01-01

    We consider a model of restricted dimers coupled to two-dimensional causal dynamical triangulations (CDT), where the dimer configurations are restricted in the sense that they do not include dimers in regions of high curvature. It is shown how the model can be solved analytically using bijections with decorated trees. At a negative critical value for the dimer fugacity the model undergoes a phase transition at which the critical exponent associated to the geometry changes. This represents the first account of an analytical study of a matter model with two-dimensional interactions coupled to CDT.

  19. Isocurvature fluctuations induce early star formation

    NARCIS (Netherlands)

    Sugiyama, N; Zaroubi, S; Silk, J

    2004-01-01

    The early reionization of the Universe inferred from the WMAP polarization results, if confirmed, poses a problem for the hypothesis that scale-invariant adiabatic density fluctuations account for large-scale structure and galaxy formation. One can only generate the required amount of early star for

  20. The Cytolethal Distending Toxin Produced by Nontyphoidal Salmonella Serotypes Javiana, Montevideo, Oranienburg, and Mississippi Induces DNA Damage in a Manner Similar to That of Serotype Typhi

    Science.gov (United States)

    Miller, Rachel A.

    2016-01-01

    ABSTRACT Select nontyphoidal Salmonella enterica (NTS) serotypes were recently found to encode the Salmonella cytolethal distending toxin (S-CDT), an important virulence factor for serotype Typhi, the causative agent of typhoid fever. Using a PCR-based assay, we determined that among 21 NTS serotypes causing the majority of food-borne salmonellosis cases in the United States, genes encoding S-CDT are conserved in isolates representing serotypes Javiana, Montevideo, and Oranienburg but that among serotype Mississippi isolates, the presence of S-CDT-encoding genes is clade associated. HeLa cells infected with representative strains of these S-CDT-positive serotypes had a significantly higher proportion of cells arrested in the G2/M phase than HeLa cells infected with representative strains of S-CDT-negative serotypes Typhimurium, Newport, and Enteritidis. The G2/M cell cycle arrest was dependent on CdtB, the active subunit of S-CDT, as infection with isogenic ΔcdtB mutants abolished their ability to induce a G2/M cell cycle arrest. Infection with S-CDT-encoding serotypes was significantly associated with activation of the host cell’s DNA damage response (DDR), a signaling cascade that is important for detecting and repairing damaged DNA. HeLa cell populations infected with S-CDT-positive serotypes had a significantly higher proportion of cells with DDR protein 53BP1 and γH2AX foci than cells infected with either S-CDT-negative serotypes or isogenic ΔcdtB strains. Intoxication with S-CDT occurred via autocrine and paracrine pathways, as uninfected HeLa cells among populations of infected cells also had an activated DDR. Overall, we show that S-CDT plays a significant role in the cellular outcome of infection with NTS serotypes. PMID:27999166

  1. Ion beam induced stress formation and relaxation in germanium

    Energy Technology Data Exchange (ETDEWEB)

    Steinbach, T., E-mail: Tobias.Steinbach@uni-jena.de [Institut für Festkörperphysik, Friedrich-Schiller-Universität Jena, Max-Wien-Platz 1, D-07743 Jena (Germany); Reupert, A.; Schmidt, E.; Wesch, W. [Institut für Festkörperphysik, Friedrich-Schiller-Universität Jena, Max-Wien-Platz 1, D-07743 Jena (Germany)

    2013-07-15

    Ion irradiation of crystalline solids leads not only to defect formation and amorphization but also to mechanical stress. In the past, many investigations in various materials were performed focusing on the ion beam induced damage formation but only several experiments were done to investigate the ion beam induced stress evolution. Especially in microelectronic devices, mechanical stress leads to several unwanted effects like cracking and peeling of surface layers as well as changing physical properties and anomalous diffusion of dopants. To study the stress formation and relaxation process in semiconductors, crystalline and amorphous germanium samples were irradiated with 3 MeV iodine ions at different ion fluence rates. The irradiation induced stress evolution was measured in situ with a laser reflection technique as a function of ion fluence, whereas the damage formation was investigated by means of Rutherford backscattering spectrometry. The investigations show that mechanical stress builds up at low ion fluences as a direct consequence of ion beam induced point defect formation. However, further ion irradiation causes a stress relaxation which is attributed to the accumulation of point defects and therefore the creation of amorphous regions. A constant stress state is reached at high ion fluences if a homogeneous amorphous surface layer was formed and no further ion beam induced phase transition took place. Based on the results, we can conclude that the ion beam induced stress evolution seems to be mainly dominated by the creation and accumulation of irradiation induced structural modification.

  2. Experimental Signatures of Anomaly Induced DCC Formation

    CERN Document Server

    Asakawa, M; Müller, B

    2002-01-01

    We discuss possible experimental signatures related to the formation of domains of disoriented chiral condensate (DCC) triggered by the axial anomaly in relativistic heavy ion collisions. Our predictions make use of the feature of the anomaly effect that is coherent over a large region of space, but opposite in sign above and below the ion scattering plane. We predict an enhancement of the fraction of neutral pions compared to all pions, which depends on the angle of emission with respect to the scattering plane and is concentrated at small transverse momentum and small rapidity in the center-of-mass frame.

  3. 番茄CDT2同源基因RNA干涉载体的构建及遗传转化研究%Construction and transformation of RNAi vector of tomato homologue CDT2

    Institute of Scientific and Technical Information of China (English)

    李颖楠; 冯媛媛; 刘永胜

    2011-01-01

    真核生物CDT2是CUL4-DDB1 E3泛素复合体的组成部分,在细胞周期调控、DNA复制与损伤修复中起到重要作用.本研究克隆了番茄CDT2同源基因片段并构建了CDT2基因RNA干涉植物表达载体pBI121-CDT2-RNAi.通过根癌农杆菌介导转入番茄子叶,经组织培养成功获得转基因植株.半定量RT-PCR分析显示,转基因植株叶片内CD T2的表达量明显低于野生型植株.转基因植株叶片叶绿素含量比野生型明显升高.该研究结果揭示番茄CDT2基因的功能做出了新的尝试.%The eukaryote CDTZ gene is part of CUL4-DDB1 E3 ubiquitin complex. They play an important role in cell cycle. DNA replication and repair regulation. In this study,homologue CDT2 gene was cloned in tomato and a RNA interference (RNAi) vector of CDT2 was constructed. The construct was introduced into tomato cv. Ailsa Craig by means of Agrobacterium-mediated transformation. Analysis of semi-quantitative RT-PCR revealed a distinct reduction of endogenous CDT2 expression levels in the RNAi transgenic lines compared to that of wild-type plants. The Chlorophyll content of leaves in the RNAi repression lines was significantly elevated. The results show us a new way to modify fruit nutritional quality in tomato through gene engineering.

  4. Debris disc formation induced by planetary growth

    CERN Document Server

    Kobayashi, Hiroshi

    2014-01-01

    Several hundred stars older than 10 million years have been observed to have infrared excesses. These observations are explained by dust grains formed by the collisional fragmentation of hidden planetesimals. Such dusty planetesimal discs are known as debris discs. In a dynamically cold planetesimal disc, collisional coagulation of planetesimals produces planetary embryos which then stir the surrounding leftover planetesimals. Thus, the collisional fragmentation of planetesimals that results from planet formation forms a debris disc. We aim to determine the properties of the underlying planetesimals in debris discs by numerically modelling the coagulation and fragmentation of planetesimal populations. The brightness and temporal evolution of debris discs depend on the radial distribution of planetesimal discs, the location of their inner and outer edges, their total mass, and the size of planetesimals in the disc. We find that a radially narrow planetesimal disc is most likely to result in a debris disc that ...

  5. CDT coupled to dimer matter: An analytical approach via tree bijections

    CERN Document Server

    Atkin, Max R

    2012-01-01

    We review a recently obtained analytical solution of a restricted so-called hard dimers model coupled to two-dimensional CDT. The combinatorial solution is obtained via bijections of causal triangulations with dimers and decorated trees. We show that the scaling limit of this model can also be obtained from a multi-critical point of the transfer matrix for dynamical triangulations of triangles and squares when one disallows for spatial topology changes to occur.

  6. Catalysis of Dialanine Formation by Glycine in the Salt-Induced Peptide Formation Reaction.

    Science.gov (United States)

    Suwannachot, Yuttana; Rode, Bernd M.

    1998-02-01

    Mutual catalysis of amino acids in the salt-induced peptide formation (SIPF) reaction is demonstrated for the case of glycine/alanine. The presence of glycine enhances dialanine formation by a factor up to 50 and enables dialanine formation at much lower alanine concentrations. The actual amounts of glycine play an important role for this catalytic effect, the optimal glycine concentration is 1/8 of the alanine concentration. The mechanism appears to be based on the formation of the intermediate Gly-Ala-Ala tripeptide, connected to one coordination site of copper(II) ion, and subsequent hydrolysis to dialanine and glycine.

  7. Formation of redbacks via accretion induced collapse

    CERN Document Server

    Smedley, Sarah L; Ferrario, Lilia; Wickramasinghe, Dayal T

    2014-01-01

    We examine the growing class of binary millisecond pulsars known as redbacks. In these systems the pulsar's companion has a mass between 0.1 and about 0.5 solar masses in an orbital period of less than 1.5 days. All show extended radio eclipses associated with circumbinary material. They do not lie on the period-companion mass relation expected from the canonical intermediate-mass X-ray binary evolution in which the companion filled its Roche lobe as a red giant and has now lost its envelope and cooled as a white dwarf. The redbacks lie closer to, but usually at higher period than, the period-companion mass relation followed by cataclysmic variables and low-mass X-ray binaries. In order to turn on as a pulsar mass accretion on to a neutron star must be sufficiently weak, considerably weaker than expected in systems with low-mass main-sequence companions driven together by magnetic braking or gravitational radiation. If a neutron star is formed by accretion induced collapse of a white dwarf as it approaches th...

  8. Geometry-induced protein pattern formation.

    Science.gov (United States)

    Thalmeier, Dominik; Halatek, Jacob; Frey, Erwin

    2016-01-19

    Protein patterns are known to adapt to cell shape and serve as spatial templates that choreograph downstream processes like cell polarity or cell division. However, how can pattern-forming proteins sense and respond to the geometry of a cell, and what mechanistic principles underlie pattern formation? Current models invoke mechanisms based on dynamic instabilities arising from nonlinear interactions between proteins but neglect the influence of the spatial geometry itself. Here, we show that patterns can emerge as a direct result of adaptation to cell geometry, in the absence of dynamical instability. We present a generic reaction module that allows protein densities robustly to adapt to the symmetry of the spatial geometry. The key component is an NTPase protein that cycles between nucleotide-dependent membrane-bound and cytosolic states. For elongated cells, we find that the protein dynamics generically leads to a bipolar pattern, which vanishes as the geometry becomes spherically symmetrical. We show that such a reaction module facilitates universal adaptation to cell geometry by sensing the local ratio of membrane area to cytosolic volume. This sensing mechanism is controlled by the membrane affinities of the different states. We apply the theory to explain AtMinD bipolar patterns in [Formula: see text] EcMinDE Escherichia coli. Due to its generic nature, the mechanism could also serve as a hitherto-unrecognized spatial template in many other bacterial systems. Moreover, the robustness of the mechanism enables self-organized optimization of protein patterns by evolutionary processes. Finally, the proposed module can be used to establish geometry-sensitive protein gradients in synthetic biological systems.

  9. Tailored Cyclodextrin Pore Blocker Protects Mammalian Cells from Clostridium difficile Binary Toxin CDT

    Directory of Open Access Journals (Sweden)

    Maurice Roeder

    2014-07-01

    Full Text Available Some Clostridium difficile strains produce, in addition to toxins A and B, the binary toxin Clostridium difficile transferase (CDT, which ADP-ribosylates actin and may contribute to the hypervirulence of these strains. The separate binding and translocation component CDTb mediates transport of the enzyme component CDTa into mammalian target cells. CDTb binds to its receptor on the cell surface, CDTa assembles and CDTb/CDTa complexes are internalised. In acidic endosomes, CDTb mediates the delivery of CDTa into the cytosol, most likely by forming a translocation pore in endosomal membranes. We demonstrate that a seven-fold symmetrical positively charged β-cyclodextrin derivative, per-6-S-(3-aminomethylbenzylthio-β-cyclodextrin, which was developed earlier as a potent inhibitor of the translocation pores of related binary toxins of Bacillus anthracis, Clostridium botulinum and Clostridium perfringens, protects cells from intoxication with CDT. The pore blocker did not interfere with the CDTa-catalyzed ADP-ribosylation of actin or toxin binding to Vero cells but inhibited the pH-dependent membrane translocation of CDTa into the cytosol. In conclusion, the cationic β-cyclodextrin could serve as the lead compound in a development of novel pharmacological strategies against the CDT-producing strains of C. difficile.

  10. Bubble-Induced Star Formation in Dwarf Irregular Galaxies

    CERN Document Server

    Kawata, Daisuke; Barnes, David J; Grand, Robert J J; Rahimi, Awat

    2013-01-01

    To study the star formation and feedback mechanism, we simulate the evolution of an isolated dwarf irregular galaxy (dIrr) in a fixed dark matter halo, similar in size to WLM. We use the new version of our original N-body/smoothed particle chemodynamics code, GCD+, which adopts improved hydrodynamics, metal diffusion between the gas particles and new modelling of star formation and stellar wind and supernovae (SNe) feedback. Comparing the simulations with and without stellar feedback effects, we demonstrate that the collisions of bubbles produced by strong feedback can induce star formation in a more widely spread area. We also demonstrate that the metallicity in star forming regions is kept low due to the mixing of the metal-rich bubbles and the metal-poor inter-stellar medium. Our simulations also suggest that the bubble-induced star formation leads to many counter-rotating stars. The bubble-induced star formation could be a dominant mechanism to maintain star formation in dIrrs, which is different from lar...

  11. Signaling events in pathogen-induced macrophage foam cell formation.

    Science.gov (United States)

    Shaik-Dasthagirisaheb, Yazdani B; Mekasha, Samrawit; He, Xianbao; Gibson, Frank C; Ingalls, Robin R

    2016-08-01

    Macrophage foam cell formation is a key event in atherosclerosis. Several triggers induce low-density lipoprotein (LDL) uptake by macrophages to create foam cells, including infections with Porphyromonas gingivalis and Chlamydia pneumoniae, two pathogens that have been linked to atherosclerosis. While gene regulation during foam cell formation has been examined, comparative investigations to identify shared and specific pathogen-elicited molecular events relevant to foam cell formation are not well documented. We infected mouse bone marrow-derived macrophages with P. gingivalis or C. pneumoniae in the presence of LDL to induce foam cell formation, and examined gene expression using an atherosclerosis pathway targeted plate array. We found over 30 genes were significantly induced in response to both pathogens, including PPAR family members that are broadly important in atherosclerosis and matrix remodeling genes that may play a role in plaque development and stability. Six genes mainly involved in lipid transport were significantly downregulated. The response overall was remarkably similar and few genes were regulated in a pathogen-specific manner. Despite very divergent lifestyles, P. gingivalis and C. pneumoniae activate similar gene expression profiles during foam cell formation that may ultimately serve as targets for modulating infection-elicited foam cell burden, and progression of atherosclerosis.

  12. Suppression of T cell-induced osteoclast formation

    Energy Technology Data Exchange (ETDEWEB)

    Karieb, Sahar; Fox, Simon W., E-mail: Simon.fox@plymouth.ac.uk

    2013-07-12

    Highlights: •Genistein and coumestrol prevent activated T cell induced osteoclast formation. •Anti-TNF neutralising antibodies prevent the pro-osteoclastic effect of activated T cells. •Phytoestrogens inhibit T cell derived TNF alpha and inflammatory cytokine production. •Phytoestrogens have a broader range of anti-osteoclastic actions than other anti-resorptives. -- Abstract: Inhibition of T cell derived cytokine production could help suppress osteoclast differentiation in inflammatory skeletal disorders. Bisphosphonates are typically prescribed to prevent inflammatory bone loss but are not tolerated by all patients and are associated with an increased risk of osteonecrosis of the jaw. In light of this other anti-resorptives such as phytoestrogens are being considered. However the effect of phytoestrogens on T cell-induced osteoclast formation is unclear. The effect of genistein and coumestrol on activated T cell-induced osteoclastogenesis and cytokine production was therefore examined. Concentrations of genistein and coumestrol (10{sup −7} M) previously shown to directly inhibit osteoclast formation also suppressed the formation of TRAP positive osteoclast induced by con A activated T cells, which was dependent on inhibition of T cell derived TNF-α. While both reduced osteoclast formation their mechanism of action differed. The anti-osteoclastic effect of coumestrol was associated with a dual effect on con A induced T cell proliferation and activation; 10{sup −7} M coumestrol significantly reducing T cell number (0.36) and TNF-α (0.47), IL-1β (0.23) and IL-6 (0.35) expression, whereas genistein (10{sup −7} M) had no effect on T cell number but a more pronounced effect on T cell differentiation reducing expression of TNF-α (0.49), IL-1β (0.52), IL-6 (0.71) and RANKL (0.71). Phytoestrogens therefore prevent the pro-osteoclastic action of T cells suggesting they may have a role in the control of inflammatory bone loss.

  13. Laser-induced pattern formation from homogeneous polyisoprene solutions

    Institute of Scientific and Technical Information of China (English)

    Lin Dian-Yang; Li Ming; Wang Shu-Jie; Lü Zhi-Wei

    2008-01-01

    This paper reports that the pattern formation in homogeneous solutions of polyisoprene in toluene saturated with C60 induced by a continuous-wave visible laser is observed experimentally. The transmitted beam patterns change with the increase of the laser irradiation time. In the initial phase, the patterns with concentric ring-shaped structure are formed. In the end, the patterns become speckle-shaped. The incubation time of the transmitted beam widening is inversely proportional to the laser power density and solution concentration. The pattern formation results from the optical-field-induced refractive index changes in the solutions, but the mechanism of optical-field-induced refractive index changes in the polymer solutions needs to be further studied.

  14. CDK1-dependent inhibition of the E3 ubiquitin ligase CRL4CDT2 ensures robust transition from S Phase to Mitosis.

    Science.gov (United States)

    Rizzardi, Lindsay F; Coleman, Kate E; Varma, Dileep; Matson, Jacob P; Oh, Seeun; Cook, Jeanette Gowen

    2015-01-02

    Replication-coupled destruction of a cohort of cell cycle proteins ensures efficient and precise genome duplication. Three proteins destroyed during replication via the CRL4(CDT2) ubiquitin E3 ligase, CDT1, p21, and SET8 (PR-SET7), are also essential or important during mitosis, making their reaccumulation after S phase a critical cell cycle event. During early and mid-S phase and during DNA repair, proliferating cell nuclear antigen (PCNA) loading onto DNA (PCNA(DNA)) triggers the interaction between CRL4(CDT2) and its substrates, resulting in their degradation. We have discovered that, beginning in late S phase, PCNA(DNA) is no longer sufficient to trigger CRL4(CDT2)-mediated degradation. A CDK1-dependent mechanism that blocks CRL4(CDT2) activity by interfering with CDT2 recruitment to chromatin actively protects CRL4(CDT2) substrates. We postulate that deliberate override of replication-coupled destruction allows anticipatory accumulation in late S phase. We further show that (as for CDT1) de novo SET8 reaccumulation is important for normal mitotic progression. In this manner, CDK1-dependent CRL4(CDT2) inactivation contributes to efficient transition from S phase to mitosis.

  15. Structural basis of Mcm2-7 replicative helicase loading by ORC-Cdc6 and Cdt1.

    Science.gov (United States)

    Yuan, Zuanning; Riera, Alberto; Bai, Lin; Sun, Jingchuan; Nandi, Saikat; Spanos, Christos; Chen, Zhuo Angel; Barbon, Marta; Rappsilber, Juri; Stillman, Bruce; Speck, Christian; Li, Huilin

    2017-03-01

    To initiate DNA replication, the origin recognition complex (ORC) and Cdc6 load an Mcm2-7 double hexamer onto DNA. Without ATP hydrolysis, ORC-Cdc6 recruits one Cdt1-bound Mcm2-7 hexamer, thus forming an ORC-Cdc6-Cdt1-Mcm2-7 (OCCM) helicase-loading intermediate. Here we report a 3.9-Å structure of Saccharomyces cerevisiae OCCM on DNA. Flexible Mcm2-7 winged-helix domains (WHDs) engage ORC-Cdc6. A three-domain Cdt1 configuration embraces Mcm2, Mcm4, and Mcm6, thus comprising nearly half of the hexamer. The Cdt1 C-terminal domain extends to the Mcm6 WHD, which binds the Orc4 WHD. DNA passes through the ORC-Cdc6 and Mcm2-7 rings. Origin DNA interaction is mediated by an α-helix within Orc4 and positively charged loops within Orc2 and Cdc6. The Mcm2-7 C-tier AAA+ ring is topologically closed by an Mcm5 loop that embraces Mcm2, but the N-tier-ring Mcm2-Mcm5 interface remains open. This structure suggests a loading mechanism of the first Cdt1-bound Mcm2-7 hexamer by ORC-Cdc6.

  16. Structure formation in the universe from texture induced fluctuation

    CERN Document Server

    Durrer, R; Ruth Durrer; Zhi-hong Zhou

    1995-01-01

    The topic of this letter is structure formation with topological defects. We first present a partially new, fully local and gauge invariant system of perturbation equations to treat microwave background and dark matter fluctuations induced by topological defects (or any other type of seeds). We show that this treatment is extremly well suited for linear numerical analysis of structure formation by applying it to the texture scenario. Our numerical results cover a larger dynamical range than previous investigations and are complementary since we use substantially different methods.

  17. A CDT-Based Heuristic Zone Design Approach for Economic Census Investigators

    Directory of Open Access Journals (Sweden)

    Changixu Cheng

    2015-01-01

    Full Text Available This paper addresses a special zone design problem for economic census investigators that is motivated by a real-world application. This paper presented a heuristic multikernel growth approach via Constrained Delaunay Triangulation (CDT. This approach not only solved the barriers problem but also dealt with the polygon data in zoning procedure. In addition, it uses a new heuristic method to speed up the zoning process greatly on the premise of the required quality of zoning. At last, two special instances for economic census were performed, highlighting the performance of this approach.

  18. Gravitationally induced particle production and its impact on structure formation

    CERN Document Server

    Nunes, Rafael C

    2016-01-01

    In this paper we investigate the influence of a continuous particles creation processes on the linear and nonlinear matter clustering, and its consequences on the weak lensing effect induced by structure formation. We study the line of sight behavior of the contribution to the bispectrum signal at a given angular multipole $l$, showing that the scale where the nonlinear growth overcomes the linear effect depends strongly of particles creation rate.

  19. Induced dicentric chromosome formation promotes genomic rearrangements and tumorigenesis.

    Science.gov (United States)

    Gascoigne, Karen E; Cheeseman, Iain M

    2013-07-01

    Chromosomal rearrangements can radically alter gene products and their function, driving tumor formation or progression. However, the molecular origins and evolution of such rearrangements are varied and poorly understood, with cancer cells often containing multiple, complex rearrangements. One mechanism that can lead to genomic rearrangements is the formation of a "dicentric" chromosome containing two functional centromeres. Indeed, such dicentric chromosomes have been observed in cancer cells. Here, we tested the ability of a single dicentric chromosome to contribute to genomic instability and neoplastic conversion in vertebrate cells. We developed a system to transiently and reversibly induce dicentric chromosome formation on a single chromosome with high temporal control. We find that induced dicentric chromosomes are frequently damaged and mis-segregated during mitosis, and that this leads to extensive chromosomal rearrangements including translocations with other chromosomes. Populations of pre-neoplastic cells in which a single dicentric chromosome is induced acquire extensive genomic instability and display hallmarks of cellular transformation including anchorage-independent growth in soft agar. Our results suggest that a single dicentric chromosome could contribute to tumor initiation.

  20. Nanoparticle formation by ozonolysis of inducible plant volatiles

    Directory of Open Access Journals (Sweden)

    J. Joutsensaari

    2005-01-01

    Full Text Available We present the first laboratory experiments of aerosol formation from oxidation of volatile organic species emitted by living plants, a process which for half a century has been known to take place in the atmosphere. We have treated white cabbage crops with methyl jasmonate in order to induce the production of monoterpenes and certain less-volatile sesqui- and homoterpenes. Ozone was introduced into the growth chamber in which the crops were placed, and the subsequent aerosol formation and growth of aerosols were monitored by measuring the particle size distributions continuously during the experiments. Our observations show similar particle formation rates as in the atmosphere but much higher growth rates. The results indicate that the concentrations of nonvolatile oxidation products of plant released precursors needed to induce the nucleation are roughly an order-of-magnitude higher than their concentrations during atmospheric nucleation events. Our results therefore suggest that atmospheric nucleation events proceed via condensation of oxidized organics on pre-existing molecular clusters rather than via their homogeneous or ion-induced nucleation.

  1. A PCR-RFLP assay to detect and type cytolethal distending toxin (cdt) genes in Campylobacter hyointestinalis

    Science.gov (United States)

    HATANAKA, Noritoshi; KAMEI, Kazumasa; SOMROOP, Srinuan; AWASTHI, Sharda Prasad; ASAKURA, Masahiro; MISAWA, Naoaki; HINENOYA, Atsushi; YAMASAKI, Shinji

    2016-01-01

    Campylobacter hyointestinalis is considered as an emerging zoonotic pathogen. We have recently identified two types of cytolethal distending toxin (cdt) gene in C. hyointestinalis and designated them as Chcdt-I and Chcdt-II. In this study, we developed a PCR-restriction fragment length polymorphism (RFLP) assay that can differentiate Chcdt-I from Chcdt-II. When the PCR-RFLP assay was applied to 17 other Campylobacter strains and 25 non-Campylobacter strains, PCR products were not obtained irrespective of their cdt gene-possession, indicating that the specificity of the PCR-RFLP assay was 100%. In contrast, when the PCR-RFLP assay was applied to 35 C. hyointestinalis strains including 23 analyzed in the previous study and 12 newly isolated from pigs and bovines, all of them showed the presence of cdt genes. Furthermore, a restriction digest by EcoT14-I revealed that 29 strains contained both Chcdt-I and Chcdt-II and 6 strains contained only Chcdt-II, showing 100% sensitivity. Unexpectedly, however, PCR products obtained from 7 C. hyointestinalis strains were not completely digested by EcoT14-I. Nucleotide sequence analysis revealed that the undigested PCR product was homologous to cdtB but not to Chcdt-IB or Chcdt-IIB, indicating the presence of another cdt gene-variant. Then, we further digested the PCR products with DdeI in addition to EcoT14-I, showing that all three cdt genes, including a possible new Chcdt variant, could be clearly differentiated. Thus, the PCR-RFLP assay developed in this study is a valuable tool for evaluating the Chcdt gene-profile of bacteria. PMID:27916784

  2. Impact-Induced Clay Mineral Formation and Distribution on Mars

    Science.gov (United States)

    Rivera-Valentin, E. G.; Craig, P. I.

    2015-01-01

    Clay minerals have been identified in the central peaks and ejecta blankets of impact craters on Mars. Several studies have suggested these clay minerals formed as a result of impact induced hydrothermalism either during Mars' Noachian era or more recently by the melting of subsurface ice. Examples of post-impact clay formation is found in several locations on Earth such as the Mjolnir and Woodleigh Impact Structures. Additionally, a recent study has suggested the clay minerals observed on Ceres are the result of impact-induced hydrothermal processes. Such processes may have occurred on Mars, possibly during the Noachian. Distinguishing between clay minerals formed preor post-impact can be accomplished by studying their IR spectra. In fact, showed that the IR spectra of clay minerals is greatly affected at longer wavelengths (i.e. mid-IR, 5-25 micron) by impact-induced shock deformation while the near-IR spectra (1.0-2.5 micron) remains relatively unchanged. This explains the discrepancy between NIR and MIR observations of clay minerals in martian impact craters noted. Thus, it allows us to determine whether a clay mineral formed from impact-induced hydrothermalism or were pre-existing and were altered by the impact. Here we study the role of impacts on the formation and distribution of clay minerals on Mars via a fully 3-D Monte Carlo cratering model, including impact- melt production using results from modern hydrocode simulations. We identify regions that are conducive to clay formation and the location of clay minerals post-bombardment.

  3. Inactivation of the CRL4-CDT2-SET8/p21 ubiquitylation and degradation axis underlies the therapeutic efficacy of pevonedistat in melanoma

    Directory of Open Access Journals (Sweden)

    Mouadh Benamar

    2016-08-01

    Research in Context: The identification of new molecular targets and effective inhibitors is of utmost significance for the clinical management of melanoma. This study identifies CDT2, a substrate receptor for the CRL4 ubiquitin ligase, as a prognostic marker and therapeutic target in melanoma. CDT2 is required for melanoma cell proliferation and inhibition of CRL4CDT2 by pevonedistat suppresses melanoma in vitro and in vivo through the induction of DNA rereplication and senescence through the stabilization of the CRL4CDT2 substrates p21 and SET8. Pevonedistat also synergizes with vemurafenib in vivo and suppresses vemurafenib-resistant melanoma cells. These findings show a significant promise for targeting CRL4CDT2 therapeutically.

  4. Jet-induced star formation by a microquasar

    CERN Document Server

    Mirabel, I F; Rodriguez, L F; Sauvage, M

    2014-01-01

    Theoretical and observational work show that jets from AGN can trigger star formation. However, in the Milky Way the first -and so far- only clear case of relativistic jets inducing star formation has been found in the surroundings of the microquasar GRS 1915+105. Here we summarize the multiwavelength observations of two compact star formation IRAS sources axisymmetrically located and aligned with the position angle of the sub-arcsec relativistic jets from the stellar black hole binary GRS 1915+105 (Mirabel & Rodriguez 1994). The observations of these two star forming regions at centimeter (Rodriguez & Mirabel 1998), millimeter and infrared (Chaty et al. 2001) wavelengths had suggested -despite the large uncertainties in the distances a decade ago- that the jets from GRS 1915+105 are triggering along the radio jet axis the formation of massive stars in a radio lobe of bow shock structure. Recently, Reid et al.(2014) found that the jet source and the IRAS sources are at the same distance, enhancing the...

  5. Noise induced pattern formation of oscillation growth in traffic flow

    CERN Document Server

    Tian, Junfang; Treiber, Martin

    2016-01-01

    Noise is able to induce diverse patterns in physical and interdisciplinary extended systems. This Letter investigates the role of noise in pattern formation of traffic flow, which is a typical self-driven system far from equilibrium. We demonstrate that noise is necessary to correctly describe the observed spatiotemporal dynamics of growing traffic oscillation in the car following process. A heuristic analysis qualitatively explains the concave growth of the oscillation amplitude along the vehicles of a platoon. Based on this analysis, we propose a simple car-following model containing indifference regions and acceleration noise described by Brownian motion which reproduces well the experimental and empirical observations. Our study indicates that noise might also play an important role in pattern formation in other biological or socio-economic systems that are subject to stochasticity.

  6. Liquid Jet Formation in Laser-Induced Forward Transfer

    Science.gov (United States)

    Brasz, C. Frederik

    Laser-induced forward transfer (LIFT) is a direct-write technique capable of printing precise patterns of a wide variety of materials. In this process, a laser pulse is focused through a transparent support and absorbed in a thin donor film, propelling material onto an adjacent acceptor substrate. For fluid materials, this transfer occurs through the formation of a narrow liquid jet, which eventually pinches off due to surface tension. This thesis examines in detail the fluid mechanics of the jet formation process occurring in LIFT. The main focus is on a variant of LIFT known as blister-actuated LIFT (BA-LIFT), in which the laser pulse is absorbed in an ink-coated polymer layer, rapidly deforming it locally into a blister to induce liquid jet formation. The early-time response of a fluid layer to a deforming boundary is analyzed with a domain perturbation method and potential-flow simulations, revealing scalings for energy and momentum transfer to the fluid and providing physical insight on how and why a jet forms in BA-LIFT. The remaining chapters explore more complex applications and modifications of LIFT. One is the possibility of high-repetition rate printing and limits on time delay and separation between pulses imposed by a tilting effect found for adjacent jets. Another examines a focusing effect achieved by perturbing the interface with ring-shaped disturbances. The third contains an experimental study of LIFT using a silver paste as the donor material instead of a Newtonian liquid. The transfer mechanism is significantly different, although with repeated pulses at one location, a focusing effect is again observed. All three of these chapters investigate how perturbations to the interface can strongly influence the jet formation process.

  7. Formation of step bunches induced by flow in solution

    OpenAIRE

    Inaba, Masashi; Sato, Masahide

    2012-01-01

    We study the formation of step bunches induced by flow in solution during growth. In our previous study [M. Inaba and M. Sato: J. Phys. Soc. Jpn. 80 (2011) 074606], we showed that the step-down flow in solution causes bunching. In this research, we study the dependence of step behavior on some parameters. With a slow flow, the separation and coalescence between steps and bunches occur frequently during step bunching. With increasing flow rate, the frequency decreases and tight bunches are for...

  8. Strangeness production and hypernucleus formation in antiproton induced reactions

    CERN Document Server

    Feng, Zhao-Qing

    2015-01-01

    Formation mechanism of fragments with strangeness in collisions of antiprotons on nuclei has been investigated within the Lanzhou quantum molecular dynamics (LQMD) transport approach combined with a statistical model (GEMINI) for describing the decays of excited fragments. Production of strange particles in the antiproton induced nuclear reactions is modeled within the LQMD model, in which all possible reaction channels such as elastic scattering, annihilation, charge exchange and inelastic scattering in antibaryon-baryon, baryon-baryon and meson-baryon collisions have been included. A coalescence approach is developed for constructing hyperfragments in phase space after de-excitation of nucleonic fragments. The combined approach could describe the production of fragments in low-energy antiproton induced reactions. Hyperfragments are formed within the narrower rapidities and lower kinetic energies. It has advantage to produce heavier hyperfragments and hypernuclides with strangeness s=-2 (double-$\\Lambda$ fra...

  9. Elevated carbohydrate-deficient transferrin (CDT) and its normalization on dietary treatment as a useful biochemical test for hereditary fructose intolerance and galactosemia.

    Science.gov (United States)

    Pronicka, Ewa; Adamowicz, Maciej; Kowalik, Agnieszka; Płoski, Rafał; Radomyska, Barbara; Rogaszewska, Małgorzata; Rokicki, Dariusz; Sykut-Cegielska, Jolanta

    2007-07-01

    Abnormalities in protein glycosylation are reported in fructosemia (HFI) and galactosemia, although, particularly in HFI, the published data are limited to single cases. The purpose was to investigate the usefulness of the carbohydrate-deficient transferrin (CDT) profile for identification and monitoring of these disorders. First we analyzed CDT values before and shortly after the diagnosis in 10 cases of HFI and 17 cases of galactosemia. In all patients, elevated CDT levels were found that significantly (p fructose-restricted diet. We found an elevated CDT level on 104 from 134 tests (mean 11.3 +/- 5.5%, control 1.5%-6.2%). The fructose intake was found to be 90 +/- 70 mg/kg/d, and the diet was unbalanced. A number of patients presented lower height, elevated urinary uric acid excretion, and hypercalciuria. In conclusion, abnormal percentage of CDT (%CDT) values may allow prompt detection of HFI (or galactosemia). Persistence of some abnormalities in HFI on treatment may be caused by trace amounts of fructose ingestion and/or a deficient diet. Regular %CDT measurements are suggested for HFI treatment monitoring.

  10. Laser-induced atomic adsorption: a mechanism for nanofilm formation

    CERN Document Server

    Martins, Weliton S; Oriá, Marcos; Chevrollier, Martine

    2013-01-01

    We demonstrate and interpret a technique of laser-induced formation of thin metallic films using alkali atoms on the window of a dense-vapour cell. We show that this intriguing photo-stimulated process originates from the adsorption of Cs atoms via the neutralisation of Cs$^+$ ions by substrate electrons. The Cs$^+$ ions are produced via two-photon absorption by excited Cs atoms very close to the surface, which enables the transfer of the laser spatial intensity profile to the film thickness. An initial decrease of the surface work function is required to guarantee Cs$^+$ neutralisation and results in a threshold in the vapour density. This understanding of the film growth mechanism may facilitate the development of new techniques of laser-controlled lithography, starting from thermal vapours.

  11. Inducing vortex formation in multilayered circular dots using remanent curves

    Science.gov (United States)

    Kim, Dong-Ok; Ryeol Lee, Dong; Choi, Yongseong; Metlushko, Vitali; Park, Jihwey; Kim, Jae-Young; Bong Lee, Ki

    2012-11-01

    We report field manipulation of magnetic vortex states in Co(30 nm)/Cu(3 nm)/Ni80Fe20 (20 nm)-multilayer dot arrays via remanent curve. The element-resolved resonant x-ray magnetic measurements, combined with micromagnetic simulations, show vortex formation in the Co layer but not in the NiFe layer along the major hysteresis loop. Although the two magnetic layers are not directly coupled due to the presence of the Cu interlayer, the NiFe layer is strongly influenced by the dipolar field from uncompensated magnetic poles in the Co layer. Using remanent curves, we demonstrate that the single vortex state can be induced simultaneously in both layers.

  12. Fibroblast-like synoviocytes induce calcium mineral formation and deposition.

    Science.gov (United States)

    Sun, Yubo; Mauerhan, David R; Franklin, Atiya M; Zinchenko, Natalia; Norton, Harry James; Hanley, Edward N; Gruber, Helen E

    2014-01-01

    Calcium crystals are present in the synovial fluid of 65%-100% patients with osteoarthritis (OA) and 20%-39% patients with rheumatoid arthritis (RA). This study sought to investigate the role of fibroblast-like synoviocytes (FLSs) in calcium mineral formation. We found that numerous genes classified in the biomineral formation process, including bone gamma-carboxyglutamate (gla) protein/osteocalcin, runt-related transcription factor 2, ankylosis progressive homolog, and parathyroid hormone-like hormone, were differentially expressed in the OA and RA FLSs. Calcium deposits were detected in FLSs cultured in regular medium in the presence of ATP and FLSs cultured in chondrogenesis medium in the absence of ATP. More calcium minerals were deposited in the cultures of OA FLSs than in the cultures of RA FLSs. Examination of the micromass stained with nonaqueous alcoholic eosin indicated the presence of birefringent crystals. Phosphocitrate inhibited the OA FLSs-mediated calcium mineral deposition. These findings together suggest that OA FLSs are not passive bystanders but are active players in the pathological calcification process occurring in OA and that potential calcification stimuli for OA FLSs-mediated calcium deposition include ATP and certain unidentified differentiation-inducing factor(s). The OA FLSs-mediated pathological calcification process is a valid target for the development of disease-modifying drug for OA therapy.

  13. Fibroblast-Like Synoviocytes Induce Calcium Mineral Formation and Deposition

    Directory of Open Access Journals (Sweden)

    Yubo Sun

    2014-01-01

    Full Text Available Calcium crystals are present in the synovial fluid of 65%–100% patients with osteoarthritis (OA and 20%–39% patients with rheumatoid arthritis (RA. This study sought to investigate the role of fibroblast-like synoviocytes (FLSs in calcium mineral formation. We found that numerous genes classified in the biomineral formation process, including bone gamma-carboxyglutamate (gla protein/osteocalcin, runt-related transcription factor 2, ankylosis progressive homolog, and parathyroid hormone-like hormone, were differentially expressed in the OA and RA FLSs. Calcium deposits were detected in FLSs cultured in regular medium in the presence of ATP and FLSs cultured in chondrogenesis medium in the absence of ATP. More calcium minerals were deposited in the cultures of OA FLSs than in the cultures of RA FLSs. Examination of the micromass stained with nonaqueous alcoholic eosin indicated the presence of birefringent crystals. Phosphocitrate inhibited the OA FLSs-mediated calcium mineral deposition. These findings together suggest that OA FLSs are not passive bystanders but are active players in the pathological calcification process occurring in OA and that potential calcification stimuli for OA FLSs-mediated calcium deposition include ATP and certain unidentified differentiation-inducing factor(s. The OA FLSs-mediated pathological calcification process is a valid target for the development of disease-modifying drug for OA therapy.

  14. Gibberellin-induced formation of tension wood in angiosperm trees.

    Science.gov (United States)

    Funada, Ryo; Miura, Tatsuhiko; Shimizu, Yousuke; Kinase, Takanori; Nakaba, Satoshi; Kubo, Takafumi; Sano, Yuzou

    2008-05-01

    After gibberellin had been applied to the vertical stems of four species of angiosperm trees for approximately 2 months, we observed eccentric radial growth that was due to the enhanced growth rings on the sides of stems to which gibberellin had been applied. Moreover, the application of gibberellin resulted in the formation of wood fibers in which the thickness of inner layers of cell walls was enhanced. These thickened inner layers of cell walls were unlignified or only slightly lignified. In addition, cellulose microfibrils on the innermost surface of these thickened inner layers of cell walls were oriented parallel or nearly parallel to the longitudinal axis of the fibers. Such thickened inner layers of cell walls had features similar to those of gelatinous layers in the wood fibers of tension wood, which are referred to as gelatinous fibers. Our anatomical and histochemical investigations indicate that the application of gibberellin can induce the formation of tension wood on vertical stems of angiosperm trees in the absence of gravitational stimulus.

  15. SET8 is degraded via PCNA-coupled CRL4(CDT2) ubiquitylation in S phase and after UV irradiation

    DEFF Research Database (Denmark)

    Jørgensen, Stine; Eskildsen, Morten; Fugger, Kasper

    2011-01-01

    . In this study, we show that SET8 is targeted for degradation during S phase by the CRL4(CDT2) ubiquitin ligase in a proliferating cell nuclear antigen (PCNA)-dependent manner. SET8 degradation requires a conserved degron responsible for its interaction with PCNA and recruitment to chromatin where ubiquitylation...... occurs. Efficient degradation of SET8 at the onset of S phase is required for the regulation of chromatin compaction status and cell cycle progression. Moreover, the turnover of SET8 is accelerated after ultraviolet irradiation dependent on the CRL4(CDT2) ubiquitin ligase and PCNA. Removal of SET8...... supports the modulation of chromatin structure after DNA damage. These results demonstrate a novel regulatory mechanism, linking for the first time the ubiquitin-proteasome system with rapid degradation of a histone methyltransferase to control cell proliferation....

  16. CUL4-DDB1-CDT2 E3 Ligase Regulates the Molecular Clock Activity by Promoting Ubiquitination-Dependent Degradation of the Mammalian CRY1.

    Science.gov (United States)

    Tong, Xin; Zhang, Deqiang; Guha, Anirvan; Arthurs, Blake; Cazares, Victor; Gupta, Neil; Yin, Lei

    2015-01-01

    The CUL4-DDB1 E3 ligase complex serves as a critical regulator in various cellular processes, including cell proliferation, DNA damage repair, and cell cycle progression. However, whether this E3 ligase complex regulates clock protein turnover and the molecular clock activity in mammalian cells is unknown. Here we show that CUL4-DDB1-CDT2 E3 ligase ubiquitinates CRY1 and promotes its degradation both in vitro and in vivo. Depletion of the major components of this E3 ligase complex, including Ddb1, Cdt2, and Cdt2-cofactor Pcna, leads to CRY1 stabilization in cultured cells or in the mouse liver. CUL4A-DDB1-CDT2 E3 ligase targets lysine 585 within the C-terminal region of CRY1 protein, shown by the CRY1 585KA mutant's resistance to ubiquitination and degradation mediated by the CUL4A-DDB1 complex. Surprisingly, both depletion of Ddb1 and over-expression of Cry1-585KA mutant enhance the oscillatory amplitude of the Bmal1 promoter activity without altering its period length, suggesting that CUL4A-DDB1-CDT2 E3 targets CRY1 for degradation and reduces the circadian amplitude. All together, we uncovered a novel biological role for CUL4A-DDB1-CDT2 E3 ligase that regulates molecular circadian behaviors via promoting ubiquitination-dependent degradation of CRY1.

  17. Laser-induced jetting and controlled droplet formation

    Science.gov (United States)

    Pascu, Mihail Lucian; Andrei, Ionut Relu; Delville, Jean-Pierre

    2016-12-01

    The article reports, in the general context of developing techniques to generate microjets, nanojets and even individual nanodroplets, a new method to obtain such formations by interaction of a single laser pulse at 532 nm with an individual/single mother droplet in pendant position in open air. The beam energy per pulse is varied between 0.25 and 1 mJ, the focus diameter is 90 μm, and the droplet's volumes are either 3 μl or 3.5 μl. Droplet's shape evolution and jet emission at impact with laser pulse was visualised with a high speed camera working at 10 kfps. Reproducible jets and/or separated microdroplets and nanodroplets are obtained which shows potential for applications in particular in jet printing. It is demonstrated that it becomes possible to play with the geometrical symmetry of both laser excitation and liquid in order to manage the number and the orientation of an induced microjet and consequently to actuate the orientation and the production of nanodroplets by light.

  18. Suilysin-induced Platelet-Neutrophil Complexes Formation is Triggered by Pore Formation-dependent Calcium Influx

    Science.gov (United States)

    Zhang, Shengwei; Zheng, Yuling; Chen, Shaolong; Huang, Shujing; Liu, Keke; Lv, Qingyu; Jiang, Yongqiang; Yuan, Yuan

    2016-01-01

    Platelet activation and platelet–neutrophil interactions have been found to be involved in inflammation, organ failure and soft-tissue necrosis in bacterial infections. Streptococcus suis, an emerging human pathogen, can cause streptococcal toxic-shock syndrome (STSS) similarly to Streptococcus pyogenes. Currently, S. suis–platelet interactions are poorly understood. Here, we found that suilysin (SLY), the S. suis cholesterol-dependent cytolysin (CDC), was the sole stimulus of S. suis that induced platelet-neutrophil complexes (PNC) formation. Furthermore, P-selectin released in α-granules mediated PNC formation. This process was triggered by the SLY-induced pore forming-dependent Ca2+ influx. Moreover, we demonstrated that the Ca2+ influx triggered an MLCK-dependent pathway playing critical roles in P-selectin activation and PNC formation, however, PLC-β-IP3/DAG-MLCK and Rho-ROCK-MLCK signalling were not involved. Additionally, the “outside-in” signalling had a smaller effect on the SLY-induced P-selectin release and PNC formation. Interestingly, other CDCs including pneumolysin and streptolysin O have also been found to induce PNC formation in a pore forming-dependent Ca2+ influx manner. It is possible that the bacterial CDC-mediated PNC formation is a similar response mechanism used by a wide range of bacteria. These findings may provide useful insight for discovering potential therapeutic targets for S. suis-associated STSS. PMID:27830834

  19. Non-canonical CRL4A/4B(CDT2 interacts with RAD18 to modulate post replication repair and cell survival.

    Directory of Open Access Journals (Sweden)

    Sarah Sertic

    Full Text Available The Cullin-4(CDT2 E3 ubiquitin ligase plays an essential role in DNA replication origin licensing directing degradation of several licensing factors at the G1/S transition in order to prevent DNA re-replication. Recently a RAD18-independent role of Cullin-4(CDT2 in PCNA monoubiquitylation has been proposed. In an effort to better understand the function of Cullin-4(CDT2 E3 ubiquitin ligase in mammalian Post-Replication Repair during an unperturbed S-phase, we show that down-regulation of Cullin-4(CDT2 leads to two distinguishable independent phenotypes in human cells that unveil at least two independent roles of Cullin-4(CDT2 in S-phase. Apart from the re-replication preventing activity, we identified a non-canonical Cullin-4(CDT2 complex, containing both CUL4A and CUL4B, associated to the COP9 signalosome, that controls a RAD18-dependent damage avoidance pathway essential during an unperturbed S-phase. Indeed, we show that the non-canonical Cullin-4A/4B(CDT2 complex binds to RAD18 and it is required to modulate RAD18 protein levels onto chromatin and the consequent dynamics of PCNA monoubiquitylation during a normal S-phase. This function prevents replication stress, ATR hyper-signaling and, ultimately, apoptosis. A very similar PRR regulatory mechanism has been recently described for Spartan. Our findings uncover a finely regulated process in mammalian cells involving Post-Replication Repair factors, COP9 signalosome and a non-canonical Cullin4-based E3 ligase which is essential to tolerate spontaneous damage and for cell survival during physiological DNA replication.

  20. Water-Induced Blister Formation in a Thin Film Polymer

    NARCIS (Netherlands)

    Berkelaar, R.P.; Bampoulis, P.; Dietrich, E.; Jansen, H.P.; Zhang, X.; Kooij, E.S.; Lohse, D.; Zandvliet, Harold J.W.

    2015-01-01

    A failure mechanism of thin film polymers immersed in water is presented: the formation of blisters. The growth of blisters is counterintuitive as the substrates were noncorroding and the polymer does not swell in water. We identify osmosis as the driving force behind the blister formation. The dyna

  1. Water induced blister formation in a thin film polymer

    NARCIS (Netherlands)

    Berkelaar, R.P.; Bampoulis, P.; Dietrich, E.; Jansen, H.P.; Zhang, Xuehua; Kooij, E.S.; Lohse, D.; Zandvliet, H.J.W.

    2015-01-01

    A failure mechanism of thin film polymers immersed in water is presented: the formation of blisters. The growth of blisters is counterintuitive as the substrates were noncorroding and the polymer does not swell in water. We identify osmosis as the driving force behind the blister formation. The dyna

  2. Ram pressure induced star formation in Abell 3266

    Science.gov (United States)

    Bonsall, Brittany

    An X-ray observation of the merging galaxy cluster Abell 3266 was obtained via the ROSAT PSPC. This information, along with spectroscopic data from the WIde-field Nearby Galaxy-clusters Survey (i.e. WINGS), were used to investigate whether ram pressure is a mechanism that influences star formation. Galaxies exhibiting ongoing star formation are identified by the presence of strong Balmer lines (Hbeta), known to correspond to early type stars. Older galaxies where a rapid increase in star formation has recently ceased, known as E+A galaxies, are identified by strong Hbeta absorption coupled with little to no [OII] emission. The correlation between recent star formation and "high" ram pressure, as defined by Kapferer et al. (2009) as ≥ 5 x 10-11 dyn cm-2, was tested and lead to a contradiction of the previously held belief that ram pressure influences star formation on the global cluster scale.

  3. Application of a high throughput method of biomarker discovery to improvement of the EarlyCDT(®-Lung Test.

    Directory of Open Access Journals (Sweden)

    Isabel K Macdonald

    Full Text Available BACKGROUND: The National Lung Screening Trial showed that CT screening for lung cancer led to a 20% reduction in mortality. However, CT screening has a number of disadvantages including low specificity. A validated autoantibody assay is available commercially (EarlyCDT®-Lung to aid in the early detection of lung cancer and risk stratification in patients with pulmonary nodules detected by CT. Recent advances in high throughput (HTP cloning and expression methods have been developed into a discovery pipeline to identify biomarkers that detect autoantibodies. The aim of this study was to demonstrate the successful clinical application of this strategy to add to the EarlyCDT-Lung panel in order to improve its sensitivity and specificity (and hence positive predictive value, (PPV. METHODS AND FINDINGS: Serum from two matched independent cohorts of lung cancer patients were used (n = 100 and n = 165. Sixty nine proteins were initially screened on an abridged HTP version of the autoantibody ELISA using protein prepared on small scale by a HTP expression and purification screen. Promising leads were produced in shake flask culture and tested on the full assay. These results were analyzed in combination with those from the EarlyCDT-Lung panel in order to provide a set of re-optimized cut-offs. Five proteins that still displayed cancer/normal differentiation were tested for reproducibility and validation on a second batch of protein and a separate patient cohort. Addition of these proteins resulted in an improvement in the sensitivity and specificity of the test from 38% and 86% to 49% and 93% respectively (PPV improvement from 1 in 16 to 1 in 7. CONCLUSION: This is a practical example of the value of investing resources to develop a HTP technology. Such technology may lead to improvement in the clinical utility of the EarlyCDT--Lung test, and so further aid the early detection of lung cancer.

  4. Induced dicentric chromosome formation promotes genomic rearrangements and tumorigenesis

    OpenAIRE

    Gascoigne, Karen E; Cheeseman, Iain M.

    2013-01-01

    Chromosomal rearrangements can radically alter gene products and their function, driving tumor formation or progression. However, the molecular origins and evolution of such rearrangements are varied and poorly understood, with cancer cells often containing multiple, complex rearrangements. One mechanism that can lead to genomic rearrangements is the formation of a “dicentric” chromosome containing two functional centromeres. Indeed, such dicentric chromosomes have been observed in cancer cel...

  5. Formation of globular clusters induced by external ultraviolet radiation

    CERN Document Server

    Hasegawa, Kenji; Kitayama, Tetsu

    2009-01-01

    We present a novel scenario for globular cluster (GC) formation, where the ultraviolet (UV) background radiation effectively works so as to produce compact star clusters. Here, we explore the formation of GCs in UV radiation fields. For this purpose, we calculate baryon and dark matter (DM) dynamics in spherical symmetry, incorporating the self-shielding effects by solving the radiative transfer of UV radiation. In addition, we prescribe the star formation in cooled gas components and pursue the dynamics of formed stars. As a result, we find that the evolution of subgalactic objects in UV background radiation are separated into three types, that is, (1) prompt star formation, where less massive clouds ~10^{5-8} M_sun are promptly self-shielded and undergo star formation, (2) delayed star formation, where photoionized massive clouds >10^8 M_sun collapse despite high thermal pressure and are eventually self-shielded to form stars in a delayed fashion, and (3) supersonic infall, where photoionized less massive c...

  6. Argon ion beam induced surface pattern formation on Si

    Energy Technology Data Exchange (ETDEWEB)

    Hofsäss, H.; Bobes, O.; Zhang, K. [2nd Institute of Physics, Faculty of Physics, University Göttingen, Friedrich-Hund-Platz 1, 37077 Göttingen (Germany)

    2016-01-21

    The development of self-organized surface patterns on Si due to noble gas ion irradiation has been studied extensively in the past. In particular, Ar ions are commonly used and the pattern formation was analyzed as function of ion incidence angle, ion fluence, and ion energies between 250 eV and 140 keV. Very few results exist for the energy regime between 1.5 keV and 10 keV and it appears that pattern formation is completely absent for these ion energies. In this work, we present experimental data on pattern formation for Ar ion irradiation between 1 keV and 10 keV and ion incidence angles between 50° and 75°. We confirm the absence of patterns at least for ion fluences up to 10{sup 18} ions/cm{sup 2}. Using the crater function formalism and Monte Carlo simulations, we calculate curvature coefficients of linear continuum models of pattern formation, taking into account contribution due to ion erosion and recoil redistribution. The calculations consider the recently introduced curvature dependence of the erosion crater function as well as the dynamic behavior of the thickness of the ion irradiated layer. Only when taking into account these additional contributions to the linear theory, our simulations clearly show that that pattern formation is strongly suppressed between about 1.5 keV and 10 keV, most pronounced at 3 keV. Furthermore, our simulations are now able to predict whether or not parallel oriented ripple patterns are formed, and in case of ripple formation the corresponding critical angles for the whole experimentally studied energies range between 250 eV and 140 keV.

  7. Freeze/thaw-induced embolism: probability of critical bubble formation depends on speed of ice formation

    Directory of Open Access Journals (Sweden)

    Sanna eSevanto

    2012-06-01

    Full Text Available Bubble formation in the conduits of woody plants sets a challenge for uninterrupted water transportation from the soil up to the canopy. Freezing and thawing of stems has been shown to increase the number of air-filled (embolized conduits, especially in trees with large conduit diameters. Despite numerous experimental studies, the mechanisms leading to bubble formation during freezing have not been addressed theoretically. We used classical nucleation theory and fluid mechanics to show which mechanisms are most likely to be responsible for bubble formation during freezing and what parameters determine the likelihood of the process. Our results confirm the common assumption that bubble formation during freezing is most likely due to gas segregation by ice. If xylem conduit walls are not permeable to the salts expelled by ice during the freezing process, osmotic pressures high enough for air seeding could be created. The build-up rate of segregated solutes in front of the ice-water interface depends equally on conduit diameter and freezing velocity. Therefore, bubble formation probability depends on these variables. The dependence of bubble formation probability on freezing velocity means that the experimental results obtained for cavitation threshold conduit diameters during freeze/thaw cycles depend on the experimental setup; namely sample size and cooling rate. The velocity dependence also suggests that to avoid bubble formation during freezing trees should have narrow conduits where freezing is likely to be fast (e.g. branches or outermost layer of the xylem. Avoidance of bubble formation during freezing could thus be one piece of the explanation why xylem conduit size of temperate and boreal zone trees varies quite systematically.

  8. ElectronTransfer Induced Ring Opening of α-Epoxyketones: Spirodioxolane Formation

    Directory of Open Access Journals (Sweden)

    Farzad Nikpour

    2002-01-01

    Full Text Available Stereospecific formation of spirodioxolanes has been observed on electron transfer induced ring opening of α-epoxyketones by 2,4,6-triphenylpyrylium tetrafluoroborate in the presence of cyclohexanone

  9. Comparison of cage and mast with the alcohol markers CDT, gamma-GT, ALAT, ASAT and MCV.

    Science.gov (United States)

    Wetterling, T; Kanitz, R D; Rumpf, H J; Hapke, U; Fischer, D

    1998-01-01

    Many alcoholics deny abuse. To screen greater samples for alcohol dependence, short questionnaires, e.g. the CAGE or MAST are often applied. Frequently laboratory parameters [i.e. 'alcohol markers', such as carbohydrate-deficient transferrin (CDT), gamma-glutamyl transferase or mean corpuscular volume of erythrocytes] are used to support the diagnosis of long-standing heavy alcohol consumption. In this study, the self-ratings (CAGE and MAST) were compared with the above laboratory parameters in an unselected sample of 204 patients admitted to a general hospital. The sensitivities, specificities, and positive (PPV) as well as negative predictive values of the CAGE, the MAST, and the alcohol markers were calculated along with the reported alcohol consumption or the ICD-10 diagnosis as standard. According to recent harmful alcohol consumption levels (women >225 g/week: men >350 g/week), the sensitivities and the PPVs were rather low in all tests (sensitivity 95%) and PPV (about 90%). CDT revealed the best PPV of all alcohol markers (60%). However, the sensitivity of the CAGE, MAST, and the alcohol markers for the ICD-10 diagnosis was rather poor (<60%). This low sensitivity impedes the usefulness of these questionnaires and alcohol markers as screening tests for alcoholism in general hospitals.

  10. EGA Protects Mammalian Cells from Clostridium difficile CDT, Clostridium perfringens Iota Toxin and Clostridium botulinum C2 Toxin.

    Science.gov (United States)

    Schnell, Leonie; Mittler, Ann-Katrin; Sadi, Mirko; Popoff, Michel R; Schwan, Carsten; Aktories, Klaus; Mattarei, Andrea; Azarnia Tehran, Domenico; Montecucco, Cesare; Barth, Holger

    2016-04-01

    The pathogenic bacteria Clostridium difficile, Clostridium perfringens and Clostridium botulinum produce the binary actin ADP-ribosylating toxins CDT, iota and C2, respectively. These toxins are composed of a transport component (B) and a separate enzyme component (A). When both components assemble on the surface of mammalian target cells, the B components mediate the entry of the A components via endosomes into the cytosol. Here, the A components ADP-ribosylate G-actin, resulting in depolymerization of F-actin, cell-rounding and eventually death. In the present study, we demonstrate that 4-bromobenzaldehyde N-(2,6-dimethylphenyl)semicarbazone (EGA), a compound that protects cells from multiple toxins and viruses, also protects different mammalian epithelial cells from all three binary actin ADP-ribosylating toxins. In contrast, EGA did not inhibit the intoxication of cells with Clostridium difficile toxins A and B, indicating a possible different entry route for this toxin. EGA does not affect either the binding of the C2 toxin to the cells surface or the enzyme activity of the A components of CDT, iota and C2, suggesting that this compound interferes with cellular uptake of the toxins. Moreover, for C2 toxin, we demonstrated that EGA inhibits the pH-dependent transport of the A component across cell membranes. EGA is not cytotoxic, and therefore, we propose it as a lead compound for the development of novel pharmacological inhibitors against clostridial binary actin ADP-ribosylating toxins.

  11. CAIPIRINHA-Dixon-TWIST (CDT)-volume-interpolated breath-hold examination (VIBE) for dynamic liver imaging: Comparison of gadoterate meglumine, gadobutrol and gadoxetic acid

    Energy Technology Data Exchange (ETDEWEB)

    Budjan, Johannes, E-mail: Johannes.Budjan@umm.de [Institute of Clinical Radiology and Nuclear Medicine, University Medical Center Mannheim, Medical Faculty Mannheim—Heidelberg University, Mannheim (Germany); Ong, Melissa; Riffel, Philipp [Institute of Clinical Radiology and Nuclear Medicine, University Medical Center Mannheim, Medical Faculty Mannheim—Heidelberg University, Mannheim (Germany); Morelli, John N. [Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, MD (United States); Michaely, Henrik J.; Schoenberg, Stefan O.; Haneder, Stefan [Institute of Clinical Radiology and Nuclear Medicine, University Medical Center Mannheim, Medical Faculty Mannheim—Heidelberg University, Mannheim (Germany)

    2014-11-15

    Highlights: • We examined the influence of different clinically used contrast agents on the image quality of a new sequence called CDT-VIBE for dynamic MRI of the liver. • CDT-VIBE is a robust sequence for clinical routine as it provides good image quality regardless of the utilized contrast agent. • In average, more than 3 hepatic arterial dominant phases are acquired with the CDT-VIBE sequence regardless of the contrast agent. - Abstract: Purpose: CAIPIRINHA-Dixon-TWIST (CDT)-VIBE is a robust method for abdominal magnetic resonance imaging providing both high spatial and high temporal resolution. The purpose of this study was to examine the influence of different gadolinium based contrast agents (GBCA) on image quality (IQ) with CDT-VIBE. Materials and methods: In this IRB-approved, retrospective, inter-individual comparison study, 86 patients scanned at 3T were included. Within 28 s, 14 high-resolution 3D datasets were acquired using CDT-VIBE. 37 patients received 0.1 mmol/kg gadoterate meglumine, 28 patients 0.1 mmol/kg gadobutrol, and 19 patients 0.1 mL/kg gadoxetic acid. Two blinded, board-certified radiologists assessed the image quality on a 5 point scale, as well as the number of hepatic arterial dominant (HAD) phases. Results: Regardless of the GBCA utilized, CDT-VIBE resulted in good IQ in terms of best IQ achieved among all 14 datasets (gadobutrol 4.3, gadoterate meglumine 3.9, gadoxetic acid 3.7). With respect to worst IQ, the three groups showed statistically significant differences with gadobutrol receiving the highest rating (3.6) and gadoxetic acid the lowest (2.4) (gadoterate meglumine 3.0; 0.0014 < p < 0.0485). No statistically significant differences were found in the mean number of acquired HAD phases (gadobutrol 3.4, gadoterate meglumine 3.9, gadoxetic acid 3.1; 0.18 < p < 0.57). Conclusion: Different gadolinium-based contrast agents can be utilized for dynamic liver imaging with CDT-VIBE resulting in good image quality.

  12. Time-resolved measurement of single pulse femtosecond laser-induced periodic surface structure formation

    OpenAIRE

    Kafka, K. R. P.; D. R. Austin; Li, H.; Yi, A; Cheng, J.; Chowdhury, E. A.

    2015-01-01

    Time-resolved diffraction microscopy technique has been used to observe the formation of laser-induced periodic surface structures (LIPSS) from the interaction of a single femtosecond laser pulse (pump) with a nano-scale groove mechanically formed on a single-crystal Cu substrate. The interaction dynamics (0-1200 ps) was captured by diffracting a time-delayed, frequency-doubled pulse from nascent LIPSS formation induced by the pump with an infinity-conjugate microscopy setup. The LIPSS ripple...

  13. Formation of liquid inclusion induced light scatter in KDP (DKDP) crystals

    Institute of Scientific and Technical Information of China (English)

    孙洵; 孙大亮; 许心光; 王正平; 付有君; 王圣来; 曾红; 李毅平; 于锡玲; 高樟寿

    2001-01-01

    We describe in this paper the formation of liquid inclusion induced light scatter in potassium dihydrogen phosphate (KDP) crystal and deuterated potassium dihydrogen phosphate (DKDP) crystals. The measurement has been done with an atomic force microscope (AFM). The mechanism of formation of liquid inclusion scatter has been proposed and the effect of super-saturation discussed.

  14. Spontaneous formation of optically induced surface relief gratings

    CERN Document Server

    Leblond, H; Ahamadi-kandjani, S; Nunzi, J -M; Ortyl, E; Kucharski, S

    2009-01-01

    A model based on Fick's law of diffusion as a phenomenological description of the molecular motion, and on the coupled mode theory, is developped to describe single-beam surface relief grating formation in azopolymers thin films. It allows to explain the mechanism of spontaneous patterning, and self-organization. It allows also to compute the surface relief profile and its evolution in time with good agreement with experiments.

  15. NGC6240: Merger-Induced Star Formation & Gas Dynamics

    CERN Document Server

    Engel, H; Genzel, R; Tacconi, L J; Hicks, E K S; Sturm, E; Naab, T; Johansson, P H; Karl, S J; Max, C E; Medling, A; van der Werf, P P

    2010-01-01

    We present spatially resolved integral field spectroscopic K-band data at a resolution of 0.13" (60pc) and interferometric CO(2-1) line observations of the prototypical merging system NGC6240. Despite the clear rotational signature, the stellar kinematics in the two nuclei are dominated by dispersion. We use Jeans modelling to derive the masses and the mass-to-light ratios of the nuclei. Combining the luminosities with the spatially resolved Br-gamma equivalent width shows that only 1/3 of the K-band continuum from the nuclei is associated with the most recent star forming episode; and that less than 30% of the system's bolometric luminosity and only 9% of its stellar mass is due to this starburst. The star formation properties, calculated from typical merger star formation histories, demonstrate the impact of different assumptions about the star formation history. The properties of the nuclei, and the existence of a prominent old stellar population, indicate that the nuclei are remnants of the progenitor gal...

  16. Aflatoxin B1 Induces Reactive Oxygen Species-Mediated Autophagy and Extracellular Trap Formation in Macrophages

    Science.gov (United States)

    An, Yanan; Shi, Xiaochen; Tang, Xudong; Wang, Yang; Shen, Fengge; Zhang, Qiaoli; Wang, Chao; Jiang, Mingguo; Liu, Mingyuan; Yu, Lu

    2017-01-01

    Aflatoxins are a group of highly toxic mycotoxins with high carcinogenicity that are commonly found in foods. Aflatoxin B1 (AFB1) is the most toxic member of the aflatoxin family. A recent study reported that AFB1 can induce autophagy, but whether AFB1 can induce extracellular traps (ETs) and the relationships among innate immune responses, reactive oxygen species (ROS), and autophagy and the ETs induced by AFB1 remain unknown. Here, we demonstrated that AFB1 induced a complete autophagic process in macrophages (MΦ) (THP-1 cells and RAW264.7 cells). In addition, AFB1 induced the generation of MΦ ETs (METs) in a dose-dependent manner. In particular, the formation of METs significantly reduced the AFB1 content. Further analysis using specific inhibitors showed that the inhibition of either autophagy or ROS prevented MET formation caused by AFB1, indicating that autophagy and ROS were required for AFB1-induced MET formation. The inhibition of ROS prevented autophagy, indicating that ROS generation occurred upstream of AFB1-induced autophagy. Taken together, these data suggest that AFB1 induces ROS-mediated autophagy and ETs formation and an M1 phenotype in MΦ. PMID:28280716

  17. Radiation-induced defect formation in chalcogenide glasses

    Energy Technology Data Exchange (ETDEWEB)

    Shpotyuk, O.I.; Filipecki, J. [Physics Institute of Pedagogical University of Czestochowa, Al. Armii Krajowej 13/15, Czestochowa 42201 (Poland); Kozdras, A. [Physics Laboratory of Opole Technical University, 75 ul. Ozimska, Opole, PL-45370 (Poland); Kavetskyy, T.S. [Lviv Scientific Research Institute of Materials of Scientific Research Company ' Carat' , Stryjska Str. 202, Lviv, UA-79031 (Ukraine)

    2003-10-01

    The modified model of native and radiation-induced microvoid-type positron traps in vitreous chalcogenide semiconductors is developed to explain compositional features of positron annihilation lifetime measurements in stoichiometric As{sub 2}S{sub 3}-GeS{sub 2} and non-stoichiometric As{sub 2}S{sub 3}-Ge{sub 2}S{sub 3} chalcogenide glasses before and after {gamma}-irradiation.

  18. Flow induced streamer formation in particle laden complex flows

    Science.gov (United States)

    Debnath, Nandini; Hassanpourfard, Mahtab; Ghosh, Ranajay; Trivedi, Japan; Thundat, Thomas; Kumar, Aloke

    2016-11-01

    We study the combined flow of a polyacrylamide (PAM)solution with polystyrene (PS) nanoparticles, through a microfluidic device containing an array of micropillars. The flow is characterized by a very low Reynolds number (Re= 20), PS nanoparticles localize near pillar walls to form thin slender string-like structures, which we call 'streamers' due to their morphology. Post-formation, these streamers show significant viscous behavior for short observational time-scales, and at longer observational time scales elastic response dominates. Our abiotic streamers could provide a framework for understanding similar structures that often form in biological systems. PhD student, Department of Mechanical Engineering.

  19. Polarization force-induced changes in the dust sheath formation

    Energy Technology Data Exchange (ETDEWEB)

    Mayout, Saliha; Bentabet, Karima; Tribeche, Mouloud [Plasma Physics Group (PPG), Theoretical Physics Laboratory (TPL), Faculty of Physics, University of Bab-Ezzouar, USTHB, BP 32, El Alia, Algiers 16111 (Algeria)

    2015-09-15

    The modifications arising in the dusty plasma sheath structure due to the presence of polarization forces acting on the dust grains are investigated. The corresponding appropriate Bohm criterion for sheath formation is obtained. It is found that the critical Mach number, beyond which the dusty plasma electrostatic sheath sets in, decreases whenever the polarization effects become important. In addition, when the polarization force dominates over the electrical one, the dust plasma sheath cannot set in. This happens whenever the dust grain size exceeds a critical threshold. Moreover, the sheath electrostatic potential-gradient becomes abruptly steep, and the sheath thickness becomes broader as the polarization force effects strengthen.

  20. Flare induced penumbra formation in the sunspot of NOAA 10838

    OpenAIRE

    Padinhatteeri, Sreejith; K., Sankarasubramanian

    2010-01-01

    We have observed formation of penumbrae on a pore in the active region NOAA10838 using Dunn Solar Telescope at NSO,Sunpot,USA. Simultaneous observations using different instruments (DLSP,UBF,Gband and CaK) provide us with vector magnetic field at photosphere, intensity images and Doppler velocity at different heights from photosphere to chromosphere. Results from our analysis of this particular data-set suggests that penumbrae are formed as a result of relaxation of magnetic field due to a fl...

  1. BMP9-Induced Osteogenetic Differentiation and Bone Formation of Muscle-Derived Stem Cells

    Directory of Open Access Journals (Sweden)

    Li Xiang

    2012-01-01

    Full Text Available Efficient osteogenetic differentiation and bone formation from muscle-derived stem cells (MDSCs should have potential clinical applications in treating nonunion fracture healing or bone defects. Here, we investigate osteogenetic differentiation ability of MDSCs induced by bone morphogenetic protein 9 (BMP9 in vitro and bone formation ability in rabbit radius defects repairing model. Rabbit's MDSCs were extracted by type I collagenase and trypsin methods, and BMP9 was introduced into MDSCs by infection with recombinant adenovirus. Effects of BMP9-induced osteogenetic differentiation of MDSCs were identified with alkaline phosphatase (ALP activity and expression of later marker. In stem-cell implantation assay, MDSCs have also shown valuable potential bone formation ability induced by BMP9 in rabbit radius defects repairing test. Taken together, our findings suggest that MDSCs are potentiated osteogenetic stem cells which can be induced by BMP9 to treat large segmental bone defects, nonunion fracture, and/or osteoporotic fracture.

  2. Field-induced layer formation in dipolar nanofilms.

    Science.gov (United States)

    Jordanovic, Jelena; Klapp, Sabine H L

    2008-07-18

    Using molecular dynamics simulations, we demonstrate that the layering of confined colloidal particles with dipolar interactions, such as ferrofluids, in slablike geometries can be controlled by homogeneous external fields. For suitable surface separations, strong fields directed perpendicular to the film plane do not only align the particles but create additional layers in the system. The reverse effect occurs with an in-plane field which can induce a collapse of layers. Both effects are accompanied by pronounced particle rearrangements in lateral directions. Our simulation results are consistent with recent experiments of ferrofluids at surfaces.

  3. Induced sclerotium formation exposes new bioactive metabolites from Aspergillus sclerotiicarbonarius.

    Science.gov (United States)

    Petersen, Lene M; Frisvad, Jens C; Knudsen, Peter B; Rohlfs, Marko; Gotfredsen, Charlotte H; Larsen, Thomas O

    2015-10-01

    Sclerotia are known to be fungal survival structures, and induction of sclerotia may prompt production of otherwise undiscovered metabolites. Aspergillus sclerotiicarbonarius (IBT 28362) was investigated under sclerotium producing conditions, which revealed a highly altered metabolic profile. Four new compounds were isolated from cultivation under sclerotium formation conditions and their structures elucidated using different analytical techniques (HRMS, UV, 1D and 2D NMR). This included sclerolizine, an alkylated and oxidized pyrrolizine, the new emindole analog emindole SC and two new carbonarins; carbonarins I and J. We have identified the three latter as true sclerotial metabolites. All metabolites were tested for antifungal and antiinsectan activity, and sclerolizine and carbonarin I displayed antifungal activity against Candida albicans, while all four showed antiinsectan activity. These results demonstrate induction of sclerotia as an alternative way of triggering otherwise silent biosynthetic pathways in filamentous fungi for the discovery of novel bioactive secondary metabolites.

  4. Flare induced penumbra formation in the sunspot of NOAA 10838

    CERN Document Server

    Padinhatteeri, Sreejith

    2010-01-01

    We have observed formation of penumbrae on a pore in the active region NOAA10838 using Dunn Solar Telescope at NSO,Sunpot,USA. Simultaneous observations using different instruments (DLSP,UBF,Gband and CaK) provide us with vector magnetic field at photosphere, intensity images and Doppler velocity at different heights from photosphere to chromosphere. Results from our analysis of this particular data-set suggests that penumbrae are formed as a result of relaxation of magnetic field due to a flare happening at the same time. Images in \\Halpha\\ show the flare (C 2.9 as per GOES) and vector magnetic fields show a re-orientation and reduction in the global $\\alpha$ value (a measure of twist). We feel such relaxation of loop structures due to reconnections or flare could be one of the way by which field lines fall back to the photosphere to form penumbrae.

  5. Bacteraemia with Campylobacter jejuni: no association with the virulence genes iam, cdtB, capA or virB.

    Science.gov (United States)

    Nielsen, H; Persson, S; Olsen, K E P; Ejlertsen, T; Kristensen, B; Schønheyder, H C

    2010-03-01

    The role of bacterial genes in the determination of the clinical spectrum of Campylobacter jejuni infection is unclear. We compared clinical isolates from invasive blood-stream infection with stool isolates from gastroenteritis and found no association of the putative virulence genes iam, capA, virB and cdtB with clinical presentation.

  6. Secondary aerosol formation from stress-induced biogenic emissions and possible climate feedbacks

    Directory of Open Access Journals (Sweden)

    Th. F. Mentel

    2013-09-01

    Full Text Available Atmospheric aerosols impact climate by scattering and absorbing solar radiation and by acting as ice and cloud condensation nuclei. Biogenic secondary organic aerosols (BSOAs comprise an important component of atmospheric aerosols. Biogenic volatile organic compounds (BVOCs emitted by vegetation are the source of BSOAs. Pathogens and insect attacks, heat waves and droughts can induce stress to plants that may impact their BVOC emissions, and hence the yield and type of formed BSOAs, and possibly their climatic effects. This raises questions of whether stress-induced changes in BSOA formation may attenuate or amplify effects of climate change. In this study we assess the potential impact of stress-induced BVOC emissions on BSOA formation for tree species typical for mixed deciduous and Boreal Eurasian forests. We studied the photochemical BSOA formation for plants infested by aphids in a laboratory setup under well-controlled conditions and applied in addition heat and drought stress. The results indicate that stress conditions substantially modify BSOA formation and yield. Stress-induced emissions of sesquiterpenes, methyl salicylate, and C17-BVOCs increase BSOA yields. Mixtures including these compounds exhibit BSOA yields between 17 and 33%, significantly higher than mixtures containing mainly monoterpenes (4–6% yield. Green leaf volatiles suppress SOA formation, presumably by scavenging OH, similar to isoprene. By classifying emission types, stressors and BSOA formation potential, we discuss possible climatic feedbacks regarding aerosol effects. We conclude that stress situations for plants due to climate change should be considered in climate–vegetation feedback mechanisms.

  7. Glycation of Wild-Type Apomyoglobin Induces Formation of Highly Cytotoxic Oligomeric Species.

    Science.gov (United States)

    Iannuzzi, Clara; Carafa, Vincenzo; Altucci, Lucia; Irace, Gaetano; Borriello, Margherita; Vinciguerra, Roberto; Sirangelo, Ivana

    2015-11-01

    Protein glycation is a non-enzymatic, irreversible modification of protein amino groups by reactive carbonyl species leading to the formation of advanced glycation end products (AGEs). Several proteins implicated in neurodegenerative diseases have been found to be glycated in vivo and the extent of glycation is related to the pathologies of the patients. Although it is now accepted that there is a direct correlation between AGEs formation and the development of neurodegenerative diseases related to protein misfolding and amyloid aggregation, several questions still remain unanswered: whether glycation is the triggering event or just an additional factor acting on the aggregation pathway. We have recently shown that glycation of the amyloidogenic W7FW14F apomyoglobin mutant significantly accelerates the amyloid fibrils formation providing evidence that glycation actively participates to the process. In the present study, to test if glycation can be considered also a triggering factor in amyloidosis, we evaluated the ability of different glycation agents to induce amyloid aggregation in the soluble wild-type apomyoglobin. Our results show that glycation covalently modifies apomyoglobin and induces conformational changes that lead to the formation of oligomeric species that are not implicated in amyloid aggregation. Thus, AGEs formation does not trigger amyloid aggregation in the wild-type apomyoglobin but only induce the formation of soluble oligomeric species able to affect cell viability. The molecular bases of cell toxicity induced by AGEs formed upon glycation of wild-type apomyoglobin have been also investigated.

  8. Fibrinogen-Induced Streptococcus mutans Biofilm Formation and Adherence to Endothelial Cells

    Directory of Open Access Journals (Sweden)

    Telma Blanca Lombardo Bedran

    2013-01-01

    Full Text Available Streptococcus mutans, the predominant bacterial species associated with dental caries, can enter the bloodstream and cause infective endocarditis. The aim of this study was to investigate S. mutans biofilm formation and adherence to endothelial cells induced by human fibrinogen. The putative mechanism by which biofilm formation is induced as well as the impact of fibrinogen on S. mutans resistance to penicillin was also evaluated. Bovine plasma dose dependently induced biofilm formation by S. mutans. Of the various plasma proteins tested, only fibrinogen promoted the formation of biofilm in a dose-dependent manner. Scanning electron microscopy observations revealed the presence of complex aggregates of bacterial cells firmly attached to the polystyrene support. S. mutans in biofilms induced by the presence of fibrinogen was markedly resistant to the bactericidal effect of penicillin. Fibrinogen also significantly increased the adherence of S. mutans to endothelial cells. Neither S. mutans cells nor culture supernatants converted fibrinogen into fibrin. However, fibrinogen is specifically bound to the cell surface of S. mutans and may act as a bridging molecule to mediate biofilm formation. In conclusion, our study identified a new mechanism promoting S. mutans biofilm formation and adherence to endothelial cells which may contribute to infective endocarditis.

  9. Graphene-Induced Pore Formation on Cell Membranes

    Science.gov (United States)

    Duan, Guangxin; Zhang, Yuanzhao; Luan, Binquan; Weber, Jeffrey K.; Zhou, Royce W.; Yang, Zaixing; Zhao, Lin; Xu, Jiaying; Luo, Judong; Zhou, Ruhong

    2017-01-01

    Examining interactions between nanomaterials and cell membranes can expose underlying mechanisms of nanomaterial cytotoxicity and guide the design of safer nanomedical technologies. Recently, graphene has been shown to exhibit potential toxicity to cells; however, the molecular processes driving its lethal properties have yet to be fully characterized. We here demonstrate that graphene nanosheets (both pristine and oxidized) can produce holes (pores) in the membranes of A549 and Raw264.7 cells, substantially reducing cell viability. Electron micrographs offer clear evidence of pores created on cell membranes. Our molecular dynamics simulations reveal that multiple graphene nanosheets can cooperate to extract large numbers of phospholipids from the membrane bilayer. Strong dispersion interactions between graphene and lipid-tail carbons result in greatly depleted lipid density within confined regions of the membrane, ultimately leading to the formation of water-permeable pores. This cooperative lipid extraction mechanism for membrane perforation represents another distinct process that contributes to the molecular basis of graphene cytotoxicity. PMID:28218295

  10. Flow-Induced Control of Pattern Formation in Chemical Systems

    Science.gov (United States)

    Berenstein, Igal; Beta, Carsten

    Since Alan Turing's seminal paper in 1952, the study of spatio-temporal patterns that arise in systems of reacting and diffusing components has grown into an immense and vibrant realm of scientific research. This field includes not only chemical systems but spans many areas of science as diverse as cell and developmental biology, ecology, geosciences, or semiconductor physics. For several decades research in this field has concentrated on the vast variety of patterns that can emerge in reaction-diffusion systems and on the underlying instabilities. In the 1990s, stimulated by the pioneering work of Ott, Grebogi and Yorke, control of pattern formation arose as a new topical focus and gradually developed into an entire new field of research. On the one hand, research interests concentrated on control and suppression of undesired dynamical states, in particular on control of chaos. On the other hand, the design and engineering of particular space-time patterns became a major focus in this field that motivates ongoing scientific effort until today...

  11. Cooling-induced structure formation and evolution in collapsars

    CERN Document Server

    Batta, Aldo

    2013-01-01

    The collapse of massive rotating stellar cores and the associated accretion onto the newborn compact object is thought to power long gamma ray bursts (GRBs). The physical scale and dynamics of the accretion disk are initially set by the angular momentum distribution in the progenitor, and the physical conditions make neutrino emission the main cooling agent in the flow. The formation and evolution of structure in these disks is potentially very relevant for the energy release and its time variability, which ultimately imprint on the observed GRB properties. To begin to characterize these, taking into account the three dimensional nature of the problem, we have carried out an initial set of calculations of the collapse of rotating polytropic cores in three dimensions, making use of a pseudo-relativistic potential and a simplified cooling prescription. We focus on the effects of self gravity and cooling on the overall morphology and evolution of the flow for a given rotation rate in the context of the collapsar...

  12. The LuxS based quorum sensing governs lactose induced biofilm formation by Bacillus subtilis

    Directory of Open Access Journals (Sweden)

    Danielle eDuanis-Assaf

    2016-01-01

    Full Text Available Bacillus species present a major concern in the dairy industry as they can form biofilms in pipelines and on surfaces of equipment and machinery used in the entire line of production. These biofilms represent a continuous hygienic problem and can lead to serious economic losses due to food spoilage and equipment impairment. Biofilm formation by Bacillus subtilis is apparently dependent on LuxS quorum sensing (QS by Autoinducer-2 (AI-2. However, the link between sensing environmental cues and AI-2 induced biofilm formation remains largely unknown. The aim of this study is to investigate the role of lactose, the primary sugar in milk, on biofilm formation by B. subtilis and its possible link to QS processes. Our phenotypic analysis shows that lactose induces formation of biofilm bundles as well as formation of colony type biofilms. Furthermore, using reporter strain assays, we observed an increase in AI-2 production by B. subtilis in response to lactose in a dose dependent manner. Moreover, we found that expression of eps and tapA operons, responsible for extracellular matrix synthesis in B. subtilis, were notably up-regulated in response to lactose. Importantly, we also observed that LuxS is essential for B. subtilis biofilm formation in the presence of lactose. Overall, our results suggest that lactose may induce biofilm formation by B. subtilis through the LuxS pathway.

  13. Novel Resorbable and Osteoconductive Calcium Silicophosphate Scaffold Induced Bone Formation

    Directory of Open Access Journals (Sweden)

    Patricia Ros-Tárraga

    2016-09-01

    Full Text Available This aim of this research was to develop a novel ceramic scaffold to evaluate the response of bone after ceramic implantation in New Zealand (NZ rabbits. Ceramics were prepared by the polymer replication method and inserted into NZ rabbits. Macroporous scaffolds with interconnected round-shaped pores (0.5–1.5 mm = were prepared. The scaffold acted as a physical support where cells with osteoblastic capability were found to migrate, develop processes, and newly immature and mature bone tissue colonized on the surface (initially and in the material’s interior. The new ceramic induced about 62.18% ± 2.28% of new bone and almost complete degradation after six healing months. An elemental analysis showed that the gradual diffusion of Ca and Si ions from scaffolds into newly formed bone formed part of the biomaterial’s resorption process. Histological and radiological studies demonstrated that this porous ceramic scaffold showed biocompatibility and excellent osteointegration and osteoinductive capacity, with no interposition of fibrous tissue between the implanted material and the hematopoietic bone marrow interphase, nor any immune response after six months of implantation. No histological changes were observed in the various organs studied (para-aortic lymph nodes, liver, kidney and lung as a result of degradation products being released.

  14. Toward standardization of carbohydrate-deficient transferrin (CDT) measurements: II. Performance of a laboratory network running the HPLC candidate reference measurement procedure and evaluation of a candidate reference material.

    Science.gov (United States)

    Helander, Anders; Wielders, Jos P M; Jeppsson, Jan-Olof; Weykamp, Cas; Siebelder, Carla; Anton, Raymond F; Schellenberg, François; Whitfield, John B

    2010-11-01

    Carbohydrate-deficient transferrin (CDT) is a descriptive term used for a temporary change in the transferrin glycosylation profile caused by alcohol, and used as a biomarker of chronic high alcohol consumption. The use of an array of methods for measurement of CDT in various absolute or relative amounts, and sometimes covering different transferrin glycoforms, has complicated the comparability of results and caused confusion among medical staff. This situation prompted initiation of an IFCC Working Group on CDT standardization. This second publication of the WG-CDT covers the establishment of a network of reference laboratories running a high-performance liquid chromatography (HPLC) candidate reference measurement procedure, and evaluation of candidate secondary reference materials. The network laboratories demonstrated good and reproducible performance and thus can be used to assign target values for calibrators and controls. A candidate secondary reference material based on native human serum lyophilized with a cryo-/lyoprotectant to prevent protein denaturation was found to be commutable and stable during storage. A proposed strategy for calibration of different CDT methods is also presented. In an external quality assurance study involving 66 laboratories and covering the current routine CDT assays (HPLC, capillary electrophoresis and immunoassay), recalculation of observed results based on the nominal values for the candidate calibrator reduced the overall coefficient of variation from 18.9% to 5.5%. The logistics for distribution of reference materials and review of results were found to be functional, indicating that a full reference system for CDT may soon be available.

  15. Time-resolved measurement of single pulse femtosecond laser-induced periodic surface structure formation

    CERN Document Server

    Kafka, K R P; Li, H; Yi, A; Cheng, J; Chowdhury, E A

    2015-01-01

    Time-resolved diffraction microscopy technique has been used to observe the formation of laser-induced periodic surface structures (LIPSS) from the interaction of a single femtosecond laser pulse (pump) with a nano-scale groove mechanically formed on a single-crystal Cu substrate. The interaction dynamics (0-1200 ps) was captured by diffracting a time-delayed, frequency-doubled pulse from nascent LIPSS formation induced by the pump with an infinity-conjugate microscopy setup. The LIPSS ripples are observed to form sequentially outward from the groove edge, with the first one forming after 50 ps. A 1-D analytical model of electron heating and surface plasmon polariton (SPP) excitation induced by the interaction of incoming laser pulse with the groove edge qualitatively explains the time-evloution of LIPSS formation.

  16. Ion-induced pattern formation on indium tin oxide for alignment of liquid crystals

    Energy Technology Data Exchange (ETDEWEB)

    Škereň, T., E-mail: tomas.skeren@fjfi.cvut.cz [Instituut voor Kern-en Stralingsfysica, KU Leuven, Celestijnenlaan 200D, B-3001 Leuven Belgium (Belgium); Czech Technical University in Prague, Faculty of Nuclear Sciences and Physical Engineering, Břehová 7, 115 19 Prague 1 (Czech Republic); Doornaert, D. [Laboratory for Acoustics and Thermal Physics, Department of Physics and Astronomy, KU Leuven, B-3001 Heverlee (Belgium); Wave Propagation and Signal Processing Research Group, KU Leuven Campus Kortrijk, E. Sabbelaan 53, B-8500 Kortrijk (Belgium); Glorieux, C. [Laboratory for Acoustics and Thermal Physics, Department of Physics and Astronomy, KU Leuven, B-3001 Heverlee (Belgium); Modarresi, H. [Instituut voor Kern-en Stralingsfysica, KU Leuven, Celestijnenlaan 200D, B-3001 Leuven Belgium (Belgium); Guan, T. [Departement Elektrotechniek ESAT-MICAS, KU Leuven, Kasteelpark Arenberg 10, B-3001 Leuven (Belgium); Temst, K. [Instituut voor Kern-en Stralingsfysica, KU Leuven, Celestijnenlaan 200D, B-3001 Leuven Belgium (Belgium); Vandervorst, W. [Instituut voor Kern-en Stralingsfysica, KU Leuven, Celestijnenlaan 200D, B-3001 Leuven Belgium (Belgium); IMEC, Kapeldreef 75, B-3001 Leuven (Belgium); Vantomme, A. [Instituut voor Kern-en Stralingsfysica, KU Leuven, Celestijnenlaan 200D, B-3001 Leuven Belgium (Belgium)

    2015-08-31

    Indium tin oxide (ITO) is broadly used as a transparent conducting material for electrodes in optoelectronic devices. Irradiation of ITO with low energy ions can result in the formation of periodic surface nanopatterns which can serve as an alternative for the polymer alignment layer in liquid crystal devices. We investigated the formation of the ion-induced surface nanopatterns on ITO with focus on the influence of the crystalline structure of the material. We find that the crystallinity plays a crucial role in the pattern formation, with no pattern developing on an amorphous ITO surface. We discuss these findings in the context of the state-of-the-art theory for ion-induced patterning. We show that the ion-induced pattern plays a critical role in the liquid crystal alignment on ITO surfaces.

  17. Automobile diesel exhaust particles induce lipid droplet formation in macrophages in vitro.

    Science.gov (United States)

    Cao, Yi; Jantzen, Kim; Gouveia, Ana Cecilia Damiao; Skovmand, Astrid; Roursgaard, Martin; Loft, Steffen; Møller, Peter

    2015-07-01

    Exposure to diesel exhaust particles (DEP) has been associated with adverse cardiopulmonary health effects, which may be related to dysregulation of lipid metabolism and formation of macrophage foam cells. In this study, THP-1 derived macrophages were exposed to an automobile generated DEP (A-DEP) for 24h to study lipid droplet formation and possible mechanisms. The results show that A-DEP did not induce cytotoxicity. The production of reactive oxygen species was only significantly increased after exposure for 3h, but not 24h. Intracellular level of reduced glutathione was increased after 24h exposure. These results combined indicate an adaptive response to oxidative stress. Exposure to A-DEP was associated with significantly increased formation of lipid droplets, as well as changes in lysosomal function, assessed as reduced LysoTracker staining. In conclusion, these results indicated that exposure to A-DEP may induce formation of lipid droplets in macrophages in vitro possibly via lysosomal dysfunction.

  18. Radiation-induced defects formation in Bi-containing vitreous chalcogenides

    Energy Technology Data Exchange (ETDEWEB)

    Shpotyuk, O.; Vakiv, M.; Balitska, V.; Kovalskiy, A. [Institute of Materials, Lvov (Ukraine)

    1997-12-01

    Processes of formation and annihilation of coordination defects in As{sub 2}Se{sub 3}Bi{sub y} and (As{sub 2}Se{sub 3})(Bi{sub 2}Se{sub 3}){sub y} amorphous chalcogenide semiconductors induced by influence of Co{sup 60} gamma-irradiation are investigated by photoelectric spectroscopy method. It is obtained that radiation-induced changes of photoelectrical properties on bioconcentration of As{sub 2}Se{sub 3}Bi{sub y} glasses are characterized by anomalous concentration dependence. The nature of this effect is associated with diamagnetic coordination defects formation. (author). 19 refs, 3 figs.

  19. Motility of Pseudomonas aeruginosa contributes to SOS-inducible biofilm formation.

    Science.gov (United States)

    Chellappa, Shakinah T; Maredia, Reshma; Phipps, Kara; Haskins, William E; Weitao, Tao

    2013-12-01

    DNA-damaging antibiotics such as ciprofloxacin induce biofilm formation and the SOS response through autocleavage of SOS-repressor LexA in Pseudomonas aeruginosa. However, the biofilm-SOS connection remains poorly understood. It was investigated with 96-well and lipid biofilm assays. The effects of ciprofloxacin were examined on biofilm stimulation of the SOS mutant and wild-type strains. The stimulation observed in the wild-type in which SOS was induced was reduced in the mutant in which LexA was made non-cleavable (LexAN) and thus SOS non-inducible. Therefore, the stimulation appeared to involve SOS. The possible mechanisms of inducible biofilm formation were explored by subproteomic analysis of outer membrane fractions extracted from biofilms. The data predicted an inhibitory role of LexA in flagellum function. This premise was tested first by functional and morphological analyses of flagellum-based motility. The flagellum swimming motility decreased in the LexAN strain treated with ciprofloxacin. Second, the motility-biofilm assay was performed, which tested cell migration and biofilm formation. The results showed that wild-type biofilm increased significantly over the LexAN. These results suggest that LexA repression of motility, which is the initial event in biofilm development, contributes to repression of SOS-inducible biofilm formation.

  20. Ciprofloxacin causes persister formation by inducing the TisB toxin in Escherichia coli.

    Directory of Open Access Journals (Sweden)

    Tobias Dörr

    2010-02-01

    Full Text Available Bacteria induce stress responses that protect the cell from lethal factors such as DNA-damaging agents. Bacterial populations also form persisters, dormant cells that are highly tolerant to antibiotics and play an important role in recalcitrance of biofilm infections. Stress response and dormancy appear to represent alternative strategies of cell survival. The mechanism of persister formation is unknown, but isolated persisters show increased levels of toxin/antitoxin (TA transcripts. We have found previously that one or more components of the SOS response induce persister formation after exposure to a DNA-damaging antibiotic. The SOS response induces several TA genes in Escherichia coli. Here, we show that a knockout of a particular SOS-TA locus, tisAB/istR, had a sharply decreased level of persisters tolerant to ciprofloxacin, an antibiotic that causes DNA damage. Step-wise administration of ciprofloxacin induced persister formation in a tisAB-dependent manner, and cells producing TisB toxin were tolerant to multiple antibiotics. TisB is a membrane peptide that was shown to decrease proton motive force and ATP levels, consistent with its role in forming dormant cells. These results suggest that a DNA damage-induced toxin controls production of multidrug tolerant cells and thus provide a model of persister formation.

  1. Study on the Formation of Urea or Salt Induced Vesicles in Built-system Surfactant

    Institute of Scientific and Technical Information of China (English)

    Chang Gang HU; Hui XIE; Gan Zuo LI; Ya AN; Zhong Ni WANG; Xiao Yi ZHANG; Jing Ping TIAN

    2005-01-01

    The spontaneous formation of vesicles in the aqueous of cationic surfactant phosphate(PTA) and anionic surfactant sodium dodecyl sulfate (SDS) at certain mixing ratios have obtained1.The addition of urea or NaI will expand the range of spontaneous vesicle formation. The fact is demonstrated by negative-staining transmission electron microscope(TEM) and dynamic light scattering(DLS) methods. The phenomenon especially in the part of urea is reported by us at first.Mechanism of urea/NaI-induced vesicles formation is discussed from the viewpoint of the molecular geometry packing parameter f, conformation and interaction.

  2. Biphasic function of focal adhesion kinase in endothelial tube formation induced by fibril-forming collagens.

    Science.gov (United States)

    Nakamura, Junko; Shigematsu, Satoshi; Yamauchi, Keishi; Takeda, Teiji; Yamazaki, Masanori; Kakizawa, Tomoko; Hashizume, Kiyoshi

    2008-10-03

    Migration and tube formation of endothelial cells are important in angiogenesis and require a coordinated response to the extra-cellular matrix (ECM) and growth factor. Since focal adhesion kinase (FAK) integrates signals from both ECM and growth factor, we investigated its role in angiogenesis. Type I and II collagens are fibril-forming collagens and stimulate human umbilical vein endothelial cells (HUVECs) to form tube structure. Although knockdown of FAK restrained cell motility and resulted in inhibition of tube formation, FAK degradation and tube formation occurred simultaneously after incubation with fibril-forming collagens. The compensation for the FAK degradation by a calpain inhibitor or transient over-expression of FAK resulted in disturbance of tube formation. These phenomena are specific to fibril-forming collagens and mediated via alpha2beta1 integrin. In conclusion, our data indicate that FAK is functioning in cell migration, but fibril-forming collagen-induced FAK degradation is necessary for endothelial tube formation.

  3. Refractive Index Change and Color Center Formation in LiYF_4 Crystal Induced by a Femtosecond Laser

    Institute of Scientific and Technical Information of China (English)

    2003-01-01

    The refractive index change and color centers formation in LiYF4 crystal at room temperature are induced by a femtosecond laser irradiation. A mechanism for refractive index change and color centers formation is proposed.

  4. Refractive Index Change and Color Center Formation in LiYF4 Crystal Induced by a Femtosecond Laser

    Institute of Scientific and Technical Information of China (English)

    Quanzhong Zhao; Jianrong Qiu; Lüyun Yang; Xiongwei Jiang; Congshan Zhu

    2003-01-01

    The refractive index change and color centers formation in LiYF4 crystal at room temperature are induced by a femtosecond laser irradiation. A mechanism for refractive index change and color centers formation is proposed.

  5. A role for muscarinic receptors in neutrophil extracellular trap formation and levamisole-induced autoimmunity

    Science.gov (United States)

    Carmona-Rivera, Carmelo; Purmalek, Monica M.; Moore, Erica; Waldman, Meryl; Walter, Peter J.; Garraffo, H. Martin; Phillips, Karran A.; Preston, Kenzie L.; Graf, Jonathan; Grayson, Peter C.

    2017-01-01

    Levamisole, an anthelmintic drug with cholinergic properties, has been implicated in cases of drug-induced vasculitis when added to cocaine for profit purposes. Neutrophil extracellular trap (NET) formation is a cell death mechanism characterized by extrusion of chromatin decorated with granule proteins. Aberrant NET formation and degradation have been implicated in idiopathic autoimmune diseases that share features with levamisole-induced autoimmunity as well as in drug-induced autoimmunity. This study’s objective was to determine how levamisole modulates neutrophil biology and its putative effects on the vasculature. Murine and human neutrophils exposed to levamisole demonstrated enhanced NET formation through engagement of muscarinic subtype 3 receptor. Levamisole-induced NETosis required activation of Akt and the RAF/MEK/ERK pathway, ROS induction through the nicotinamide adenine dinucleotide phosphate oxidase, and peptidylarginine deiminase activation. Sera from two cohorts of patients actively using levamisole-adulterated cocaine displayed autoantibodies against NET components. Cutaneous biopsy material obtained from individuals exposed to levamisole suggests that neutrophils produce NETs in areas of vasculitic inflammation and thrombosis. NETs generated by levamisole were toxic to endothelial cells and impaired endothelium-dependent vasorelaxation. Stimulation of muscarinic receptors on neutrophils by cholinergic agonists may contribute to the pathophysiology observed in drug-induced autoimmunity through the induction of inflammatory responses and neutrophil-induced vascular damage. PMID:28194438

  6. A role for muscarinic receptors in neutrophil extracellular trap formation and levamisole-induced autoimmunity.

    Science.gov (United States)

    Carmona-Rivera, Carmelo; Purmalek, Monica M; Moore, Erica; Waldman, Meryl; Walter, Peter J; Garraffo, H Martin; Phillips, Karran A; Preston, Kenzie L; Graf, Jonathan; Kaplan, Mariana J; Grayson, Peter C

    2017-02-09

    Levamisole, an anthelmintic drug with cholinergic properties, has been implicated in cases of drug-induced vasculitis when added to cocaine for profit purposes. Neutrophil extracellular trap (NET) formation is a cell death mechanism characterized by extrusion of chromatin decorated with granule proteins. Aberrant NET formation and degradation have been implicated in idiopathic autoimmune diseases that share features with levamisole-induced autoimmunity as well as in drug-induced autoimmunity. This study's objective was to determine how levamisole modulates neutrophil biology and its putative effects on the vasculature. Murine and human neutrophils exposed to levamisole demonstrated enhanced NET formation through engagement of muscarinic subtype 3 receptor. Levamisole-induced NETosis required activation of Akt and the RAF/MEK/ERK pathway, ROS induction through the nicotinamide adenine dinucleotide phosphate oxidase, and peptidylarginine deiminase activation. Sera from two cohorts of patients actively using levamisole-adulterated cocaine displayed autoantibodies against NET components. Cutaneous biopsy material obtained from individuals exposed to levamisole suggests that neutrophils produce NETs in areas of vasculitic inflammation and thrombosis. NETs generated by levamisole were toxic to endothelial cells and impaired endothelium-dependent vasorelaxation. Stimulation of muscarinic receptors on neutrophils by cholinergic agonists may contribute to the pathophysiology observed in drug-induced autoimmunity through the induction of inflammatory responses and neutrophil-induced vascular damage.

  7. Auxin-induced hydrogen sulfide generation is involved in lateral root formation in tomato.

    Science.gov (United States)

    Fang, Tao; Cao, Zeyu; Li, Jiale; Shen, Wenbiao; Huang, Liqin

    2014-03-01

    Similar to auxin, hydrogen sulfide (H2S), mainly produced by l-cysteine desulfhydrase (DES; EC 4.4.1.1) in plants, could induce lateral root formation. The objective of this study was to test whether H2S is also involved in auxin-induced lateral root development in tomato (Solanum lycopersicum L.) seedlings. We observed that auxin depletion-induced down-regulation of transcripts of SlDES1, decreased DES activity and endogenous H2S contents, and the inhibition of lateral root formation were rescued by sodium hydrosulfide (NaHS, an H2S donor). However, No additive effects were observed when naphthalene acetic acid (NAA) was co-treated with NaHS (lower than 10 mM) in the induction of lateral root formation. Subsequent work revealed that a treatment with NAA or NaHS could simultaneously induce transcripts of SlDES1, DES activity and endogenous H2S contents, and thereafter the stimulation of lateral root formation. It was further confirmed that H2S or HS(-), not the other sulfur-containing components derived from NaHS, was attributed to the stimulative action. The inhibition of lateral root formation and decreased of H2S metabolism caused by an H2S scavenger hypotaurine (HT) were reversed by NaHS, but not NAA. Molecular evidence revealed that both NaHS- or NAA-induced modulation of some cell cycle regulatory genes, including the up-regulation of SlCDKA;1, SlCYCA2;1, together with simultaneous down-regulation of SlKRP2, were differentially reversed by HT pretreatment. To summarize, above results clearly suggested that H2S might, at least partially, act as a downstream component of auxin signaling to trigger lateral root formation.

  8. ANA deficiency enhances bone morphogenetic protein-induced ectopic bone formation via transcriptional events.

    Science.gov (United States)

    Miyai, Kentaro; Yoneda, Mitsuhiro; Hasegawa, Urara; Toita, Sayaka; Izu, Yayoi; Hemmi, Hiroaki; Hayata, Tadayoshi; Ezura, Yoichi; Mizutani, Shuki; Miyazono, Kohei; Akiyoshi, Kazunari; Yamamoto, Tadashi; Noda, Masaki

    2009-04-17

    Ectopic bone formation after joint replacement or brain injury in humans is a serious complication that causes immobility of joints and severe pain. However, mechanisms underlying such ectopic bone formation are not fully understood. Bone morphogenetic protein (BMPs) are defined as inducers of ectopic bone formation, and they are regulated by several types of inhibitors. ANA is an antiproliferative molecule that belongs to Tob/BTG family, but its activity in bone metabolism has not been known. Here, we examined the role of ANA on ectopic bone formation activity of BMP. In ANA-deficient and wild-type mice, BMP2 was implanted to induce ectopic bone formation in muscle. ANA deficiency increased mass of newly formed bone in vivo compared with wild-type based on 3D-muCT analyses. ANA mRNA was expressed in bone in vivo as well as in osteoblastic cells in vitro. Such ANA mRNA levels were increased by BMP2 treatment in MC3T3-E1 osteoblastic cells. Overexpression of ANA suppressed BMP-induced expression of luciferase reporter gene linked to BMP response elements in these cells. Conversely, ANA mRNA knockdown by small interference RNA enhanced the BMP-dependent BMP response element reporter expression. It also enhanced BMP-induced osteoblastic differentiation in muscle-derived C2C12 cells. Immunoprecipitation assay indicated that ANA interacts with Smad8. Thus, ANA is a suppressor of ectopic bone formation induced by BMP, and this inhibitory ANA activity is a part of the negative feedback regulation of BMP function.

  9. Gentamicin induces efaA expression and biofilm formation in Enterococcus faecalis.

    Science.gov (United States)

    Kafil, Hossein Samadi; Mobarez, Ashraf Mohabati; Moghadam, Mehdi Forouzandeh; Hashemi, Zahra Sadat; Yousefi, Mehdi

    2016-03-01

    Enterococci have been ranked among the leading causes of nosocomial bacteremia and urinary tract infection. This study aimed to investigate the effect of ampicillin, vancomycin, gentamicin and ceftizoxime on biofilm formation and gene expression of colonization factors on Enterococcus faecalis. Twelve clinical isolates of E. faecalis were used to investigate the effect of antibiotics on biofilm formation and gene expression of efaA, asa1, ebpA, esp and ace. Flow system assay and Microtiter plates were used for biofilm assay. Two hundred clinical isolates were used for confirming the effect of antibiotics on biofilm formation. Ampicillin, vancomycin and ceftizoxime did not have any significant effect on biofilm formation, but gentamicin induced biofilm formation in 89% of isolates. In twelve selected isolate gentamicin increased expression of esp (+50.9%) and efaA (+33.9%) genes and reduced or maintained expression of others (asa1:-47.4%, ebpA: 0, ace:-19.2%). Vancomycin increased expression of esp (+89.1%) but reduced the others (asa1: -34.9%, ebpA:-11%, ace:-30%, efaA:-60%). Ceftizoxime increased slightly ebpA (+19.7%) and reduced others (asa1:-66.2%, esp:-35%, ace:-28.1%, efaA:-38.4%). and ampicillin strongly increased expression of ace (+231%), esp (+131%) and ebpA (+83%) but reduced others (asa1:-85.5%, efaA:-47.4%). The findings of the present study showed that antibiotics may have a role in biofilm formation and sustainability of enterococci, especially in case of gentamicin. efaA gene may have an important role, especially in antibiotic induced biofilm formation by gentamicin. Experiments with efaA mutants are needed to investigate the exact effect of efaA on biofilm formation with antibiotic induced cells.

  10. Heat-induced whey protein isolate fibrils: Conversion, hydrolysis, and disulphide bond formation

    NARCIS (Netherlands)

    Bolder, S.G.; Vasbinder, A.; Sagis, L.M.C.; Linden, van der E.

    2007-01-01

    Fibril formation of individual pure whey proteins and whey protein isolate (WPI) was studied. The heat-induced conversion of WPI monomers into fibrils at pH 2 and low ionic strength increased with heating time and protein concentration. Previous studies, using a precipitation method, size-exclusion

  11. The formation of light-induced gratings in the rigid eosine K solution in gelatin

    Science.gov (United States)

    Vorob'ev, A. A.; Kolchanova, S. A.; Sizykh, A. G.; Sul'Kis, I. G.

    1992-03-01

    The mechanism of the formation of light-induced amplitude gratings in the rigid eosine K solution in gelatin is investigated. It is shown that spatial modulation of the absorptance of the recording medium is caused by the transformation of the dye into a colorless form in the process of photosensitized proton transfer from gelatin to the eosine.

  12. Autophagy is induced by anti-neutrophil cytoplasmic Abs and promotes neutrophil extracellular traps formation.

    Science.gov (United States)

    Sha, Li-Li; Wang, Huan; Wang, Chen; Peng, Hong-Ying; Chen, Min; Zhao, Ming-Hui

    2016-11-01

    Dysregulated neutrophil extracellular traps (NETs) formation contributes to the pathogenesis of anti-neutrophil cytoplasmic Ab (ANCA)-associated vasculitis (AAV). Increasing evidence indicates that autophagy is involved in the process of NETs formation. In this study, we aimed to investigate whether ANCA could induce autophagy in the process of NETs formation. Autophagy was detected using live cell imaging, microtubule-associated protein light chain 3B (LC3B) accumulation and Western blotting. The results showed that autophagy vacuolization was detected in neutrophils treated with ANCA-positive IgG by live cell imaging. This effect was enhanced by rapamycin, the autophagy inducer, and weakened by 3-methyladenine (3-MA), the autophagy inhibitor. In line with these results, the autophagy marker, LC3B, showed a punctate distribution pattern in the neutrophils stimulated with ANCA-positive IgG. In the presence of rapamycin, LC3B accumulation was further increased; however, this effect was attenuated by 3-MA. Moreover, incubated with ANCA-positive IgG, the NETosis rate significantly increased compared with the unstimulated group. And, the rate significantly increased or decreased in the neutrophils pretreated with rapamycin or 3-MA, respectively, as compared with the cells incubated with ANCA-positive IgG. Overall, this study demonstrates that autophagy is induced by ANCA and promotes ANCA-induced NETs formation.

  13. Mechanisms of femtosecond LIPSS formation induced by periodic surface temperature modulation

    Science.gov (United States)

    Gurevich, Evgeny L.

    2016-06-01

    Here we analyze the formation of laser-induced periodic surface structures (LIPSS) on metal surfaces upon single femtosecond laser pulses. Most of the existing models of the femtosecond LIPSS formation discuss only the appearance of a periodic modulation of the electron and ion temperatures. However the mechanism how the inhomogeneous surface temperature distribution induces the periodically-modulated surface profile under the conditions corresponding to ultrashort-pulse laser ablation is still not clear. Estimations made on the basis of different hydrodynamic instabilities allow to sort out mechanisms, which can bridge the gap between the temperature modulation and the LIPSS. The proposed theory shows that the periodic structures can be generated by single ultrashort laser pulses due to ablative instabilities. The Marangoni and Rayleigh-Bénard convection on the contrary cannot cause the LIPSS formation.

  14. Auxin effectively induces the formation of the secondary abscission zone in Bryophyllum calycinum Salisb. (Crassulaceae

    Directory of Open Access Journals (Sweden)

    Marian Saniewski

    2016-05-01

    Full Text Available We have found that auxin, indole-3-acetic acid (IAA substantially induces the formation of the secondary abscission zone in stem and petiole explants and in decapitated stem and petiole after excision of blade in intact plants of Bryophyllum calycinum when IAA at a concentration of 0.1% as lanolin paste was applied in the middle of these organs. The secondary abscission zone was formed at a few mm above of the treatment with IAA, and senescence of the part above abscission zone was observed. IAA additionally applied on the top of explants or top of the dacapitated stem or the debladed petiole totally prevented the secondary abscission zone formation and senescence induced by IAA applied in the middle of these organs. Possible mechanisms of the formation of the secondary abscission zone are discussed in terms of the interaction of auxin and ethylene.

  15. A Forward Genetic Screen for Molecules Involved in Pheromone-Induced Dauer Formation in Caenorhabditis elegans

    Science.gov (United States)

    Neal, Scott J.; Park, JiSoo; DiTirro, Danielle; Yoon, Jason; Shibuya, Mayumi; Choi, Woochan; Schroeder, Frank C.; Butcher, Rebecca A.; Kim, Kyuhyung; Sengupta, Piali

    2016-01-01

    Animals must constantly assess their surroundings and integrate sensory cues to make appropriate behavioral and developmental decisions. Pheromones produced by conspecific individuals provide critical information regarding environmental conditions. Ascaroside pheromone concentration and composition are instructive in the decision of Caenorhabditis elegans to either develop into a reproductive adult or enter into the stress-resistant alternate dauer developmental stage. Pheromones are sensed by a small set of sensory neurons, and integrated with additional environmental cues, to regulate neuroendocrine signaling and dauer formation. To identify molecules required for pheromone-induced dauer formation, we performed an unbiased forward genetic screen and identified phd (pheromone response-defective dauer) mutants. Here, we describe new roles in dauer formation for previously identified neuronal molecules such as the WD40 domain protein QUI-1 and MACO-1 Macoilin, report new roles for nociceptive neurons in modulating pheromone-induced dauer formation, and identify tau tubulin kinases as new genes involved in dauer formation. Thus, phd mutants define loci required for the detection, transmission, or integration of pheromone signals in the regulation of dauer formation. PMID:26976437

  16. A Forward Genetic Screen for Molecules Involved in Pheromone-Induced Dauer Formation in Caenorhabditis elegans

    Directory of Open Access Journals (Sweden)

    Scott J. Neal

    2016-05-01

    Full Text Available Animals must constantly assess their surroundings and integrate sensory cues to make appropriate behavioral and developmental decisions. Pheromones produced by conspecific individuals provide critical information regarding environmental conditions. Ascaroside pheromone concentration and composition are instructive in the decision of Caenorhabditis elegans to either develop into a reproductive adult or enter into the stress-resistant alternate dauer developmental stage. Pheromones are sensed by a small set of sensory neurons, and integrated with additional environmental cues, to regulate neuroendocrine signaling and dauer formation. To identify molecules required for pheromone-induced dauer formation, we performed an unbiased forward genetic screen and identified phd (pheromone response-defective dauer mutants. Here, we describe new roles in dauer formation for previously identified neuronal molecules such as the WD40 domain protein QUI-1 and MACO-1 Macoilin, report new roles for nociceptive neurons in modulating pheromone-induced dauer formation, and identify tau tubulin kinases as new genes involved in dauer formation. Thus, phd mutants define loci required for the detection, transmission, or integration of pheromone signals in the regulation of dauer formation.

  17. A Forward Genetic Screen for Molecules Involved in Pheromone-Induced Dauer Formation in Caenorhabditis elegans.

    Science.gov (United States)

    Neal, Scott J; Park, JiSoo; DiTirro, Danielle; Yoon, Jason; Shibuya, Mayumi; Choi, Woochan; Schroeder, Frank C; Butcher, Rebecca A; Kim, Kyuhyung; Sengupta, Piali

    2016-05-03

    Animals must constantly assess their surroundings and integrate sensory cues to make appropriate behavioral and developmental decisions. Pheromones produced by conspecific individuals provide critical information regarding environmental conditions. Ascaroside pheromone concentration and composition are instructive in the decision of Caenorhabditis elegans to either develop into a reproductive adult or enter into the stress-resistant alternate dauer developmental stage. Pheromones are sensed by a small set of sensory neurons, and integrated with additional environmental cues, to regulate neuroendocrine signaling and dauer formation. To identify molecules required for pheromone-induced dauer formation, we performed an unbiased forward genetic screen and identified phd (pheromone response-defective dauer) mutants. Here, we describe new roles in dauer formation for previously identified neuronal molecules such as the WD40 domain protein QUI-1 and MACO-1 Macoilin, report new roles for nociceptive neurons in modulating pheromone-induced dauer formation, and identify tau tubulin kinases as new genes involved in dauer formation. Thus, phd mutants define loci required for the detection, transmission, or integration of pheromone signals in the regulation of dauer formation.

  18. Physical and biological data collected with CDT, fluorometer, and SeaSoar aboard the ship WECOMA as part of Global Ocean Ecosystem Dynamics (GLOBEC) in the North Pacific Ocean from May 30 to June 16 2000 (NODC Accession 0000986)

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — Physical and biological data collected with CDT, fluorometer, and SeaSoar aboard the ship WECOMA in the North Pacific Ocean from May 30 to June 16 2000. These data...

  19. Determination of the absolute 32S/34S ratio of IAEA-S-1 reference material and V-CDT sulfur isotope standard

    Institute of Scientific and Technical Information of China (English)

    丁悌平; 白瑞梅; 李延河; 万德芳; 邹晓秋; 张青莲

    1999-01-01

    The absolute 32S/34S ratios of IAEA-S-1 reference material and V-CDT standard are determined. For cross-checking, two sets of synthetic isotope mixtures are prepared from high purity 32S and 34S-enriched materials in different forms: the first set is prepared from BaSO4 whereas the second is prepared from Ag2S. The sulfur isotope analyses are done by using SF6 method with a MAT-251 EM mass spectrometer. The resulting 32S/34S ratio of IAEAS-1 reference material is 22.656 4±0. 006 0, and that of V-CDT is 22. 649 6±0. 006 0.

  20. Suppressor Analysis of CRL4Cdt2 Defective and cdc48-353 Temperature Sensitive Mutants in Fission Yeast

    DEFF Research Database (Denmark)

    Marinova, Irina Nikolaeva

    upon entry into S-phase and following DNA damage via CRL4Cdt2-mediated ubiquitylation, which also requires interaction with proliferating cell nuclear antigen (PCNA). Spd1 is a negative regulator of ribonucleotide reductase (RNR), the activity of which is required for deoxyribonucleotide (d...... show that Spd1 amino acid residues V40 and S43 are important for its function as an inhibitor of DNA synthesis, as the spd1-V40G and spd1-S43L mutants were identified as spontaneous suppressors of the defective phenotypes exhibited by cells with abrogated CRL4Cdt2 pathway. We confirm...... that these mutations alleviate the checkpoint dependency, the DNA damage sensitivity and the meiotic defects associated with Spd1 accumulation. Further analysis showed that whereas the V40G and S43L substitutions do not have a significant impact on Suc22R2 nuclear import function of Spd1, they affect the interaction...

  1. Critical Role of AKT Protein in Myeloma-induced Osteoclast Formation and Osteolysis*

    Science.gov (United States)

    Cao, Huiling; Zhu, Ke; Qiu, Lugui; Li, Shuai; Niu, Hanjie; Hao, Mu; Yang, Shengyong; Zhao, Zhongfang; Lai, Yumei; Anderson, Judith L.; Fan, Jie; Im, Hee-Jeong; Chen, Di; Roodman, G. David; Xiao, Guozhi

    2013-01-01

    Abnormal osteoclast formation and osteolysis are the hallmarks of multiple myeloma (MM) bone disease, yet the underlying molecular mechanisms are incompletely understood. Here, we show that the AKT pathway was up-regulated in primary bone marrow monocytes (BMM) from patients with MM, which resulted in sustained high expression of the receptor activator of NF-κB (RANK) in osteoclast precursors. The up-regulation of RANK expression and osteoclast formation in the MM BMM cultures was blocked by AKT inhibition. Conditioned media from MM cell cultures activated AKT and increased RANK expression and osteoclast formation in BMM cultures. Inhibiting AKT in cultured MM cells decreased their growth and ability to promote osteoclast formation. Of clinical significance, systemic administration of the AKT inhibitor LY294002 blocked the formation of tumor tissues in the bone marrow cavity and essentially abolished the MM-induced osteoclast formation and osteolysis in SCID mice. The level of activating transcription factor 4 (ATF4) protein was up-regulated in the BMM cultures from multiple myeloma patients. Adenoviral overexpression of ATF4 activated RANK expression in osteoclast precursors. These results demonstrate a new role of AKT in the MM promotion of osteoclast formation and bone osteolysis through, at least in part, the ATF4-dependent up-regulation of RANK expression in osteoclast precursors. PMID:24005670

  2. The influence of projectile ion induced chemistry on surface pattern formation

    Science.gov (United States)

    Karmakar, Prasanta; Satpati, Biswarup

    2016-07-01

    We report the critical role of projectile induced chemical inhomogeneity on surface nanostructure formation. Experimental inconsistency is common for low energy ion beam induced nanostructure formation in the presence of uncontrolled and complex contamination. To explore the precise role of contamination on such structure formation during low energy ion bombardment, a simple and clean experimental study is performed by selecting mono-element semiconductors as the target and chemically inert or reactive ion beams as the projectile as well as the source of controlled contamination. It is shown by Atomic Force Microscopy, Cross-sectional Transmission Electron Microscopy, and Electron Energy Loss Spectroscopy measurements that bombardment of nitrogen-like reactive ions on Silicon and Germanium surfaces forms a chemical compound at impact zones. Continuous bombardment of the same ions generates surface instability due to unequal sputtering and non-uniform re-arrangement of the elemental atom and compound. This instability leads to ripple formation during ion bombardment. For Argon-like chemically inert ion bombardment, the chemical inhomogeneity induced boost is absent; as a result, no ripples are observed in the same ion energy and fluence.

  3. Kartogenin induces cartilage-like tissue formation in tendon-bone junction

    Institute of Scientific and Technical Information of China (English)

    Jianying Zhang; James H-C Wang

    2014-01-01

    Tendon-bone junctions (TBJs) are frequently injured, especially in athletic settings. Healing of TBJ injuries is slow and is often repaired with scar tissue formation that compromises normal function. This study explored the feasibility of using kartogenin (KGN), a biocompound, to enhance the healing of injured TBJs. We first determined the effects of KGN on the proliferation and chondrogenic differentiation of rabbit bone marrow stromal cells (BMSCs) and patellar tendon stem/progenitor cells (PTSCs) in vitro. KGN enhanced cell proliferation in both cell types in a concentration-dependent manner and induced chondrogenic differentiation of stem cells, as demonstrated by high expression levels of chondrogenic markers aggrecan, collagen II and Sox-9. Besides, KGN induced the formation of cartilage-like tissues in cell cultures, as observed through the staining of abundant proteoglycans, collagen II and osteocalcin. When injected into intact rat patellar tendons in vivo, KGN induced cartilage-like tissue formation in the injected area. Similarly, when KGN was injected into experimentally injured rat Achilles TBJs, wound healing in the TBJs was enhanced, as evidenced by the formation of extensive cartilage-like tissues. These results suggest that KGN may be used as an effective cell-free clinical therapy to enhance the healing of injured TBJs.

  4. Human CDT1 associates with CDC7 and recruits CDC45 to chromatin during S phase

    DEFF Research Database (Denmark)

    Ballabeni, Andrea; Zamponi, Raffaela; Caprara, Greta;

    2009-01-01

    The initiation of DNA replication is a tightly controlled process that involves the formation of distinct complexes at origins of DNA replication at specific periods of the cell cycle. Pre-Replicative Complexes are formed during telophase and early G1. They rearrange at the start of S phase to form...

  5. Heme oxygenase-1 is involved in sodium hydrosulfide-induced lateral root formation in tomato seedlings.

    Science.gov (United States)

    Fang, Tao; Li, Jiale; Cao, Zeyu; Chen, Meng; Shen, Wei; Huang, Liqin

    2014-06-01

    By using pharmacological and molecular approaches, we discovered the involvement of HO-1 in NaHS-induced lateral root formation in tomato seedlings. Heme oxygenase-1 (HO-1) and hydrogen sulfide (H2S) regulate various responses to abiotic stress and root development, but their involvement in the simultaneous regulation of plant lateral root (LR) formation is poorly understood. In this report, we observed that the exogenously applied H2S donor sodium hydrosulfide (NaHS) and the HO-1 inducer hemin induce LR formation in tomato seedlings by triggering intracellular signaling events involving the induction of tomato HO-1 (SlHO-1), and the modulation of cell cycle regulatory genes, including the up-regulation of SlCDKA;1 and SlCYCA2;1, and simultaneous down-regulation of SlKRP2. The response of NaHS in the induction of LR formation was impaired by the potent inhibition of HO-1, which was further blocked when 50 % saturation of carbon monoxide (CO) aqueous solution, one of the catalytic by-products of HO-1, was added. Further molecular evidence revealed that the NaHS-modulated gene expression of cell cycle regulatory genes was sensitive to the inhibition of HO-1 and reversed by cotreatment with CO. The impairment of LR density and length as well as lateral root primordia number, the decreased tomato HO-1 gene expression and HO activity caused by an H2S scavenger hypotaurine were partially rescued by the addition of NaHS, hemin and CO (in particular). Together, these results revealed that at least in our experimental conditions, HO-1 might be involved in NaHS-induced tomato LR formation. Additionally, the use of NaHS and hemin compounds in crop root organogenesis should be explored.

  6. Modelling nanoparticles formation in the plasma plume induced by nanosecond pulsed lasers

    Energy Technology Data Exchange (ETDEWEB)

    Girault, M. [Laboratoire Interdisciplinaire Carnot de Bourgogne (ICB), UMR 6303 CNRS-Universite de Bourgogne, 9 Av. A. Savary, BP 47 870, F-21078 Dijon Cedex (France); Centre Lasers Intenses et Applications (CELIA), Universite de Bordeaux 1, 43 rue Pierre Noailles, Talence (France); Hallo, L., E-mail: hallo@celia.u-bordeaux1.fr [CEA CESTA, 15 Avenue des Sablieres CS 60001, 33116 Le Barp Cedex (France); Centre Lasers Intenses et Applications (CELIA), Universite de Bordeaux 1, 43 rue Pierre Noailles, Talence (France); Lavisse, L.; Lucas, M.C. Marco de [Laboratoire Interdisciplinaire Carnot de Bourgogne (ICB), UMR 6303 CNRS-Universite de Bourgogne, 9 Av. A. Savary, BP 47 870, F-21078 Dijon Cedex (France); Hebert, D. [CEA CESTA, 15 Avenue des Sablieres CS 60001, 33116 Le Barp Cedex (France); Potin, V.; Jouvard, J.-M. [Laboratoire Interdisciplinaire Carnot de Bourgogne (ICB), UMR 6303 CNRS-Universite de Bourgogne, 9 Av. A. Savary, BP 47 870, F-21078 Dijon Cedex (France)

    2012-09-15

    Highlights: Black-Right-Pointing-Pointer Nanoparticles spatial localization in the plume induced by a pulsed laser. Black-Right-Pointing-Pointer Plasma plume obtained by laser irradiation. Black-Right-Pointing-Pointer Particles and debris formation. Black-Right-Pointing-Pointer Powder generation. Black-Right-Pointing-Pointer Conditions of formation. - Abstract: Nanoparticles formation in a laser-induced plasma plume in the ambient air has been investigated by using numerical simulations and physical models. For high irradiances, or for ultrashort laser pulses, nanoparticles are formed by condensation, as fine powders, in the expanding plasma for very high pairs of temperature and pressure. At lower irradiances, or nanosecond laser pulses, another thermodynamic paths are possible, which cross the liquid-gas transition curve while laser is still heating the target and the induced plasma. In this work, we explore the growth of nanoparticles in the plasma plume induced by nanosecond pulsed lasers as a function of the laser irradiance. Moreover, the influence of the ambient gas has also been investigated.

  7. Blockade of advanced glycation end-product formation restores ischemia-induced angiogenesis in diabetic mice.

    Science.gov (United States)

    Tamarat, Radia; Silvestre, Jean-Sébastien; Huijberts, Maya; Benessiano, Joelle; Ebrahimian, Teni G; Duriez, Micheline; Wautier, Marie-Paule; Wautier, Jean Luc; Lévy, Bernard I

    2003-07-08

    We hypothesized that formation of advanced glycation end products (AGEs) associated with diabetes reduces matrix degradation by metalloproteinases (MMPs) and contributes to the impairment of ischemia-induced angiogenesis. Mice were treated or not with streptozotocin (40 mg/kg) and streptozotocin plus aminoguanidine (AGEs formation blocker, 50 mg/kg). After 8 weeks of treatment, hindlimb ischemia was induced by right femoral artery ligature. Plasma AGE levels were strongly elevated in diabetic mice when compared with control mice (579 +/- 21 versus 47 +/- 4 pmol/ml, respectively; P < 0.01). Treatment with aminoguanidine reduced AGE plasma levels when compared with untreated diabetic mice (P < 0.001). After 28 days of ischemia, ischemic/nonischemic leg angiographic score, capillary density, and laser Doppler skin-perfusion ratios were 1.4-, 1.5-, and 1.4-fold decreased in diabetic mice in reference to controls (P < 0.01). Treatment with aminoguanidine completely normalized ischemia-induced angiogenesis in diabetic mice. We next analyzed the role of proteolysis in AGE formation-induced hampered neovascularization process. After 3 days of ischemia, MMP-2 activity and MMP-3 and MMP-13 protein levels were increased in untreated and aminoguanidine-treated diabetic mice when compared with controls (P < 0.05). Despite this activation of the MMP pathway, collagenolysis was decreased in untreated diabetic mice. Conversely, treatment of diabetic mice with aminoguanidine restored collagenolysis toward levels found in control mice. In conclusion, blockade of AGE formation by aminoguanidine normalizes impaired ischemia-induced angiogenesis in diabetic mice. This effect is probably mediated by restoration of matrix degradation processes that are disturbed as a result of AGE accumulation.

  8. Formats

    Directory of Open Access Journals (Sweden)

    Gehmann, Ulrich

    2012-03-01

    Full Text Available In the following, a new conceptual framework for investigating nowadays’ “technical” phenomena shall be introduced, that of formats. The thesis is that processes of formatting account for our recent conditions of life, and will do so in the very next future. It are processes whose foundations have been laid in modernity and which will further unfold for the time being. These processes are embedded in the format of the value chain, a circumstance making them resilient to change. In addition, they are resilient in themselves since forming interconnected systems of reciprocal causal circuits.Which leads to an overall situation that our entire “Lebenswelt” became formatted to an extent we don’t fully realize, even influencing our very percep-tion of it.

  9. Schisantherin A suppresses osteoclast formation and wear particle-induced osteolysis via modulating RANKL signaling pathways

    Energy Technology Data Exchange (ETDEWEB)

    He, Yi; Zhang, Qing; Shen, Yi; Chen, Xia; Zhou, Feng; Peng, Dan, E-mail: xyeypd@163.com

    2014-07-04

    Highlights: • Schisantherin A suppresses osteoclasts formation and function in vitro. • Schisantherin A impairs RANKL signaling pathway. • Schisantherin A suppresses osteolysis in vivo. • Schisantherin A may be used for treating osteoclast related diseases. - Abstract: Receptor activator of NF-κB ligand (RANKL) plays critical role in osteoclastogenesis. Targeting RANKL signaling pathways has been a promising strategy for treating osteoclast related bone diseases such as osteoporosis and aseptic prosthetic loosening. Schisantherin A (SA), a dibenzocyclooctadiene lignan isolated from the fruit of Schisandra sphenanthera, has been used as an antitussive, tonic, and sedative agent, but its effect on osteoclasts has been hitherto unknown. In the present study, SA was found to inhibit RANKL-induced osteoclast formation and bone resorption. The osteoclastic specific marker genes induced by RANKL including c-Src, SA inhibited OSCAR, cathepsin K and TRAP in a dose dependent manner. Further signal transduction studies revealed that SA down-regulate RANKL-induced nuclear factor-kappaB (NF-κB) signaling activation by suppressing the phosphorylation and degradation of IκBα, and subsequently preventing the NF-κB transcriptional activity. Moreover, SA also decreased the RANKL-induced MAPKs signaling pathway, including JNK and ERK1/2 posphorylation while had no obvious effects on p38 activation. Finally, SA suppressed the NF-κB and MAPKs subsequent gene expression of NFATc1 and c-Fos. In vivo studies, SA inhibited osteoclast function and exhibited bone protection effect in wear-particle-induced bone erosion model. Taken together, SA could attenuate osteoclast formation and wear particle-induced osteolysis by mediating RANKL signaling pathways. These data indicated that SA is a promising therapeutic natural compound for the treatment of osteoclast-related prosthesis loosening.

  10. Swift heavy ion irradiation induced nanograin formation in CdTe thin films

    Science.gov (United States)

    Survase, Smita; Narayan, Himanshu; Sulania, I.; Thakurdesai, Madhavi

    2016-11-01

    Swift Heavy Ion (SHI) irradiation is a unique technique for nanograin formation through grain fragmentation. Contrary to the generally reported SHI irradiation induced grain growth on CdTe thin films, we report fragmentation leading to nanograin formation. Thermally evaporated polycrystalline CdTe thin films were irradiated with 100 MeV 197Au, 107Ag and 58Ni ions beams up to a fluence of 5 × 1012 ions/cm2. Scanning Electron Microscopy (SEM) and Atomic Force Microscopy (AFM) were carried out for surface analysis before and after irradiation. SEM micrographs indicate that the larger grains in the as-deposited films were fragmented into smaller grains due to irradiation. The extent of fragmentation was found to increase with increasing electronic energy loss (Se). AFM pictures also supported the irradiation induced fragmentation. Structural characterization was done using X-ray Diffraction (XRD) technique. The ion induced strain and dislocation density were calculated from the XRD data. Both the strain and dislocation density were found to increase with increasing Se . The observed grain fragmentation is explained on the basis of a combined effect of strain induced disintegration of grains after the Coulomb explosion, and an 'incomplete' re-crystallization of the molten thermal spikes. Moreover, the optical band gap Eg (1.5 eV for as-deposited film), determined from UV-vis spectroscopy, increased with Se, and possibly because of ion induced strain and defect annealing.

  11. Inhibition of Cariogenic Plaque Formation on Root Surface with Polydopamine-Induced-Polyethylene Glycol Coating

    Directory of Open Access Journals (Sweden)

    May Lei Mei

    2016-05-01

    Full Text Available Root caries prevention has been a challenge for clinicians due to its special anatomical location, which favors the accumulation of dental plaque. Researchers are looking for anti-biofouling material to inhibit bacterial growth on exposed root surfaces. This study aimed to develop polydopamine-induced-polyethylene glycol (PEG and to study its anti-biofouling effect against a multi-species cariogenic biofilm on the root dentine surface. Hydroxyapatite disks and human dentine blocks were divided into four groups for experiments. They received polydopamine-induced-PEG, PEG, polydopamine, or water application. Contact angle, quartz crystal microbalance, and Fourier transform infrared spectroscopy were used to study the wetting property, surface affinity, and an infrared spectrum; the results indicated that PEG was induced by polydopamine onto a hydroxyapatite disk. Salivary mucin absorption on hydroxyapatite disks with polydopamine-induced-PEG was confirmed using spectrophotometry. The growth of a multi-species cariogenic biofilm on dentine blocks with polydopamine-induced-PEG was assessed and monitored by colony-forming units, confocal laser scanning microscopy, and scanning electron microscopy. The results showed that dentine with polydopamine-induced-PEG had fewer bacteria than other groups. In conclusion, a novel polydopamine-induced-PEG coating was developed. Its anti-biofouling effect inhibited salivary mucin absorption and cariogenic biofilm formation on dentine surface and thus may be used for the prevention of root dentine caries.

  12. Ar + induced interfacial mixing and phase formation in the Al/Cr system

    Science.gov (United States)

    Kim, H. K.; Kim, S. O.; Song, J. H.; Kim, K. W.; Woo, J. J.; Whang, C. N.; Smith, R. J.

    1991-07-01

    Evaporated Al/Cr bilayer thin films were irradiated by 80 keV Ar + at doses in the range from 1 × 10 15 to 2 × 10 16 Ar +/cm 2 at room temperature in order to investigate the Ar + induced interfacial mixing behavior and the phase formation and transition by Ar + bombardment. Ion bombardment induces intermixing across the Al/Cr interface and mixing variance increases with increasing ion dose. Cascade and thermal spike models are found to be not adequate for the ion beam mixing mechanism at room temperature in this system. The Al 13Cr 2 phase is formed as an initial phase by ion beam mixing and then transforms into the Al 11Cr 2 or Al 4Cr phases at subsequent ion bombardment. This result is discussed in terms of the enhanced atomic mobility and the thermodynamical driving force by introducing the concept of an effective heat of formation.

  13. Osteoclasts secrete non-bone derived signals that induce bone formation

    DEFF Research Database (Denmark)

    Karsdal, Morten A; Neutzsky-Wulff, Anita V; Dziegiel, Morten Hanefeld

    2008-01-01

    Bone turnover is a highly regulated process, where bone resorption in the normal healthy individual always is followed by bone formation in a manner referred to as coupling. Patients with osteopetrosis caused by defective acidification of the resorption lacuna have severely decreased resorption, ...... secrete non-bone derived factors, which induce preosteoblasts to form bone-like nodules, potentially explaining the imbalanced coupling seen in osteopetrotic patients....

  14. Vaccine-induced myositis with intramuscular sterile abscess formation: MRI and ultrasound findings

    Energy Technology Data Exchange (ETDEWEB)

    Polat, Ahmet Veysel; Bekci, Tumay; Selcuk, Mustafa Bekir [Ondokuz Mayis University, Department of Radiology, Faculty of Medicine, Samsun (Turkey); Dabak, Nevzat [Ondokuz Mayis University, Department of Orthopaedics and Traumatology, Faculty of Medicine, Samsun (Turkey); Ulu, Esra Meltem Kayahan [Samsun Medical Park Hospital, Department of Radiology, Samsun (Turkey)

    2015-12-15

    Although limb swelling is a well-known complication of vaccination, its rarity and wide band of differential diagnosis of limb swelling make it a diagnostic challenge. In this case report, we describe three cases of vaccine-induced myositis with intramuscular sterile abscess formation in patients with limb swelling and their magnetic resonance imaging and ultrasonography findings. Both radiologists and clinicians should be familiar with this rare entity, its clinical and imaging spectrum, and follow-up strategies. (orig.)

  15. Aqueous 4-nitrophenol decomposition and hydrogen peroxide formation induced by contact glow discharge electrolysis.

    Science.gov (United States)

    Liu, Yongjun; Wang, Degao; Sun, Bing; Zhu, Xiaomei

    2010-09-15

    Liquid-phase decomposition of 4-nitrophenol (4-NP) and formation of hydrogen peroxide (H(2)O(2)) induced by contact glow discharge electrolysis (CGDE) were investigated. Experimental results showed that the decays of 4-NP and total organic carbon (TOC) obeyed the first-order and pseudo-first-order reaction kinetics, respectively. The major intermediate products were 4-nitrocatechol, hydroquinone, benzoquinone, hydroxyhydroquinone, organic acids and nitrite ion. The final products were carbon dioxide and nitrate ion. The initial formation rate of H(2)O(2) decreased linearly with increasing initial concentration of 4-NP. Addition of iron ions, especially ferric ion, to the solution significantly enhanced the 4-NP removal due to the additional hydroxyl radical formation through Fenton's reaction. A reaction pathway is proposed based on the degradation kinetics and the distribution of intermediate products.

  16. Oil spill dispersants induce formation of marine snow by phytoplankton-associated bacteria.

    Science.gov (United States)

    van Eenennaam, Justine S; Wei, Yuzhu; Grolle, Katja C F; Foekema, Edwin M; Murk, AlberTinka J

    2016-03-15

    Unusually large amounts of marine snow, including Extracellular Polymeric Substances (EPS), were formed during the 2010 Deepwater Horizon oil spill. The marine snow settled with oil and clay minerals as an oily sludge layer on the deep sea floor. This study tested the hypothesis that the unprecedented amount of chemical dispersants applied during high phytoplankton densities in the Gulf of Mexico induced high EPS formation. Two marine phytoplankton species (Dunaliella tertiolecta and Phaeodactylum tricornutum) produced EPS within days when exposed to the dispersant Corexit 9500. Phytoplankton-associated bacteria were shown to be responsible for the formation. The EPS consisted of proteins and to lesser extent polysaccharides. This study reveals an unexpected consequence of the presence of phytoplankton. This emphasizes the need to test the action of dispersants under realistic field conditions, which may seriously alter the fate of oil in the environment via increased marine snow formation.

  17. Polarization dependent formation of femtosecond laser-induced periodic surface structures near stepped features

    Science.gov (United States)

    Murphy, Ryan D.; Torralva, Ben; Adams, David P.; Yalisove, Steven M.

    2014-06-01

    Laser-induced periodic surface structures (LIPSS) are formed near 110 nm-tall Au microstructured edges on Si substrates after single-pulse femtosecond irradiation with a 150 fs pulse centered near a 780 nm wavelength. We investigate the contributions of Fresnel diffraction from step-edges and surface plasmon polariton (SPP) excitation to LIPSS formation on Au and Si surfaces. For certain laser polarization vector orientations, LIPSS formation is dominated by SPP excitation; however, when SPP excitation is minimized, Fresnel diffraction dominates. The LIPSS orientation and period distributions are shown to depend on which mechanism is activated. These results support previous observations of the laser polarization vector influencing LIPSS formation on bulk surfaces.

  18. Polarization dependent formation of femtosecond laser-induced periodic surface structures near stepped features

    Energy Technology Data Exchange (ETDEWEB)

    Murphy, Ryan D. [Applied Physics Program, University of Michigan, Ann Arbor, Michigan 48109 (United States); Torralva, Ben [Department of Atmospheric, Oceanic and Space Sciences, University of Michigan, Ann Arbor, Michigan 48109 (United States); Adams, David P. [Sandia National Laboratories, Albuquerque, New Mexico 87123 (United States); Yalisove, Steven M. [Department of Materials Science and Engineering, University of Michigan, Ann Arbor, Michigan 48109 (United States)

    2014-06-09

    Laser-induced periodic surface structures (LIPSS) are formed near 110 nm-tall Au microstructured edges on Si substrates after single-pulse femtosecond irradiation with a 150 fs pulse centered near a 780 nm wavelength. We investigate the contributions of Fresnel diffraction from step-edges and surface plasmon polariton (SPP) excitation to LIPSS formation on Au and Si surfaces. For certain laser polarization vector orientations, LIPSS formation is dominated by SPP excitation; however, when SPP excitation is minimized, Fresnel diffraction dominates. The LIPSS orientation and period distributions are shown to depend on which mechanism is activated. These results support previous observations of the laser polarization vector influencing LIPSS formation on bulk surfaces.

  19. 3D finite element modeling of chip formation and induced damage in machining Fiber reinforced composites

    Directory of Open Access Journals (Sweden)

    R. El Alaiji

    2015-07-01

    Full Text Available With the increasing demand for composite materials in many applications such as aerospace and automotive, their behavior needs to be thoroughly investigated, especially during and after failure. In the present work a three-dimensional (3D finite element (FE model is developed to study the machining of unidirectional (UD carbon fiber reinforced polymer composite (CFRP. Chip formation process and ply damage modes such as matrix cracking, fiber matrix shear, and fiber failure are modeled by degrading the material properties. The 3D Hashin failure criteria are used and implemented in the commercial finite element program Abaqus, using a VUMAT subroutine. The objective of this study is to understand the 3D chip formation process and to analyze the cutting induced damage from initiation stage until complete chip formation. The effect of fiber orientation on cutting forces is investigated. The numerical results have been compared with experimental results taken from the literature and showing a good agreement.

  20. Carnosine's effect on amyloid fibril formation and induced cytotoxicity of lysozyme.

    Directory of Open Access Journals (Sweden)

    Josephine W Wu

    Full Text Available Carnosine, a common dipeptide in mammals, has previously been shown to dissemble alpha-crystallin amyloid fibrils. To date, the dipeptide's anti-fibrillogensis effect has not been thoroughly characterized in other proteins. For a more complete understanding of carnosine's mechanism of action in amyloid fibril inhibition, we have investigated the effect of the dipeptide on lysozyme fibril formation and induced cytotoxicity in human neuroblastoma SH-SY5Y cells. Our study demonstrates a positive correlation between the concentration and inhibitory effect of carnosine against lysozyme fibril formation. Molecular docking results show carnosine's mechanism of fibrillogenesis inhibition may be initiated by binding with the aggregation-prone region of the protein. The dipeptide attenuates the amyloid fibril-induced cytotoxicity of human neuronal cells by reducing both apoptotic and necrotic cell deaths. Our study provides solid support for carnosine's amyloid fibril inhibitory property and its effect against fibril-induced cytotoxicity in SH-SY5Y cells. The additional insights gained herein may pave way to the discovery of other small molecules that may exert similar effects against amyloid fibril formation and its associated neurodegenerative diseases.

  1. cAMP prevents TNF-induced apoptosis through inhibiting DISC complex formation in rat hepatocytes

    Energy Technology Data Exchange (ETDEWEB)

    Bhattacharjee, Rajesh [Department of Surgery, University of Pittsburgh Medical Center, Pittsburgh, PA 15213 (United States); Xiang, Wenpei [Department of Surgery, University of Pittsburgh Medical Center, Pittsburgh, PA 15213 (United States); Family Planning Research Institute, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, People' s Republic of China (China); Wang, Yinna [Vascular Medicine Institute, University of Pittsburgh School of Medicine, 10051-5A BST 3, 3501 Fifth Avenue, Pittsburgh, PA 15261 (United States); Zhang, Xiaoying [Department of Medicine/Endocrinology Division, University of Pittsburgh Medical Center, 200 Lothrop St., Pittsburgh, PA 15213 (United States); Billiar, Timothy R., E-mail: billiartr@upmc.edu [Department of Surgery, University of Pittsburgh Medical Center, Pittsburgh, PA 15213 (United States)

    2012-06-22

    Highlights: Black-Right-Pointing-Pointer cAMP blocks cell death induced by TNF and actinomycin D in cultured hepatocytes. Black-Right-Pointing-Pointer cAMP blocks NF-{kappa}B activation induced by TNF and actinomycin D. Black-Right-Pointing-Pointer cAMP blocks DISC formation following TNF and actinomycin D exposure. Black-Right-Pointing-Pointer cAMP blocks TNF signaling at a proximal step. -- Abstract: Tumor necrosis factor {alpha} (TNF) is a pleiotropic proinflammatory cytokine that plays a role in immunity and the control of cell proliferation, cell differentiation, and apoptosis. The pleiotropic nature of TNF is due to the formation of different signaling complexes upon the binding of TNF to its receptor, TNF receptor type 1 (TNFR1). TNF induces apoptosis in various mammalian cells when the cells are co-treated with a transcription inhibitor like actinomycin D (ActD). When TNFR1 is activated, it recruits an adaptor protein, TNF receptor-associated protein with death domain (TRADD), through its cytoplasmic death effector domain (DED). TRADD, in turn, recruits other signaling proteins, including TNF receptor-associated protein 2 (TRAF2) and receptor-associated protein kinase (RIPK) 1, to form a complex. Subsequently, this complex combines with FADD and procaspase-8, converts into a death-inducing signaling complex (DISC) to induce apoptosis. Cyclic AMP (cAMP) is a second messenger that regulates various cellular processes such as cell proliferation, gene expression, and apoptosis. cAMP analogues are reported to act as anti-apoptotic agents in various cell types, including hepatocytes. We found that a cAMP analogue, dibutyryl cAMP (db-cAMP), inhibits TNF + ActD-induced apoptosis in rat hepatocytes. The protein kinase A (PKA) inhibitor KT-5720 reverses this inhibitory effect of cAMP on apoptosis. Cytoprotection by cAMP involves down-regulation of various apoptotic signal regulators like TRADD and FADD and inhibition of caspase-8 and caspase-3 cleavage. We also found

  2. THE COUNTER-JET FORMATION IN AN AIR BUBBLE INDUCED BY THE IMPACT OF SHOCK WAVES

    Institute of Scientific and Technical Information of China (English)

    BAI Li-xin; XU Wei-lin; LI Chao; GAO Yan-dong

    2011-01-01

    The interaction of an air bubble (isolated in water or attached to a boundary) with shock waves induced by electric sparks is investigated by high-speed photography.The interaction is closely related to the counter-jet induced by the impact of shock waves.The formation of a counter-jet in an air bubble is related to the liquid jet formed in the same air bubble,but the mechanism is different with that of the counter-jet formation in a collapsing cavitation bubble.The formation of a counter-jet in an air bubble is related to discharge energy,air bubble size and radius of shock wave.With a given energy of the spark discharge,the formation of a counter-jet in an air bubble is related to δ/ε (the ratio of the dimensionless bubble-bubble distance to the dimensionless air bubble radius).The counter-jet will only be produced when δ/ε is in the range of 1.2-2.2.The counter-jet in an air bubble is of an important nuclei-generating mechanism.

  3. Brain-derived neurotrophic factor mediates estradiol-induced dendritic spine formation in hippocampal neurons.

    Science.gov (United States)

    Murphy, D D; Cole, N B; Segal, M

    1998-09-15

    Dendritic spines are of major importance in information processing and memory formation in central neurons. Estradiol has been shown to induce an increase of dendritic spine density on hippocampal neurons in vivo and in vitro. The neurotrophin brain-derived neurotrophic factor (BDNF) recently has been implicated in neuronal maturation, plasticity, and regulation of GABAergic interneurons. We now demonstrate that estradiol down-regulates BDNF in cultured hippocampal neurons to 40% of control values within 24 hr of exposure. This, in turn, decreases inhibition and increases excitatory tone in pyramidal neurons, leading to a 2-fold increase in dendritic spine density. Exogenous BDNF blocks the effects of estradiol on spine formation, and BDNF depletion with a selective antisense oligonucleotide mimics the effects of estradiol. Addition of BDNF antibodies also increases spine density, and diazepam, which facilitates GABAergic neurotransmission, blocks estradiol-induced spine formation. These observations demonstrate a functional link between estradiol, BDNF as a potent regulator of GABAergic interneurons, and activity-dependent formation of dendritic spines in hippocampal neurons.

  4. cAMP prevents TNF-induced apoptosis through inhibiting DISC complex formation in rat hepatocytes.

    Science.gov (United States)

    Bhattacharjee, Rajesh; Xiang, Wenpei; Wang, Yinna; Zhang, Xiaoying; Billiar, Timothy R

    2012-06-22

    Tumor necrosis factor α (TNF) is a pleiotropic proinflammatory cytokine that plays a role in immunity and the control of cell proliferation, cell differentiation, and apoptosis. The pleiotropic nature of TNF is due to the formation of different signaling complexes upon the binding of TNF to its receptor, TNF receptor type 1 (TNFR1). TNF induces apoptosis in various mammalian cells when the cells are co-treated with a transcription inhibitor like actinomycin D (ActD). When TNFR1 is activated, it recruits an adaptor protein, TNF receptor-associated protein with death domain (TRADD), through its cytoplasmic death effector domain (DED). TRADD, in turn, recruits other signaling proteins, including TNF receptor-associated protein 2 (TRAF2) and receptor-associated protein kinase (RIPK) 1, to form a complex. Subsequently, this complex combines with FADD and procaspase-8, converts into a death-inducing signaling complex (DISC) to induce apoptosis. Cyclic AMP (cAMP) is a second messenger that regulates various cellular processes such as cell proliferation, gene expression, and apoptosis. cAMP analogues are reported to act as anti-apoptotic agents in various cell types, including hepatocytes. We found that a cAMP analogue, dibutyryl cAMP (db-cAMP), inhibits TNF+ActD-induced apoptosis in rat hepatocytes. The protein kinase A (PKA) inhibitor KT-5720 reverses this inhibitory effect of cAMP on apoptosis. Cytoprotection by cAMP involves down-regulation of various apoptotic signal regulators like TRADD and FADD and inhibition of caspase-8 and caspase-3 cleavage. We also found that cAMP exerts its affect at the proximal level of TNF signaling by inhibiting the formation of the DISC complex upon the binding of TNF to TNFR1. In conclusion, our study shows that cAMP prevents TNF+ActD-induced apoptosis in rat hepatocytes by inhibiting DISC complex formation.

  5. Formation of strain-induced quantum dots in gated semiconductor nanostructures

    Directory of Open Access Journals (Sweden)

    Ted Thorbeck

    2015-08-01

    Full Text Available A long-standing mystery in the field of semiconductor quantum dots (QDs is: Why are there so many unintentional dots (also known as disorder dots which are neither expected nor controllable. It is typically assumed that these unintentional dots are due to charged defects, however the frequency and predictability of the location of the unintentional QDs suggests there might be additional mechanisms causing the unintentional QDs besides charged defects. We show that the typical strains in a semiconductor nanostructure from metal gates are large enough to create strain-induced quantum dots. We simulate a commonly used QD device architecture, metal gates on bulk silicon, and show the formation of strain-induced QDs. The strain-induced QD can be eliminated by replacing the metal gates with poly-silicon gates. Thus strain can be as important as electrostatics to QD device operation operation.

  6. Formation of strain-induced quantum dots in gated semiconductor nanostructures

    Energy Technology Data Exchange (ETDEWEB)

    Thorbeck, Ted, E-mail: tcthorbeck@wisc.edu [Quantum Measurement Division, NIST, Gaithersburg, Maryland (United States); Joint Quantum Institute and Dept. of Physics, University of Maryland, College Park, Maryland (United States); Zimmerman, Neil M. [Quantum Measurement Division, NIST, Gaithersburg, Maryland (United States)

    2015-08-15

    A long-standing mystery in the field of semiconductor quantum dots (QDs) is: Why are there so many unintentional dots (also known as disorder dots) which are neither expected nor controllable. It is typically assumed that these unintentional dots are due to charged defects, however the frequency and predictability of the location of the unintentional QDs suggests there might be additional mechanisms causing the unintentional QDs besides charged defects. We show that the typical strains in a semiconductor nanostructure from metal gates are large enough to create strain-induced quantum dots. We simulate a commonly used QD device architecture, metal gates on bulk silicon, and show the formation of strain-induced QDs. The strain-induced QD can be eliminated by replacing the metal gates with poly-silicon gates. Thus strain can be as important as electrostatics to QD device operation operation.

  7. Characterization of glutamate-induced formation of N- acylphosphatidylethanolamine and N-acylethanolamine in cultured neocortical neurons

    DEFF Research Database (Denmark)

    Hansen, Harald S.; Lauritzen, L.; Strand, A.M.;

    1997-01-01

    Glutamate-induced formation of N-acylethanolamine (NAE) and N- acylphosphatidylethanolamine (NAPE) was studied in primary cultures of mouse neocortical neurons prelabeled with [C]ethanolamine. The formation of these two lipids was dependent on the maturity of the cell culture; i.e., no glutamate......-stimulated mouse astrocytes, rat Leydig cells and cardiomyocytes, and several other cells. These results suggest that the glutamate-induced formation of NAPE and NAE was mediated by the NMDA receptor and the formation of these lipids may be associated with neuronal death.......-quinoxaline-2,3-dione (CNQX). In 6-day-old cultures, exposure to NMDA (100 µM for 24 h) induced a linear increase in the formation of NAPE and NAE as well as a 40-50% neuronal death, as measured by a decrease in cellular formazan formation [3-(4,5-dimethylthiazol-2-yl)- 2,5-diphenyltetrazolium bromide (MTT...

  8. Lateral inhibition-induced pattern formation controlled by the size and geometry of the cell.

    Science.gov (United States)

    Seirin Lee, Sungrim

    2016-09-01

    Pattern formation in development biology is one of the fundamental processes by which cells change their functions. It is based on the communication of cells via intra- and intercellular dynamics of biochemicals. Thus, the cell is directly involved in biochemical interactions. However, many theoretical approaches describing biochemical pattern formation have usually neglected the cell's role or have simplified the subcellular process without considering cellular aspects despite the cell being the environment where biochemicals interact. On the other hand, recent experimental observations suggest that a change in the physical conditions of cell-to-cell contact can result in a change in cell fate and tissue patterning in a lateral inhibition system. Here we develop a mathematical model by which biochemical dynamics can be directly observed with explicitly expressed cell structure and geometry in higher dimensions, and reconsider pattern formation by lateral inhibition of the Notch-Delta signaling pathway. We explore how the physical characteristic of cell, such as cell geometry or size, influences the biochemical pattern formation in a multi-cellular system. Our results suggest that a property based on cell geometry can be a novel mechanism for symmetry breaking inducing cell asymmetry. We show that cell volume can critically influence cell fate determination and pattern formation at the tissue level, and the surface area of the cell-to-cell contact can directly affect the spatial range of patterning.

  9. Jet-induced star formation in 3C 285 and Minkowski Object

    CERN Document Server

    Salomé, Q; Combes, F

    2014-01-01

    How efficiently star formation proceeds in galaxies is still an open question. Recent studies suggest that AGN can regulate the gas accretion and thus slow down star formation (negative feedback). However, evidence of AGN positive feedback has also been observed in a few radio galaxies (eg. Centaurus A). Here we present CO observations of 3C 285 and Minkowski Object (MO), which are examples of jet-induced star formation. A spot (named 09.6) aligned with the 3C 285 radio jet, at a projected distance of ~70 kpc from the galaxy centre, shows star formation, detected in optical emission. MO is located along the jet of NGC 541 and also shows star formation. To know the distribution of molecular gas along the jets is a way to study the physical processes at play in the AGN interaction with the intergalactic medium. We observed CO lines in 3C 285, NGC 541, 09.6 and MO with the IRAM-30m telescope. In the central galaxies, the spectra present a double-horn profile, typical of a rotation pattern, from which we are able...

  10. Numerical modelling of tooth enamel subsurface lesion formation induced by dental plaque.

    Science.gov (United States)

    Ilie, O; van Turnhout, A G; van Loosdrecht, M C M; Picioreanu, C

    2014-01-01

    Using a one-dimensional mathematical model that couples tooth demineralisation and remineralisation with metabolic processes occurring in the dental plaque, two mechanisms for subsurface lesion formation were evaluated. It was found that a subsurface lesion can develop only as the result of alternating periods of demineralisation (acid attack during sugar consumption) and remineralisation (resting period) in tooth enamel with uniform mineral composition. It was also shown that a minimum plaque thickness that can induce an enamel lesion exists. The subsurface lesion formation can also be explained by assuming the existence of a fluoride-containing layer at the tooth surface that decreases enamel solubility. A nearly constant thickness of the surface layer was obtained with both proposed mechanisms. Sensitivity analysis showed that surface layer formation is strongly dependent on the length of remineralisation and demineralisation cycles. The restoration period is very important and the numerical simulations support the observation that often consumption of sugars is a key factor in caries formation. The calculated profiles of mineral content in enamel are similar to those observed experimentally. Most probably, both studied mechanisms interact in vivo in the process of caries development, but the simplest explanation for subsurface lesion formation remains the alternation between demineralisation and remineralisation cycles without any pre-imposed gradients.

  11. Sub-inhibitory concentrations of penicillin G induce biofilm formation by field isolates of Actinobacillus pleuropneumoniae.

    Science.gov (United States)

    Hathroubi, S; Fontaine-Gosselin, S-È; Tremblay, Y D N; Labrie, J; Jacques, M

    2015-09-30

    Actinobacillus pleuropneumoniae is a Gram-negative bacterium and causative agent of porcine pleuropneumonia. This is a highly contagious disease that causes important economic losses to the swine industry worldwide. Penicillins are extensively used in swine production and these antibiotics are associated with high systemic clearance and low oral bioavailability. This may expose A. pleuropneumoniae to sub-inhibitory concentrations of penicillin G when the antibiotic is administered orally. Our goal was to evaluate the effect of sub-minimum inhibitory concentration (MIC) of penicillin G on the biofilm formation of A. pleuropneumoniae. Biofilm production of 13 field isolates from serotypes 1, 5a, 7 and 15 was tested in the presence of sub-MIC of penicillin G using a polystyrene microtiter plate assay. Using microscopy techniques and enzymatic digestion, biofilm architecture and composition were also characterized after exposure to sub-MIC of penicillin G. Sub-MIC of penicillin G significantly induced biofilm formation of nine isolates. The penicillin G-induced biofilms contained more poly-N-acetyl-D-glucosamine (PGA), extracellular DNA and proteins when compared to control biofilms grown without penicillin G. Additionally, penicillin G-induced biofilms were sensitive to DNase which was not observed with the untreated controls. Furthermore, sub-MIC of penicillin G up-regulated the expression of pgaA, which encodes a protein involved in PGA synthesis, and the genes encoding the envelope-stress sensing two-component regulatory system CpxRA. In conclusion, sub-MICs of penicillin G significantly induce biofilm formation and this is likely the result of a cell envelope stress sensed by the CpxRA system resulting in an increased production of PGA and other matrix components.

  12. Evidence of liquid phase during laser-induced periodic surface structures formation induced by accumulative ultraviolet picosecond laser beam

    Energy Technology Data Exchange (ETDEWEB)

    Huynh, T. T. D.; Petit, A.; Semmar, N., E-mail: nadjib.semmar@univ-orleans.fr [GREMI, UMR7344, CNRS/University of Orleans, 14 rue d' Issoudun, BP6744, 45067 Orleans Cedex 2 (France); Vayer, M. [ICMN, UMR 7374, CNRS/University of Orleans, 1b rue de la Ferollerie, CS 40059, 45071 Orleans Cedex (France); Sauldubois, A. [CME, UFR Sciences, University of Orleans, 1 Rue de Chartres, BP 6759, 45067 Orleans Cedex 2 (France)

    2015-11-09

    Laser-induced periodic surface structures (LIPSS) were formed on Cu/Si or Cu/glass thin films using Nd:YAG laser beam (40 ps, 10 Hz, and 30 mJ/cm{sup 2}). The study of ablation threshold is always achieved over melting when the variation of the number of pulses increases from 1 to 1000. But the incubation effect is leading to reduce the threshold of melting as increasing the number of laser pulse. Also, real time reflectivity signals exhibit typical behavior to stress the formation of a liquid phase during the laser-processing regime and helps to determine the threshold of soft ablation. Atomic Force Microscopy (AFM) analyses have shown the topology of the micro-crater containing regular spikes with different height. Transmission Electron Microscopy (TEM) allows finally to show three distinguished zones in the close region of isolated protrusions. The central zone is a typical crystallized area of few nanometers surrounded by a mixed poly-crystalline and amorphous area. Finally, in the region far from the protrusion zone, Cu film shows an amorphous structure. The real time reflectivity, AFM, and HR-TEM analyses evidence the formation of a liquid phase during the LIPSS formation in the picosecond regime.

  13. Evidence of liquid phase during laser-induced periodic surface structures formation induced by accumulative ultraviolet picosecond laser beam

    Science.gov (United States)

    Huynh, T. T. D.; Vayer, M.; Sauldubois, A.; Petit, A.; Semmar, N.

    2015-11-01

    Laser-induced periodic surface structures (LIPSS) were formed on Cu/Si or Cu/glass thin films using Nd:YAG laser beam (40 ps, 10 Hz, and 30 mJ/cm2). The study of ablation threshold is always achieved over melting when the variation of the number of pulses increases from 1 to 1000. But the incubation effect is leading to reduce the threshold of melting as increasing the number of laser pulse. Also, real time reflectivity signals exhibit typical behavior to stress the formation of a liquid phase during the laser-processing regime and helps to determine the threshold of soft ablation. Atomic Force Microscopy (AFM) analyses have shown the topology of the micro-crater containing regular spikes with different height. Transmission Electron Microscopy (TEM) allows finally to show three distinguished zones in the close region of isolated protrusions. The central zone is a typical crystallized area of few nanometers surrounded by a mixed poly-crystalline and amorphous area. Finally, in the region far from the protrusion zone, Cu film shows an amorphous structure. The real time reflectivity, AFM, and HR-TEM analyses evidence the formation of a liquid phase during the LIPSS formation in the picosecond regime.

  14. Nf1+/- monocytes/macrophages induce neointima formation via CCR2 activation.

    Science.gov (United States)

    Bessler, Waylan K; Kim, Grace; Hudson, Farlyn Z; Mund, Julie A; Mali, Raghuveer; Menon, Keshav; Kapur, Reuben; Clapp, D Wade; Ingram, David A; Stansfield, Brian K

    2016-03-15

    Persons with neurofibromatosis type 1 (NF1) have a predisposition for premature and severe arterial stenosis. Mutations in the NF1 gene result in decreased expression of neurofibromin, a negative regulator of p21(Ras), and increases Ras signaling. Heterozygous Nf1 (Nf1(+/-)) mice develop a marked arterial stenosis characterized by proliferating smooth muscle cells (SMCs) and a predominance of infiltrating macrophages, which closely resembles arterial lesions from NF1 patients. Interestingly, lineage-restricted inactivation of a single Nf1 allele in monocytes/macrophages is sufficient to recapitulate the phenotype observed in Nf1(+/-) mice and to mobilize proinflammatory CCR2+ monocytes into the peripheral blood. Therefore, we hypothesized that CCR2 receptor activation by its primary ligand monocyte chemotactic protein-1 (MCP-1) is critical for monocyte infiltration into the arterial wall and neointima formation in Nf1(+/-) mice. MCP-1 induces a dose-responsive increase in Nf1(+/-) macrophage migration and proliferation that corresponds with activation of multiple Ras kinases. In addition, Nf1(+/-) SMCs, which express CCR2, demonstrate an enhanced proliferative response to MCP-1 when compared with WT SMCs. To interrogate the role of CCR2 activation on Nf1(+/-) neointima formation, we induced neointima formation by carotid artery ligation in Nf1(+/-) and WT mice with genetic deletion of either MCP1 or CCR2. Loss of MCP-1 or CCR2 expression effectively inhibited Nf1(+/-) neointima formation and reduced macrophage content in the arterial wall. Finally, administration of a CCR2 antagonist significantly reduced Nf1(+/-) neointima formation. These studies identify MCP-1 as a potent chemokine for Nf1(+/-) monocytes/macrophages and CCR2 as a viable therapeutic target for NF1 arterial stenosis.

  15. Pomegranate extract induces ellagitannin metabolite formation and changes stool microbiota in healthy volunteers.

    Science.gov (United States)

    Li, Zhaoping; Henning, Susanne M; Lee, Ru-Po; Lu, Qing-Yi; Summanen, Paula H; Thames, Gail; Corbett, Karen; Downes, Julia; Tseng, Chi-Hong; Finegold, Sydney M; Heber, David

    2015-08-01

    The health benefits of pomegranate (POM) consumption are attributed to ellagitannins and their metabolites, formed and absorbed in the intestine by the microbiota. In this study twenty healthy participants consumed 1000 mg of POM extract daily for four weeks. Based on urinary and fecal content of the POM metabolite urolithin A (UA), we observed three distinct groups: (1) individuals with no baseline UA presence but induction of UA formation by POM extract consumption (n = 9); (2) baseline UA formation which was enhanced by POM extract consumption (N = 5) and (3) no baseline UA production, which was not inducible (N = 6). Compared to baseline the phylum Actinobacteria was increased and Firmicutes decreased significantly in individuals forming UA (producers). Verrucomicrobia (Akkermansia muciniphila) was 33 and 47-fold higher in stool samples of UA producers compared to non-producers at baseline and after 4 weeks, respectively. In UA producers, the genera Butyrivibrio, Enterobacter, Escherichia, Lactobacillus, Prevotella, Serratia and Veillonella were increased and Collinsella decreased significantly at week 4 compared to baseline. The consumption of pomegranate resulted in the formation of its metabolites in some but not all participants. POM extract consumption may induce health benefits secondary to changes in the microbiota.

  16. Formation mechanism of photo-induced nested wrinkles on siloxane-photomonomer hybrid film

    Energy Technology Data Exchange (ETDEWEB)

    Suzuki, Kazumasa [Department of Materials Science, Osaka Prefecture University, Sakai, Osaka 599-8531 (Japan); International Laboratory of Materials Science and Nanotechnology (iLMNT), Osaka Prefecture University, Sakai, Osaka 599-8531 (Japan); Laboratorio di Scienz (Italy); Tokudome, Yasuaki, E-mail: masa@photomater.com; Takahashi, Masahide, E-mail: masa@photomater.com [Department of Materials Science, Osaka Prefecture University, Sakai, Osaka 599-8531 (Japan); International Laboratory of Materials Science and Nanotechnology (iLMNT), Osaka Prefecture University, Sakai, Osaka 599-8531 (Japan)

    2014-10-21

    Nested wrinkle structures, hierarchical surface wrinkles of different periodicities of sub-μm and tens-μm, have been fabricated on a siloxane-photomonomer hybrid film via a photo-induced surface polymerization of acrylamide. The formation mechanism of the nested wrinkle structures is examined based on a time-dependent structure observation and chemical composition analyses. In-situ observation of the evolving surface structure showed that sub-μm scale wrinkles first formed, subsequently the tens-μm scale ones did. In-situ FT-IR analysis indicated that the nested wrinkles formation took place along with the development of siloxane network of under layer. A cross sectional observation of the film revealed that the film was composed of three layers. FT-IR spectra of the film revealed that the surface and interior layers were polyacrylamide rich layer and siloxane-polymer rich layer, respectively. The intermediate layer formed as a diffusion layer by migration of acrylamide from interior to the surface. These three layers have different chemical compositions and therefore different mechanical characteristics, which allows the wrinkle formation. Shrinkage of siloxane-polymer interior layers, as a result of polycondensation of siloxane network, induced mechanical instabilities at interlayers, to form the nested wrinkle structures.

  17. Stromal cell-derived factor-1 potentiates bone morphogenetic protein-2 induced bone formation.

    Science.gov (United States)

    Higashino, Kosaku; Viggeswarapu, Manjula; Bargouti, Maggie; Liu, Hui; Titus, Louisa; Boden, Scott D

    2011-02-01

    The mechanisms driving bone marrow stem cell mobilization are poorly understood. A recent murine study found that circulating bone marrow-derived osteoprogenitor cells (MOPCs) were recruited to the site of recombinant human bone morphogenetic protein-2 (BMP-2)-induced bone formation. Stromal cell-derived factor-1α (SDF-1α) and its cellular receptor CXCR4 have been shown to mediate the homing of stem cells to injured tissues. We hypothesized that chemokines, such as SDF-1, are also involved with mobilization of bone marrow cells. The CD45(-) fraction is a major source of MOPCs. In this report we determined that the addition of BMP-2 or SDF-1 to collagen implants increased the number of MOPCs in the peripheral blood. BMP-2-induced mobilization was blocked by CXCR4 antibody, confirming the role of SDF-1 in mobilization. We determined for the first time that addition of SDF-1 to implants containing BMP-2 enhances mobilization, homing of MOPCs to the implant, and ectopic bone formation induced by suboptimal BMP-2 doses. These results suggest that SDF-1 increases the number of osteoprogenitor cells that are mobilized from the bone marrow and then home to the implant. Thus, addition of SDF-1 to BMP-2 may improve the efficiency of BMPs in vivo, making their routine use for orthopaedic applications more affordable and available to more patients.

  18. Caenorhabditis elegans star formation and negative chemotaxis induced by infection with corynebacteria.

    Science.gov (United States)

    Antunes, Camila Azevedo; Clark, Laura; Wanuske, Marie-Therès; Hacker, Elena; Ott, Lisa; Simpson-Louredo, Liliane; de Luna, Maria das Gracas; Hirata, Raphael; Mattos-Guaraldi, Ana Luíza; Hodgkin, Jonathan; Burkovski, Andreas

    2016-01-01

    Caenorhabditis elegans is one of the major model systems in biology based on advantageous properties such as short life span, transparency, genetic tractability and ease of culture using an Escherichia coli diet. In its natural habitat, compost and rotting plant material, this nematode lives on bacteria. However, C. elegans is a predator of bacteria, but can also be infected by nematopathogenic coryneform bacteria such Microbacterium and Leucobacter species, which display intriguing and diverse modes of pathogenicity. Depending on the nematode pathogen, aggregates of worms, termed worm-stars, can be formed, or severe rectal swelling, so-called Dar formation, can be induced. Using the human and animal pathogens Corynebacterium diphtheriae and Corynebacterium ulcerans as well as the non-pathogenic species Corynebacterium glutamicum, we show that these coryneform bacteria can also induce star formation slowly in worms, as well as a severe tail-swelling phenotype. While C. glutamicum had a significant, but minor influence on survival of C. elegans, nematodes were killed after infection with C. diphtheriae and C. ulcerans. The two pathogenic species were avoided by the nematodes and induced aversive learning in C. elegans.

  19. Clostridium perfringens TpeL Induces Formation of Stress Fibers via Activation of RhoA-ROCK Signaling Pathway.

    Science.gov (United States)

    Nagahama, Masahiro; Ohkubo, Akiko; Kinouchi, Yoshihito; Kobayashi, Keiko; Miyamoto, Kazuaki; Takehara, Masaya; Sakurai, Jun

    2015-01-01

    Clostridium perfringens TpeL belongs to a family of large clostridial glucosylating cytotoxins. TpeL modifies Rac1 and Ras subfamily proteins. Herein we report TpeL-induced formation of stress fibers via RhoA-Rho kinase (ROCK) signaling. A recombinant protein (TpeL1-525) derived from the TpeL N-terminal catalytic domain in the presence of streptolysin O (SLO) induced the formation of actin stress fibers in Madin-Darby canine kidney (MDCK) cells in a dose-dependent manner. The RhoA/ROCK pathway is known to control the formation of stress fibers. We examined the role of the RhoA/ROCK pathway in TpeL-induced formation of stress fibers. TpeL1-525-induced formation of stress fibers was inhibited by the ROCK inhibitor, Y27632 and Rho protein inhibitor, C3 transferase. TpeL1-525 activated RhoA and ROCK in a dose-dependent manner. C3 transferase blocked TpeL1-525-induced activation of RhoA and ROCK whereas Y27632 inhibited TpeL-induced activation of ROCK. These results demonstrate for the first time that TpeL induces the formation of stress fibers by activating the RhoA/ROCK signaling pathway.

  20. Platelet size and density affect shear-induced thrombus formation in tortuous arterioles

    Science.gov (United States)

    Chesnutt, Jennifer K. W.; Han, Hai-Chao

    2013-10-01

    Thrombosis accounts for 80% of deaths in patients with diabetes mellitus. Diabetic patients demonstrate tortuous microvessels and larger than normal platelets. Large platelets are associated with increased platelet activation and thrombosis, but the physical effects of large platelets in the microscale processes of thrombus formation are not clear. Therefore, the objective of this study was to determine the physical effects of mean platelet volume (MPV), mean platelet density (MPD) and vessel tortuosity on platelet activation and thrombus formation in tortuous arterioles. A computational model of the transport, shear-induced activation, collision, adhesion and aggregation of individual platelets was used to simulate platelet interactions and thrombus formation in tortuous arterioles. Our results showed that an increase in MPV resulted in a larger number of activated platelets, though MPD and level of tortuosity made little difference on platelet activation. Platelets with normal MPD yielded the lowest amount of mural thrombus. With platelets of normal MPD, the amount of mural thrombus decreased with increasing level of tortuosity but did not have a simple monotonic relationship with MPV. The physical mechanisms associated with MPV, MPD and arteriole tortuosity play important roles in platelet activation and thrombus formation.

  1. A Hydrogel's Formation Device for Quick Analysis of Liquid Samples Using Laser-Induced Breakdown Spectroscopy

    Science.gov (United States)

    Guo, Guangmeng; Wang, Jie; Bian, Fang; Tian, Di; Fan, Qingwen

    2016-06-01

    The laser-induced breakdown spectroscopy technique has irreplaceable advantages in the field of detection due to its multi-phase specimen detection ability. The development of the LIBS technique for liquid analysis is obstructed by its inherent drawbacks like the surface ripples and extinction of emitted intensity, which make it unpractical. In this work, an in-situ hydrogel formation sampling device was designed and used the hydrogel as the detection phase of LIBS for Cu, Cr and Al in an aqueous solution. With the measured amount of resin placed in the device, the formed hydrogel could be obtained within 20 s after putting the device into water solution. The formed hydrogel could be directly analyzed by LIBS and reflect the elemental information of the water sample. The prominent performance made this hydrogel's formation device especially suitable for quick in-situ environmental liquid analysis using LIBS.

  2. Editing VEGFR2 Blocks VEGF-Induced Activation of Akt and Tube Formation

    Science.gov (United States)

    Huang, Xionggao; Zhou, Guohong; Wu, Wenyi; Ma, Gaoen; D'Amore, Patricia A.; Mukai, Shizuo; Lei, Hetian

    2017-01-01

    Purpose Vascular endothelial growth factor receptor 2 (VEGFR2) plays a key role in VEGF-induced angiogenesis. The goal of this project was to test the hypothesis that editing genomic VEGFR2 loci using the technology of clustered regularly interspaced palindromic repeats (CRISPR)-associated DNA endonuclease (Cas)9 in Streptococcus pyogenes (SpCas9) was able to block VEGF-induced activation of Akt and tube formation. Methods Four 20 nucleotides for synthesizing single-guide RNAs based on human genomic VEGFR2 exon 3 loci were selected and cloned into a lentiCRISPR v2 vector, respectively. The DNA fragments from the genomic VEGFR2 exon 3 of transduced primary human retinal microvascular endothelial cells (HRECs) were analyzed by Sanger DNA sequencing, surveyor nuclease assay, and next-generation sequencing (NGS). In the transduced cells, expression of VEGFR2 and VEGF-stimulated signaling events (e.g., Akt phosphorylation) were determined by Western blot analyses; VEGF-induced cellular responses (proliferation, migration, and tube formation) were examined. Results In the VEGFR2-sgRNA/SpCas9–transduced HRECs, Sanger DNA sequencing indicated that there were mutations, and NGS demonstrated that there were 83.57% insertion and deletions in the genomic VEGFR2 locus; expression of VEGFR2 was depleted in the VEGFR2-sgRNA/SpCas9–transduced HRECs. In addition, there were lower levels of Akt phosphorylation in HRECs with VEGFR2-sgRNA/SpCas9 than those with LacZ-sgRNA/SpCas9, and there was less VEGF-stimulated Akt activation, proliferation, migration, or tube formation in the VEGFR2-depleted HRECs than those treated with aflibercept or ranibizumab. Conclusions The CRISPR-SpCas9 technology is a potential novel approach to prevention of pathologic angiogenesis. PMID:28241310

  3. Ketoprofen-induced formation of amino acid photoadducts: possible explanation for photocontact allergy to ketoprofen.

    Science.gov (United States)

    Karlsson, Isabella; Persson, Elin; Ekebergh, Andreas; Mårtensson, Jerker; Börje, Anna

    2014-07-21

    Photocontact allergy is a well-known side effect of topical preparations of the nonsteroidal anti-inflammatory drug ketoprofen. Photocontact allergy to ketoprofen appears to induce a large number of photocross allergies to both structurally similar and structurally unrelated compounds. Contact and photocontact allergies are explained by structural modification of skin proteins by the allergen. This complex is recognized by the immune system, which initiates an immune response. We have studied ketoprofen's interaction with amino acids to better understand ketoprofen's photoallergenic ability. Irradiation of ketoprofen and amino acid analogues resulted in four different ketoprofen photodecarboxylation products (6-9) together with a fifth photoproduct (5). Dihydroquinazoline 5 was shown to be a reaction product between the indole moiety of 3-methylindole (Trp analogue) and the primary amine benzylamine (Lys analogue). In presence of air, dihydroquinazoline 5 quickly degrades into stable quinazolinone 12. The corresponding quinazolinone (17) was formed upon irradiation of ketoprofen and the amino acids N-acetyl-l-Trp ethyl ester and l-Lys ethyl ester. The formation of these models of an immunogenic complex starts with the ketoprofen-sensitized formation of singlet oxygen, which reacts with the indole moiety of Trp. The formed intermediate subsequently reacts with the primary amino functionality of Lys, or its analogue, to form a Trp-Lys adduct or a mimic thereof. The formation of a specific immunogenic complex that does not contain the allergen but that can still induce photocontact allergy would explain the large number of photocross allergies with ketoprofen. These allergens do not have to be structurally similar as long as they can generate singlet oxygen. To the best of our knowledge, there is no other suggested explanation for ketoprofen's photoallergenic properties that can account for the observed photocross allergies. The formation of a specific immunogenic

  4. Melatonin Reduces Cataract Formation and Aldose Reductase Activity in Lenses of Streptozotocin-induced Diabetic Rat

    Directory of Open Access Journals (Sweden)

    Marjan Khorsand

    2016-07-01

    Full Text Available Background: The relationship between the high activity of aldose reductase (AR and diabetic cataract formation has been previously investigated. The purpose of the present study was to determine the preventing effect of melatonin on streptozotocin (STZ-induced diabetic cataract in rats. Methods: 34 adult healthy male Sprague-Dawely rats were divided into four groups. Diabetic control and diabetic+melatonin received a single dose of STZ (50 mg/kg, intraperitoneally, whereas the normal control and normal+melatonin received vehicle. The melatonin groups were gavaged with melatonin (5 mg/kg daily for a period of 8 weeks, whereas the rats in the normal control and diabetic control groups received only the vehicle. The rats’ eyes were examined every week and cataract formation scores (0-4 were determined by slit-lamp microscope. At the end of the eighth week, the rats were sacrificed and markers of the polyol pathway and antioxidative (Glutathione, GSH in their lens were determined. The levels of blood glucose, HbA1c and plasma malondialdhyde (MDA, as a marker of lipid peroxidation, were also measured. Results: Melatonin prevented STZ-induced hyperglycemia by decreased blood glucose and HbA1c levels. Slit lamp examination indicated that melatonin delayed cataract progression in diabetic rats. The results revealed that melatonin feeding increased the GSH levels, decreased the activities of AR and sorbitol dehydrogenase (SDH and sorbitol formation in catractous lenses as well as plasma MDA content. Conclusion: In summary, for the first time we demonstrated that melatonin delayed the formation and progression of cataract in diabetic rat lenses.

  5. New observations on formation of thermally induced martensite in Fe–30%Ni–1%Pd alloy

    Indian Academy of Sciences (India)

    Gokcen Yildiz; Yasin Gokturk Yildiz; Saffet Nezir

    2013-02-01

    Kinetical, morphological, crystallographical and thermal characteristics of thermally induced martensite in an Fe–30%Ni–1%Pd alloy has been studied by scanning electron microscopy (SEM), transmission electron microscopy (TEM), differential scanning calorimetry (DSC) and X-ray diffraction method. Kinetics of transformation was found to be as athermal. SEM and TEM observations and X-ray method revealed ' () martensite formation in the austenite phase of alloy by thermal effect. The crystallographic orientation relationship between austenite and ' () martensite was found to be having Kurdjumov–Sachs (K–S) type relationship. In addition, the lattice parameters of austenite and martensite phases were calculated from X-ray diffraction patterns.

  6. Oligo-lysine Induced Formation of Silica Particles in Neutral Silicate Solution

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    Oligo-(lysine)n (n = 1-4) containing different numbers of lysine residues was used to induce the condensation of silicic acid to form silica particles in neutral silicate solution. It was found that the condensation rate and the formation of silica particles are dependent on the number of lysine residues in an oligo-lysine. Oligo-lysine with more lysine residues can link more silicic acid together to form a matrix that promotes the effective aggregation of the condensed silica pieces to form large silica particles.

  7. Auxin effectively induces the formation of the secondary abscission zone in Bryophyllum calycinum Salisb. (Crassulaceae)

    OpenAIRE

    Marian Saniewski; Justyna Góraj-Koniarska; Eleonora Gabryszewska; Kensuke Miyamoto; Junichi Ueda

    2016-01-01

    We have found that auxin, indole-3-acetic acid (IAA) substantially induces the formation of the secondary abscission zone in stem and petiole explants and in decapitated stem and petiole after excision of blade in intact plants of Bryophyllum calycinum when IAA at a concentration of 0.1% as lanolin paste was applied in the middle of these organs. The secondary abscission zone was formed at a few mm above of the treatment with IAA, and senescence of the part above abscission zone was observed....

  8. Microwave-induced formation of platinum nanostructured networks with superior electrochemical activity and stability.

    Science.gov (United States)

    Jia, Falong; Wang, Fangfang; Lin, Yun; Zhang, Lizhi

    2011-12-16

    Platinum nanostructured networks (PNNs) can be synthesized through the chemical reduction of H(2)PtCl(6) by benzyl alcohol under microwave irradiation without the introduction of any surfactants, templates, or seeds. The synthesis route utilizes benzyl alcohol as both the reductant and the structure-directing agent, and thus, the process is particularly simple and highly repeatable. The formation of the PNN structure was ascribed to the collision-induced fusion of Pt nanocrystals owing to the cooperative functions of microwave irradiation and benzyl alcohol. Compared with a commercial Pt/C catalyst, the as-prepared PNNs possessed superior electrochemical activity and stability on the oxidation of methanol because of the unique 3D nanostructured networks and abundant defects formed during the assembly process. This study may provide a facile microwave-induced approach for the synthesis of other 3D nanostructured noble metals or their alloys.

  9. Eugenol prevents amyloid formation of proteins and inhibits amyloid-induced hemolysis

    Science.gov (United States)

    Dubey, Kriti; Anand, Bibin G.; Shekhawat, Dolat Singh; Kar, Karunakar

    2017-02-01

    Eugenol has attracted considerable attention because of its potential for many pharmaceutical applications including anti-inflammatory, anti-tumorigenic and anti-oxidant properties. Here, we have investigated the effect of eugenol on amyloid formation of selected globular proteins. We find that both spontaneous and seed-induced aggregation processes of insulin and serum albumin (BSA) are significantly suppressed in the presence of eugenol. Isothermal titration calorimetric data predict a single binding site for eugenol-insulin complex confirming the affinity of eugenol for native soluble insulin species. We also find that eugenol suppresses amyloid-induced hemolysis. Our findings reveal the inherent ability of eugenol to stabilize native proteins and to delay the conversion of protein species of native conformation into β-sheet assembled mature fibrils, which seems to be crucial for its inhibitory effect.

  10. Valproic Acid-Induced Severe Acute Pancreatitis with Pseudocyst Formation: Report of a Case.

    Science.gov (United States)

    Ray, Sukanta; Khamrui, Sujan; Kataria, Mohnish; Biswas, Jayanta; Saha, Suman

    2015-08-01

    Valproic acid is the most widely used anti-epilep-tic drug in children, and it is probably the most frequent cause of drug-induced acute pancreatitis. Outcomes for patients with valproic acid-associated pancreatitis vary from full recovery after discontinuation of the drug to severe acute pancreatitis and death. Here, we present a case of valproic acid-induced severe acute pancreatitis with pseudocyst formation in a 10-year-old girl with cerebral palsy and generalized tonic-clonic seizure. There was no resolution of the pseudocyst after discontinuation of valproic acid. The patient became symptomatic with a progressive increase in the size of the pseudocyst. She was successfully treated with cystogastrostomy and was well at 12-month follow-up.

  11. Tolerogenic nanoparticles to induce immunologic tolerance: Prevention and reversal of FVIII inhibitor formation.

    Science.gov (United States)

    Zhang, Ai-Hong; Rossi, Robert J; Yoon, Jeongheon; Wang, Hong; Scott, David W

    2016-03-01

    The immune response of hemophilia A patients to administered FVIII is a major complication that obviates this very therapy. We have recently described the use of synthetic, biodegradable nanoparticles carrying rapamycin and FVIII peptide antigens, to induce antigen-specific tolerance. Herein we test the tolerogenicity of nanoparticles that contains full length FVIII protein in hemophilia A mice, focusing on anti-FVIII humoral immune response. As expected, recipients of tolerogenic nanoparticles remained unresponsive to FVIII despite multiple challenges for up to 6 months. Furthermore, therapeutic treatments in FVIII-immunized mice with pre-existing anti-FVIII antibodies resulted in diminished antibody titers, albeit efficacy required longer therapy with the tolerogenic nanoparticles. Interestingly, durable FVIII-specific tolerance was also achieved in animals co-administered with FVIII admixed with nanoparticles encapsulating rapamycin alone. These results suggest that nanoparticles carrying rapamycin and FVIII can be employed to induce specific tolerance to prevent and even reverse inhibitor formation.

  12. Deciphering How Pore Formation Causes Strain-Induced Membrane Lysis of Lipid Vesicles.

    Science.gov (United States)

    Jackman, Joshua A; Goh, Haw Zan; Zhdanov, Vladimir P; Knoll, Wolfgang; Cho, Nam-Joon

    2016-02-01

    Pore formation by membrane-active antimicrobial peptides is a classic strategy of pathogen inactivation through disruption of membrane biochemical gradients. It remains unknown why some membrane-active peptides also inhibit enveloped viruses, which do not depend on biochemical gradients. Here, we employ a label-free biosensing approach based on simultaneous quartz crystal microbalance-dissipation and ellipsometry measurements in order to investigate how a pore-forming, virucidal peptide destabilizes lipid vesicles in a surface-based experimental configuration. A key advantage of the approach is that it enables direct kinetic measurement of the surface-bound peptide-to-lipid (P:L) ratio. Comprehensive experiments involving different bulk peptide concentrations and biologically relevant membrane compositions support a unified model that membrane lysis occurs at or above a critical P:L ratio, which is at least several-fold greater than the value corresponding to the onset of pore formation. That is consistent with peptide-induced pores causing additional membrane strain that leads to lysis of highly curved membranes. Collectively, the work presents a new model that describes how peptide-induced pores may destabilize lipid membranes through a membrane strain-related lytic process, and this knowledge has important implications for the design and application of membrane-active peptides.

  13. Comparison of free radicals formation induced by cold atmospheric plasma, ultrasound, and ionizing radiation.

    Science.gov (United States)

    Rehman, Mati Ur; Jawaid, Paras; Uchiyama, Hidefumi; Kondo, Takashi

    2016-09-01

    Plasma medicine is increasingly recognized interdisciplinary field combining engineering, physics, biochemistry and life sciences. Plasma is classified into two categories based on the temperature applied, namely "thermal" and "non-thermal" (i.e., cold atmospheric plasma). Non-thermal or cold atmospheric plasma (CAP) is produced by applying high voltage electric field at low pressures and power. The chemical effects of cold atmospheric plasma in aqueous solution are attributed to high voltage discharge and gas flow, which is transported rapidly on the liquid surface. The argon-cold atmospheric plasma (Ar-CAP) induces efficient reactive oxygen species (ROS) in aqueous solutions without thermal decomposition. Their formation has been confirmed by electron paramagnetic resonance (EPR) spin trapping, which is reviewed here. The similarities and differences between the plasma chemistry, sonochemistry, and radiation chemistry are explained. Further, the evidence for free radical formation in the liquid phase and their role in the biological effects induced by cold atmospheric plasma, ultrasound and ionizing radiation are discussed.

  14. [Effect of dexamethasone on indomethacin-induced gastric erosion formation upon duration of the hormonal action].

    Science.gov (United States)

    Podvigina, T T; Morozova, O Iu; Bagaeva, T R; Filaretova, L P

    2009-07-01

    The aim of the study was to verify a dependence of dexamethasone effect on the gastric erosion formation upon duration of the hormonal action. Gastric erosions were induced by indometha cin (35 mg/kg, sc) in male rats after 24-hour fasting. The rats were given a single injection of dexamethasone at a dose of 1 mg/kg and they underwent the ulcerogenic stimulus (indomethacin) at va rious time points after the hormonal injection (1, 6, 12, 18, 24 hours as well as 3, 5, 7 days). The control rats were given dexamethasone vehicle. In 4 hours after indomethacin injection gastric erosions, corticosterone and blood glucose levels, as well as body and thymus weights were examined. The results obtained demonstrate a dependence ofdexamethasone effect on the gastric erosion formation upon duration of its action: dexamethasone attenuated or aggravated indomethacin-induced gastric erosions depending on the time of its injection. Gastroprotective action of dexamethasone was observed in the case of its injection 1, 6, and 12 hours before indomethacin. The further increase in the time interval caused transformation of gastroprotective action of dexamethasone against ulcerogenic effect. The data obtained suggest that a disturbance of carbohydrate regulation accompanied with the signs of catabolic effects of the glucocorticoid may be responsible for the ulcerogenic action of dexamethasone.

  15. Effect of radiation-induced emission of Schottky defects on the formation of colloids in alkali halides

    NARCIS (Netherlands)

    Dubinko, [No Value; Vainshtein, DI; Den Hartog, HW

    2003-01-01

    Formation of vacancy clusters in irradiated crystals is considered taking into account radiation-induced Schottky defect emission (RSDE) from extended defects. RSDE acts in the opposite direction compared with Frenkel pair production, and it results in the radiation-induced recovery processes. In th

  16. Ion beam induced single phase nanocrystalline TiO{sub 2} formation

    Energy Technology Data Exchange (ETDEWEB)

    Rukade, Deepti A. [Department of Physics, University of Mumbai, Mumbai 400098 (India); Tribedi, L.C. [Tata Institute of Fundamental Research, Homi Bhabha Road, Colaba, Mumbai 400005 (India); Bhattacharyya, Varsha, E-mail: varsha.b1.physics@gmail.com [Department of Physics, University of Mumbai, Mumbai 400098 (India)

    2014-06-15

    Single phase TiO{sub 2} nanostructures are fabricated by oxygen ion implantation (60 keV) at fluence ranging from 1×10{sup 16} ions/cm{sup 2} to 1×10{sup 17} ions/cm{sup 2} in titanium thin films deposited on fused silica substrate and subsequent thermal annealing in argon atmosphere. GAXRD and Raman spectroscopy study reveals formation of single rutile phases of TiO{sub 2}. Particle size is found to vary from 29 nm to 35 nm, establishing nanostructure formation. Nanostructure formation is also confirmed by the quantum confinement effect manifested by the blueshift of the UV–vis absorption spectra. Photoluminescence spectra show peaks corresponding to TiO{sub 2} rutile phase and reveal the presence of oxygen defects due to implantation. The controlled synthesis of single phase nanostructure is attributed to ion induced defects and post-implantation annealing. It is observed that the size of the nanostructures formed is strongly dependent on the ion fluence.

  17. Ionic liquid-induced formation of the α-helical structure of β-lactoglobulin.

    Science.gov (United States)

    Takekiyo, Takahiro; Koyama, Yoshihiro; Yamazaki, Kumiko; Abe, Hiroshi; Yoshimura, Yukihiro

    2013-09-01

    Structural modification of bovine milk β-lactoglobulin (β-LG) in aqueous 1-butyl-3-methylimidazolium nitrate ([bmim][NO3]) and ethylammonium nitrate ([EAN][NO3]) solutions has been investigated by Fourier transform infrared and circular dichroism spectroscopy. Remarkably, high ionic liquid (IL) concentrations (>15 mol %IL) caused formation of a non-native α-helical structure of β-LG and disruption of its tertiary structure. Furthermore, while [bmim][NO3] promoted protein aggregation, [EAN][NO3] inhibited it probably owing to differences in the unique solution structure (nanoheterogeneity) of the ILs by the different cationic species. The IL-induced α-helical formation of β-LG shows a behavior similar to the alcohol denaturation, but a disordered structure-rich state was observed in the β-α transition process by adding IL, in contrast to the case of an aqueous alcohol solution of protein. We propose that the molten salt-like property of aqueous IL solutions strongly support α-helical formation of proteins.

  18. Surface Nanostructure Formations in an AISI 316L Stainless Steel Induced by Pulsed Electron Beam Treatment

    Directory of Open Access Journals (Sweden)

    Yang Cai

    2015-01-01

    Full Text Available High current pulsed electron beam (HCPEB is an efficient technique for surface modifications of metallic materials. In the present work, the formations of surface nanostructures in an AISI 316L stainless steel induced by direct HCPEB treatment and HCPEB alloying have been investigated. After HCPEB Ti alloying, the sample surface contained a mixture of the ferrite and austenite phases with an average grain size of about 90 nm, because the addition of Ti favors the formation of ferrite. In contrast, electron backscattered diffraction (EBSD analyses revealed no structural refinement on the direct HCPEB treated sample. However, transmission electron microscope (TEM observations showed that fine cells having an average size of 150 nm without misorientations, as well as nanosized carbide particles, were formed in the surface layer after the direct HCPEB treatment. The formation of nanostructures in the 316L stainless steel is therefore attributed to the rapid solidification and the generation of different phases other than the steel substrate in the melted layer.

  19. Core–shell formation in self-induced InAlN nanorods

    Science.gov (United States)

    Palisaitis, J.; Hsiao, C.-L.; Hultman, L.; Birch, J.; Persson, P. O. Å.

    2017-03-01

    We have examined the early stages of self-induced InAlN core–shell nanorod (NR) formation processes on amorphous carbon substrates in plan-view geometry by means of transmission electron microscopy methods. The results show that the grown structure phase separates during the initial moments of deposition into a majority of Al-rich InAlN and a minority of In-enriched InAlN islands. The islands possess polygonal shapes and are mainly oriented along a crystallographic c-axis. The growth proceeds with densification and coalescence of the In-enriched islands, resulting in a base for the In-enriched NR cores with shape transformation to hexagonal. The Al-rich shell formation around such early cores is observed at this stage. The matured core–shell structure grows axially and radially, eventually reaching a steady growth state which is dominated by the axial NR growth. We discuss the NR formation mechanism by considering the adatom surface kinetics, island surface energy, phase separation of InAlN alloys, and incoming flux directions during dual magnetron sputter epitaxy.

  20. Heat-induced structure formation in metal films generated by single ultrashort laser pulses

    Science.gov (United States)

    Koch, Jürgen; Unger, Claudia; Chichkov, Boris N.

    2012-03-01

    Ultrashort pulsed lasers are increasingly used in micromachining applications. Their short pulse lengths lead to well defined thresholds for the onset of material ablation and to the formation of only very small heat affected zones, which can be practically neglected in the majority of cases. Structure sizes down to the sub-micron range are possible in almost all materials - including heat sensitive materials. Ultrashort pulse laser ablation - even though called "cold ablation" - in fact is a heat driven process. Ablation takes place after a strong and fast temperature increase carrying away most of the heat with the ablated particles. This type of heat convection is not possible when reducing the laser fluence slightly below the ablation threshold. In this case temperature decreases slower giving rise to heat-induced material deformations and melt dynamics. After cooling down protruding structures can remain - ablation-free laser surface structuring is possible. Structure formation is boosted on thin metal films and offers best reproducibility and broadest processing windows for metals with high ductility and weak electron phonon coupling strength. All approaches to understand the process formation are currently based only on images of the final structures. The pump-probe imaging investigations presented here lead to a better process understanding.

  1. Gravity-induced modification of auxin transport and distribution for peg formation in cucumber seedlings

    Science.gov (United States)

    Kamada, M.; Fujii, N.; Higashitani, A.; Takahashi, H.

    Cucumber seedlings grown in microgravity developed a peg on each side of the transition zone between hypocotyl and root, whereas seedlings grown in a horizontal position on the ground developed a peg on the concave (lower) side of the gravitropically bending transition zone. Using an auxin-inducible gene, CS-IAA1, we showed that upon gravistimulation the auxin concentration on the upper side of the horizontally placed transition zone is reduced to a level below the threshold necessary for peg formation. In this study, to elucidate the role of auxin in the lateral placement of peg formation, we measured the contents of endogenous auxin in the transition zone. The content of free IAA was lower and conjugated IAA was more abundant on the upper side of the transition zone of the gravistimulated seedlings compared with the lower side. These results support the idea that a decrease in auxin level due to a modification of auxin transport or metabolism causes the suppression of peg formation on the upper side of the transition zone in a horizontal position. Cucumber seedlings treated with auxin transport inhibitors exhibited agravitropic growth and developed a peg on each side of the transition zone. Application of auxin transport inhibitors caused an increase in CS-IAA1 mRNA (an auxin-inducible gene) at the transition zone. To analyze auxin transport system for peg formation, we isolated auxin influx carrier, CS-AUX1, and auxin efflux carrier, CS-PIN1, from cucumber plants. The accumulation of CS-AUX1 and CS-PIN1 mRNAs was observed at vascular tissue and epidermis in the transition zone. The level of CS-AUX1 mRNA was lower on the upper side of the transition zone in a horizontal position. The results suggest that the transition zone is an additional source of auxin, and that both influx and efflux of auxin in the cells of the transition zone control cytoplasmic concentration of auxin for peg formation.

  2. Retinol induces morphological alterations and proliferative focus formation through free radicalmediated activation of multiple signaling pathways

    Institute of Scientific and Technical Information of China (English)

    Daniel Pens GELAIN; Matheus Augusto de Bittencourt PASQUALI; Fernanda Freitas CAREGNATO; Mauro Antonio Alves CASTRO; José Claudio Fonseca MOREIRA

    2012-01-01

    Aim:Toxicity of retinol (vitamin A)has been previously associated with apoptosis and/or cell malignant transformation.Thus,we investigated the pathways involved in the induction of proliferation,deformation and proliferative focus formation by retinol in cultured Sertoli cells of rats.Methods:Sertoli cells were isolated from immature rats and cultured.The cells were subjected to a 24-h treatment with different concentrations of retinol.Parameters of oxidative stress and cytotoxicity were analyzed.The effects of the p38 inhibitor SB203580(10 μmol/L),the JNK inhibitor SP600125 (10 μmol/L),the Akt inhibitor LY294002 (10 μmol/L),the ERK inhibitor U0126 (10 μmol/L)the pan-PKC inhibitor G(O)6983 (10 μmol/L)and the PKA inhibitor H89 (1 μmol/L)on morphological and proliferative/transformationassociated modifications were studied.Results:Retinol (7 and 14 μmol/L)significantly increases the reactive species production in Sertoli cells,inhibition of p38,JNK,ERK1/2,Akt,and PKA suppressed retinol-induced[3H]dT incorporation into the cells,while PKC inhibition had no effect.ERK1/2 and p38 inhibition also blocked retinol-induced proliferative focus formation in the cells,while Akt and JNK inhibition partially decreased focus formation.ERK1/2 and p38 inhibition hindered transformation-associated deformation in retinol-treated cells,while other treatments had no effect.Conclusion:Our results suggest that activation of multiple kinases is responsible for morphological and proliferative changes associated to malignancy development in Sertoli cells by retinol at the concentrations higher than physiological level.

  3. ROLE OF ENDOGENOUS CARBON MONOXIDE IN NEOINTIMAL FORMATION INDUCED BY BALLOON-INJURY IN RAT AORTA

    Institute of Scientific and Technical Information of China (English)

    1999-01-01

    Objective.The present study investigated the role of endogenous carbon monoxide(CO)in the pathogenesis of neointimal formation induced by balloon injury in rat.Method.Endothelial denudation of the left common carotid artery of rat was carried out by three passages of a Fogarty 2F balloon catheter.DNA,collagen and elastin contents of each intima-media were estimated;and heme oxygenase(HO)activity and CO production in vascular smooth muscle cell(VSMC)were measured after administration of HO inhibitor.Result.Our data showed that neointima occurred in the rat on day 7 and day 21 after balloon injury,and at the same time HO activity and CO production in VSMC were markedly increased.Administration of HO inhibitor,zinc deuteroporphyrin 2,4-bisglycol(ZnDPBG),could effectively inhibit HO activity and CO production,significantly enhance neointimal formation(aortic intima/media ratio were 21.4±1.8% vs 17.6±2.0%,P<0.05 on day 7;and 30.5±2.4% vs 23.0±2.2%,P<0.01 on day 21,respectively,compared with balloon alone group).Conclusion.We concluded that 1)inhibition of CO production may enhance neointimal formation induced by endothelial denudation,implying endogenous CO play an protective role in response to vascular injury,and 2)induction of HO activity may be applied clinically for preventing restenosis after angioplasty.

  4. Ion-induced Processing of Cosmic Silicates: A Possible Formation Pathway to GEMS

    Science.gov (United States)

    Jäger, C.; Sabri, T.; Wendler, E.; Henning, Th.

    2016-11-01

    Ion-induced processing of dust grains in the interstellar medium and in protoplanetary and planetary disks plays an important role in the entire dust cycle. We have studied the ion-induced processing of amorphous MgFeSiO4 and Mg2SiO4 grains by 10 and 20 keV protons and 90 keV Ar+ ions. The Ar+ ions were used to compare the significance of the light protons with that of heavier, but chemically inert projectiles. The bombardment was performed in a two-beam irradiation chamber for in situ ion-implantation at temperatures of 15 and 300 K and Rutherford Backscattering Spectroscopy to monitor the alteration of the silicate composition under ion irradiation. A depletion of oxygen from the silicate structure by selective sputtering of oxygen from the surface of the grains was observed in both samples. The silicate particles kept their amorphous structure, but the loss of oxygen caused the reduction of ferrous (Fe2+) ions and the formation of iron inclusions in the MgFeSiO4 grains. A few Si inclusions were produced in the iron-free magnesium silicate sample pointing to a much less efficient reduction of Si4+ and formation of metallic Si inclusions. Consequently, ion-induced processing of magnesium-iron silicates can produce grains that are very similar to the glassy grains with embedded metals and sulfides frequently observed in interplanetary dust particles and meteorites. The metallic iron inclusions are strong absorbers in the NIR range and therefore a ubiquitous requirement to increase the temperature of silicate dust grains in IR-dominated astrophysical environments such as circumstellar shells or protoplanetary disks.

  5. Chlamydia pneumoniae infection in mice induces chronic lung inflammation, iBALT formation, and fibrosis.

    Directory of Open Access Journals (Sweden)

    Madhulika Jupelli

    Full Text Available Chlamydia pneumoniae (CP lung infection can induce chronic lung inflammation and is associated with not only acute asthma but also COPD exacerbations. However, in mouse models of CP infection, most studies have investigated specifically the acute phase of the infection and not the longer-term chronic changes in the lungs. We infected C57BL/6 mice with 5 × 10(5 CP intratracheally and monitored inflammation, cellular infiltrates and cytokine levels over time to investigate the chronic inflammatory lung changes. While bacteria numbers declined by day 28, macrophage numbers remained high through day 35. Immune cell clusters were detected as early as day 14 and persisted through day 35, and stained positive for B, T, and follicular dendritic cells, indicating these clusters were inducible bronchus associated lymphoid tissues (iBALTs. Classically activated inflammatory M1 macrophages were the predominant subtype early on while alternatively activated M2 macrophages increased later during infection. Adoptive transfer of M1 but not M2 macrophages intratracheally 1 week after infection resulted in greater lung inflammation, severe fibrosis, and increased numbers of iBALTS 35 days after infection. In summary, we show that CP lung infection in mice induces chronic inflammatory changes including iBALT formations as well as fibrosis. These observations suggest that the M1 macrophages, which are part of the normal response to clear acute C. pneumoniae lung infection, result in an enhanced acute response when present in excess numbers, with greater inflammation, tissue injury, and severe fibrosis.

  6. The genetic basis of constitutive and herbivore-induced ESP-independent nitrile formation in Arabidopsis.

    Science.gov (United States)

    Burow, Meike; Losansky, Anja; Müller, René; Plock, Antje; Kliebenstein, Daniel J; Wittstock, Ute

    2009-01-01

    Glucosinolates are a group of thioglucosides that are components of an activated chemical defense found in the Brassicales. Plant tissue damage results in hydrolysis of glucosinolates by endogenous thioglucosidases known as myrosinases. Spontaneous rearrangement of the aglucone yields reactive isothiocyanates that are toxic to many organisms. In the presence of specifier proteins, alternative products, namely epithionitriles, simple nitriles, and thiocyanates with different biological activities, are formed at the expense of isothiocyanates. Recently, simple nitriles were recognized to serve distinct functions in plant-insect interactions. Here, we show that simple nitrile formation in Arabidopsis (Arabidopsis thaliana) ecotype Columbia-0 rosette leaves increases in response to herbivory and that this increase is independent of the known epithiospecifier protein (ESP). We combined phylogenetic analysis, a screen of Arabidopsis mutants, recombinant protein characterization, and expression quantitative trait locus mapping to identify a gene encoding a nitrile-specifier protein (NSP) responsible for constitutive and herbivore-induced simple nitrile formation in Columbia-0 rosette leaves. AtNSP1 is one of five Arabidopsis ESP homologues that promote simple nitrile, but not epithionitrile or thiocyanate, formation. Four of these homologues possess one or two lectin-like jacalin domains, which share a common ancestry with the jacalin domains of the putative Arabidopsis myrosinase-binding proteins MBP1 and MBP2. A sixth ESP homologue lacked specifier activity and likely represents the ancestor of the gene family with a different biochemical function. By illuminating the genetic and biochemical bases of simple nitrile formation, our study provides new insights into the evolution of metabolic diversity in a complex plant defense system.

  7. Calcification preceding new bone formation induced by demineralized bone matrix gelatin.

    Science.gov (United States)

    Yamashita, K; Takagi, T

    1992-03-01

    Demineralized bone matrix gelatin (BMG) was implanted into the skeletal muscle of Sprague-Dawley (S.D.) rats, and histological changes were examined 3, 5, 7, 10 and 15 days later. Before bone formation, a specific calcification process was found in most of the BMG from day 5 and 7 after implantation. The heterotopic calcified sites were not always consistent with the sites of the alkaline phosphatase activity. It was considered that this calcification progresses without any cellular components, and we distinguished this type of calcification as "acellular mineral deposition" from the calcification which occurs in new bone formation. This "acellular mineral deposition" was first observed as small spherical calcified deposits in the BMG on day 7 after implantation; these deposits then gradually grew and fused with each other. Some multinucleated cells appeared near the site of calcification on day 7 after implantation, but osteoblasts or osteoblast-like cells were scarcely observed around the calcified deposits in BMG until day 7. Vascularization was often observed near the "acellular mineral deposition" and the new bone formation. Fourier transform infrared spectroscopy showed that the calcified deposits in BMG were composed of hydroxyapatite, carbonateapatite and other calcium phosphate components, and that the first two components became prominent with time. It is believed that the "acellular mineral deposition" is due to the deposition of calcium and phosphate into the BMG by a process of heterogenic nucleation that does not involve osteoblasts or matrix vesicles. Bone formation induced by the BMG occurred after the "acellular mineral deposition." The experimental calcification shown in this paper seems a useful model for the study of biocalcification.

  8. Influence of crystal orientation on the formation of femtosecond laser-induced periodic surface structures and lattice defects accumulation

    Science.gov (United States)

    Sedao, Xxx; Maurice, Claire; Garrelie, Florence; Colombier, Jean-Philippe; Reynaud, Stéphanie; Quey, Romain; Pigeon, Florent

    2014-04-01

    The influence of crystal orientation on the formation of femtosecond laser-induced periodic surface structures (LIPSS) has been investigated on a polycrystalline nickel sample. Electron Backscatter Diffraction characterization has been exploited to provide structural information within the laser spot on irradiated samples to determine the dependence of LIPSS formation and lattice defects (stacking faults, twins, dislocations) upon the crystal orientation. Significant differences are observed at low-to-medium number of laser pulses, outstandingly for (111)-oriented surface which favors lattice defects formation rather than LIPSS formation.

  9. Influence of crystal orientation on the formation of femtosecond laser-induced periodic surface structures and lattice defects accumulation

    Energy Technology Data Exchange (ETDEWEB)

    Sedao, Xxx; Garrelie, Florence, E-mail: florence.garrelie@univ-st-etienne.fr; Colombier, Jean-Philippe; Reynaud, Stéphanie; Pigeon, Florent [Université de Lyon, CNRS, UMR5516, Laboratoire Hubert Curien, Université de Saint Etienne, Jean Monnet, F-42023 Saint-Etienne (France); Maurice, Claire; Quey, Romain [Ecole Nationale Supérieure des Mines de Saint-Etienne, CNRS, UMR5307, Laboratoire Georges Friedel, F-42023 Saint-Etienne (France)

    2014-04-28

    The influence of crystal orientation on the formation of femtosecond laser-induced periodic surface structures (LIPSS) has been investigated on a polycrystalline nickel sample. Electron Backscatter Diffraction characterization has been exploited to provide structural information within the laser spot on irradiated samples to determine the dependence of LIPSS formation and lattice defects (stacking faults, twins, dislocations) upon the crystal orientation. Significant differences are observed at low-to-medium number of laser pulses, outstandingly for (111)-oriented surface which favors lattice defects formation rather than LIPSS formation.

  10. Cell colony formation induced by Xenopus egg extract as a marker for improvement of cloned blastocyst formation in pig

    DEFF Research Database (Denmark)

    Liu, Ying; Østrup, Olga; Li, Juan

    2011-01-01

    method based on the colony formation of cells after extract treatment, and subsequent in vitro cloning efficiency using treated cells as chromatin donors. Porcine fetal fibroblasts were treated with each batch of extract, and cultured in embryonic stem cell (ES) medium for 12 days. The number of forming...... colonies in treated cells was counted on Day 7 after extract treatment and significant variability was detected between different batches of extract. Similarly, when using cells from colonies at Days 7 to 8 after treatment for handmade cloning, increased blastocyst formation rates were observed after...... the cells were treated with a batch showing higher colony formation. In conclusion, assessment of cell colony formation may be used as selection marker for Xenopus egg extract used for pretreatment of donor cells prior to cloning....

  11. Wounding induces changes in cytokinin and auxin content in potato tuber, but does not induce formation of gibberellins.

    Science.gov (United States)

    Lulai, Edward C; Suttle, Jeffrey C; Olson, Linda L; Neubauer, Jonathan D; Campbell, Larry G; Campbell, Michael A

    2016-02-01

    Cytokinin, auxin and gibberellin contents in resting and wound-responding potato tubers have not been fully determined and coordinated with wound-healing processes. Using a well-defined wound-healing model system, hormone content and expression of genes associated with hormone turnover were determined in tubers following wounding. Changes in hormone content were coordinated with: (I) formation and completion of the wound closing layer (0-5/6 days), and (II) initiation of phellogen and wound periderm formation (∼ 7 days). Quantifiable amounts of biologically active cytokinins (Z, DZ and IP) were not detected in resting or wound-responding tubers. However, the precursor IPA and catabolic product c-ZOG were found in small amounts in resting and wound-responding tubers. Wound-induced activation of cytokinin biosynthesis was suggested by an increase in t-ZR and c-ZR content at 0.5 days and large increases in IPA and c-ZR content by 3 days and throughout 7 days after wounding suggesting roles in II, but little or no role in I. Expression of key genes involved in cytokinin metabolism followed similar profiles with transcripts decreasing through 3 days and then increasing at 5-7 days after wounding. Both free IAA and IAA-Asp were present in resting tubers. While IAA-Asp was no longer present by 3 days after wounding, IAA content nearly doubled by 5 days and was more than 4-fold greater at 7 days compared to that in resting tuber (0 day) suggesting roles in II, but little or no role in I. Gibberellins were not present in quantifiable amounts in resting or wound-responding tubers. These results suggest that bio-active cytokinins are wound-induced, but their residency is temporal and highly regulated. The transient presence of active cytokinins and corresponding increases in IAA content strongly suggest their involvement in the regulation of wound periderm development. The absence of gibberellins indicates that they are not a regulatory component of wound-healing processes.

  12. CFD-DEM Simulations of Current-Induced Dune Formation and Morphological Evolution

    CERN Document Server

    Sun, Rui

    2015-01-01

    Understanding the fundamental mechanisms of sediment transport, particularly those during the formation and evolution of bedforms, is of critical scientific importance and has engineering relevance. Traditional approaches of sediment transport simulations heavily rely on empirical models, which are not able to capture the physics-rich, regime-dependent behaviors of the process. With the increase of available computational resources in the past decade, CFD-DEM (computational fluid dynamics-discrete element method) has emerged as a viable high-fidelity method for the study of sediment transport. However, a comprehensive, quantitative study of the generation and migration of different sediment bed patterns using CFD-DEM is still lacking. In this work, current-induced sediment transport problems in a wide range of regimes are simulated, including 'flat bed in motion', `small dune', `vortex dune' and suspended transport. Simulations are performed by using SediFoam, an open-source, massively parallel CFD-DEM solver...

  13. ANALYSIS OF NANO CHANNEL FORMATION IN QUARTZ CUBES BY LASER-INDUCED PROCESS

    Institute of Scientific and Technical Information of China (English)

    QIN S.J.; Li Wen J.

    2004-01-01

    A novel laser processing technique was developed for making channels in the nano regime in this paper. A Nd:YAG laser was used to dry fabricate micro channels (25μm~100μm diameter) in a 1 cm3 fused silica substrate by thermal-induced processing. By controlling the locations of these initiating micro channels on a silica cube, 1D-controllable self-connecting nano fractures can be formed as rectangular channels. These nano channels are smooth and with extremely high aspect ratio (~104 depth to width ratio). A possible mechanism is proposed to explain the formation of the nano channels. This laser-based nano channel fabrication technique is fast and inexpensive, and with potential applications in capillary electrophoresis and electro-osmosis driven nano-filtration.

  14. Solvent-induced chirality control in the enantioseparation of 1-phenylethylamine via diastereomeric salt formation.

    Science.gov (United States)

    Kodama, Koichi; Kimura, Yuria; Shitara, Hiroaki; Yasutake, Mikio; Sakurai, Rumiko; Hirose, Takuji

    2011-04-01

    Solvent-induced chirality control in the enantioseparation of 1-phenylethylamine 1 by N-(p-toluenesulfonyl)-(S)-phenylalanine 2 via diastereomeric salt formation was studied. (S)-1·(S)-2 was preferentially crystallized as a less-soluble salt from aqueous alcohol, while (R)-1·(S)-2 salt was mainly obtained by addition of solvents with a six-membered ring such as dioxane, cyclohexane, tetrahydropyran, and cyclohexene to 2-propanol. Further investigations were carried out from the viewpoints of molecular structures, optical rotation measurement, and X-ray crystallographic analyses. Crystallographic analyses have revealed that incorporation of the six-membered ring solvent molecule in (R)-1·(S)-2 without hydrogen bonds changed the molecular conformation of (S)-2 to stabilize the salt, which changed the selectivity of 1 in the enantioseparation.

  15. Formation of Benzyl Carbanion in Collision-Induced Dissociation of Deprotonated Phenylalanine Homologues.

    Science.gov (United States)

    Sekimoto, Kanako; Matsuda, Natsuki; Takayama, Mitsuo

    2014-01-01

    The fragmentation behavior of deprotonated L-phenylalanine (Phe) and its homologues including L-homophenylalanine (HPA) and L-phenylglycine (PG) was investigated using collision-induced dissociation mass spectrometry coupled with a negative ion atmospheric pressure corona discharge ionization (APCDI) technique. The deprotonated molecules [M-H](-) fragmented to lose unique neutral species, e.g., the loss of NH3, CO2, toluene and iminoglycine for [Phe-H](-); styrene and ethenamine/CO2 for [HPA-H](-); and CO2 for [PG-H](-). All of the fragmentations observed are attributable to the formation of intermediates and/or product ions which include benzyl carbanions having resonance-stabilized structures. The carbanions are formed via proton rearrangement through a transition state or via a simple dissociation reaction. These results suggest that the principal factor governing the fragmentation behavior of deprotonated Phe homologues is the stability of the intermediate and/or product ion structures.

  16. Atomistic explanation of shear-induced amorphous band formation in boron carbide.

    Science.gov (United States)

    An, Qi; Goddard, William A; Cheng, Tao

    2014-08-29

    Boron carbide (B4C) is very hard, but its applications are hindered by stress-induced amorphous band formation. To explain this behavior, we used density function theory (Perdew-Burke-Ernzerhof flavor) to examine the response to shear along 11 plausible slip systems. We found that the (0111)/ slip system has the lowest shear strength (consistent with previous experimental studies) and that this slip leads to a unique plastic deformation before failure in which a boron-carbon bond between neighboring icosahedral clusters breaks to form a carbon lone pair (Lewis base) on the C within the icosahedron. Further shear then leads this Lewis base C to form a new bond with the Lewis acidic B in the middle of a CBC chain. This then initiates destruction of this icosahedron. The result is the amorphous structure observed experimentally. We suggest how this insight could be used to strengthen B4C.

  17. Ion-beam-induced nanodots formation from Au/Si thin films on quartz surface

    Energy Technology Data Exchange (ETDEWEB)

    Datta, D.P.; Siva, V.; Singh, A. [School of Physical Sciences, National Institute of Science Education and Research (NISER), Bhubaneswar, Jatni - 752050, Odisha (India); Joshi, S.R. [Institute of Physics, Sachivalaya Marg, Bhubaneswar 751005, Odisha (India); Kanjilal, D. [Inter University Accelerator Centre, Aruna Asaf Ali Marg, New Delhi 110067 (India); Sahoo, P.K., E-mail: pratap.sahoo@niser.ac.in [School of Physical Sciences, National Institute of Science Education and Research (NISER), Bhubaneswar, Jatni - 752050, Odisha (India)

    2016-07-15

    We report the synthesis of Si nanodots on quartz surface using ion irradiation. When a bi-layer of ultrathin Au and Si on quartz surface is irradiated by 500 keV Xe-ion beam, the bi-layer spontaneously transforms into nanodots at a fluence of 5 × 10{sup 14} ions cm{sup −2}. The spatial density and diameter of the nanodots are reduced with increase in applied ion fluence. The nanostructures exhibit photoluminescence in the visible range at room temperature where the intensity and wavelength depends upon ion fluence. The observed evolution seems to be correlated to ion beam mixing induced silicide formation at Au–Si interface.

  18. Formation mechanism and modulation of electromagnetically induced transparency-like transmission in side-coupled structures

    Institute of Scientific and Technical Information of China (English)

    杨辉; 李宏建; 许秀科; 何智慧; 王云; 徐国均

    2015-01-01

    Based on Fabry model and finite-different time-domain (FDTD) method, the plasmonic structure composed of a metal-insulator-metal (MIM) bus waveguide and a side-coupled resonator was investigated. It is found that the transmission features can be regulated by the cavity width and coupling distance. Electromagnetically induced transparency (EIT)-like transmission can be excited by adding anidentical resonator on the pre-existing structure. Combining the foregoing theoretical analysis with coupled mode theory (CMT), the formation process of the EIT-like transmission was detailedly analyzed. EIT-like transmission can also be excited in plasmonic structure with two detuned resonators. By altering the structure parameters, the transparency window can be purposefully modulated. With themeritsof compact structure and simplicity in fabrication, the proposed structures may have a broad prospect of applications in highly integrated optical circuits.

  19. Moderation of calpain activity promotes neovascular integration and lumen formation during VEGF-induced pathological angiogenesis.

    Directory of Open Access Journals (Sweden)

    Mien V Hoang

    Full Text Available BACKGROUND: Successful neovascularization requires that sprouting endothelial cells (ECs integrate to form new vascular networks. However, architecturally defective, poorly integrated vessels with blind ends are typical of pathological angiogenesis induced by vascular endothelial growth factor-A (VEGF, thereby limiting the utility of VEGF for therapeutic angiogenesis and aggravating ischemia-related pathologies. Here we investigated the possibility that over-exuberant calpain activity is responsible for aberrant VEGF neovessel architecture and integration. Calpains are a family of intracellular calcium-dependent, non-lysosomal cysteine proteases that regulate cellular functions through proteolysis of numerous substrates. METHODOLOGY/PRINCIPAL FINDINGS: In a mouse skin model of VEGF-driven angiogenesis, retroviral transduction with dominant-negative (DN calpain-I promoted neovessel integration and lumen formation, reduced blind ends, and improved vascular perfusion. Moderate doses of calpain inhibitor-I improved VEGF-driven angiogenesis similarly to DN calpain-I. Conversely, retroviral transduction with wild-type (WT calpain-I abolished neovessel integration and lumen formation. In vitro, moderate suppression of calpain activity with DN calpain-I or calpain inhibitor-I increased the microtubule-stabilizing protein tau in endothelial cells (ECs, increased the average length of microtubules, increased actin cable length, and increased the interconnectivity of vascular cords. Conversely, WT calpain-I diminished tau, collapsed microtubules, disrupted actin cables, and inhibited integration of cord networks. Consistent with the critical importance of microtubules for vascular network integration, the microtubule-stabilizing agent taxol supported vascular cord integration whereas microtubule dissolution with nocodazole collapsed cord networks. CONCLUSIONS/SIGNIFICANCE: These findings implicate VEGF-induction of calpain activity and impairment of

  20. Prion-induced and spontaneous formation of transmissible toxicity in PrP transgenic Drosophila.

    Science.gov (United States)

    Thackray, Alana M; Di, Ying; Zhang, Chang; Wolf, Hanna; Pradl, Lydia; Vorberg, Ina; Andréoletti, Olivier; Bujdoso, Raymond

    2014-10-01

    Prion diseases are fatal transmissible neurodegenerative diseases of various mammalian species. Central to these conditions is the conversion of the normal host prion protein PrP(C) into the abnormal prion conformer PrP(Sc). Mature PrP(C) is attached to the plasma membrane by a glycosylphosphatidylinositol anchor, whereas during biosynthesis and metabolism cytosolic and secreted forms of the protein may arise. The role of topological PrP(C) variants in the mechanism of prion formation and prion-induced neurotoxicity during prion disease remains undefined. In the present study we investigated whether Drosophila transgenic for ovine PrP targeted to the plasma membrane, to the cytosol or for secretion, could produce transmissible toxicity following exposure to exogenous ovine prions. Although all three topological variants of PrP were efficiently expressed in Drosophila, cytosolic PrP was conformationally distinct and required denaturation before recognition by immunobiochemical methods. Adult Drosophila transgenic for pan neuronally expressed ovine PrP targeted to the plasma membrane, to the cytosol or for secretion exhibited a decreased locomotor activity after exposure at the larval stage to ovine prions. Proteinase K-resistant PrP(Sc) was detected by protein misfolding cyclic amplification in prion-exposed Drosophila transgenic for membrane-targeted PrP. Significantly, head homogenate from all three variants of prion-exposed PrP transgenic Drosophila induced a decreased locomotor activity when transmitted to PrP recipient flies. Drosophila transgenic for PrP targeted for secretion exhibited a spontaneous locomotor defect in the absence of prion exposure that was transmissible in PrP transgenic flies. Our data are consistent with the formation of transmissible prions in PrP transgenic Drosophila.

  1. TIMP-1 Induces α-Smooth Muscle Actin in Fibroblasts to Promote Urethral Scar Formation

    Directory of Open Access Journals (Sweden)

    Yinglong Sa

    2015-04-01

    Full Text Available Background/Aims: Tissue inhibitor of metalloproteinases-1 (TIMP-1 has been reported to upregulate in urethral scar. However, the underlying molecular mechanisms remain undefined. Methods: Here, we studied levels of TIMP-1 and α-smooth muscle actin (α-SMA in the fibroblasts isolated from urethral scar tissues, compared to the fibroblasts isolated from normal urethra. Then we either overexpressed TIMP-1, or inhibited TIMP-1 by lentiviruses carrying a transgene or a short hairpin small interfering RNA for TIMP-1 in human fibroblasts. We examined the effects of modulation of TIMP-1 on α-SMA, and on epithelial-mesenchymal transition (EMT-related genes. We also studied the underlying mechanisms. Results: We detected significantly higher levels of TIMP-1 and α-smooth muscle actin (α-SMA in the fibroblasts isolated from urethral scar tissues, compared to the fibroblasts isolated from normal urethra. Moreover, the levels of TIMP-1 and α-SMA strongly correlated. Moreover, we found that TIMP-1 significantly increased levels of α-SMA, transforming growth factor β 1 (TGFβ1, Collagen I and some other key factors related to an enhanced EMT, suggesting that TIMP-1 may induce transformation of fibroblasts into myofibroblasts to promote tissue EMT to enhance the formation of urethral scar. Moreover, increases in TIMP-1 also induced an increase in fibroblast cell growth and cell invasion, in an ERK/MAPK-signaling-dependent manner. Conclusion: Our study thus highlights a pivotal role of TIMP-1 in urethral scar formation.

  2. Numerical simulations of bubble-induced star formation in dwarf irregular galaxies with a novel stellar feedback scheme

    Science.gov (United States)

    Kawata, Daisuke; Gibson, Brad K.; Barnes, David J.; Grand, Robert J. J.; Rahimi, Awat

    2014-02-01

    To study the star formation and feedback mechanism, we simulate the evolution of an isolated dwarf irregular galaxy (dIrr) in a fixed dark matter halo, similar in size to Wolf-Lundmark-Melotte, using a new stellar feedback scheme. We use the new version of our original N-body/smoothed particle chemodynamics code, GCD+, which adopts improved hydrodynamics, metal diffusion between the gas particles and new modelling of star formation and stellar wind and supernovae feedback. Comparing the simulations with and without stellar feedback effects, we demonstrate that the collisions of bubbles produced by strong feedback can induce star formation in a more widely spread area. We also demonstrate that the metallicity in star-forming regions is kept low due to the mixing of the metal-rich bubbles and the metal-poor interstellar medium. Our simulations also suggest that the bubble-induced star formation leads to many counter-rotating stars. The bubble-induced star formation could be a dominant mechanism to maintain star formation in dIrrs, which is different from larger spiral galaxies where the non-axisymmetric structures, such as spiral arms, are a main driver of star formation.

  3. Asbestos inhalation induces reactive nitrogen species and nitrotyrosine formation in the lungs and pleura of the rat.

    Science.gov (United States)

    Tanaka, S; Choe, N; Hemenway, D R; Zhu, S; Matalon, S; Kagan, E

    1998-01-01

    To determine whether asbestos inhalation induces the formation of reactive nitrogen species, three groups of rats were exposed intermittently over 2 wk to either filtered room air (sham-exposed) or to chrysotile or crocidolite asbestos fibers. The rats were killed at 1 or 6 wk after exposure. At 1 wk, significantly greater numbers of alveolar and pleural macrophages from asbestos-exposed rats than from sham-exposed rats demonstrated inducible nitric oxide synthase protein immunoreactivity. Alveolar macrophages from asbestos-exposed rats also generated significantly greater nitrite formation than did macrophages from sham-exposed rats. Strong immunoreactivity for nitrotyrosine, a marker of peroxynitrite formation, was evident in lungs from chrysotile- and crocidolite-exposed rats at 1 and 6 wk. Staining was most evident at alveolar duct bifurcations and within bronchiolar epithelium, alveolar macrophages, and the visceral and parietal pleural mesothelium. Lungs from sham-exposed rats demonstrated minimal immunoreactivity for nitrotyrosine. Significantly greater quantities of nitrotyrosine were detected by ELISA in lung extracts from asbestos-exposed rats than from sham-exposed rats. These findings suggest that asbestos inhalation can induce inducible nitric oxide synthase activation and peroxynitrite formation in vivo, and provide evidence of a possible alternative mechanism of asbestos-induced injury to that thought to be induced by Fenton reactions. PMID:9664087

  4. Picosecond laser-induced formation of spikes in a single crystal superalloy

    Energy Technology Data Exchange (ETDEWEB)

    Zhang Wei [State Key Laboratory for Advanced Metals and Materials, University of Science and Technology Beijing, Beijing 100083 (China); State Key Laboratory of Transient Optics and Photonics, Xi' an Institute of Optics and Precision Mechanics of Chinese Academy of Sciences, Xi' an Shaanxi 710119 (China); Cheng Guanghua [State Key Laboratory of Transient Optics and Photonics, Xi' an Institute of Optics and Precision Mechanics of Chinese Academy of Sciences, Xi' an Shaanxi 710119 (China); Feng Qiang, E-mail: qfeng@skl.ustb.edu.cn [State Key Laboratory for Advanced Metals and Materials, University of Science and Technology Beijing, Beijing 100083 (China); National Center for Materials Service Safety, University of Science and Technology Beijing, Beijing 100083 (China); Cao Lamei [National Key Laboratory of Science and Technology on Advanced High Temperature Structural Materials, Beijing Institute of Aeronautical Materials, Beijing 100095 (China)

    2012-09-15

    Highlights: Black-Right-Pointing-Pointer Transition from ripples to spikes with pulse number. Black-Right-Pointing-Pointer Laser fluence has a significant effect on the spike separation. Black-Right-Pointing-Pointer Relationship between structures and their parametric dependence is established. Black-Right-Pointing-Pointer Capillary waves are responsible for the formation of spikes. - Abstract: The characteristics of laser-induced periodic surface structures (LIPSS) were investigated after laser irradiation with different pulse duration under a certain range of laser fluence (0.25 {<=} {Phi} {<=} 1.91 J/cm{sup 2}) and pulse number (11 {<=} N {<=} 560). Spikes were generated by picosecond laser irradiation in ambient air, in comparison with only periodic ripple structures introduced by nanosecond and femtosecond laser irradiation. Microstructural investigations indicate that these spikes were initiated by the fragment of periodic ripple ridges or corrugation on the smooth surface with subsequent pulses, and their separation increased with increasing the laser fluence. Surface capillary waves associated with the resolidification process can be employed to explain the formation of spikes by picosecond laser irradiation.

  5. Simvastatin reduces endotoxin-induced acute lung injury by decreasing neutrophil recruitment and radical formation.

    Directory of Open Access Journals (Sweden)

    Jochen Grommes

    Full Text Available INTRODUCTION: Treatment of acute lung injury (ALI remains an unsolved problem in intensive care medicine. As simvastatin exerts protective effects in inflammatory diseases we explored its effects on development of ALI and due to the importance of neutrophils in ALI also on neutrophil effector functions. METHODS: C57Bl/6 mice were exposed to aerosolized LPS (500 µg/ml for 30 min. The count of alveolar, interstitial, and intravasal neutrophils were assessed 4 h later by flow cytometry. Lung permeability changes were assessed by FITC-dextran clearance and albumin content in the BAL fluid. In vitro, we analyzed the effect of simvastatin on neutrophil adhesion, degranulation, apoptosis, and formation of reactive oxygen species. To monitor effects of simvastatin on bacterial clearance we performed phagocytosis and bacterial killing studies in vitro as well as sepsis experiments in mice. RESULTS: Simvastatin treatment before and after onset of ALI reduces neutrophil influx into the lung as well as lung permeability indicating the protective role of simvastatin in ALI. Moreover, simvastatin reduces the formation of ROS species and adhesion of neutrophils without affecting apoptosis, bacterial phagocytosis and bacterial clearance. CONCLUSION: Simvastatin reduces recruitment and activation of neutrophils hereby protecting from LPS-induced ALI. Our results imply a potential role for statins in the management of ALI.

  6. Kinetic aspects of the formation of aluminium oxide by use of a microwave-induced plasma.

    Science.gov (United States)

    Quade, A; Steffen, H; Hippler, R; Wulff, H

    2002-10-01

    The oxidation of thin aluminium layers in a microwave plasma has been investigated to determine the kinetics of oxide growth. Thin Al-coatings were oxidized by means of a variety of gas mixtures, characterized by different partial pressures of oxygen, in microwave-induced plasmas of different power. To study the whole kinetic process the Al-metal and the oxide formed were investigated by means of a combination of grazing incidence X-ray reflectometry (GIXR) and grazing incidence X-ray diffractometry (GIXRD). XPS and FTIR spectroscopy confirmed the formation of stoichiometric Al(2)O(3). The alumina formed is X-ray amorphous. Quantitative description of oxide formation was achieved indirectly by determination of the decrease in the integrated intensity of the Al(111)-peak and the total thickness of the whole coating. These values enabled calculation of kinetic data. It was found that oxide growth was a combination of two simultaneous processes - diffusion and sputter processes. The diffusion coefficient D (cm(2) s(-1)) and the sputter rate S (nm s(-1)) were determined. The effect of the composition of the gas mixture, microwave power, and concentration of activated oxygen species on the oxidation process will be discussed. For calculation of the activation energy, E(A), of this plasma-enhanced diffusion process the temperature-dependence of D was investigated.

  7. Formation of Pu(III) colloids observed by laser-induced breakdown detection

    Energy Technology Data Exchange (ETDEWEB)

    Cho, H. R.; Cha, W.; Park, K. K.; Jung, E. C. [Korea Atomic Energy Research Institute, Daejeon (Korea, Republic of)

    2015-05-15

    In the present work, the reduction conditions were controlled through electrolysis. An electrochemical cell with a Teflon vessel and quartz tubes containing electrodes were installed in a glove-box purged with Ar gas to prepare plutonium samples at different pHs under reducing condition. The concentration of hydrogen ions (H{sup +}) of plutonium solutions was reduced using an electric current from a Ag/AgCl reference electrode to a Pt working electrode, which called coulometric pH titration. The electrolytic reducing condition maintains the dominant oxidation state of Pu(III). Soluble species were investigated using absorption spectroscopy adopting a liquid waveguide capillary cell (LWCC) which has an optical path length of 100 cm. The formation of plutonium hydroxide colloids and solubility were determined by laser-induced breakdown detection (LIBD). Electrolytic reduction was a useful method to investigate the hydrolysis, colloid formation and solubility of Pu(III) hydroxide. The oxidation state of Pu(III) maintained well during the reduction of hydrogen ions being comparable to strong reducing agents such as Fe powder. The determined solubility product was lower than the reported data by Felmy et al. . The existence of Pu(IV), which can result in lower solubility investigated by measurement of redox potentials of samples will be presented in detail.

  8. Role of Excessive Autophagy Induced by Mechanical Overload in Vein Graft Neointima Formation: Prediction and Prevention

    Science.gov (United States)

    Chang, Ya-Ju; Huang, Hui-Chun; Hsueh, Yuan-Yu; Wang, Shao-Wei; Su, Fong-Chin; Chang, Chih-Han; Tang, Ming-Jer; Li, Yi-Shuan; Wang, Shyh-Hau; Shung, Kirk K.; Chien, Shu; Wu, Chia-Ching

    2016-02-01

    Little is known regarding the interplays between the mechanical and molecular bases for vein graft restenosis. We elucidated the stenosis initiation using a high-frequency ultrasonic (HFU) echogenicity platform and estimated the endothelium yield stress from von-Mises stress computation to predict the damage locations in living rats over time. The venous-arterial transition induced the molecular cascades for autophagy and apoptosis in venous endothelial cells (ECs) to cause neointimal hyperplasia, which correlated with the high echogenicity in HFU images and the large mechanical stress that exceeded the yield strength. The ex vivo perfusion of arterial laminar shear stress to isolated veins further confirmed the correlation. EC damage can be rescued by inhibiting autophagy formation using 3-methyladenine (3-MA). Pretreatment of veins with 3-MA prior to grafting reduced the pathological increases of echogenicity and neointima formation in rats. Therefore, this platform provides non-invasive temporal spatial measurement and prediction of restenosis after venous-arterial transition as well as monitoring the progression of the treatments.

  9. Human germ cell formation in xenotransplants of induced pluripotent stem cells carrying X chromosome aneuploidies.

    Science.gov (United States)

    Dominguez, Antonia A; Chiang, H Rosaria; Sukhwani, Meena; Orwig, Kyle E; Reijo Pera, Renee A

    2014-09-22

    Turner syndrome is caused by complete or partial loss of the second sex chromosome and is characterized by spontaneous fetal loss in >90% of conceptions. Survivors possess an array of somatic and germline clinical characteristics. Induced pluripotent stem cells (iPSCs) offer an opportunity for insight into genetic requirements of the X chromosome linked to Turner syndrome. We derived iPSCs from Turner syndrome and control individuals and examined germ cell development as a function of X chromosome composition. We demonstrate that two X chromosomes are not necessary for reprogramming or maintenance of pluripotency and that there are minimal differences in gene expression, at the single cell level, linked to X chromosome aneuploidies. Formation of germ cells, as assessed in vivo through a murine xenotransplantation model, indicated that undifferentiated iPSCs, independent of X chromosome composition, are capable of forming germ-cell-like cells (GCLCs) in vivo. In combination with clinical data regarding infertility in women with X chromosome aneuploidies, results suggest that two intact X chromosomes are not required for human germ cell formation, qualitatively or quantitatively, but rather are likely to be required for maintenance of human germ cells to adulthood.

  10. Surface transition on ice induced by the formation of a grain boundary.

    Directory of Open Access Journals (Sweden)

    Christian Pedersen

    Full Text Available Interfaces between individual ice crystals, usually referred to as grain boundaries, play an important part in many processes in nature. Grain boundary properties are, for example, governing the sintering processes in snow and ice which transform a snowpack into a glacier. In the case of snow sintering, it has been assumed that there are no variations in surface roughness and surface melting, when considering the ice-air interface of an individual crystal. In contrast to that assumption, the present work suggests that there is an increased probability of molecular surface disorder in the vicinity of a grain boundary. The conclusion is based on the first detailed visualization of the formation of an ice grain boundary. The visualization is enabled by studying ice crystals growing into contact, at temperatures between -20°C and -15°C and pressures of 1-2 Torr, using Environmental Scanning Electron Microscopy. It is observed that the formation of a grain boundary induces a surface transition on the facets in contact. The transition does not propagate across facet edges. The surface transition is interpreted as the spreading of crystal dislocations away from the grain boundary. The observation constitutes a qualitatively new finding, and can potentially increase the understanding of specific processes in nature where ice grain boundaries are involved.

  11. Changes in chemical interactions and protein conformation during heat-induced wheat gluten gel formation.

    Science.gov (United States)

    Wang, Kai-Qiang; Luo, Shui-Zhong; Zhong, Xi-Yang; Cai, Jing; Jiang, Shao-Tong; Zheng, Zhi

    2017-01-01

    In order to elucidate the heat-induced wheat gluten gel formation mechanism, changes in chemical interactions and protein conformation were investigated during gelation. The contribution of ionic and hydrogen bonds were found to decrease from 0.746 and 4.133g/L to 0.397 and 2.733g/L, respectively, as the temperature increased from 25 to 90°C. Moreover, the free SH content remarkably decreased from 37.91 to 19.79μmol/g during gelation. Ultraviolet absorption spectra and intrinsic fluorescence spectra suggested that wheat gluten unfolded during the heating process. In addition, wheat gluten gels treated at 80 and 90°C exhibited a "steric hindrance" effect, which can be attributed to the formation of aggregates. Fourier transform infrared spectra suggested that the random coil content increased at low temperatures (40 and 50°C), whereas the content of intermolecular β-sheets due to protein aggregation increased from 38.10% to 44.28% when the gelation temperature was 90°C.

  12. Decompression-induced bubble formation in salmonids: comparison to gas bubble disease.

    Science.gov (United States)

    Beyer, D L; D'Aoust, B G; Smith, L S

    1976-12-01

    The relationship of gas bubble disease (GBD) in fish to decompression-induced bubble formation was investigated with salmonids. Acute bioassays were used to determine equilibration times for critical effects in fish decompressed from depths to 200 fsw. It was found that equilibration of critical tissues was complete in 60-90 min. Salmonids and air-breathers are sensitive to decompressions at similar levels of supersaturation if elimination of excess gas following decompression is unrestricted. However, if elimination is restricted, bubble formation and growth increase accordingly. Tests with mixtures of He-O2, Ar-O2, N2-O2 (80% inert gas: 20% O2) and pure oxygen demonstrated that gas solubility as well as supersaturation (delta P), pressure ratio (initial pressure: final pressure), and absolute pressure must be considered in setting tolerance limits for any decompression. Gases with higher solubility are more likely to produce bubbles upon decompression. Oxygen, however, does not follow this relationship until higher pressures are reached, probably owing to its function in metabolism and in binding with hemoglobin. Tissue responses observed in both GBD and decompressed fish involved similar pathological effects at acute exposures. The circulatory system was consistently affected by bubbles that occluded vessels and blocked flow through the heart.

  13. Pyk2 regulates megakaryocyte-induced increases in osteoblast number and bone formation.

    Science.gov (United States)

    Cheng, Ying-Hua; Hooker, R Adam; Nguyen, Khanh; Gerard-O'Riley, Rita; Waning, David L; Chitteti, Brahmananda R; Meijome, Tomas E; Chua, Hui Lin; Plett, Artur P; Orschell, Christie M; Srour, Edward F; Mayo, Lindsey D; Pavalko, Fredrick M; Bruzzaniti, Angela; Kacena, Melissa A

    2013-06-01

    Preclinical and clinical evidence from megakaryocyte (MK)-related diseases suggests that MKs play a significant role in maintaining bone homeostasis. Findings from our laboratories reveal that MKs significantly increase osteoblast (OB) number through direct MK-OB contact and the activation of integrins. We, therefore, examined the role of Pyk2, a tyrosine kinase known to be regulated downstream of integrins, in the MK-mediated enhancement of OBs. When OBs were co-cultured with MKs, total Pyk2 levels in OBs were significantly enhanced primarily because of increased Pyk2 gene transcription. Additionally, p53 and Mdm2 were both decreased in OBs upon MK stimulation, which would be permissive of cell cycle entry. We then demonstrated that OB number was markedly reduced when Pyk2-/- OBs, as opposed to wild-type (WT) OBs, were co-cultured with MKs. We also determined that MKs inhibit OB differentiation in the presence and absence of Pyk2 expression. Finally, given that MK-replete spleen cells from GATA-1-deficient mice can robustly stimulate OB proliferation and bone formation in WT mice, we adoptively transferred spleen cells from these mice into Pyk2-/- recipient mice. Importantly, GATA-1-deficient spleen cells failed to stimulate an increase in bone formation in Pyk2-/- mice, suggesting in vivo the important role of Pyk2 in the MK-induced increase in bone volume. Further understanding of the signaling pathways involved in the MK-mediated enhancement of OB number and bone formation will facilitate the development of novel anabolic therapies to treat bone loss diseases.

  14. Do seed VLCFAs trigger spongy tissue formation in Alphonso mango by inducing germination?

    Indian Academy of Sciences (India)

    Seshadri Shivashankar; Manoharan Sumathi; Tapas Kumar Roy

    2015-06-01

    Spongy tissue is a physiological disorder in Alphonso mango caused by the inception of germination-associated events during fruit maturation on the tree, rendering the fruit inedible. Inter-fruit competition during active fruit growth is a major contributing factor for the disorder which leads to reduced fat content in spongy tissue affected fruits. This study was, therefore, carried out to determine the possible association between seed fats and ST formation. The study of the fat content during fruit growth showed that it increased gradually from 40% fruit maturity. At 70% maturity, however, there was a sudden increase of fat content of whole fruit, leading to acute competition and resulting in differential allocation of resources among developing fruits. As a result, the seed in spongy-tissue-affected mature ripe fruit showed a marked drop in the levels of fats and the two very long chain fatty acids (VLCFAs), tetracosanoic acid and hexacosanoic acid together with an increase of linolenic acid and a fall in oleic acid contents, which are known to be key determinants for the initiation of pre-germination events in seed. Subsequently, a rise in the level of cytokinin and gibberellins in ST seed associated with a fall in abscisic acid level clearly signalled the onset of germination. Concurrently, a significant reduction in the ratio of linolenic acid/linoleic acid in pulp led to the loss of membrane integrity, cell death and the eventual formation of spongy tissue. Based on the above, it is concluded that a significant reduction in the biosynthesis of VLCFAs in seeds during fruit growth might trigger pre-germination events followed by a cascade of biochemical changes in the pulp, leading to lipid peroxidation and membrane injury in pulp culminating in ST development. Thus, this study presents crucial experimental evidence to highlight the critical role played by VLCFAs in inducing ST formation in Alphonso mango during the pre-harvest phase of fruit growth.

  15. Do seed VLCFAs trigger spongy tissue formation in Alphonso mango by inducing germination?

    Science.gov (United States)

    Shivashankar, Seshadri; Sumathi, Manoharan

    2015-06-01

    Spongy tissue is a physiological disorder in Alphonso mango caused by the inception of germination-associated events during fruit maturation on the tree, rendering the fruit inedible. Inter-fruit competition during active fruit growth is a major contributing factor for the disorder which leads to reduced fat content in spongy tissue affected fruits. This study was, therefore, carried out to determine the possible association between seed fats and ST formation. The study of the fat content during fruit growth showed that it increased gradually from 40 percent fruit maturity. At 70 percent maturity, however, there was a sudden increase of fat content of whole fruit, leading to acute competition and resulting in differential allocation of resources among developing fruits. As a result, the seed in spongy-tissue-affected mature ripe fruit showed a marked drop in the levels of fats and the two very long chain fatty acids (VLCFAs), tetracosanoic acid and hexacosanoic acid together with an increase of linolenic acid and a fall in oleic acid contents, which are known to be key determinants for the initiation of pre-germination events in seed. Subsequently, a rise in the level of cytokinin and gibberellins in ST seed associated with a fall in abscisic acid level clearly signalled the onset of germination. Concurrently, a significant reduction in the ratio of linolenic acid/linoleic acid in pulp led to the loss of membrane integrity, cell death and the eventual formation of spongy tissue. Based on the above, it is concluded that a significant reduction in the biosynthesis of VLCFAs in seeds during fruit growth might trigger pre-germination events followed by a cascade of biochemical changes in the pulp, leading to lipid peroxidation and membrane injury in pulp culminating in ST development. Thus, this study presents crucial experimental evidence to highlight the critical role played by VLCFAs in inducing ST formation in Alphonso mango during the pre-harvest phase of fruit

  16. Adiponectin deficiency enhances colorectal carcinogenesis and liver tumor formation induced by azoxymethane in mice

    Institute of Scientific and Technical Information of China (English)

    Tamao Nishihara; Shinji Tamura; Norio Hayashi; Hiroyasu Iishi; Iichiro Shimornura; Miyako Baba; Morihiro Matsuda; Masahiro Inoue; Yasuko Nishizawa; Atsunori Fukuhara; Hiroshi Arald; Shinji Kihara; Tohru Funahashi

    2008-01-01

    AIM: To investigate the causal relationship between hypoadiponectinemia and colorectal carcinogenesis in in vivo experimental model, and to determine the con-tribution of adiponectin deficiency to colorectal cancer development and proliferation. METHODS: We examined the influence of adiponectin deficiency on colorectal carcinogenesis induced by the administration of azoxymethane (AOM) (7.5 mg/kg, in-traperitoneal injection once a week for 8 wk), by using adiponectin-knockout (KO) mice. RESULTS: At 53 wk after the first AOM treatment, KOmice developed larger and histologically more progres-sive colorectal tumors with greater frequency com-pared with wild-type (WT) mice, although the tumor incidence was not different between WT and KO mice. KO mice showed increased cell proliferation of colorec-tal tumor cells, which correlated with the expression levels of cyclooxygenase-2 (COX-2) in the colorectal tumors. In addition, KO mice showed higher incidence and frequency of liver tumors after AOI treatment. Thirteen percent of WT mice developed liver tumors, and these WT mice had only a single tumor. In contrast, 50% of K.O mice developed liver tumors, and 58% of these KO mice had multiple tumors. CONCLUSION: Adiponectin deficiency enhances colorectal carcinogenesis and liver tumor formation induced by AOM in mice. This study strongly suggests that hypoadiponectinemia could be involved in the pathogenesis for colorectal cancer and liver tumor in human subjects.

  17. Fragmentation and the formation of primordial protostars: the possible role of Collision Induced Emission

    CERN Document Server

    Ripamonti, E; Ripamonti, Emanuele; Abel, Tom

    2004-01-01

    The mechanisms which could lead to chemo-thermal instabilities and fragmentation during the formation of primordial protostars are investigated analytically. We introduce approximations for H2 cooling rates bridging the optically thin and thick regimes. These allow us to discuss instabilities up to densities when protostars become optically thick to continuum radiation (n~10^16 cm^-3). During the collapse, instability arises at two different stages: at low density (n~10^8-10^11 cm^-3), it is due to fast 3-body reactions converting H into H2; at high density (n>10^13 cm^-3), it is due to Collisional Induced Emission (CIE). In agreement with the 3D simulations, we find that the instability at low densities cannot lead to fragmentation, because fluctuations do not survive turbulent mixing, and because their growth is slow. The situation at high density is similar. The CIE-induced instability is as weak as the low density one, with similar ratios of growth and dynamical time scales. Fluctuation growth time is lon...

  18. Submillimetre Network Formation by Light-induced Hybridization of Zeptomole-level DNA

    Science.gov (United States)

    Iida, Takuya; Nishimura, Yushi; Tamura, Mamoru; Nishida, Keisuke; Ito, Syoji; Tokonami, Shiho

    2016-12-01

    Macroscopic unique self-assembled structures are produced via double-stranded DNA formation (hybridization) as a specific binding essential in biological systems. However, a large amount of complementary DNA molecules are usually required to form an optically observable structure via natural hybridization, and the detection of small amounts of DNA less than femtomole requires complex and time-consuming procedures. Here, we demonstrate the laser-induced acceleration of hybridization between zeptomole-level DNA and DNA-modified nanoparticles (NPs), resulting in the assembly of a submillimetre network-like structure at the desired position with a dramatic spectral modulation within several minutes. The gradual enhancement of light-induced force and convection facilitated the two-dimensional network growth near the air-liquid interface with optical and fluidic symmetry breakdown. The simultaneous microscope observation and local spectroscopy revealed that the assembling process and spectral change are sensitive to the DNA sequence. Our findings establish innovative guiding principles for facile bottom-up production via various biomolecular recognition events.

  19. Numerical model of the glacially-induced intraplate earthquakes and faults formation

    Science.gov (United States)

    Petrunin, Alexey; Schmeling, Harro

    2016-04-01

    According to the plate tectonics, main earthquakes are caused by moving lithospheric plates and are located mainly at plate boundaries. However, some of significant seismic events may be located far away from these active areas. The nature of the intraplate earthquakes remains unclear. It is assumed, that the triggering of seismicity in the eastern Canada and northern Europe might be a result of the glacier retreat during a glacial-interglacial cycle (GIC). Previous numerical models show that the impact of the glacial loading and following isostatic adjustment is able to trigger seismicity in pre-existing faults, especially during deglaciation stage. However this models do not explain strong glaciation-induced historical earthquakes (M5-M7). Moreover, numerous studies report connection of the location and age of major faults in the regions undergone by glaciation during last glacial maximum with the glacier dynamics. This probably imply that the GIC might be a reason for the fault system formation. Our numerical model provides analysis of the strain-stress evolution during the GIC using the finite volume approach realised in the numerical code Lapex 2.5D which is able to operate with large strains and visco-elasto-plastic rheology. To simulate self-organizing faults, the damage rheology model is implemented within the code that makes possible not only visualize faulting but also estimate energy release during the seismic cycle. The modeling domain includes two-layered crust, lithospheric mantle and the asthenosphere that makes possible simulating elasto-plastic response of the lithosphere to the glaciation-induced loading (unloading) and viscous isostatic adjustment. We have considered three scenarios for the model: horizontal extension, compression and fixed boundary conditions. Modeling results generally confirm suppressing seismic activity during glaciation phases whereas retreat of a glacier triggers earthquakes for several thousand years. Tip of the glacier

  20. Myeloperoxidase formation of PAF receptor ligands induces PAF receptor-dependent kidney injury during ethanol consumption.

    Science.gov (United States)

    Latchoumycandane, Calivarathan; Nagy, Laura E; McIntyre, Thomas M

    2015-09-01

    Cytochrome P450 2E1 (CYP2E1) induction and oxidative metabolism of ethanol in hepatocytes inflame and damage liver. Chronic ethanol ingestion also induces kidney dysfunction, which is associated with mortality from alcoholic hepatitis. Whether the kidney is directly affected by ethanol or is secondary to liver damage is not established. We found that CYP2E1 was induced in kidney tubules of mice chronically ingesting a modified Lieber-deCarli liquid ethanol diet. Phospholipids of kidney tubules were oxidized and fragmented in ethanol-fed mice with accumulation of azelaoyl phosphatidylcholine (Az-PC), a nonbiosynthetic product formed only by oxidative truncation of polyunsaturated phosphatidylcholine. Az-PC stimulates the inflammatory PAF receptor (PTAFR) abundantly expressed by neutrophils and kidney tubules, and inflammatory cells and myeloperoxidase-containing neutrophils accumulated in the kidneys of ethanol-fed mice after significant hysteresis. Decreased kidney filtration and induction of the acute kidney injury biomarker KIM-1 in tubules temporally correlated with leukocyte infiltration. Genetic ablation of PTAFR reduced accumulation of PTAFR ligands and reduced leukocyte infiltration into kidneys. Loss of this receptor in PTAFR(-/-) mice also suppressed oxidative damage and kidney dysfunction without affecting CYP2E1 induction. Neutrophilic inflammation was responsible for ethanol-induced kidney damage, because loss of neutrophil myeloperoxidase in MPO(-/-) mice was similarly protective. We conclude that ethanol catabolism in renal tubules results in a self-perpetuating cycle of CYP2E1 induction, local PTAFR ligand formation, and neutrophil infiltration and activation that leads to myeloperoxidase-dependent oxidation and damage to kidney function. Hepatocytes do not express PTAFR, so this oxidative cycle is a local response to ethanol catabolism in the kidney.

  1. Supramolecular coordination chemistry in aqueous solution: lanthanide ion-induced triple helix formation.

    Science.gov (United States)

    Lessmann, J J; Horrocks, W D

    2000-07-24

    The self-assembly of dinuclear triple helical lanthanide ion complexes (helicates), in aqueous solution, is investigated utilizing laser-induced, lanthanide luminescence spectroscopy. A series of dinuclear lanthanide (III) helicates (Ln(III)) based on 2,6-pyridinedicarboxylic acid (dipicolinic acid, dpa) coordinating units was synthesized by linking two dpa moieties using the organic diamines (1R,2R)-diaminocyclohexane (chxn-R,R) and 4,4'-diaminodiphenylmethane (dpm). Luminescence excitation spectroscopy of the Eu3+ 7F0-->5D0 transition shows the apparent cooperative formation of neutral triple helical complexes in aqueous solution, with a [Eu2L3] stoichiometry. Eu3+ excitation peak wavelengths and excited-state lifetimes correspond to those of the [Eu(dpa)3]3- model complex. CD studies of the Nd(III) helicate Nd2(dpa-chxn-R,R)3 reveal optical activity of the f-f transitions, indicating that the chiral linking group induces a stable chirality at the metal ion center. Molecular mechanics calculations using CHARMm suggest that the delta delta configuration at the Nd3+ ion centers is induced by the chxn-R,R linker. Stability constants were determined for both ligands with Eu3+, yielding identical results: log K = 31.6 +/- 0.2 (K in units of M-4). Metal-metal distances calculated from Eu3+-->Nd3+ energy-transfer experiments show that the complexes have metal-metal distances close to those calculated by molecular modeling. The fine structure in the Tb3+ emission bands is consistent with the approximate D3 symmetry as anticipated for helicates.

  2. Glioblastoma-derived Leptin Induces Tube Formation and Growth of Endothelial Cells: Comparison with VEGF Effects

    Directory of Open Access Journals (Sweden)

    Otvos Laszlo

    2011-07-01

    Full Text Available Abstract Background Leptin is a pleiotropic hormone whose mitogenic and angiogenic activity has been implicated in the development and progression of several malignancies, including brain tumors. In human brain cancer, especially in glioblastoma multiforme (GBM, leptin and its receptor (ObR are overexpressed relative to normal tissue. Until present, the potential of intratumoral leptin to exert proangiogenic effects on endothelial cells has not been addressed. Using in vitro models, we investigated if GBM can express leptin, if leptin can affect angiogenic and mitogenic potential of endothelial cells, and if its action can be inhibited with specific ObR antagonists. Leptin effects were compared with that induced by the best-characterized angiogenic regulator, VEGF. Results We found that GBM cell lines LN18 and LN229 express leptin mRNA and LN18 cells secrete detectable amounts of leptin protein. Both lines also expressed and secreted VEGF. The conditioned medium (CM of LN18 and LN 229 cultures as well as 200 ng/mL pure leptin or 50 ng/mL pure VEGF stimulated proliferation of human umbilical vein endothelial cells (HUVEC at 24 h of treatment. Mitogenic effects of CM were ~2-fold greater than that of pure growth factors. Furthermore, CM treatment of HUVEC for 24 h increased tube formation by ~5.5-fold, while leptin increased tube formation by ~ 80% and VEGF by ~60% at 8 h. The mitogenic and angiogenic effects of both CM were blocked by Aca 1, a peptide ObR antagonist, and by SU1498, which inhibits the VEGF receptor. The best anti-angiogenic and cytostatic effects of Aca1 were obtained with 10 nM and 25 nM, respectively, while for SU1498, the best growth and angiogenic inhibition was observed at 5 μM. The combination of 5 μM SU1498 and Aca1 at 25 nM (growth inhibition or at 10 nM (reduction of tube formation produced superior effects compared with single agent treatments. Conclusions Our data provide the first evidence that LN18 and LN 229 human

  3. Quantitative analysis of Hedgehog gradient formation using an inducible expression system

    Directory of Open Access Journals (Sweden)

    Brodsky Michael

    2007-05-01

    Full Text Available Abstract Background The Hedgehog (Hh family of secreted growth factors are morphogens that act in development to direct growth and patterning. Mutations in human Hh and other Hh pathway components have been linked to human diseases. Analysis of Hh distribution during development indicates that cholesterol modification and receptor mediated endocytosis affect the range of Hh signaling and the cellular localization of Hh. Results We have used an inducible, cell type-specific expression system to characterize the three-dimensional distribution of newly synthesized, GFP-tagged Hh in the developing Drosophila wing. Following induction of Hh-GFP expression in posterior producing cells, punctate structures containing Hh-GFP were observed in the anterior target cells. The distance of these particles from the expressing cells was quantified to determine the shape of the Hh gradient at different time points following induction. The majority of cholesterol-modified Hh-GFP was found associated with cells near the anterior/posterior (A/P boundary, which express high levels of Hh target genes. Without cholesterol, the Hh gradient was flatter, with a lower percentage of particles near the source and a greater maximum distance. Inhibition of Dynamin-dependent endocytosis blocked formation of intracellular Hh particles, but did not prevent movement of newly synthesized Hh to the apical or basolateral surfaces of target cells. In the absence of both cholesterol and endocytosis, Hh particles accumulated in the extracellular space. Staining for the Hh receptor Ptc revealed four categories of Hh particles: cytoplasmic with and without Ptc, and cell surface with and without Ptc. Interestingly, mainly cholesterol-modified Hh is detected in the cytoplasmic particles lacking Ptc. Conclusion We have developed a system to quantitatively analyze Hh distribution during gradient formation. We directly demonstrate that inhibition of Dynamin-dependent endocytosis is not

  4. Base pairing enhances fluorescence and favors cyclobutane dimer formation induced upon absorption of UVA radiation by DNA.

    Science.gov (United States)

    Banyasz, Akos; Vayá, Ignacio; Changenet-Barret, Pascale; Gustavsson, Thomas; Douki, Thierry; Markovitsi, Dimitra

    2011-04-13

    The photochemical properties of the DNA duplex (dA)(20)·(dT)(20) are compared with those of the parent single strands. It is shown that base pairing increases the probability of absorbing UVA photons, probably due to the formation of charge-transfer states. UVA excitation induces fluorescence peaking at ∼420 nm and decaying on the nanosecond time scale. The fluorescence quantum yield, the fluorescence lifetime, and the quantum yield for cyclobutane dimer formation increase upon base pairing. Such behavior contrasts with that of the UVC-induced processes.

  5. Inhibitory effects of eugenol on RANKL-induced osteoclast formation via attenuation of NF-κB and MAPK pathways.

    Science.gov (United States)

    Deepak, Vishwa; Kasonga, Abe; Kruger, Marlena C; Coetzee, Magdalena

    2015-06-01

    Bone loss diseases are often associated with increased receptor activator of NF-κB ligand (RANKL)-induced osteoclast formation. Compounds that can attenuate RANKL-mediated osteoclast formation are of great biomedical interest. Eugenol, a phenolic constituent of clove oil possesses medicinal properties; however, its anti-osteoclastogenic potential is unexplored hitherto. Here, we found that eugenol dose-dependently inhibited the RANKL-induced multinucleated osteoclast formation and TRAP activity in RAW264.7 macrophages. The underlying molecular mechanisms included the attenuation of RANKL-mediated degradation of IκBα and subsequent activation of NF-κB pathway. Furthermore, increase in phosphorylation and activation of RANKL-induced mitogen-activated protein kinase pathways (MAPK) was perturbed by eugenol. RANKL-induced expression of osteoclast-specific marker genes such as TRAP, cathepsin K (CtsK) and matrix metalloproteinase-9 (MMP-9) was remarkably downregulated by eugenol. These findings provide the first line of evidence that eugenol mediated attenuation of RANKL-induced NF-κB and MAPK pathways could synergistically contribute to the inhibition of osteoclast formation. Eugenol could be developed as therapeutic agent against diseases with excessive osteoclast activity.

  6. Induced Core Formation Time in Subcritical Magnetic Clouds by Large-Scale Trans-Alfv\\'enic Flows

    CERN Document Server

    Kudoh, Takahiro

    2014-01-01

    We clarify the mechanism of accelerated core formation by large-scale nonlinear flows in subcritical magnetic clouds by finding a semi-analytical formula for the core formation time and describing the physical processes that lead to them. Recent numerical simulations show that nonlinear flows induce rapid ambipolar diffusion that leads to localized supercritical regions that can collapse. Here, we employ non-ideal magnetohydrodynamic simulations including ambipolar diffusion for gravitationally stratified sheets threaded by vertical magnetic fields. One of the horizontal dimensions is eliminated, resulting in a simpler two-dimensional simulation that can clarify the basic process of accelerated core formation. A parameter study of simulations shows that the core formation time is inversely proportional to the square of the flow speed when the flow speed is greater than the Alfv\\'en speed. We find a semi-analytical formula that explains this numerical result. The formula also predicts that the core formation t...

  7. Fluorescent adduct formation with terbium: a novel strategy for transferrin glycoform identification in human body fluids and carbohydrate-deficient transferrin HPLC method validation.

    Science.gov (United States)

    Sorio, Daniela; De Palo, Elio Franco; Bertaso, Anna; Bortolotti, Federica; Tagliaro, Franco

    2017-02-01

    This paper puts forward a new method for the transferrin (Tf) glycoform analysis in body fluids that involves the formation of a transferrin-terbium fluorescent adduct (TfFluo). The key idea is to validate the analytical procedure for carbohydrate-deficient transferrin (CDT), a traditional biochemical serum marker to identify chronic alcohol abuse. Terbium added to a human body-fluid sample produced TfFluo. Anion exchange HPLC technique, with fluorescence detection (λ exc 298 nm and λ em 550 nm), permitted clear separation and identification of Tf glycoform peaks without any interfering signals, allowing selective Tf sialoforms analysis in human serum and body fluids (cadaveric blood, cerebrospinal fluid, and dried blood spots) hampered for routine test. Serum samples (n = 78) were analyzed by both traditional absorbance (Abs) and fluorescence (Fl) HPLC methods and CDT% levels demonstrated a significant correlation (p body fluid analysis. Its sensitivity and absence of interferences extend clinical applications being reliable for CDT assay on body fluids usually not suitable for routine test. Graphical Abstract The formation of a transferrin-terbium fluorescent adduct can be used to analyze the transferrin glycoforms. The HPLC method for carbohydrate-deficient transferrin (CDT%) measurement was validated and employed to determine the levels in different body fluids.

  8. Microcodium: An extensive review and a proposed non-rhizogenic biologically induced origin for its formation

    Science.gov (United States)

    Kabanov, Pavel; Anadón, Pere; Krumbein, Wolfgang E.

    2008-04-01

    Microcodium has been previously described as a mainly Cenozoic calcification pattern ascribed to various organisms. A review of the available literature and our data reveal two peaks in Microcodium abundance; the Moscovian-early Permian and the latest Cretaceous-Paleogene. A detailed analysis of late Paleozoic and Cenozoic examples leads to the following new conclusions. Typical Microcodium-forming unilayered 'corn-cob' aggregates of elongated grains and thick multilayered (palisade) replacing structures cannot be linked to smaller-grained intracellular root calcifications, as became widely accepted after the work of Klappa [Klappa, C.F., 1979. Calcified filaments in Quaternary calcretes: organo-mineral interactions in the subaerial vadose environment. J. Sediment. Petrol. 49, 955-968.] Typical Microcodium is recognized from the early Carboniferous (with doubtful Devonian reports) to Quaternary as a biologically induced mineralization formed via dissolution/precipitation processes in various aerobic Ca-rich soil and subsoil terrestrial environments. Morphology and δ13C signatures of Microcodium suggest that neither plants, algae, or roots and root-associated mycorrhiza regulate the formation of these fossil structures. Non-recrystallized Microcodium grains basically consist of slender (1.5-4 μm) curved radiating monocrystalline prisms with occasionally preserved hyphae-like morphology. Thin (0.5-3 μm) hypha-like canals can also be observed. These supposed hyphae may belong to actinobacteria. However, thin fungal mycelia cannot be excluded. We propose a model of Microcodium formation involving a mycelial saprotrophic organism responsible for substrate corrosion and associated bacteria capable of consuming acidic metabolites and CaCO 3 reprecipitation into the Microcodium structures.

  9. Formation and evolution of a hairpin vortex induced by subharmonic sinuous low-speed streaks

    Energy Technology Data Exchange (ETDEWEB)

    Li, Jian; Dong, Gang; Lu, Ziheng, E-mail: dgvehicle@yahoo.com [State Key Laboratory of Transient Physics, Nanjing University of Science and Technology, Nanjing, 210094, Jiangsu Province, People’s Republic of China (China)

    2014-10-01

    In this paper, a process of the formation and evolution of hairpin vortices, which originated from the interaction between the spanwise-aligned low-speed streaks with a subharmonic sinuous (SS) oscillation mode, is studied using a direct numerical simulation method in a small periodic local region of an incompressible plane channel flow. The initial artificial perturbations are used to excite the SS-mode oscillation of two spanwise-aligned low-speed streaks in such a flow. A new mechanism of formation and decay of the hairpin vortices is proposed in which the shear layer induced by the spanwise collision and merging between the low-speed streaks is emphasized. Our results show that the streamwise vortices can be induced by the SS-mode streaks and then developed into an X-like pattern at the initial stage due to the mutual induction effect. The X-like vortices further enhance the spanwise oscillation and lift-up of the two streaks that thus lead to the spanwise collision and merging of the low-speed streaks and produce a low-speed region in high-speed fluid. The strong shear layer between the high- and low-speed fluids gives rise to the spanwise vorticity that connects the X-like streamwise vortices and forms the Λ-like vortex. Once the low-speed region entirely enters the high-speed fluid, the shear layer shows the ring shape and results in the transition from a Λ-like vortex to Ω-like one. After that, the viscous diffusion of the low-speed region in the high-speed fluid leads to the decay of the Ω-like vortex; the collision and merging of the low-speed streaks simultaneously reoccur upstream and give birth to a secondary Λ-like vortex, which exhibits behavior that is nearly similar with that of the primary one. Although the hairpin vortex packet is not observed in the present plane channel flow, the regeneration of the hairpin vortex suggests that this type of vortical structure plays an important role in the wall-bounded flow. (paper)

  10. Diploid oocyte formation and tetraploid embryo development induced by cytochalasin B in bovine.

    Science.gov (United States)

    Bai, Chunling; Liu, Hui; Liu, Ying; Wu, Xia; Cheng, Lei; Bou, Shorgan; Li, Guang-Peng

    2011-02-01

    Tetraploid embryos are a useful model for postimplantation development of polyploidy cells, and tetraploid cells are an advantage in studies for chimeras yielding offspring completely derived from embryo stem cells or induced pluripotent cells. This study was designed to investigate the effects of cytochalasin B (CB) on bovine oocyte meiosis, and to induce the formation of diploid oocytes and tetraploid embryos. The results showed that: (1) incubation of oocytes in CB at ≥2.0 μg/mL concentrations for 24 h significantly decreased oocyte maturation and the matured oocytes' haploid composition. Over 50% of the CB-treated oocytes did not expel PB1 (non-PB1), and most of the non-PB1 oocytes contained 2n (60) chromosomes. (2) Pretreatment of oocytes with CB at concentrations of 7.5 and 15 μg/mL for 10 h significantly decreased oocyte maturation. Posttreatment of oocytes with CB resulted in most of the oocytes containing 2n chromosomes. (3) The parthenogenetic blastocysts (25-28%) derived from the non-PB1 oocytes of posttreatment group was significantly higher than that from pretreatment, whole period treatment, and the control oocytes (12-16%). (4) Cytogenetic analysis of the embryos derived from CB-treated non-PB1 oocytes resulted in 74% of the one-cell stage embryos being 4n = 120 chromosomes, 82% of two-cell stage embryos contained 4n chromosomes in each blastomere, and 75% of the blastocysts were tetraploidy (4n = 120). (6) The stopped uncleaved one-cell embryos showed an amazing phenomenon of over 15% of them containing extra chromosomes, which suggested multiple DNA duplication occurred within 40 h after activation. In conclusion, CB inhibits PB1 extrusion, disfigures spindle structure, decreases oocyte maturation, and results in formation of diploid (2n or 4c) oocytes. The diploid oocytes resulted in a higher development of tetraploid embryos, which would be a unique approach for the production of tetraploid embryos in bovine.

  11. Time-resolved measurement of single pulse femtosecond laser-induced periodic surface structure formation induced by a pre-fabricated surface groove.

    Science.gov (United States)

    Kafka, K R P; Austin, D R; Li, H; Yi, A Y; Cheng, J; Chowdhury, E A

    2015-07-27

    Time-resolved diffraction microscopy technique has been used to observe the formation of laser-induced periodic surface structures (LIPSS) from the interaction of a single femtosecond laser pulse (pump) with a nano-scale groove mechanically formed on a single-crystal Cu substrate. The interaction dynamics (0-1200 ps) was captured by diffracting a time-delayed, frequency-doubled pulse (probe) from nascent LIPSS formation induced by the pump with an infinity-conjugate microscopy setup. The LIPSS ripples are observed to form asynchronously, with the first one forming after 50 ps and others forming sequentially outward from the groove edge at larger time delays. A 1-D analytical model of electron heating including both the laser pulse and surface plasmon polariton excitation at the groove edge predicts ripple period, melt spot diameter, and qualitatively explains the asynchronous time-evolution of LIPSS formation.

  12. CFD-DEM simulations of current-induced dune formation and morphological evolution

    Science.gov (United States)

    Sun, Rui; Xiao, Heng

    2016-06-01

    Understanding the fundamental mechanisms of sediment transport, particularly those during the formation and evolution of bedforms, is of critical scientific importance and has engineering relevance. Traditional approaches of sediment transport simulations heavily rely on empirical models, which are not able to capture the physics-rich, regime-dependent behaviors of the process. With the increase of available computational resources in the past decade, CFD-DEM (computational fluid dynamics-discrete element method) has emerged as a viable high-fidelity method for the study of sediment transport. However, a comprehensive, quantitative study of the generation and migration of different sediment bed patterns using CFD-DEM is still lacking. In this work, current-induced sediment transport problems in a wide range of regimes are simulated, including 'flat bed in motion', 'small dune', 'vortex dune' and suspended transport. Simulations are performed by using SediFoam, an open-source, massively parallel CFD-DEM solver developed by the authors. This is a general-purpose solver for particle-laden flows tailed for particle transport problems. Validation tests are performed to demonstrate the capability of CFD-DEM in the full range of sediment transport regimes. Comparison of simulation results with experimental and numerical benchmark data demonstrates the merits of CFD-DEM approach. In addition, the improvements of the present simulations over existing studies using CFD-DEM are presented. The present solver gives more accurate prediction of sediment transport rate by properly accounting for the influence of particle volume fraction on the fluid flow. In summary, this work demonstrates that CFD-DEM is a promising particle-resolving approach for probing the physics of current-induced sediment transport.

  13. Intermittent Hypoxia-Induced Carotid Body Chemosensory Potentiation and Hypertension Are Critically Dependent on Peroxynitrite Formation

    Directory of Open Access Journals (Sweden)

    Esteban A. Moya

    2016-01-01

    Full Text Available Oxidative stress is involved in the development of carotid body (CB chemosensory potentiation and systemic hypertension induced by chronic intermittent hypoxia (CIH, the main feature of obstructive sleep apnea. We tested whether peroxynitrite (ONOO−, a highly reactive nitrogen species, is involved in the enhanced CB oxygen chemosensitivity and the hypertension during CIH. Accordingly, we studied effects of Ebselen, an ONOO− scavenger, on 3-nitrotyrosine immunoreactivity (3-NT-ir in the CB, the CB chemosensory discharge, and arterial blood pressure (BP in rats exposed to CIH. Male Sprague-Dawley rats were exposed to CIH (5% O2, 12 times/h, 8 h/day for 7 days. Ebselen (10 mg/kg/day was administrated using osmotic minipumps and BP measured with radiotelemetry. Compared to the sham animals, CIH-treated rats showed increased 3-NT-ir within the CB, enhanced CB chemosensory responses to hypoxia, increased BP response to acute hypoxia, and hypertension. Rats treated with Ebselen and exposed to CIH displayed a significant reduction in 3-NT-ir levels (60.8 ± 14.9 versus 22.9 ± 4.2 a.u., reduced CB chemosensory response to 5% O2 (266.5 ± 13.4 versus 168.6 ± 16.8 Hz, and decreased mean BP (116.9 ± 13.2 versus 82.1 ± 5.1 mmHg. Our results suggest that CIH-induced CB chemosensory potentiation and hypertension are critically dependent on ONOO− formation.

  14. Formation of tRNA granules in the nucleus of heat-induced human cells

    Energy Technology Data Exchange (ETDEWEB)

    Miyagawa, Ryu [Radioisotope Center, The University of Tokyo, 2-11-16 Yayoi, Bunkyo-ku, Tokyo 113-0032 (Japan); Department of Biological Science, Graduate School of Science, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8654 (Japan); Mizuno, Rie [Radioisotope Center, The University of Tokyo, 2-11-16 Yayoi, Bunkyo-ku, Tokyo 113-0032 (Japan); Watanabe, Kazunori, E-mail: watanabe@ric.u-tokyo.ac.jp [Radioisotope Center, The University of Tokyo, 2-11-16 Yayoi, Bunkyo-ku, Tokyo 113-0032 (Japan); Ijiri, Kenichi [Radioisotope Center, The University of Tokyo, 2-11-16 Yayoi, Bunkyo-ku, Tokyo 113-0032 (Japan); Department of Biological Science, Graduate School of Science, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8654 (Japan)

    2012-02-03

    Highlights: Black-Right-Pointing-Pointer tRNAs are tranlocated into the nucleus in heat-induced HeLa cells. Black-Right-Pointing-Pointer tRNAs form the unique granules in the nucleus. Black-Right-Pointing-Pointer tRNA ganules overlap with nuclear stress granules. -- Abstract: The stress response, which can trigger various physiological phenomena, is important for living organisms. For instance, a number of stress-induced granules such as P-body and stress granule have been identified. These granules are formed in the cytoplasm under stress conditions and are associated with translational inhibition and mRNA decay. In the nucleus, there is a focus named nuclear stress body (nSB) that distinguishes these structures from cytoplasmic stress granules. Many splicing factors and long non-coding RNA species localize in nSBs as a result of stress. Indeed, tRNAs respond to several kinds of stress such as heat, oxidation or starvation. Although nuclear accumulation of tRNAs occurs in starved Saccharomyces cerevisiae, this phenomenon is not found in mammalian cells. We observed that initiator tRNA{sup Met} (Meti) is actively translocated into the nucleus of human cells under heat stress. During this study, we identified unique granules of Meti that overlapped with nSBs. Similarly, elongator tRNA{sup Met} was translocated into the nucleus and formed granules during heat stress. Formation of tRNA granules is closely related to the translocation ratio. Then, all tRNAs may form the specific granules.

  15. Deformation-induced silica redistribution in banded iron formation, Hamersley Province, Australia

    Science.gov (United States)

    Egglseder, Mathias S.; Cruden, Alexander R.; Tomkins, Andrew G.; Wilson, Christopher J. L.

    2016-12-01

    The formation of banded iron formations (BIF) remains controversial despite their potential to provide key information on Precambrian atmospheres and hydrospheres. It is widely agreed that BIF are chemical sedimentary rocks comprising alternating layers of iron oxides and chert formed from poorly known precursor phases. Many models address the chemical transformation of such precursor iron oxide phases into BIF during compaction and diagenesis. However, the formation of chert and the influence of physical forces in this process have received less attention. Microstructural analysis of BIF from the Hamersley Province (Western Australia) reveals that significant amounts of silica were redistributed by dissolution-precipitation creep during both diagenesis and regional-scale deformation. This physicochemical process led to silica remobilisation and volume loss by stress-induced dissolution of microcrystalline quartz in an aqueous fluid. The dissolved solid phase was transported by diffusion and fluid flow along grain boundaries or within available porosity and then reprecipitated in low-pressure zones, leading to local volume increase. These processes were further enhanced by rheological contrasts between different minerals, resulting in significant variations of chert band thickness. Microstructural observations combined with quantitative microfabric analysis reveal domains of crystallographic preferred orientations (CPO) in quartz grains within chert layers. The CPO fabrics record strain regimes (e.g., pure and simple shear, extension and shortening) that modified quartz aggregates by dissolution-precipitation creep, providing new insights into the metamorphic and deformation history of BIF. We document microstructures that indicate that non-coaxial deformation was active during diagenesis and subsequent deformation of the Hamersley Province BIF. Further, relatively undeformed chert layers may have been similarly affected by significant amounts of dissolution

  16. Mechanisms of formation and function of eosinophil lipid bodies: inducible intracellular sites involved in arachidonic acid metabolism

    Directory of Open Access Journals (Sweden)

    Bozza Patricia T

    1997-01-01

    Full Text Available Lipid bodies, inducible lipid-rich cytoplasmic inclusions, are characteristically abundant in cells associated with inflammation, including eosinophils. Here we reviewed the formation and function of lipid bodies in human eosinophils. We now have evidence that the formation of lipid bodies is not attributable to adverse mechanisms, but is centrally mediated by specific signal transduction pathways. Arachidonic acid and other cis fatty acids by an NSAID-inhibitable process, diglycerides, and PAF by a 5-lipoxygenase dependent pathway are potent stimulators of lipid body induction. Lipid body formation develops rapidly by processes that involve PKC, PLC, and de novo mRNA and protein synthesis. These structures clearly serve as repositoires of arachidonyl-phospholipids and are more than inert depots. Specific enzymes, including cytosolic phospholipase A2, MAP kinases, lipoxygenases and cyclooxygenases, associate with lipid bodies. Lipid bodies appear to be dynamic, organelle-like structures involved in intracellular pathways of lipid mobilization and metabolism. Indeed, increases in lipid body numbers correlated with enhanced production of both lipoxygenase- and cyclooxygenase-derived eicosanoids. We hypothesize that lipid bodies are distinct inducible sites for generating eicosanoids as paracrine mediators with varied activities in inflammation. The capacity of lipid body formation to be specifically and rapidly induced in leukocytes enhances eicosanoid mediator formation, and conversely pharmacologic inhibition of lipid body induction represents a potential novel and specific target for anti-inflammatory therapy.

  17. The homing of bone marrow MSCs to non-osseous sites for ectopic bone formation induced by osteoinductive calcium phosphate.

    NARCIS (Netherlands)

    Song, G.; Habibovic, P.; Bao, C.; Hu, J.; Blitterswijk, van C.A.; Yuan, H.; Chen, W.; Xu, H.H.K.

    2013-01-01

    Osteoinductive biomaterials are promising for bone repair. There is no direct proof that bone marrow mesenchymal stem cells (BMSCs) home to non-osseous sites and participate in ectopic bone formation induced by osteoinductive bioceramics. The objective of this study was to use a sex-mismatched beagl

  18. Formation and Collapse of Quiescent Cloud Cores Induced by Dynamic Compressions

    CERN Document Server

    Gómez, Gilberto C; Shadmehri, Mohsen; Vázquez-Semadeni, Enrique

    2007-01-01

    We present numerical hydrodynamical simulations of the formation, evolution and gravitational collapse of isothermal molecular cloud cores induced by generic turbulent compressions in spherical geometry. A compressive wave is set up in a constant sub-Jeans density distribution. As the wave travels through the simulation grid, a shock-bounded layer is formed. The inner shock of this layer reaches and bounces off the center, leaving behind a central core with an initial almost uniform density distribution, surrounded by an envelope consisting of the material in the shock-bounded shell, with a power-law density profile with index close to -2 even in non-collapsing cases. The resulting density structure resembles a quiescent core of radius < 0.1 pc, with a Bonnor-Ebert-like (BE-like) profile, although it has significant dynamical differences: it is initially non-self-gravitating and confined by the ram pressure of the infalling material, and consequently, growing continuously in mass and size. With the appropi...

  19. Formation of a disordered solid via a shock-induced transition in a dense particle suspension.

    Science.gov (United States)

    Petel, Oren E; Frost, David L; Higgins, Andrew J; Ouellet, Simon

    2012-02-01

    Shock wave propagation in multiphase media is typically dominated by the relative compressibility of the two components of the mixture. The difference in the compressibility of the components results in a shock-induced variation in the effective volume fraction of the suspension tending toward the random-close-packing limit for the system, and a disordered solid can take form within the suspension. The present study uses a Hugoniot-based model to demonstrate this variation in the volume fraction of the solid phase as well as a simple hard-sphere model to investigate the formation of disordered structures within uniaxially compressed model suspensions. Both models are discussed in terms of available experimental plate impact data in dense suspensions. Through coordination number statistics of the mesoscopic hard-sphere model, comparisons are made with the trends of the experimental pressure-volume fraction relationship to illustrate the role of these disordered structures in the bulk properties of the suspensions. A criterion for the dynamic stiffening of suspensions under high-rate dynamic loading is suggested as an analog to quasi-static jamming based on the results of the simulations.

  20. Mycobacterium abscessus-Induced Granuloma Formation Is Strictly Dependent on TNF Signaling and Neutrophil Trafficking

    Science.gov (United States)

    Bernut, Audrey; Nguyen-Chi, Mai; Kremer, Laurent

    2016-01-01

    Mycobacterium abscessus is considered the most common respiratory pathogen among the rapidly growing non-tuberculous mycobacteria. Infections with M. abscessus are increasingly found in patients with chronic lung diseases, especially cystic fibrosis, and are often refractory to antibiotic therapy. M. abscessus has two morphotypes with distinct effects on host cells and biological responses. The smooth (S) variant is recognized as the initial airway colonizer while the rough (R) is known to be a potent inflammatory inducer associated with invasive disease, but the underlying immunopathological mechanisms of the infection remain unsolved. We conducted a comparative stepwise dissection of the inflammatory response in S and R pathogenesis by monitoring infected transparent zebrafish embryos. Loss of TNFR1 function resulted in increased mortality with both variants, and was associated with unrestricted intramacrophage bacterial growth and decreased bactericidal activity. The use of transgenic zebrafish lines harboring fluorescent macrophages and neutrophils revealed that neutrophils, like macrophages, interact with M. abscessus at the initial infection sites. Impaired TNF signaling disrupted the IL8-dependent neutrophil mobilization, and the defect in neutrophil trafficking led to the formation of aberrant granulomas, extensive mycobacterial cording, unrestricted bacterial growth and subsequent larval death. Our findings emphasize the central role of neutrophils for the establishment and maintenance of the protective M. abscessus granulomas. These results also suggest that the TNF/IL8 inflammatory axis is necessary for protective immunity against M. abscessus and may be of clinical relevance to explain why immunosuppressive TNF therapy leads to the exacerbation of M. abscessus infections. PMID:27806130

  1. The shock-induced star formation sequence resulting from a constant spiral pattern speed

    Energy Technology Data Exchange (ETDEWEB)

    Martínez-García, Eric E.; Puerari, Ivânio, E-mail: ericmartinez@inaoep.mx, E-mail: puerari@inaoep.mx [Instituto Nacional de Astrofísica, Óptica y Electrónica (INAOE), Aptdo. Postal 51 y 216, 72000 Puebla, Puebla (Mexico)

    2014-08-01

    We utilize a suite of multiwavelength data of nine nearby spirals to analyze the shock-induced star formation sequence that may result from a constant spiral pattern speed. The sequence involves tracers as the H I, CO 24 μm, and FUV, where the spiral arms were analyzed with Fourier techniques in order to obtain their azimuthal phases as a function of radius. It was found that only two of the objects, NGC 628 and NGC 5194, present coherent phases resembling the theoretical expectations, as indicated by the phase shifts of CO- 24 μm. The evidence is more clear for NGC 5194 and moderate for NGC 628. It was also found that the phase shifts are different for the two spiral arms. With the exception on NGC 3627, a two-dimensional Fourier analysis showed that the rest of the objects do not exhibit bi-symmetric spiral structures of stellar mass, i.e., grand-design spirals. A phase order inversion indicates a corotation radius of ∼89'' for NGC 628 and ∼202'' for NGC 5194. For these two objects, the CO-Hα phase shifts corroborate the CO-24 μm azimuthal offsets. Also for NGC 5194, the CO-70 μm, CO-140 μm, and CO-250 μm phase shifts indicate a corotation region.

  2. Hypocellular scar formation or aberrant fibrosis induced by an intrastromal corneal ring: a case report

    Directory of Open Access Journals (Sweden)

    Ramkumar Hema L

    2011-08-01

    Full Text Available Abstract Introduction Intrastromal corneal rings or segments are approved for the treatment of myopia and astigmatism associated with keratoconus. We describe a clinicopathological case of intrastromal corneal rings. For the first time, the molecular pathological findings of intrastromal corneal rings in the cornea are illustrated. Case presentation A 47-year-old African-American man with a history of keratoconus and failure in using a Rigid Gas Permeable contact lens received an intrastromal corneal ring implant in his left eye. Due to complications, penetrating keratoplasty was performed. The intrastromal corneal ring channels were surrounded by a dense acellular (channel haze and/or hypocellular (acidophilic densification collagen scar and slightly edematous keratocytes. Mild macrophage infiltration was found near the inner aspect of the intrastromal corneal rings. Molecular analyses of the microdissected cells surrounding the intrastromal corneal ring channels and central corneal stroma revealed 10 times lower relative expression of IP-10/CXCL10 mRNA and two times higher CCL5 mRNA in the cells surrounding the intrastromal corneal ring, as compared to the central corneal stroma. IP-10/CXCL10 is a fibrotic and angiostatic chemokine produced by macrophages, endothelial cells and fibroblasts. Conclusion An intrastromal corneal ring implant can induce hypocellular scar formation and mild inflammation, which may result from aberrant release of fibrosis-related chemokines.

  3. Graphene Induces Formation of Pores That Kill Spherical and Rod-Shaped Bacteria.

    Science.gov (United States)

    Pham, Vy T H; Truong, Vi Khanh; Quinn, Matthew D J; Notley, Shannon M; Guo, Yachong; Baulin, Vladimir A; Al Kobaisi, Mohammad; Crawford, Russell J; Ivanova, Elena P

    2015-08-25

    Pristine graphene, its derivatives, and composites have been widely reported to possess antibacterial properties. Most of the studies simulating the interaction between bacterial cell membranes and the surface of graphene have proposed that the graphene-induced bacterial cell death is caused either by (1) the insertion of blade-like graphene-based nanosheets or (2) the destructive extraction of lipid molecules by the presence of the lipophilic graphene. These simulation studies have, however, only take into account graphene-cell membrane interactions where the graphene is in a dispersed form. In this paper, we report the antimicrobial behavior of graphene sheet surfaces in an attempt to further advance the current knowledge pertaining to graphene cytotoxicity using both experimental and computer simulation approaches. Graphene nanofilms were fabricated to exhibit different edge lengths and different angles of orientation in the graphene sheets. These substrates were placed in contact with Pseudomonas aeruginosa and Staphylococcus aureus bacteria, where it was seen that these substrates exhibited variable bactericidal efficiency toward these two pathogenic bacteria. It was demonstrated that the density of the edges of the graphene was one of the principal parameters that contributed to the antibacterial behavior of the graphene nanosheet films. The study provides both experimental and theoretical evidence that the antibacterial behavior of graphene nanosheets arises from the formation of pores in the bacterial cell wall, causing a subsequent osmotic imbalance and cell death.

  4. Cholesterol is essential for mitosis progression and its deficiency induces polyploid cell formation.

    Science.gov (United States)

    Fernández, Carlos; Lobo Md, María del Val T; Gómez-Coronado, Diego; Lasunción, Miguel A

    2004-10-15

    As an essential component of mammalian cell membranes, cells require cholesterol for proliferation, which is either obtained from plasma lipoproteins or synthesized intracellularly from acetyl-CoA. In addition to cholesterol, other non-sterol mevalonate derivatives are necessary for DNA synthesis, such as the phosphorylated forms of isopentane, farnesol, geranylgeraniol, and dolichol. The aim of the present study was to elucidate the role of cholesterol in mitosis. For this, human leukemia cells (HL-60) were incubated in a cholesterol-free medium and treated with SKF 104976, which inhibits cholesterol biosynthesis by blocking sterol 14alpha-demethylase, and the expression of relevant cyclins in the different phases of the cell cycle was analyzed by flow cytometry. Prolonged cholesterol starvation induced the inhibition of cytokinesis and the formation of polyploid cells, which were multinucleated and had mitotic aberrations. Supplementing the medium with cholesterol completely abolished these effects, demonstrating they were specifically due to cholesterol deficiency. This is the first evidence that cholesterol is essential for mitosis completion and that, in the absence of cholesterol, the cells fail to undergo cytokinesis, entered G1 phase at higher DNA ploidy (tetraploidy), and then progressed through S (rereplication) into G2, generating polyploid cells.

  5. Formation and annihilation of intrinsic defects induced by electronic excitation in high-purity crystalline SiO{sub 2}

    Energy Technology Data Exchange (ETDEWEB)

    Kajihara, Koichi [Department of Applied Chemistry, Graduate School of Urban Environmental Sciences, Tokyo Metropolitan University, 1-1 Minami-Osawa, Hachioji 192-0397 (Japan); Skuja, Linards [Institute of Solid State Physics, University of Latvia, Kengaraga iela 8, LV1063 Riga (Latvia); Hosono, Hideo [Materials and Structures Laboratory and Frontier Research Center, Tokyo Institute of Technology, 4259 Nagatsuta, Midori-ku, Yokohama 226-8503 (Japan)

    2013-04-14

    Formation and thermal annihilation of intrinsic defects in {alpha}-quartz were examined using high-purity samples, while minimizing the contributions of reactions involving metallic impurities. Electronic excitation with {sup 60}Co {gamma}-rays was employed to avoid radiation-induced amorphization. The results clearly show that formation of oxygen vacancies (Si-Si bonds) as a result of decomposition of regular Si-O-Si bonds (Frenkel process) is the dominant intrinsic defect process. Compared with amorphous SiO{sub 2}, in {alpha}-quartz, the formation yield of Si-Si bonds is an order of magnitude smaller, the 7.6 eV optical absorption band is less broadened, and their thermal annihilation is complete at a lower temperature, around the {alpha}-{beta} quartz transition. In contrast, radiation-induced interstitial oxygen atoms practically do not form interstitial oxygen molecules.

  6. Mutual Amino Acid Catalysis in Salt-Induced Peptide Formation Supports this Mechanism's Role in Prebiotic Peptide Evolution

    Science.gov (United States)

    Suwannachot, Yuttana; Rode, Bernd M.

    1999-10-01

    The presence of some amino acids and dipeptides under the conditions of the salt-induced peptide formation reaction (aqueous solution at 85 °C, Cu(II) and NaCl) has been found to catalyze the formation of homopeptides of other amino acids, which are otherwise produced only in traces or not at all by this reaction. The condensation of Val, Leu and Lys to form their homodipeptides can occur to a considerable extent due to catalytic effects of other amino acids and related compounds, among which glycine, histidine, diglycine and diketopiperazine exhibit the most remarkable activity. These findings also lead to a modification of the table of amino acid sequences preferentially formed by the salt-induced peptide formation (SIPF) reaction, previously used for a comparison with the sequence preferences in membrane proteins of primitive organisms

  7. Photo-induced formation of nitrous acid (HONO) on protein surfaces

    Science.gov (United States)

    Meusel, Hannah; Elshorbany, Yasin; Bartels-Rausch, Thorsten; Selzle, Kathrin; Lelieveld, Jos; Ammann, Markus; Pöschl, Ulrich; Su, Hang; Cheng, Yafang

    2014-05-01

    The study of nitrous acid (HONO) is of great interest, as the photolysis of HONO leads to the OH radical, which is the most important oxidant in the troposphere. HONO is directly emitted by combustion of fossil fuel and from soil biogenic nitrite (Su et al., 2011), and can also be formed by gas phase reactions of NO and OH and heterogeneous reactions of NO2. Previous atmospheric measurements have shown unexpectedly high HONO concentrations during daytime. Measured mixing ratios were about one order of magnitude higher than model simulations (Kleffmann et al. 2005, Vogel et al. 2003). The additional daytime source of HONO might be attributed to the photolysis of adsorbed nitric acid or heterogeneous photochemistry of NO2 on organic substrates, such as humic acids or polyphenolic compounds (Stemmler et al., 2006), or indirectly through nitration of phenols and subsequent photolysis of nitrophenols (Sosedova et al., 2011, Bejan et al., 2006). An important reactive surface for the heterogeneous formation of HONO could involve proteins, which are ubiquitous in the environment. They are part of coarse biological aerosol particles like pollen grains, fine particles (fragments of pollen, microorganism, plant debris) and dissolved in rainwater, soil and road dust (Miguel et al. 1999). In this project a thin film of bovine serum albumin (BSA), a model protein with 67 kDa and 21 tyrosine residues per molecule, is irradiated and exposed to nitrogen dioxide in humidified nitrogen. The formation of HONO is measured with long path absorption photometry (LOPAP). The generated HONO is in the range of 100 to 1100 ppt depending on light intensity, NO2 concentration and film thickness. Light induced HONO formation on protein surfaces is stable over the 20-hours experiment of irradiation and exposure. On the other hand, light activated proteins reacting with NO2 form nitrated proteins, as detected by liquid chromatography (LC-DAD). Our experiments on tetranitromethane (TNM) nitrated

  8. Differential roles of CIDEA and CIDEC in insulin-induced anti-apoptosis and lipid droplet formation in human adipocytes.

    Science.gov (United States)

    Ito, Minoru; Nagasawa, Michiaki; Hara, Tomoko; Ide, Tomohiro; Murakami, Koji

    2010-07-01

    Both insulin and the cell death-inducing DNA fragmentation factor-alpha-like effector (CIDE) family play important roles in apoptosis and lipid droplet formation. However, regulation of the CIDE family by insulin and the contribution of the CIDE family to insulin actions remain unclear. Here, we investigated whether insulin regulates expression of the CIDE family and which subtypes contribute to insulin-induced anti-apoptosis and lipid droplet formation in human adipocytes. Insulin decreased CIDEA and increased CIDEC but not CIDEB mRNA expression. Starvation-induced apoptosis in adipocytes was significantly inhibited when insulin decreased the CIDEA mRNA level. Small interfering RNA-mediated depletion of CIDEA inhibited starvation-induced apoptosis similarly to insulin and restored insulin deprivation-reduced adipocyte number, whereas CIDEC depletion did not. Lipid droplet size of adipocytes was increased when insulin increased the CIDEC mRNA level. In contrast, insulin-induced enlargement of lipid droplets was markedly abrogated by depletion of CIDEC but not CIDEA. Furthermore, depletion of CIDEC, but not CIDEA, significantly increased glycerol release from adipocytes. These results suggest that CIDEA and CIDEC are novel genes regulated by insulin in human adipocytes and may play key roles in the effects of insulin, such as anti-apoptosis and lipid droplet formation.

  9. Berberine promotes the development of atherosclerosis and foam cell formation by inducing scavenger receptor A expression in macrophage

    Institute of Scientific and Technical Information of China (English)

    Ke Li; Wenqi Yao; Xiudan Zheng; Kan Liao

    2009-01-01

    Berberine is identified to lower the serum cholesterol level in human and hamster through the induction of low density lipoproteins (LDL) receptor in hepatic cells. To evaluate its potential in preventing atherosclerosis, the effect of berberine on atherosclerosis development in apolipoprotein E-deficient (apoE-/-) mice was investigated, in apoE-/-mice, berberine induced in vivo foam cell formation and promoted atherosclerosis development. The foam cell for-mation induced by berberine was also observed in mouse RAW264.7 cells, as well as in mouse and human primary macrophages. By inducing scavenger receptor A (SR-A) expression in macrophages, berberine increased the uptake of modified LDL (DiO-Ac-LDL). Berberine-induced SR-A expression was also observed in macrophage foam cells in vivo and in the cells at atherosclerotic lesion. Analysis in RAW264.7 cells indicated that berberine induced SR-A ex-pression by suppressing PTEN expression, which led to sustained Akt activation. Our results suggest that to evaluate the potential of a cholesterol-reducing compound in alleviating atherosclerosis, its effect on the cells involved in ath-erosclerosis development, such as macrophages, should also be considered. Promotion of foam cell formation could counter-balance the beneficial effect of lowering serum cholesterol.

  10. CD151 gene delivery increases eNOS activity and induces ECV304 migration, proliferation and tube formation

    Institute of Scientific and Technical Information of China (English)

    Zhen-zhong ZHENO; Zheng-xiang LIU

    2007-01-01

    Aim: To investigate the effects of CD151 on the activity of endothelial NO syn-thase (eNOS), and ECV304 migration, proliferation and tube formation. Methods:pAAV-CD151 and pAAV-anti-CD151 were constructed and used to transiently transfect ECV304 mediated with Lipofectamine 2000. After transfection, the ex-pression of CD151 was measured by Western blotting. Cell migration assay was performed using Boyden transwell; proliferation assay was evaluated using the 3-[4,5-dimethylthiazol-2-yl]-2,5, diphenyltetrazolium bromide (MTT) method, and tube formation test was examined on matrigel, eNOS activity was assayed by L-[3H]citrulline production from L-[3H]arginine. The involvement of eNOS was ex-plored using an eNOS inhibitor (L-NAME) and the effects in the process were observed. Results: CD151 promotes cell migration, proliferation and tube formation.In addition, CD151 increases eNOS activity. Moreover, cell migration, prolifera-tion and tube formation induced by CD151 are inhibited when L-NAME is used,which indicates that there is an involvement of eNOS in CD151-induced cell migration, cell proliferation and tube formation. Conclusion: CD151 promotes ECV304 migration, proliferation and tube formation. The mechanism is that CD151 increases eNOS activity. This result also suggests that eNOS is involved in the angiogenic effects of CD151.

  11. IL-33 inhibits RANKL-induced osteoclast formation through the regulation of Blimp-1 and IRF-8 expression

    Energy Technology Data Exchange (ETDEWEB)

    Kiyomiya, Hiroyasu [Division of Infections and Molecular Biology, Department of Health Promotion, Kyushu Dental University, 2-6-1 Manazuru, Kokurakita-ku, Kitakyushu, Fukuoka 803-8580 (Japan); Division of Oral and Maxillofacial Surgery, Department of Science of Physical Functions, Kyushu Dental University, 2-6-1 Manazuru, Kokurakita-ku, Kitakyushu, Fukuoka 803-8580 (Japan); Ariyoshi, Wataru; Okinaga, Toshinori [Division of Infections and Molecular Biology, Department of Health Promotion, Kyushu Dental University, 2-6-1 Manazuru, Kokurakita-ku, Kitakyushu, Fukuoka 803-8580 (Japan); Kaneuji, Takeshi [Division of Oral Medicine, Department of Science of Physical Functions, Kyushu Dental University, 2-6-1 Manazuru, Kokurakita-ku, Kitakyushu, Fukuoka 803-8580 (Japan); Mitsugi, Sho [Division of Oral and Maxillofacial Surgery, Department of Science of Physical Functions, Kyushu Dental University, 2-6-1 Manazuru, Kokurakita-ku, Kitakyushu, Fukuoka 803-8580 (Japan); Sakurai, Takuma [Division of Infections and Molecular Biology, Department of Health Promotion, Kyushu Dental University, 2-6-1 Manazuru, Kokurakita-ku, Kitakyushu, Fukuoka 803-8580 (Japan); Division of Oral and Maxillofacial Surgery, Department of Science of Physical Functions, Kyushu Dental University, 2-6-1 Manazuru, Kokurakita-ku, Kitakyushu, Fukuoka 803-8580 (Japan); Habu, Manabu [Division of Oral and Maxillofacial Surgery, Department of Science of Physical Functions, Kyushu Dental University, 2-6-1 Manazuru, Kokurakita-ku, Kitakyushu, Fukuoka 803-8580 (Japan); Yoshioka, Izumi [Division of Oral Medicine, Department of Science of Physical Functions, Kyushu Dental University, 2-6-1 Manazuru, Kokurakita-ku, Kitakyushu, Fukuoka 803-8580 (Japan); Tominaga, Kazuhiro [Division of Oral and Maxillofacial Surgery, Department of Science of Physical Functions, Kyushu Dental University, 2-6-1 Manazuru, Kokurakita-ku, Kitakyushu, Fukuoka 803-8580 (Japan); and others

    2015-05-01

    Interleukin (IL)-33 is a recently discovered proinflammatory cytokine that belongs to the IL-1 family. Several studies have reported that IL-33 inhibits osteoclast differentiation. However, the mechanism of IL-33 regulation of osteoclastogenesis remains unclear. In the present study, we examined the effect of IL-33 on osteoclast formation in vitro. IL-33 suppressed osteoclast formation in both mouse bone marrow cells and monocyte/macrophage cell line RAW264.7 cells induced by receptor activator of NF-κB ligand (RANKL) and/or macrophage stimulating factor (M-CSF). IL-33 also inhibited the expression of RANKL-induced nuclear factor of activated T-cell cytoplasmic 1 (NFATc1), thereby decreasing the expression of osteoclastogenesis-related marker genes, including Cathepsin K, Osteoclast stimulatory transmembrane protein (Oc-stamp) and Tartrate-resistant acid phosphatase (Trap). Blockage of IL-33-ST2 binding suppressed the IL-33-mediated inhibition of NFATc1. RANKL-induced B-lymphocyte-induced maturation protein-1 (Blimp-1) expression was also suppressed by IL-33, which was followed by the stimulation of anti-osteoclastic genes such as interferon regulatory factor-8 (IRF-8). These results suggest that IL-33-ST2 interactions down-regulate both RANKL-induced NFATc1 activation and osteoclast differentiation via the regulation of Blimp-1 and IRF-8 expression. - Highlights: • IL-33 inhibits RANKL-induced osteoclast formation. • IL-33 has inhibitory effect on the RANKL-induced NFATc1 expression. • IL-33-induced NFATc1 suppression depends on the regulation of Blimp-1 and IRF-8.

  12. Sinomenine, theophylline, cysteine, and levamisole: Comparisons of their kinetic effects on mineral formation induced by matrix vesicles.

    Science.gov (United States)

    Li, Lina; Buchet, René; Wu, Yuqing

    2010-04-01

    The effects of sinomenine (SIN, an alkaloid extracted from the Chinese medicinal plant Sinomenium acutum used for centuries to treat rheumatic disease, including rheumatoid arthritis) on apatitic nucleation and matrix vesicle (MV)-induced mineral formation were compared with those of cysteine, levamisole, and theophylline. We found that SIN was not an inhibitor of tissue non-specific alkaline phosphatase (TNAP), a marker of biological mineralization, but confirmed that cysteine, levamisole, and theophylline were. Further, none of these four molecules directly affected the nucleation of hydroxyapatite (HA) formation, in contrast to pyrophosphate (PP(i)) which did. Incubation of 0.25-1.0mM cysteine, theophylline, or levamisole with MVs in synthetic cartilage lymph (SCL) containing AMP and Ca(2+), but not inorganic phosphate (P(i)), prolonged the induction time of mineral formation, apparently by inhibiting TNAP activity. SIN at the same levels neither inhibited TNAP activity nor affected the induction time of MV mineral formation. However, SIN did markedly delay MV-induced mineral formation in SCL containing P(i) (instead of AMP) in a manner similar to theophylline, but to a lesser extent than levamisole. Cysteine did not delay, in fact it slightly accelerated MV-induced mineral formation in Pi-containing SCL. These findings suggest that levamisole, SIN and theophylline may directly affect Ca(2+) and/or P(i) accretion during mineral formation; however, TNAP was not directly involved. The possible roles of annexins and other ion transporters, such as proteins of the solute carrier family implicated in Ca(2+) and P(i) influx are discussed.

  13. Sub-inhibitory tigecycline concentrations induce extracellular matrix binding protein Embp dependent Staphylococcus epidermidis biofilm formation and immune evasion.

    Science.gov (United States)

    Weiser, Julian; Henke, Hanae A; Hector, Nina; Both, Anna; Christner, Martin; Büttner, Henning; Kaplan, Jeffery B; Rohde, Holger

    2016-09-01

    Biofilm-associated Staphylococcus epidermidis implant infections are notoriously reluctant to antibiotic treatment. Here we studied the effect of sub-inhibitory concentrations of penicillin, oxacillin, vancomycin, daptomycin, linezolid and tigecycline on S. epidermidis 1585 biofilm formation, expression of extracellular matrix binding protein (Embp) and potential implications for S. epidermidis - macrophage interactions. Penicillin, vancomycin, daptomycin, and linezolid had no biofilm augmenting effect at any of the concentrations tested. In contrast, at sub-inhibitory concentrations tigecycline and oxacillin exhibited significant biofilm inducing activity. In S. epidermidis 1585, SarA is a negative regulator of giant 1 MDa Embp, and down regulation of sarA induces Embp-dependent assembly of a multi-layered biofilm architecture. Dot blot immune assays, confocal laser scanning microscopy, and qPCR showed that under biofilm inducing conditions, tigecycline augmented embp expression compared to the control grown without antibiotics. Conversely, expression of regulator sarA was suppressed, suggesting that tigecycline exerts its effects on embp expression through SarA. Tigecycline failed to induce biofilm formation in embp transposon mutant 1585-M135, proving that under these conditions Embp up-regulation is necessary for biofilm accumulation. As a functional consequence, tigecycline induced biofilm formation significantly impaired the up-take of S. epidermidis by mouse macrophage-like cell line J774A.1. Our data provide novel evidence for the molecular basis of antibiotic induced biofilm formation, a phenotype associated with inherently increased antimicrobial tolerance. While this could explain failure of antimicrobial therapies, persistence of S. epidermidis infections in the presence of sub-inhibitory antimicrobials is additionally propelled by biofilm-related impairment of macrophage-mediated pathogen eradication.

  14. Impact of Process Parameters on the Laser-induced Nanoparticle Formation During Keyhole Welding under Remote Conditions

    Science.gov (United States)

    Scholz, Tobias; Dickmann, Klaus; Ostendorf, Andreas

    The interaction between the vapor plume and the incident laser radiation affects remote laser welding. Relating to laser systems with an emitted wavelength around 1 μm, a significant loss mechanism can be traced back to the extinction by laser-induced particle formation. Due to the tight coupling between the particle formation and the evaporation rate inside the keyhole, the particle formation shows a strong dependence on the keyhole geometry and thus on process parameters (e.g. feed rate and laser beam power). In order to verify the relationship between particle formation and process parameters, the beam of a broadband LED was guided through the vapor plume during the welding processes with a fiber laser. The attenuated probe beam was analyzed in dependence on the wavelength. In addition, the propagation of the vapor plume was investigated by using high speed imaging.

  15. Neurokinin 1 receptor mediates membrane blebbing and sheer stress-induced microparticle formation in HEK293 cells.

    Directory of Open Access Journals (Sweden)

    Panpan Chen

    Full Text Available Cell-derived microparticles participate in intercellular communication similar to the classical messenger systems of small and macro-molecules that bind to specialized membrane receptors. Microparticles have been implicated in the regulation of a variety of complex physiopathologic processes, such as thrombosis, the control of innate and adaptive immunity, and cancer. The neurokinin 1 receptor (NK1R is a Gq-coupled receptor present on the membrane of a variety of tissues, including neurons in the central and peripheral nervous system, immune cells, endocrine and exocrine glands, and smooth muscle. The endogenous agonist of NK1R is the undecapeptide substance P (SP. We have previously described intracellular signaling mechanisms that regulate NK1R-mediated rapid cell shape changes in HEK293 cells and U373MG cells. In the present study, we show that the activation of NK1R in HEK293 cells, but not in U373MG cells, leads to formation of sheer-stress induced microparticles that stain positive with the membrane-selective fluorescent dye FM 2-10. SP-induced microparticle formation is independent of elevated intracellular calcium concentrations and activation of NK1R present on HEK293-derived microparticles triggers detectable calcium increase in SP-induced microparticles. The ROCK inhibitor Y27632 and the dynamin inhibitor dynasore inhibited membrane blebbing and microparticle formation in HEK293 cells, strongly suggesting that microparticle formation in this cell type is dependent on membrane blebbing.

  16. In site bioimaging of hydrogen sulfide uncovers its pivotal role in regulating nitric oxide-induced lateral root formation.

    Directory of Open Access Journals (Sweden)

    Yan-Jun Li

    Full Text Available Hydrogen sulfide (H2S is an important gasotransmitter in mammals. Despite physiological changes induced by exogenous H2S donor NaHS to plants, whether and how H2S works as a true cellular signal in plants need to be examined. A self-developed specific fluorescent probe (WSP-1 was applied to track endogenous H2S in tomato (Solanum lycopersicum roots in site. Bioimaging combined with pharmacological and biochemical approaches were used to investigate the cross-talk among H2S, nitric oxide (NO, and Ca(2+ in regulating lateral root formation. Endogenous H2S accumulation was clearly associated with primordium initiation and lateral root emergence. NO donor SNP stimulated the generation of endogenous H2S and the expression of the gene coding for the enzyme responsible for endogenous H2S synthesis. Scavenging H2S or inhibiting H2S synthesis partially blocked SNP-induced lateral root formation and the expression of lateral root-related genes. The stimulatory effect of SNP on Ca(2+ accumulation and CaM1 (calmodulin 1 expression could be abolished by inhibiting H2S synthesis. Ca(2+ chelator or Ca(2+ channel blocker attenuated NaHS-induced lateral root formation. Our study confirmed the role of H2S as a cellular signal in plants being a mediator between NO and Ca(2+ in regulating lateral root formation.

  17. Phosphoramide mustard exposure induces DNA adduct formation and the DNA damage repair response in rat ovarian granulosa cells.

    Science.gov (United States)

    Ganesan, Shanthi; Keating, Aileen F

    2015-02-01

    Phosphoramide mustard (PM), the ovotoxic metabolite of the anti-cancer agent cyclophosphamide (CPA), destroys rapidly dividing cells by forming NOR-G-OH, NOR-G and G-NOR-G adducts with DNA, potentially leading to DNA damage. A previous study demonstrated that PM induces ovarian DNA damage in rat ovaries. To investigate whether PM induces DNA adduct formation, DNA damage and induction of the DNA repair response, rat spontaneously immortalized granulosa cells (SIGCs) were treated with vehicle control (1% DMSO) or PM (3 or 6μM) for 24 or 48h. Cell viability was reduced (Padduct was detected after 24h of 6μM PM exposure, while the more cytotoxic G-NOR-G DNA adduct was formed after 48h by exposure to both PM concentrations. Phosphorylated H2AX (γH2AX), a marker of DNA double stranded break occurrence, was also increased by PM exposure, coincident with DNA adduct formation. Additionally, induction of genes (Atm, Parp1, Prkdc, Xrcc6, and Brca1) and proteins (ATM, γH2AX, PARP-1, PRKDC, XRCC6, and BRCA1) involved in DNA repair were observed in both a time- and dose-dependent manner. These data support that PM induces DNA adduct formation in ovarian granulosa cells, induces DNA damage and elicits the ovarian DNA repair response.

  18. Sedentary aging increases resting and exercise-induced intramuscular free radical formation.

    Science.gov (United States)

    Bailey, Damian M; McEneny, Jane; Mathieu-Costello, Odile; Henry, Robert R; James, Philip E; McCord, Joe M; Pietri, Sylvia; Young, Ian S; Richardson, Russell S

    2010-08-01

    Mitochondrial free radical formation has been implicated as a potential mechanism underlying degenerative senescence, although human data are lacking. Therefore, the present study was designed to examine if resting and exercise-induced intramuscular free radical-mediated lipid peroxidation is indeed increased across the spectrum of sedentary aging. Biopsies were obtained from the vastus lateralis in six young (26 + or - 6 yr) and six aged (71 + or - 6 yr) sedentary males at rest and after maximal knee extensor exercise. Aged tissue exhibited greater (P < 0.05 vs. the young group) electron paramagnetic resonance signal intensity of the mitochondrial ubisemiquinone radical both at rest (+138 + or - 62%) and during exercise (+143 + or - 40%), and this was further complemented by a greater increase in alpha-phenyl-tert-butylnitrone adducts identified as a combination of lipid-derived alkoxyl-alkyl radicals (+295 + or - 96% and +298 + or - 120%). Lipid hydroperoxides were also elevated at rest (0.190 + or - 0.169 vs. 0.148 + or - 0.071 nmol/mg total protein) and during exercise (0.567 + or - 0.259 vs. 0.320 + or - 0.263 nmol/mg total protein) despite a more marked depletion of ascorbate and uptake of alpha/beta-carotene, retinol, and lycopene (P < 0.05 vs. the young group). The impact of senescence was especially apparent when oxidative stress biomarkers were expressed relative to the age-related decline in mitochondrial volume density and absolute power output at maximal exercise. In conclusion, these findings confirm that intramuscular free radical-mediated lipid peroxidation is elevated at rest and during acute exercise in aged humans.

  19. Expression of the p12 subunit of human DNA polymerase δ (Pol δ), CDK inhibitor p21(WAF1), Cdt1, cyclin A, PCNA and Ki-67 in relation to DNA replication in individual cells.

    Science.gov (United States)

    Zhao, Hong; Zhang, Sufang; Xu, Dazhong; Lee, Marietta Ywt; Zhang, Zhongtao; Lee, Ernest Yc; Darzynkiewicz, Zbigniew

    2014-01-01

    We recently reported that the p12 subunit of human DNA polymerase δ (Pol δ4) is degraded by CRL4(Cdt2) which regulates the licensing factor Cdt1 and p21(WAF1) during the G1 to S transition. Presently, we performed multiparameter laser scanning cytometric analyses of changes in levels of p12, Cdt1 and p21(WAF1), detected immunocytochemically in individual cells, vis-à-vis the initiation and completion of DNA replication. The latter was assessed by pulse-labeling A549 cells with the DNA precursor ethynyl-2'-deoxyribose (EdU). The loss of p12 preceded the initiation of DNA replication and essentially all cells incorporating EdU were p12 negative. Completion of DNA replication and transition to G2 phase coincided with the re-appearance and rapid rise of p12 levels. Similar to p12 a decline of p21(WAF1) and Cdt1 was seen at the end of G1 phase and all DNA replicating cells were p21(WAF1) and Cdt1 negative. The loss of p21(WAF1) preceded that of Cdt1 and p12 and the disappearance of the latter coincided with the onset of DNA replication. Loss of p12 leads to conversion of Pol δ4 to its trimeric form, Pol δ3, so that the results provide strong support to the notion that Pol δ3 is engaged in DNA replication during unperturbed progression through the S phase of cell cycle. Also assessed was a correlation between EdU incorporation, likely reflecting the rate of DNA replication in individual cells, and the level of expression of positive biomarkers of replication cyclin A, PCNA and Ki-67 in these cells. Of interest was the observation of stronger correlation between EdU incorporation and expression of PCNA (r = 0.73) than expression of cyclin A (r = 0.47) or Ki-67 (r = 0.47).

  20. Detecção dos genes codificantes da toxina CDT, e pesquisa de fatores que influenciam na produção de hemolisinas em amostras de Campylobacter jejuni de origem avícola

    Directory of Open Access Journals (Sweden)

    Michele M. Trindade

    2015-08-01

    Full Text Available Resumo: Membros termofílicos do gênero Campylobacter são reconhecidos como importantes enteropatógenos para o ser humano e animais. A grande diversidade ecológica destes micro-organismos em diferentes habitats tais como água, animais e alimentos predispõem ao aparecimento de novos fatores de virulência. Este trabalho teve por objetivo detectar os genes codificantes da Toxina Distensiva Citoletal (CDT por meio da técnica de PCR, pesquisar a atividade de hemolisinas e a influência de soluções quelantes e de íons nesta atividade. Foram utilizadas 45 amostras de Campylobacter jejuni de origem avícola para pesquisa de atividade hemolítica, cultivadas em Caldo Triptona de Soja (TSB. Após o crescimento bacteriano, as amostras foram semeadas em Ágar tríptico de soja (TSA contendo 5% de sangue de ovino. Para verificar a influência de agentes quelantes e solução de íons na atividade hemolítica, as amostras de C. jejuni foram cultivadas em TSB contendo separadamente os quelantes EDTA, ácido acético, soluções de íons CaCl2, MgCl2 e FeCl3, em atmosfera de microaerofilia. Quanto à atividade de hemolisina de C. jejuni em placas de TSA - sangue ovino foi possível observar que houve hemólise em 40% das amostras analisadas apenas com caldo TSB. Somente o ácido acético apresentou ação quelante sobre a atividade de hemolisinas em amostras de C. jejuni semeadas em placas de TSA - sangue ovino. Para detecção dos genes cdtA, cdtB e cdtC através da técnica da Reação em Cadeia da Polimerase (PCR foram utilizadas 119 amostras de C. jejuni de origem avícola. Foi possível observar que 37,8% possuíam o perfil de genes cdtABC. Os resultados demonstraram em amostras avícolas a presença de cepas de C. jejuni com potencial virulento, devido à presença dos genes da toxina CDT e potencial hemolítico, que apresentou ação reduzida in vitro com ácido acético.

  1. Cell resistance to the Cytolethal Distending Toxin involves an association of DNA repair mechanisms

    Science.gov (United States)

    Bezine, Elisabeth; Malaisé, Yann; Loeuillet, Aurore; Chevalier, Marianne; Boutet-Robinet, Elisa; Salles, Bernard; Mirey, Gladys; Vignard, Julien

    2016-01-01

    The Cytolethal Distending Toxin (CDT), produced by many bacteria, has been associated with various diseases including cancer. CDT induces DNA double-strand breaks (DSBs), leading to cell death or mutagenesis if misrepaired. At low doses of CDT, other DNA lesions precede replication-dependent DSB formation, implying that non-DSB repair mechanisms may contribute to CDT cell resistance. To address this question, we developed a proliferation assay using human cell lines specifically depleted in each of the main DNA repair pathways. Here, we validate the involvement of the two major DSB repair mechanisms, Homologous Recombination and Non Homologous End Joining, in the management of CDT-induced lesions. We show that impairment of single-strand break repair (SSBR), but not nucleotide excision repair, sensitizes cells to CDT, and we explore the interplay of SSBR with the DSB repair mechanisms. Finally, we document the role of the replicative stress response and demonstrate the involvement of the Fanconi Anemia repair pathway in response to CDT. In conclusion, our work indicates that cellular survival to CDT-induced DNA damage involves different repair pathways, in particular SSBR. This reinforces a model where CDT-related genotoxicity primarily involves SSBs rather than DSBs, underlining the importance of cell proliferation during CDT intoxication and pathogenicity. PMID:27775089

  2. Electromagnetic particle-in-cell (PIC) method for modeling the formation of metal surface structures induced by femtosecond laser radiation

    Science.gov (United States)

    Djouder, M.; Lamrous, O.; Mitiche, M. D.; Itina, T. E.; Zemirli, M.

    2013-09-01

    The particle in cell (PIC) method coupled to the finite-difference time-domain (FDTD) method is used to model the formation of laser induced periodic surface structures (LIPSS) at the early stage of femtosecond laser irradiation of smooth metal surface. The theoretical results were analyzed and compared with experimental data taken from the literature. It was shown that the optical properties of the target are not homogeneous and the ejection of electrons is such that ripples in the electron density were obtained. The Coulomb explosion mechanism was proposed to explain the ripples formation under the considered conditions.

  3. Simultaneous formation of ablative and thermochemical laser-induced periodic surface structures on Ti film at femtosecond irradiation

    Science.gov (United States)

    Dostovalov, A. V.; Korolkov, V. P.; Babin, S. A.

    2015-03-01

    Formation of laser-induced periodic surface structures (LIPSS) on the titanium surface at the presence of sharply focused fs radiation exhibits two different regimes. Conventional ablative LIPSS with low regularity are oriented orthogonally to the polarization direction of the incident beam, while thermochemical LIPSS with highly uniform periodicity are oriented along the polarization direction. These two types of LIPSS can co-exist and influence each other for arbitrary polarization and beam scanning directions. The observed regimes help to clarify mechanisms of LIPSS formation, as well as to form LIPSS of specific shapes and degrees of regularity.

  4. The formation of radiation-induced segregation at twin bands in ion-irradiated austenitic stainless steel

    Energy Technology Data Exchange (ETDEWEB)

    Jin, Hyung-Ha; Lee, Gyeong-Geun; Kwon, Junhyun; Hwang, Seong Sik [Nuclear Materials Division, Korea Atomic Energy Research Institute, 1045 Daedeok-daero, Yuseong-gu, Daejeon 305-353 (Korea, Republic of); Shin, Chansun, E-mail: c.shin@mju.ac.kr [Department of Materials Science and Engineering, Myongji University, 116 Myongji-ro, Cheoin-gu, Youngin, Gyeonggi-do 449-728 (Korea, Republic of)

    2014-11-15

    Radiation-induced segregation (RIS) at twins was investigated using transmission electron microscopy (TEM) for ion-irradiated austenitic stainless steel. Significant RIS was found to occur at twin boundaries. TEM analysis indicates that interfacial dislocations at partially coherent twin boundaries are potential sites for strong RIS phenomenon. The RIS causes the formation of thin bands having a higher Ni and lower Cr concentration in twin bands with a width less than 15 nm. In wider twin bands, strong RIS occurs only at the outer twin boundaries, but not inside the band. The possible mechanism for the formation of the RIS thin band is discussed.

  5. Stereoselective differentiation in the Salt-induced Peptide Formation reaction and its relevance for the origin of life.

    Science.gov (United States)

    Plankensteiner, Kristof; Reiner, Hannes; Rode, Bernd M

    2005-04-01

    All living organisms on earth are almost totally made up of biomolecules of only one chiral form. For example, proteins are built almost exclusively of L-amino acids, and sugars are composed of D-saccharides, a fact that is usually referred to as biohomochirality. Its origin is the center of numerous investigations and theories but is not really elucidated yet. The results of experimental investigations of peptide formation in a prebiotically relevant scenario, as described in this paper, give indications on a possible pathway for the synthesis of homochiral L-peptides in the course of the Salt-induced Peptide Formation (SIPF) reaction.

  6. A protein kinase from Colletotrichum trifolii is induced by plant cutin and is required for appressorium formation.

    Science.gov (United States)

    Dickman, M B; Ha, Y S; Yang, Z; Adams, B; Huang, C

    2003-05-01

    When certain phytopathogenic fungi contact plant surfaces, specialized infection structures (appressoria) are produced that facilitate penetration of the plant external barrier; the cuticle. Recognition of this hydrophobic host surface must be sensed by the fungus, initiating the appropriate signaling pathway or pathways for pathogenic development. Using polymerase chain reaction and primers designed from mammalian protein kinase C sequences (PKC), we have isolated, cloned, and characterized a protein kinase from Colletotrichum trifolii, causal agent of alfalfa anthracnose. Though sequence analysis indicated conserved sequences in mammalian PKC genes, we were unable to induce activity of the fungal protein using known activators of PKC. Instead, we show that the C. trifolii gene, designated LIPK (lipid-induced protein kinase) is induced specifically by purified plant cutin or long-chain fatty acids which are monomeric constituents of cutin. PKC inhibitors prevented appressorium formation and, to a lesser extent, spore germination. Overexpression of LIPK resulted in multiple, abnormally shaped appressoria. Gene replacement of lipk yielded strains which were unable to develop appressoria and were unable to infect intact host plant tissue. However, these mutants were able to colonize host tissue following artificial wounding, resulting in typical anthracnose lesions. Taken together, these data indicate a central role in triggering infection structure formation for this protein kinase, which is induced specifically by components of the plant cuticle. Thus, the fungus is able to sense and use host surface chemistry to induce a protein kinase-mediated pathway that is required for pathogenic development.

  7. High spatial frequency laser induced periodic surface structure formation in germanium by mid-IR femtosecond pulses

    CERN Document Server

    Austin, Drake R; Lai, Yu Hang; Wang, Zhou; Zhang, Kaikai; Li, Hui; Blaga, Cosmin I; Yi, Allen Y; DiMauro, Louis F; Chowdhury, Enam A

    2016-01-01

    Formation of high spatial frequency laser induced periodic surface structures (HSFL) in germanium by femtosecond mid-IR pulses with wavelengths between $\\lambda=2.0$ and $3.6 \\; \\mathrm{\\mu m}$ was studied with varying angle of incidence and polarization. The period of these structures varied from $\\lambda/3$ to $\\lambda/8$. A modified surface-scattering model including Drude excitation and the optical Kerr effect explains spatial period scaling of HSFL across the mid-IR wavelengths. Transmission electron microscopy (TEM) shows the presence of a $30 \\; \\mathrm{n m}$ amorphous layer above the structure of crystalline germanium. Various mechanisms including two photon absorption and defect-induced amorphization are discussed as probable causes for the formation of this layer.

  8. Efficient electron-induced removal of oxalate ions and formation of copper nanoparticles from copper(II oxalate precursor layers

    Directory of Open Access Journals (Sweden)

    Kai Rückriem

    2016-06-01

    Full Text Available Copper(II oxalate grown on carboxy-terminated self-assembled monolayers (SAM using a step-by-step approach was used as precursor for the electron-induced synthesis of surface-supported copper nanoparticles. The precursor material was deposited by dipping the surfaces alternately in ethanolic solutions of copper(II acetate and oxalic acid with intermediate thorough rinsing steps. The deposition of copper(II oxalate and the efficient electron-induced removal of the oxalate ions was monitored by reflection absorption infrared spectroscopy (RAIRS. Helium ion microscopy (HIM reveals the formation of spherical nanoparticles with well-defined size and X-ray photoelectron spectroscopy (XPS confirms their metallic nature. Continued irradiation after depletion of oxalate does not lead to further particle growth giving evidence that nanoparticle formation is primarily controlled by the available amount of precursor.

  9. Formation of femtosecond laser induced surface structures on silicon : insights from numerical modeling and single pulse experiments

    CERN Document Server

    Derrien, Thibault J Y; Sarnet, Thierry; Sentis, Marc; Itina, Tatiana E

    2011-01-01

    Laser induced periodic surface structures (LIPSS) are formed by multiple irradiation of femtosecond laser on a silicon target. In this paper, we focus and discuss the surface plasmon polariton mechanism by an analysis of transient phase-matching conditions in Si on the basis of a single pulse experiment and numerical simulations. Two regimes of ripple formation mechanisms at low number of shots are identified and detailed. Correlation of numerical and experimental results is good.

  10. TCR triggering induces the formation of Lck-RACK1-actinin-1 multiprotein network affecting Lck redistribution

    OpenAIRE

    Ondrej Ballek; Jan Valečka; Martina Dobešová; Adéla Broučková; Jasper Manning; Pavel Řehulka; Jiří Stulík; Dominik Filipp

    2016-01-01

    The initiation of T-cell signaling is critically dependent on the function of the member of Src family tyrosine kinases, Lck. Upon T-cell antigen receptor (TCR) triggering, Lck kinase activity induces the nucleation of signal-transducing hubs that regulate the formation of complex signaling network and cytoskeletal rearrangement. In addition, the delivery of Lck function requires rapid and targeted membrane redistribution, but the mechanism underpinning this process is largely unknown. To gai...

  11. CoCl2, a mimic of hypoxia, induces formation of polyploid giant cells with stem characteristics in colon cancer.

    Directory of Open Access Journals (Sweden)

    Laura M Lopez-Sánchez

    Full Text Available The induction of polyploidy is considered the reproductive end of cells, but there is evidence that polyploid giant cancer cells (PGCCs contribute to cell repopulation during tumor relapse. However, the role of these cells in the development, progression and response to therapy in colon cancer remains undefined. Therefore, the main objective of this study was to investigate the generation of PGCCs in colon cancer cells and identify mechanisms of formation. Treatment of HCT-116 and Caco-2 colon cancer cells with the hypoxia mimic CoCl2 induced the formation of cells with larger cell and nuclear size (PGCCs, while the cells with normal morphology were selectively eliminated. Cytometric analysis showed that CoCl2 treatment induced G2 cell cycle arrest and the generation of a polyploid cell subpopulation with increased cellular DNA content. Polyploidy of hypoxia-induced PGCCs was confirmed by FISH analysis. Furthermore, CoCl2 treatment effectively induced the stabilization of HIF-1α, the differential expression of a truncated form of p53 (p47 and decreased levels of cyclin D1, indicating molecular mechanisms associated with cell cycle arrest at G2. Generation of PGCCs also contributed to expansion of a cell subpopulation with cancer stem cells (CSCs characteristics, as indicated by colonosphere formation assays, and enhanced chemoresistance to 5-fluorouracil and oxaliplatin. In conclusion, the pharmacological induction of hypoxia in colon cancer cells causes the formation of PGCCs, the expansion of a cell subpopulation with CSC characteristics and chemoresistance. The molecular mechanisms involved, including the stabilization of HIF-1 α, the involvement of p53/p47 isoform and cell cycle arrest at G2, suggest novel targets to prevent tumor relapse and treatment failure in colon cancer.

  12. Studies on alkaline band formation in Chara corallina: ameliorating effect of Ca2+ on inhibition induced by osmotic shock.

    Science.gov (United States)

    Shimmen, Teruo; Yonemura, Satoko; Negoro, Mio; Lucas, William J

    2003-09-01

    Although the decrease in cell turgor by application of sorbitol to the external medium did not inhibit the alkaline band formation in Chara corallina, recovery of normal turgor severely inhibited it. Alkaline-loading analysis suggested that the inhibition of alkaline band formation was caused by inhibition of HCO(3)(-) influx but not that of OH(-) efflux. In the presence of 10 mM CaCl(2), the capacity of alkaline band formation was maintained during osmotic treatment. Cells could not form alkaline bands, when plasmolysis was induced by application of sorbitol at a higher concentration. Addition of 10 mM CaCl(2) could ameliorate the inhibition caused by plasmolyis.

  13. Fabrication of internal diffraction gratings in planar fluoride glass using low-density plasma formation induced by a femtosecond laser

    Energy Technology Data Exchange (ETDEWEB)

    Cho, Sung-Hak [Nano Machining Laboratory, KIMM (Korea Institute of Machinery and Material), 171 Jang-dong, Yuseong-Gu, Daejeon 305-343 (Korea, Republic of); Materials Research and Education Center, Department of Mechanical Engineering, Auburn University, 275 Wilmore Laboratories, Auburn, AL 36849 (United States)], E-mail: shcho@kimm.re.kr; Chang, Won-Seok; Kim, Jae-Goo [Nano Machining Laboratory, KIMM (Korea Institute of Machinery and Material), 171 Jang-dong, Yuseong-Gu, Daejeon 305-343 (Korea, Republic of); Kim, Kwang-Ryul [Department of Electronics and Computer Engineering, Hanyang University, Seoul 133-791 (Korea, Republic of); Hong, Jong Wook [Materials Research and Education Center, Department of Mechanical Engineering, Auburn University, 275 Wilmore Laboratories, Auburn, AL 36849 (United States)

    2008-12-30

    The fabrication of internal diffraction gratings with photo-induced refractive index modification in planar fluoride plates was demonstrated using low-density plasma formation excited by a high-intensity femtosecond (130 fs) Ti:sapphire laser ({lambda}{sub p} = 790 nm). The refractive index modifications with diameters ranging from 350 nm to 5 {mu}m were photoinduced after plasma formation occurred upon irradiation with peak intensities of more than 1 x 10{sup 12} W/cm{sup 2}. The graded refractive index profile was fabricated to be a symmetric around from the center of the point at which low-density plasma occurred. The maximum refractive index change ({delta}n) was estimated to be 1.3 x 10{sup -2}. The low-density plasma formation (n{sub c} < 1.79 x 10{sup 27} m{sup -3}]) causes the increase of the refractive index modification with fluoride glass.

  14. The Contribution of the Fas/FasL Apoptotic Pathway in Ulcer Formation during Leishmania major-Induced Cutaneous Leishmaniasis

    Science.gov (United States)

    Eidsmo, Liv; Nylen, Susanne; Khamesipour, Ali; Hedblad, Mari-Anne; Chiodi, Francesca; Akuffo, Hannah

    2005-01-01

    Cutaneous leishmaniasis (CL), caused by the intracellular protozoan Leishmania major, is characterized by lesion formation and ulceration at the site of infection. The mechanism of ulcer formation during CL is not fully understood. The expression of Fas and FasL and the levels of apoptosis in skin biopsies and in restimulated blood mononuclear cells from patients with 1 to 7 months of L. major-induced CL were analyzed using immunohistochemistry and fluorescence-activated cell sorting analysis. The levels of soluble Fas and FasL were also analyzed by enzyme-linked immunosorbent assay. A substantial number of apoptotic keratinocytes were observed mainly in the superficial epidermis of morphologically active and healing CL skin samples. Fas expression was increased on epidermis in active CL, whereas Fas expression was similar in healing and healthy epidermis. FasL-expressing macrophages and T cells were found in subepidermal infiltrate, mainly in active disease. When CL peripheral blood mononuclear cells were restimulated with L. major, Fas was up-regulated on effector T cells, and high levels of sFasL were secreted. Supernatants from restimulated cultures induced apoptosis in human keratinocytes (HaCaT), possibly through Fas/FasL interactions. Our results indicate that FasL-expressing effector T cells and macrophages may act to induce apoptosis and ulcer formation in Fas-expressing keratinocytes during L. major infection. PMID:15793290

  15. Local delivery of siRNA using a biodegradable polymer application to enhance BMP-induced bone formation.

    Science.gov (United States)

    Manaka, Tomoya; Suzuki, Akinobu; Takayama, Kazushi; Imai, Yuuki; Nakamura, Hiroaki; Takaoka, Kunio

    2011-12-01

    Small interfering RNA (siRNA) is useful tool for specific and efficient knockdown of disease-related genes. However, in vivo applications of siRNA are limited due to difficulty in its efficient delivery to target cells. In this study, we investigated the efficacy of a biodegradable hydrogel, poly-d,l-lactic acid-p-dioxanone-polyethylene glycol block co-polymer (PLA-DX-PEG), as a siRNA carrier. PLA-DX-PEG pellets with or without fluorescein-labeled dsRNA were implanted into mouse dosal muscle pouches. The cellular uptake of dsRNA surround the polymer was confirmed by fluorescent microscopy. The fluorescence intensity was dose-dependent of the dsRNA, and exhibited a time-dependent decrease. To investigate its biological efficiency, noggin (antagonoist to BMPs) gene-silencing with siRNA (siRNA/Noggin) was examined by the amount of suppression of BMP-2-induced noggin expression and the level of performance of BMP, indicated by ectopic bone formation. Noggin gene expression induced by BMP-2 was suppressed by addition of siRNA/Noggin to the implant, and the ectopic bone formation induced by implants with both BMP-2 and siRNA/Noggin was significantly greater than those induced by implants with BMP-2 alone. These results indicate the efficacy of local delivery of siRNAs by PLA-DX-PEG polymer, which intensified bone-inducing effects of BMP and promoted new bone formation by suppressing gene expression of Noggin.

  16. Phosphoramide mustard exposure induces DNA adduct formation and the DNA damage repair response in rat ovarian granulosa cells

    Energy Technology Data Exchange (ETDEWEB)

    Ganesan, Shanthi, E-mail: shanthig@iastate.edu; Keating, Aileen F., E-mail: akeating@iastate.edu

    2015-02-01

    Phosphoramide mustard (PM), the ovotoxic metabolite of the anti-cancer agent cyclophosphamide (CPA), destroys rapidly dividing cells by forming NOR-G-OH, NOR-G and G-NOR-G adducts with DNA, potentially leading to DNA damage. A previous study demonstrated that PM induces ovarian DNA damage in rat ovaries. To investigate whether PM induces DNA adduct formation, DNA damage and induction of the DNA repair response, rat spontaneously immortalized granulosa cells (SIGCs) were treated with vehicle control (1% DMSO) or PM (3 or 6 μM) for 24 or 48 h. Cell viability was reduced (P < 0.05) after 48 h of exposure to 3 or 6 μM PM. The NOR-G-OH DNA adduct was detected after 24 h of 6 μM PM exposure, while the more cytotoxic G-NOR-G DNA adduct was formed after 48 h by exposure to both PM concentrations. Phosphorylated H2AX (γH2AX), a marker of DNA double stranded break occurrence, was also increased by PM exposure, coincident with DNA adduct formation. Additionally, induction of genes (Atm, Parp1, Prkdc, Xrcc6, and Brca1) and proteins (ATM, γH2AX, PARP-1, PRKDC, XRCC6, and BRCA1) involved in DNA repair were observed in both a time- and dose-dependent manner. These data support that PM induces DNA adduct formation in ovarian granulosa cells, induces DNA damage and elicits the ovarian DNA repair response. - Highlights: • PM forms ovarian DNA adducts. • DNA damage marker γH2AX increased by PM exposure. • PM induces ovarian DNA double strand break repair.

  17. p53 induces formation of NEAT1 lncRNA-containing paraspeckles that modulate replication stress response and chemosensitivity.

    Science.gov (United States)

    Adriaens, Carmen; Standaert, Laura; Barra, Jasmine; Latil, Mathilde; Verfaillie, Annelien; Kalev, Peter; Boeckx, Bram; Wijnhoven, Paul W G; Radaelli, Enrico; Vermi, William; Leucci, Eleonora; Lapouge, Gaëlle; Beck, Benjamin; van den Oord, Joost; Nakagawa, Shinichi; Hirose, Tetsuro; Sablina, Anna A; Lambrechts, Diether; Aerts, Stein; Blanpain, Cédric; Marine, Jean-Christophe

    2016-08-01

    In a search for mediators of the p53 tumor suppressor pathway, which induces pleiotropic and often antagonistic cellular responses, we identified the long noncoding RNA (lncRNA) NEAT1. NEAT1 is an essential architectural component of paraspeckle nuclear bodies, whose pathophysiological relevance remains unclear. Activation of p53, pharmacologically or by oncogene-induced replication stress, stimulated the formation of paraspeckles in mouse and human cells. Silencing Neat1 expression in mice, which prevents paraspeckle formation, sensitized preneoplastic cells to DNA-damage-induced cell death and impaired skin tumorigenesis. We provide mechanistic evidence that NEAT1 promotes ATR signaling in response to replication stress and is thereby engaged in a negative feedback loop that attenuates oncogene-dependent activation of p53. NEAT1 targeting in established human cancer cell lines induced synthetic lethality with genotoxic chemotherapeutics, including PARP inhibitors, and nongenotoxic activation of p53. This study establishes a key genetic link between NEAT1 paraspeckles, p53 biology and tumorigenesis and identifies NEAT1 as a promising target to enhance sensitivity of cancer cells to both chemotherapy and p53 reactivation therapy.

  18. Muramyl Dipeptide Enhances Lipopolysaccharide-Induced Osteoclast Formation and Bone Resorption through Increased RANKL Expression in Stromal Cells

    Directory of Open Access Journals (Sweden)

    Masahiko Ishida

    2015-01-01

    Full Text Available Lipopolysaccharide (LPS is bacterial cell wall component capable of inducing osteoclast formation and pathological bone resorption. Muramyl dipeptide (MDP, the minimal essential structural unit responsible for the immunological activity of peptidoglycans, is ubiquitously expressed by bacterium. In this study, we investigated the effect of MDP in LPS-induced osteoclast formation and bone resorption. LPS was administered with or without MDP into the supracalvariae of mice. The number of osteoclasts, the level of mRNA for cathepsin K and tartrate-resistant acid phosphatase (TRAP, the ratio of the bone destruction area, the level of tartrate-resistant acid phosphatase form 5b (TRACP 5b, and C-terminal telopeptides fragments of type I collagen as a marker of bone resorption in mice administrated both LPS and MDP were higher than those in mice administrated LPS or MDP alone. On the other hand, MDP had no effect on osteoclastogenesis in parathyroid hormone administrated mice. MDP enhanced LPS-induced receptor activator of NF-κB ligand (RANKL expression and Toll-like receptor 4 (TLR4 expression in vivo and in stromal cells in vitro. MDP also enhanced LPS-induced mitogen-activated protein kinase (MAPK signaling, including ERK, p38, and JNK, in stromal cells. These results suggest that MDP might play an important role in pathological bone resorption in bacterial infection diseases.

  19. Dopamine inhibits lipopolysaccharide-induced nitric oxide production through the formation of dopamine quinone in murine microglia BV-2 cells.

    Science.gov (United States)

    Yoshioka, Yasuhiro; Sugino, Yuta; Tozawa, Azusa; Yamamuro, Akiko; Kasai, Atsushi; Ishimaru, Yuki; Maeda, Sadaaki

    2016-02-01

    Dopamine (DA) has been suggested to modulate functions of glial cells including microglial cells. To reveal the regulatory role of DA in microglial function, in the present study, we investigated the effect of DA on lipopolysaccharide (LPS)-induced nitric oxide (NO) production in murine microglial cell line BV-2. Pretreatment with DA for 24 h concentration-dependently attenuated LPS-induced NO production in BV-2 cells. The inhibitory effect of DA on LPS-induced NO production was not inhibited by SCH-23390 and sulpiride, D1-like and D2-like DA receptor antagonists, respectively. In addition, pretreatment with (-)-(6aR,12bR)-4,6,6a,7,8,12b-Hexahydro-7-methylindolo[4,3-a]phenanthridin (CY 208-243) and bromocriptine, D1-like and D2-like DA receptor agonists, respectively, did not affect the LPS-induced NO production. N-Acetylcysteine, which inhibits DA oxidation, completely inhibited the effect of DA. Tyrosinase, which catalyzes the oxidation of DA to DA quionone (DAQ), accelerated the inhibitory effect of DA on LPS-induced NO production. These results suggest that DA attenuates LPS-induced NO production through the formation of DAQ in BV-2 cells.

  20. Cryptotanshinone inhibits TNF-α-induced LOX-1 expression by suppressing reactive oxygen species (ROS) formation in endothelial cells.

    Science.gov (United States)

    Ran, Xiaoli; Zhao, Wenwen; Li, Wenping; Shi, Jingshan; Chen, Xiuping

    2016-07-01

    Cryptotanshinone (CPT) is a natural compound isolated from traditional Chinese medicine Salvia miltiorrhiza Bunge. In the present study, the regulatory effect and potential mechanisms of CPT on tumor necrosis factor alpha (TNF-α) induced lectin-like receptor for oxidized low density lipoprotein (LOX-1) were investigated. Human umbilical vein endothelial cells (HUVECs) were cultured and the effect of TNF-α on LOX-1 expression at mRNA and protein levels was determined by Real-time PCR and Western blotting respectively. The formation of intracellular ROS was determined with fluorescence probe CM-DCFH2-DA. The endothelial ox-LDL uptake was evaluated with DiI-ox-LDL. The effect of CPT on LOX-1 expression was also evaluated with SD rats. TNF-α induced LOX-1 expression in a dose- and time-dependent manner in endothelial cells. TNF-α induced ROS formation, phosphorylation of NF-κB p65 and ERK, and LOX-1 expression, which were suppressed by rotenone, DPI, NAC, and CPT. NF-κB inhibitor BAY11-7082 and ERK inhibitor PD98059 inhibited TNF-α-induced LOX-1 expression. CPT and NAC suppressed TNF-α-induced LOX-1 expression and phosphorylation of NF-κB p65 and ERK in rat aorta. These data suggested that TNF-α induced LOX-1 expression via ROS activated NF-κB/ERK pathway, which could be inhibited by CPT. This study provides new insights for the anti-atherosclerotic effect of CPT.

  1. Inducible colony formation within the Scenedesmaceae: adaptive responses to infochemicals from two different herbivore taxa

    NARCIS (Netherlands)

    Verschoor, A.M.; Van der Stap, I.; Helmsing, N.R.; Lürling, M.; Van Donk, E.

    2004-01-01

    We studied the occurrence of colony formation within 40 different strains of Scenedesmaceae (Chlorococcales, Chlorophyta) in response to grazing-released infochemicals from the herbivorous zooplankters Brachionus calyciflorus Pallas (Rotifera) and Daphnia magna Strauss (Cladocera). With the exceptio

  2. Inducible colony formation within the Scenedesmaceae: Adaptive responses to infochemicals from two different herbivore taxa

    NARCIS (Netherlands)

    Verschoor, A.M.; Stap, I.; Helmsing, N.R.; Lürling, M.F.L.L.W.; Donk, van E.

    2004-01-01

    We studied the occurrence of colony formation within 40 different strains of Scenedesmaceae (Chlorococcales, Chlorophyta) in response to grazing-released infochemicals from the herbivorous zooplankters Brachionus calyciflorus Pallas (Rotifera) and Daphnia magna Strauss (Cladocera). With the exceptio

  3. Hybrid simulation research on formation mechanism of tungsten nanostructure induced by helium plasma irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Ito, Atsushi M., E-mail: ito.atsushi@nifs.ac.jp [National Institute for Fusion Science, 322-6 Oroshi-cho, Toki 509-5292 (Japan); Takayama, Arimichi; Oda, Yasuhiro [National Institute for Fusion Science, 322-6 Oroshi-cho, Toki 509-5292 (Japan); Tamura, Tomoyuki; Kobayashi, Ryo; Hattori, Tatsunori; Ogata, Shuji [Nagoya Institute of Technology, Gokiso-cho, Showa-ku, Nagoya 466-8555 (Japan); Ohno, Noriyasu; Kajita, Shin [Nagoya University, Furo-cho, Chikusa-ku, Nagoya 464-8603 (Japan); Yajima, Miyuki [National Institute for Fusion Science, 322-6 Oroshi-cho, Toki 509-5292 (Japan); Noiri, Yasuyuki [Nagoya University, Furo-cho, Chikusa-ku, Nagoya 464-8603 (Japan); Yoshimoto, Yoshihide [University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8656 (Japan); Saito, Seiki [Kushiro National College of Technology, Kushiro, Hokkaido 084-0916 (Japan); Takamura, Shuichi [Aichi Institute of Technology, 1247 Yachigusa, Yakusa-cho, Toyota 470-0392 (Japan); Murashima, Takahiro [Tohoku University, 6-3, Aramaki-Aza-Aoba, Aoba-Ward, Sendai 980-8578 (Japan); Miyamoto, Mitsutaka [Shimane University, Matsue, Shimane 690-8504 (Japan); Nakamura, Hiroaki [National Institute for Fusion Science, 322-6 Oroshi-cho, Toki 509-5292 (Japan); Nagoya University, Furo-cho, Chikusa-ku, Nagoya 464-8603 (Japan)

    2015-08-15

    The generation of tungsten fuzzy nanostructure by exposure to helium plasma is one of the important problems for the use of tungsten material as divertor plates in nuclear fusion reactors. In the present paper, the formation mechanisms of the helium bubble and the tungsten fuzzy nanostructure were investigated by using several simulation methods. We proposed the four-step process which is composed of penetration step, diffusion and agglomeration step, helium bubble growth step, and fuzzy nanostructure formation step. As the fourth step, the formation of the tungsten fuzzy nanostructure was successfully reproduced by newly developed hybrid simulation combining between molecular dynamics and Monte-Carlo method. The formation mechanism of tungsten fuzzy nanostructure observed by the hybrid simulation is that concavity and convexity of the surface are enhanced by the bursting of helium bubbles in the region around the concavity.

  4. Hybrid simulation research on formation mechanism of tungsten nanostructure induced by helium plasma irradiation

    Science.gov (United States)

    Ito, Atsushi M.; Takayama, Arimichi; Oda, Yasuhiro; Tamura, Tomoyuki; Kobayashi, Ryo; Hattori, Tatsunori; Ogata, Shuji; Ohno, Noriyasu; Kajita, Shin; Yajima, Miyuki; Noiri, Yasuyuki; Yoshimoto, Yoshihide; Saito, Seiki; Takamura, Shuichi; Murashima, Takahiro; Miyamoto, Mitsutaka; Nakamura, Hiroaki

    2015-08-01

    The generation of tungsten fuzzy nanostructure by exposure to helium plasma is one of the important problems for the use of tungsten material as divertor plates in nuclear fusion reactors. In the present paper, the formation mechanisms of the helium bubble and the tungsten fuzzy nanostructure were investigated by using several simulation methods. We proposed the four-step process which is composed of penetration step, diffusion and agglomeration step, helium bubble growth step, and fuzzy nanostructure formation step. As the fourth step, the formation of the tungsten fuzzy nanostructure was successfully reproduced by newly developed hybrid simulation combining between molecular dynamics and Monte-Carlo method. The formation mechanism of tungsten fuzzy nanostructure observed by the hybrid simulation is that concavity and convexity of the surface are enhanced by the bursting of helium bubbles in the region around the concavity.

  5. v-Src-induced nuclear localization of YAP is involved in multipolar spindle formation in tetraploid cells.

    Science.gov (United States)

    Kakae, Keiko; Ikeuchi, Masayoshi; Kuga, Takahisa; Saito, Youhei; Yamaguchi, Naoto; Nakayama, Yuji

    2017-01-01

    The protein-tyrosine kinase, c-Src, is involved in a variety of signaling events, including cell division. We have reported that v-Src, which is a mutant variant of the cellular proto-oncogene, c-Src, causes delocalization of Aurora B kinase, resulting in a furrow regression in cytokinesis and the generation of multinucleated cells. However, the effect of v-Src on mitotic spindle formation is unknown. Here we show that v-Src-expressing HCT116 and NIH3T3 cells undergo abnormal cell division, in which cells separate into more than two cells. Upon v-Src expression, the proportion of multinucleated cells is increased in a time-dependent manner. Flow cytometry analysis revealed that v-Src increases the number of cells having a ≥4N DNA content. Microscopic analysis showed that v-Src induces the formation of multipolar spindles with excess centrosomes. These results suggest that v-Src induces multipolar spindle formation by generating multinucleated cells. Tetraploidy activates the tetraploidy checkpoint, leading to a cell cycle arrest of tetraploid cells at the G1 phase, in which the nuclear exclusion of the transcription co-activator YAP plays a critical role. In multinucleated cells that are induced by cytochalasin B and the Plk1 inhibitor, YAP is excluded from the nucleus. However, v-Src prevents this nuclear exclusion of YAP through a decrease in the phosphorylation of YAP at Ser127 in multinucleated cells. Furthermore, v-Src decreases the expression level of p53, which also plays a critical role in the cell cycle arrest of tetraploid cells. These results suggest that v-Src promotes abnormal spindle formation in at least two ways: generation of multinucleated cells and a weakening of the tetraploidy checkpoint.

  6. Transmembrane TNF-α Reverse Signaling Inhibits Lipopolysaccharide-Induced Proinflammatory Cytokine Formation in Macrophages by Inducing TGF-β: Therapeutic Implications.

    Science.gov (United States)

    Pallai, Anna; Kiss, Beáta; Vereb, György; Armaka, Marietta; Kollias, George; Szekanecz, Zoltán; Szondy, Zsuzsa

    2016-02-01

    TNF-α, a potent proinflammatory cytokine, is generated in a precursor form called transmembrane (m)TNF-α that is expressed as a type II polypeptide on the surface of certain cells. mTNF-α was shown to act both as a ligand by binding to TNF-α receptors, as well as a receptor that transmits outside-to-inside (reverse) signals back into the mTNF-α-bearing cells. In this study, we show that nonactivated macrophages express basal levels of mTNF-α and respond to anti-TNF-α Abs by triggering the MAPK kinase 4 signaling pathway. The pathway induces TGF-β. Based on inhibitory experiments, the production of TGF-β1 is regulated via Jun kinases, whereas that of other TGF-βs is regulated via p38 MAPKs. Exposure to LPS further induced the expression of mTNF-α, and triggering of mTNF-α strongly suppressed the LPS-induced proinflammatory response. Neutralizing TGF-β by Abs prevented the mTNF-α-mediated suppression of LPS-induced proinflammatory cytokine formation, indicating that the immune-suppressive effect of mTNF-α is mediated via TGF-β. Although apoptotic cells are also known to suppress LPS-induced proinflammatory cytokine formation in macrophages by upregulating TGF-β, we show that they do not use the mTNF-α signaling pathway. Because TGF-β possesses a wide range of immune-suppressive effects, our data indicate that upregulation of TGF-β synthesis by those TNF-α-targeting molecules, which are able to trigger mTNF-α, might contribute to their therapeutic effect in the treatment of certain inflammatory diseases such as Crohn's disease, Wegener's granulomatosis, or sarcoidosis. Additionally, none of the TNF-α-targeting molecules is expected to interfere with the immune-silencing effects of apoptotic cells.

  7. SIRT6 reduces macrophage foam cell formation by inducing autophagy and cholesterol efflux under ox-LDL condition.

    Science.gov (United States)

    He, Jiangping; Zhang, Guangya; Pang, Qi; Yu, Cong; Xiong, Jie; Zhu, Jing; Chen, Fengling

    2017-03-09

    SIRT6 is a pivotal regulator of lipid metabolism. It is also closely connected to cardiovascular diseases, which are the main cause of death in diabetic patients. We observed a decrease in the expression of SIRT6 and key autophagy effectors (ATG5, LC3B, and LAMP1) in ox-LDL-induced foam cells, a special form of lipid-laden macrophages. In these cells, SIRT6 WT but not SIRT6 H133Y overexpression markedly reduced foam cell formation, as shown by Oil Red O staining, while inducing autophagy flux, as determined by both mRFP-GFP-LC3 labeling and transmission electron microscopy. Silencing the key autophagy initiation gene ATG5, reversed the autophagy-promoting effect of SIRT6 in ox-LDL-treated THP1 cells, as evidenced by an increase in foam cells. Cholesterol efflux assays indicated that SIRT6 overexpression in foam cells promoted cholesterol efflux, increased the levels of ABCA1 and ABCG1, and reduced miR-33 levels. By transfecting miR-33 into cells overexpressing SIRT6, we observed that reduced foam cell formation and autophagy flux induction were largely reversed. These data imply that SIRT6 plays an essential role in protecting against atherosclerosis by reducing foam cell formation through an autophagy-dependent pathway. This article is protected by copyright. All rights reserved.

  8. Blockade of the formation of insoluble ubiquitinated protein aggregates by EGCG3"Me in the alloxan-induced diabetic kidney.

    Directory of Open Access Journals (Sweden)

    Shuxian Cai

    Full Text Available BACKGROUND: Renal accumulation of reactive carbonyl compounds (RCCs has been linked to the progression of diabetic nephropathy. We previously demonstrated that carbonyl stress induces the formation of amino-carbonyl cross-links and sharply increases the content of β-sheet-rich structures, which is the seed of insoluble aggregates formation, and tea catechin (--epigallocatechin 3-gallate (EGCG can reverse this process in vitro and in vivo. In this study, methylated derivative (--epigallocatechin-3-O-(3-O-methyl-gallate (EGCG3"Me was hypothesized to neutralize carbonyl stress mediating the formation of insoluble ubiquitinated protein (IUP aggregates, and reduce the early development of diabetic nephropathy. METHODS AND RESULTS: Diabetes was induced in mice by intraperitoneally injecting alloxan monohydrate (200 mg/kg/d twice and administering EGCG3"Me by gavage for 15 d. Reagent case and western blot results showed that, in diabetic kidneys, the carbonyl proteins in the serum increased; and in insoluble protein fraction, 4-hydroxynonenal-modified proteins, IUP aggregates and p62 accumulated; FT-IR study demonstrated that the lipid content, anti-parallel β-sheet structure and aggregates increased. EGCG3"Me treatment could effectively reverse this process, even better than the negative control treatment. CONCLUSIONS: EGCG3"Me exhibiting anti-β-sheet-rich IUP aggregate properties, maybe represents a new strategy to impede the progression of diabetic nephropathy and other diabetic complications.

  9. Supernumerary Formation of Olfactory Glomeruli Induced by Chronic Odorant Exposure: A Constructivist Expression of Neural Plasticity

    Science.gov (United States)

    Valle-Leija, Pablo; Blanco-Hernández, Eduardo; Drucker-Colín, Rene; Gutiérrez-Ospina, Gabriel; Vidaltamayo, Roman

    2012-01-01

    It is accepted that sensory experience instructs the remodelling of neuronal circuits during postnatal development, after their specification has occurred. The story is less clear with regard to the role of experience during the initial formation of neuronal circuits, whether prenatal or postnatal, since this process is now supposed to be primarily influenced by genetic determinants and spontaneous neuronal firing. Here we evaluated this last issue by examining the effect that postnatal chronic exposure to cognate odorants has on the formation of I7 and M72 glomeruli, iterated olfactory circuits that are formed before and after birth, respectively. We took advantage of double knock-in mice whose I7 and M72 primary afferents express green fluorescent protein and β-galactosidase, correspondingly. Our results revealed that postnatal odorant chronic exposure led to the formation of permanent supernumerary I7 and M72 glomeruli in a dose and time dependent manner. Glomeruli in exposed mice were formed within the same regions of olfactory bulb and occupy small space volumes compared to the corresponding single circuits in non-exposed mice. We suggest that local reorganization of the primary afferents could participate in the process of formation of supernumerary glomeruli. Overall, our results support that sensory experience indeed instructs the permanent formation of specific glomeruli in the mouse olfactory bulb by means of constructivist processes. PMID:22511987

  10. Endogenous hydrogen peroxide increases biofilm formation by inducing exopolysaccharide production in Acinetobacter oleivorans DR1.

    Science.gov (United States)

    Jang, In-Ae; Kim, Jisun; Park, Woojun

    2016-02-17

    In this study, we investigated differentially expressed proteins in Acinetobacter oleivorans cells during planktonic and biofilm growth by using 2-dimensional gel electrophoresis combined with matrix-assisted laser desorption time-of-flight mass spectrometry. We focused on the role of oxidative stress resistance during biofilm formation using mutants defective in alkyl hydroperoxide reductase (AhpC) because its production in aged biofilms was enhanced compared to that in planktonic cells. Results obtained using an ahpC promoter-gfp reporter vector showed that aged biofilms expressed higher ahpC levels than planktonic cells at 48 h. However, at 24 h, ahpC expression was higher in planktonic cells than in biofilms. Deletion of ahpC led to a severe growth defect in rich media that was not observed in minimal media and promoted early biofilm formation through increased production of exopolysaccharide (EPS) and EPS gene expression. Increased endogenous H2O2 production in the ahpC mutant in rich media enhanced biofilm formation, and this enhancement was not observed in the presence of antioxidants. Exogenous addition of H2O2 promoted biofilm formation in wild type cells, which suggested that biofilm development is linked to defense against H2O2. Collectively, our data showed that EPS production caused by H2O2 stress enhances biofilm formation in A. oleivorans.

  11. Differential roles of XRCC2 in S-phase RAD51 focus formation induced by DNA replication inhibitors

    Energy Technology Data Exchange (ETDEWEB)

    Lim, C; Liu, N

    2004-05-14

    RAD51 proteins accumulate in discrete nuclear foci in response to DNA damage. Previous studies demonstrated that human RAD51 paralogs (RAD51B, RAD51C, RAD51D, XRCC2 and XRCC3) are essential for the assembly of RAD51 foci induced by ionizing radiation and cross-linking agents. Here we report that XRCC2 also plays important roles in RAD51 focus formation induced by replication arrest during S-phase of cell cycle. In wild-type hamster V79 cells treated with hydroxyurea (HU), RAD51 protein form punctuate nuclear foci, accompanied by increased RAD51 protein level in both cytoplasmic and nuclear fractions, and increased association of RAD51 with chromatin. In contrast, xrcc2 hamster mutant irs1 cells are deficient in the formation of RAD51 foci after HU treatment, suggesting that the function of XRCC2 is required for the assembly of RAD51 at HU-induced stalled replication forks. Interestingly, we found that irs1 cells are able to form intact RAD51 foci in S-phase cells treated with thymidine (TR) or aphidicolin, although irs1 cells are hypersensitive to both HU and TR. Our findings suggest that there may be two distinct pathways (XRCC2-dependent or XRCC2-independent) involved in loading of RAD51 onto stalled replication forks, probably depending upon the structure of DNA lesions.

  12. Fibre-induced lipid peroxidation leads to DNA adduct formation in Salmonella typhimurium TA104 and rat lung fibroblasts.

    Science.gov (United States)

    Howden, P J; Faux, S P

    1996-03-01

    Certain end-products of lipid peroxidation bind to DNA forming a fluorescent chromophore. Incubation of both Salmonella typhimurium TA104 and a rat lung fibroblast cell line, RFL-6, with various types of mineral fibre resulted in a time- and dose-dependent increase in DNA fluorescence. The increase in DNA fluorescence was shown to be directly related to the amount of iron that could be mobilized from the fibre surface using in vitro studies in the absence of cells or bacteria. Crocidolite and man-made vitreous fibre-21 (MMVF-21) mobilized significant quantities of iron and were significantly more active than chrysotile and refactory ceramic fibre-1 (RCF-1). Fibre-induced malondialdehyde-DNA adduct formation, the fluorescent product, was increased by incubating cells with buthionine sulfoximine and ameliorated by co-treatment with N-acetylcysteine, indicating a protective role for glutathione. Similarly, vitamin E was also shown to inhibit DNA adduct formation. These results suggest that mineral fibre-induced lipid peroxidation produced genotoxic products which can diffuse into nucleus and interact with cellular DNA. In conclusion, fibre-induced lipid peroxidation may be a possible mechanism in the genotoxic action of fibrous materials.

  13. Aminoguanidine inhibits reactive oxygen species formation, lipid peroxidation, and oxidant-induced apoptosis.

    Science.gov (United States)

    Giardino, I; Fard, A K; Hatchell, D L; Brownlee, M

    1998-07-01

    Aminoguanidine (AG) treatment, like nerve growth factor (NGF) treatment, prevents diabetes-induced apoptosis of retinal Müller cells in the rat eye, but the mechanism involved is unknown. In this study, the effects of preincubation with AG on oxidant-induced apoptosis, oxidant-induced intracellular reactive oxygen species (ROS) production, and lipid peroxidation were determined in rat retinal Müller cells and compared with the effects of NGF, a protein that protects neuronal cells from oxidative stress. The effect of AG on rabbit vitreous lipid peroxide levels was also determined. After exposure to increasing concentrations of H2O2, there was a corresponding increase in the percentage of apoptotic Müller cells. Preincubation with AG for 48 h completely inhibited oxidant-induced apoptosis in response to 10 micromol/l H2O2 (+AG 0 vs. 10 micromol/l, NS), and reduced the percentage of apoptotic cells in response to 50 micromol/l H2O2 by 50% (+AG vs. -AG, P NGF. Both AG and NGF preincubation prevented the twofold increase in oxidant-induced lipid peroxides. The fivefold increase in oxidant-induced ROS production was decreased 100% by NGF, but only 61% by AG preincubation. The twofold increase in vitreous lipid peroxide level in diabetic rabbits was completely prevented by AG treatment. AG reduced H2O2-induced benzoate hydroxylation in a dose-dependent manner. Intracellular glutathione content was unchanged. These data demonstrate that AG can act as an antioxidant in vivo, quenching hydroxyl radicals and lipid peroxidation in cells and tissues and preventing oxidant-induced apoptosis.

  14. Formation and instability of spiral wave induced by Gaussian coloured noise

    Institute of Scientific and Technical Information of China (English)

    Gan Zheng-Ning; Ma Jun; Zhang Guo-Yong; Chen Yong

    2008-01-01

    In this paper,we studied the effect of Gauesian coloured noise on the formation and instability of spiral waves described by one class of modified FitzHugh-Nagumo equation.It was found that Gaussian coloured noise plays a constructive role in the formation,transition and instability of spiral wave.Too weak or too strong noise may act against the formation of spiral waves.At a certain noise level,spiral wave is maintained in a medium,in which spiral wave cannot be observed in the absence of the noise.It is difficult to make a stable spiral wave into unstable state by Gaussian coloured noise,unless the noise level is very high.The parameter regions of Gaussian coloured noise for spiral forming and spiral instability were given and discussed with numerical simulations.

  15. Formation of globular clusters induced by external ultraviolet radiation II: Three-dimensional radiation hydrodynamics simulations

    CERN Document Server

    Abe, Makito; Hasegawa, Kenji

    2016-01-01

    We explore the possibility of the formation of globular clusters under ultraviolet (UV) background radiation. One-dimensional spherical symmetric radiation hydrodynamics (RHD) simulations by Hasegawa et al. have demonstrated that the collapse of low-mass (10^6-10^7 solar masses) gas clouds exposed to intense UV radiation can lead to the formation of compact star clusters like globular clusters (GCs) if gas clouds contract with supersonic infall velocities. However, three-dimensional effects, such as the anisotropy of background radiation and the inhomogeneity in gas clouds, have not been studied so far. In this paper, we perform three-dimensional RHD simulations in a semi-cosmological context, and reconsider the formation of compact star clusters in strong UV radiation fields. As a result, we find that although anisotropic radiation fields bring an elongated shadow of neutral gas, almost spherical compact star clusters can be procreated from a "supersonic infall" cloud, since photo-dissociating radiation supp...

  16. Redox- and non-redox-metal-induced formation of free radicals and their role in human disease.

    Science.gov (United States)

    Valko, Marian; Jomova, Klaudia; Rhodes, Christopher J; Kuča, Kamil; Musílek, Kamil

    2016-01-01

    Transition metal ions are key elements of various biological processes ranging from oxygen formation to hypoxia sensing, and therefore, their homeostasis is maintained within strict limits through tightly regulated mechanisms of uptake, storage and secretion. The breakdown of metal ion homeostasis can lead to an uncontrolled formation of reactive oxygen species, ROS (via the Fenton reaction, which produces hydroxyl radicals), and reactive nitrogen species, RNS, which may cause oxidative damage to biological macromolecules such as DNA, proteins and lipids. An imbalance between the formation of free radicals and their elimination by antioxidant defense systems is termed oxidative stress. Most vulnerable to free radical attack is the cell membrane which may undergo enhanced lipid peroxidation, finally producing mutagenic and carcinogenic malondialdehyde and 4-hydroxynonenal and other exocyclic DNA adducts. While redox-active iron (Fe) and copper (Cu) undergo redox-cycling reactions, for a second group of redox-inactive metals such as arsenic (As) and cadmium (Cd), the primary route for their toxicity is depletion of glutathione and bonding to sulfhydryl groups of proteins. While arsenic is known to bind directly to critical thiols, other mechanisms, involving formation of hydrogen peroxide under physiological conditions, have been proposed. Redox-inert zinc (Zn) is the most abundant metal in the brain and an essential component of numerous proteins involved in biological defense mechanisms against oxidative stress. The depletion of zinc may enhance DNA damage by impairing DNA repair mechanisms. Intoxication of an organism by arsenic and cadmium may lead to metabolic disturbances of redox-active copper and iron, with the occurrence of oxidative stress induced by the enhanced formation of ROS/RNS. Oxidative stress occurs when excessive formation of ROS overwhelms the antioxidant defense system, as is maintained by antioxidants such as ascorbic acid, alpha

  17. Pattern formation induced by cross-diffusion in a predator-prey system

    Institute of Scientific and Technical Information of China (English)

    Sun Gui-Quan; Jin Zhen; Liu Quan-Xing; Li Li

    2008-01-01

    This paper considers the Holling-Tanner model for predator-prey with self and cross-diffusion.From the Turing theory,it is believed that there is no Turing pattern formation for the equal self-diffusion coefficients.However,combined with cross-diffusion,it shows that the system will exhibit spotted pattern by both mathematical analysis and numerical simulations.Furthermore,nsynchrony of the predator and the prey in the space.The obtained results show that cross-diffusion plays an important role on the pattern formation of the predator-prey system.

  18. Optical field-induced surface relief formation on chalcogenide and azo-benzene polymer films

    Science.gov (United States)

    Teteris, J.; Gertners, U.

    2012-08-01

    The dependence of the surface relief formation in amorphous As2S3 and Disperse Red 1dye grafted polyurethane polymer films on the polarization state of recording light was studied. It is shown that the direction of mass transport on the film surface is determined by the direction of light electric vector and photoinduced anisotropy in the film. We propose a photoinduced dielectropfhoretic model to explain the photoinduced mass transport in amorphous films. Model is based on the photoinduced softening of the matrix, formation of defects with enhanced or decreased polarizability, and their drift under the electrical field gradient of light.

  19. Temozolomide-Induced Myelodysplasia

    Directory of Open Access Journals (Sweden)

    Ethan A. Natelson

    2010-01-01

    Full Text Available A patient who had received temozolomide (TMZ as a single agent in treatment of malignant glioma developed therapy-induced myelodysplasia (T-MDS. TMZ is an orally active imidazotetrazine which methylates guanine residues in DNA, ultimately causing single and double-strand DNA breaks leading to apoptotic cell death. TMZ does not chemically cross-link DNA and is considered a nonclassical alkylating agent, similar in structure and activity to dacarbazine. Observations on this patient, and on similarly treated others, suggest that the cumulative dose threshold (CDT for TMZ that predisposes to T-MDS and which may potentially lead to acute myeloid leukemia (T-AML is around 18000 to 20000 mg/sq m. Although the incidence of T-MDS and the predisposing CDT of TMZ may differ from that of other potentially leukemogenic compounds currently and formerly used as chemotherapeutic agents, all alkylating agents, including TMZ, should be considered potentially leukemogenic when administered long term.

  20. Water in IRC+10216: a genuine formation process by shock-induced chemistry in the inner wind

    CERN Document Server

    Cherchneff, Isabelle

    2010-01-01

    Context: The presence of water in the wind of the extreme carbon star IRC+10216 has been confirmed by the Herschel telescope. The regions where the high-J H2O lines have been detected are close to the star at radii r \\geq 15 R\\ast. Aims: We investigate the formation of water and related molecules in the periodically-shocked inner layers of IRC+10216 where dust also forms and accelerates the wind. Methods: We describe the molecular formation by a chemical kinetic network involving carbon-and oxygen-based molecules. We then apply this network to the physical conditions pertaining to the dust-formation zone which experiences the passage of pulsation- driven shocks between 1 and 5 R\\ast. We solve for a system of stiff, coupled, ordinary, and differential equations. Results: Non-equilibrium chemistry prevails in the dust-formation zone. H2O forms quickly above the photosphere from the synthesis of hydroxyl OH induced by the thermal fragmentation of CO in the hot post-shock gas. The derived abundance with respect t...

  1. UV-B Induced Generation of Reactive Oxygen Species Promotes Formation of BFA-Induced Compartments in Cells of Arabidopsis Root Apices.

    Science.gov (United States)

    Yokawa, Ken; Kagenishi, Tomoko; Baluška, František

    2015-01-01

    UV-B radiation is an important part of the electromagnetic spectrum emitted by the sun. For much of the period of biological evolution organisms have been exposed to UV radiation, and have developed diverse mechanisms to cope with this potential stress factor. Roots are usually shielded from exposure to UV by the surrounding soil, but may nevertheless be exposed to high energy radiation on the soil surface. Due to their high sensitivity to UV-B radiation, plant roots need to respond rapidly in order to minimize exposure on the surface. In addition to root gravitropism, effective light perception by roots has recently been discovered to be essential for triggering negative root phototropism in Arabidopsis. However, it is not fully understood how UV-B affects root growth and phototropism. Here, we report that UV-B induces rapid generation of reactive oxygen species which in turn promotes the formation of BFA-induced compartments in the Arabidopsis root apex. During unilateral UV-B irradiation of roots changes in auxin concentration on the illuminated side have been recorded. In conclusion, UV-B-induced and ROS-mediated stimulation of vesicle recycling promotes root growth and induces negative phototropism.

  2. UV-B induced generation of reactive oxygen species promotes formation of BFA-induced compartments in cells of Arabidopsis root apices

    Directory of Open Access Journals (Sweden)

    Ken eYokawa

    2016-01-01

    Full Text Available UV-B radiation is an important part of the electromagnetic spectrum emitted by the sun. For much of the period of biological evolution organisms have been exposed to UV radiation, and have developed diverse mechanisms to cope with this potential stress factor. Roots are usually shielded from exposure to UV by the surrounding soil, but may nevertheless be exposed to high energy radiationon the soil surface. Due to their high sensitivity to UV-B radiation, plant roots need to respond rapidly in order to minimize exposure on the surface. In addition to root gravitropism, effective light perception by roots has recently been discovered to be essential for triggering negative root phototropism in Arabidopsis. However, it is not fully understood how UV-B affects root growth and phototropism. Here, we report that UV-B induces rapid generation of reactive oxygen species which in turn promotes the formation of BFA-induced compartments in the Arabidopsis root apex. During unilateral UV-B irradiation of roots changes in auxin concentration on the illuminated side have been recorded. In conclusion, UV-B-induced and ROS-mediated stimulation of vesicle recycling promotes root growth and induces negative phototropism.

  3. Formation of laser-induced periodic surface structures on fused silica upon two-color double-pulse irradiation

    Science.gov (United States)

    Höhm, S.; Herzlieb, M.; Rosenfeld, A.; Krüger, J.; Bonse, J.

    2013-12-01

    The formation of laser-induced periodic surface structures (LIPSS) upon irradiation of fused silica with multiple irradiation sequences consisting of laser pulse pairs (50 fs single-pulse duration) of two different wavelengths (400 and 800 nm) is studied experimentally. Parallel polarized double-pulse sequences with a variable delay Δt between -10 and +10 ps and between the individual fs-laser pulses were used to investigate the LIPSS periods versus Δt. These two-color experiments reveal the importance of the ultrafast energy deposition to the silica surface by the first laser pulse for LIPSS formation. The second laser pulse subsequently reinforces the previously seeded spatial LIPSS frequencies.

  4. Formation of laser-induced periodic surface structures on fused silica upon two-color double-pulse irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Höhm, S.; Herzlieb, M.; Rosenfeld, A. [Max-Born-Institut für Nichtlineare Optik und Kurzzeitspektroskopie (MBI), Max-Born-Straße 2A, D-12489 Berlin (Germany); Krüger, J.; Bonse, J. [BAM Bundesanstalt für Materialforschung und –prüfung, Unter den Eichen 87, D-12205 Berlin (Germany)

    2013-12-16

    The formation of laser-induced periodic surface structures (LIPSS) upon irradiation of fused silica with multiple irradiation sequences consisting of laser pulse pairs (50 fs single-pulse duration) of two different wavelengths (400 and 800 nm) is studied experimentally. Parallel polarized double-pulse sequences with a variable delay Δt between −10 and +10 ps and between the individual fs-laser pulses were used to investigate the LIPSS periods versus Δt. These two-color experiments reveal the importance of the ultrafast energy deposition to the silica surface by the first laser pulse for LIPSS formation. The second laser pulse subsequently reinforces the previously seeded spatial LIPSS frequencies.

  5. Mutant KRas-Induced Mitochondrial Oxidative Stress in Acinar Cells Upregulates EGFR Signaling to Drive Formation of Pancreatic Precancerous Lesions

    Directory of Open Access Journals (Sweden)

    Geou-Yarh Liou

    2016-03-01

    Full Text Available The development of pancreatic cancer requires the acquisition of oncogenic KRas mutations and upregulation of growth factor signaling, but the relationship between these is not well established. Here, we show that mutant KRas alters mitochondrial metabolism in pancreatic acinar cells, resulting in increased generation of mitochondrial reactive oxygen species (mROS. Mitochondrial ROS then drives the dedifferentiation of acinar cells to a duct-like progenitor phenotype and progression to PanIN. This is mediated via the ROS-receptive kinase protein kinase D1 and the transcription factors NF-κB1 and NF-κB2, which upregulate expression of the epidermal growth factor, its ligands, and their sheddase ADAM17. In vivo, interception of KRas-mediated generation of mROS reduced the formation of pre-neoplastic lesions. Hence, our data provide insight into how oncogenic KRas interacts with growth factor signaling to induce the formation of pancreatic cancer.

  6. Epithelial sheet folding induces lumen formation by Madin-Darby canine kidney cells in a collagen gel.

    Directory of Open Access Journals (Sweden)

    Sumire Ishida

    Full Text Available Lumen formation is important for morphogenesis; however, an unanswered question is whether it involves the collective migration of epithelial cells. Here, using a collagen gel overlay culture method, we show that Madin-Darby canine kidney cells migrated collectively and formed a luminal structure in a collagen gel. Immediately after the collagen gel overlay, an epithelial sheet folded from the periphery, migrated inwardly, and formed a luminal structure. The inhibition of integrin-β1 or Rac1 activity decreased the migration rate of the peripheral cells after the sheets folded. Moreover, lumen formation was perturbed by disruption of apical-basolateral polarity induced by transforming growth factor-β1. These results indicate that cell migration and cell polarity play an important role in folding. To further explore epithelial sheet folding, we developed a computer-simulated mechanical model based on the rigidity of the extracellular matrix. It indicated a soft substrate is required for the folding movement.

  7. Targeting Rac1 signaling inhibits streptococcal M1 protein-induced CXC chemokine formation, neutrophil infiltration and lung injury.

    Directory of Open Access Journals (Sweden)

    Songen Zhang

    Full Text Available Infections with Streptococcus pyogenes exhibit a wide spectrum of infections ranging from mild pharyngitis to severe Streptococcal toxic shock syndrome (STSS. The M1 serotype of Streptococcus pyogenes is most commonly associated with STSS. In the present study, we hypothesized that Rac1 signaling might regulate M1 protein-induced lung injury. We studied the effect of a Rac1 inhibitor (NSC23766 on M1 protein-provoked pulmonary injury. Male C57BL/6 mice received NSC23766 prior to M1 protein challenge. Bronchoalveolar fluid and lung tissue were harvested for quantification of neutrophil recruitment, edema and CXC chemokine formation. Neutrophil expression of Mac-1 was quantified by use of flow cytometry. Quantitative RT-PCR was used to determine gene expression of CXC chemokines in alveolar macrophages. Treatment with NSC23766 decreased M1 protein-induced neutrophil infiltration, edema formation and tissue injury in the lung. M1 protein challenge markedly enhanced Mac-1 expression on neutrophils and CXC chemokine levels in the lung. Inhibition of Rac1 activity had no effect on M1 protein-induced expression of Mac-1 on neutrophils. However, Rac1 inhibition markedly decreased M1 protein-evoked formation of CXC chemokines in the lung. Moreover, NSC23766 completely inhibited M1 protein-provoked gene expression of CXC chemokines in alveolar macrophages. We conclude that these novel results suggest that Rac1 signaling is a significant regulator of neutrophil infiltration and CXC chemokine production in the lung. Thus, targeting Rac1 activity might be a potent strategy to attenuate streptococcal M1 protein-triggered acute lung damage.

  8. Radiation and chemotherapy bystander effects induce early genomic instability events: telomere shortening and bridge formation coupled with mitochondrial dysfunction.

    LENUS (Irish Health Repository)

    Gorman, Sheeona

    2012-02-01

    The bridge breakage fusion cycle is a chromosomal instability mechanism responsible for genomic changes. Radiation bystander effects induce genomic instability; however, the mechanism driving this instability is unknown. We examined if radiation and chemotherapy bystander effects induce early genomic instability events such as telomere shortening and bridge formation using a human colon cancer explant model. We assessed telomere lengths, bridge formations, mitochondrial membrane potential and levels of reactive oxygen species in bystander cells exposed to medium from irradiated and chemotherapy-treated explant tissues. Bystander cells exposed to media from 2Gy, 5Gy, FOLFOX treated tumor and matching normal tissue showed a significant reduction in telomere lengths (all p values <0.018) and an increase in bridge formations (all p values <0.017) compared to bystander cells treated with media from unirradiated tissue (0Gy) at 24h. There was no significant difference between 2Gy and 5Gy treatments, or between effects elicited by tumor versus matched normal tissue. Bystander cells exposed to media from 2Gy irradiated tumor tissue showed significant depolarisation of the mitochondrial membrane potential (p=0.012) and an increase in reactive oxygen species levels. We also used bystander cells overexpressing a mitochondrial antioxidant manganese superoxide dismutase (MnSOD) to examine if this antioxidant could rescue the mitochondrial changes and subsequently influence nuclear instability events. In MnSOD cells, ROS levels were reduced (p=0.02) and mitochondrial membrane potential increased (p=0.04). These events were coupled with a decrease in percentage of cells with anaphase bridges and a decrease in the number of cells undergoing telomere length shortening (p values 0.01 and 0.028 respectively). We demonstrate that radiation and chemotherapy bystander responses induce early genomic instability coupled with defects in mitochondrial function. Restoring mitochondrial

  9. Zinc oxide nanoparticles induce migration and adhesion of monocytes to endothelial cells and accelerate foam cell formation

    Energy Technology Data Exchange (ETDEWEB)

    Suzuki, Yuka; Tada-Oikawa, Saeko [Graduate School of Regional Innovation Studies, Mie University, Tsu (Japan); Ichihara, Gaku [Department of Occupational and Environmental Health, Nagoya University Graduate School of Medicine, Nagoya (Japan); Yabata, Masayuki; Izuoka, Kiyora [Graduate School of Regional Innovation Studies, Mie University, Tsu (Japan); Suzuki, Masako; Sakai, Kiyoshi [Nagoya City Public Health Research Institute, Nagoya (Japan); Ichihara, Sahoko, E-mail: saho@gene.mie-u.ac.jp [Graduate School of Regional Innovation Studies, Mie University, Tsu (Japan)

    2014-07-01

    Metal oxide nanoparticles are widely used in industry, cosmetics, and biomedicine. However, the effects of exposure to these nanoparticles on the cardiovascular system remain unknown. The present study investigated the effects of nanosized TiO{sub 2} and ZnO particles on the migration and adhesion of monocytes, which are essential processes in atherosclerogenesis, using an in vitro set-up of human umbilical vein endothelial cells (HUVECs) and human monocytic leukemia cells (THP-1). We also examined the effects of exposure to nanosized metal oxide particles on macrophage cholesterol uptake and foam cell formation. The 16-hour exposure to ZnO particles increased the level of monocyte chemotactic protein-1 (MCP-1) and induced the migration of THP-1 monocyte mediated by increased MCP-1. Exposure to ZnO particles also induced adhesion of THP-1 cells to HUVECs. Moreover, exposure to ZnO particles, but not TiO{sub 2} particles, upregulated the expression of membrane scavenger receptors of modified LDL and increased cholesterol uptake in THP-1 monocytes/macrophages. In the present study, we found that exposure to ZnO particles increased macrophage cholesterol uptake, which was mediated by an upregulation of membrane scavenger receptors of modified LDL. These results suggest that nanosized ZnO particles could potentially enhance atherosclerogenesis and accelerate foam cell formation. - Highlights: • Effects of metal oxide nanoparticles on foam cell formation were investigated. • Exposure to ZnO nanoparticles induced migration and adhesion of monocytes. • Exposure to ZnO nanoparticles increased macrophage cholesterol uptake. • Expression of membrane scavenger receptors of modified LDL was also increased. • These effects were not observed after exposure to TiO{sub 2} nanoparticles.

  10. Radiation and chemotherapy bystander effects induce early genomic instability events: Telomere shortening and bridge formation coupled with mitochondrial dysfunction

    Energy Technology Data Exchange (ETDEWEB)

    Gorman, Sheeona; Tosetto, Miriam [Centre for Colorectal Disease, St. Vincent' s University Hospital, Elm Park, Dublin 4 (Ireland); Lyng, Fiona; Howe, Orla [Radiation and Environmental Science Centre, Dublin Institute of Technology and St. Luke' s Hospital, Dublin (Ireland); Sheahan, Kieran; O' Donoghue, Diarmuid; Hyland, John; Mulcahy, Hugh [Centre for Colorectal Disease, St. Vincent' s University Hospital, Elm Park, Dublin 4 (Ireland); O' Sullivan, Jacintha, E-mail: jacintha.osullivan@ucd.ie [Centre for Colorectal Disease, St. Vincent' s University Hospital, Elm Park, Dublin 4 (Ireland)

    2009-10-02

    The bridge breakage fusion cycle is a chromosomal instability mechanism responsible for genomic changes. Radiation bystander effects induce genomic instability; however, the mechanism driving this instability is unknown. We examined if radiation and chemotherapy bystander effects induce early genomic instability events such as telomere shortening and bridge formation using a human colon cancer explant model. We assessed telomere lengths, bridge formations, mitochondrial membrane potential and levels of reactive oxygen species in bystander cells exposed to medium from irradiated and chemotherapy-treated explant tissues. Bystander cells exposed to media from 2 Gy, 5 Gy, FOLFOX treated tumor and matching normal tissue showed a significant reduction in telomere lengths (all p values <0.018) and an increase in bridge formations (all p values <0.017) compared to bystander cells treated with media from unirradiated tissue (0 Gy) at 24 h. There was no significant difference between 2 Gy and 5 Gy treatments, or between effects elicited by tumor versus matched normal tissue. Bystander cells exposed to media from 2 Gy irradiated tumor tissue showed significant depolarisation of the mitochondrial membrane potential (p = 0.012) and an increase in reactive oxygen species levels. We also used bystander cells overexpressing a mitochondrial antioxidant manganese superoxide dismutase (MnSOD) to examine if this antioxidant could rescue the mitochondrial changes and subsequently influence nuclear instability events. In MnSOD cells, ROS levels were reduced (p = 0.02) and mitochondrial membrane potential increased (p = 0.04). These events were coupled with a decrease in percentage of cells with anaphase bridges and a decrease in the number of cells undergoing telomere length shortening (p values 0.01 and 0.028 respectively). We demonstrate that radiation and chemotherapy bystander responses induce early genomic instability coupled with defects in mitochondrial function. Restoring

  11. A specific subtype of osteoclasts secretes factors inducing nodule formation by osteoblasts

    DEFF Research Database (Denmark)

    Henriksen, Kim; Andreassen, Kim V; Thudium, Christian S;

    2012-01-01

    little resorption, but still an induction of bone formation by osteoblasts. Mimicking the reduction in bone resorption using the V-ATPase inhibitor Diphyllin, the cysteine proteinase inhibitor E64 and the MMP-inhibitor GM6001 showed that CM from diphyllin and E64 treated osteoclasts showed reduced...

  12. Adsorbate induced surface alloy formation investigated by near ambient pressure X-ray photoelectron spectroscopy

    DEFF Research Database (Denmark)

    Nierhoff, Anders Ulrik Fregerslev; Conradsen, Christian Nagstrup; McCarthy, David Norman

    2014-01-01

    Formation of meta-stable surface-alloys can be used as a way to tune the binding strength of reaction intermediates and could therefore be used as improved catalyst materials for heterogeneous catalysis. Understanding the role of adsorbates on such alloy surfaces can provide new insights for engi...

  13. Rosuvastatin attenuates angiotensin II-induced neointimal formation after stent implantation in the rat

    NARCIS (Netherlands)

    van der Harst, Pim; Groenewegen, Hendrik C.; Roks, Anton J. M.; Buikema, Hendrik; Zijlstra, Felix; van Gilst, Wiek H.; de Smet, Bart J. G. L.

    2008-01-01

    Objective We investigated the efficacy of oral rosuvastatin treatment to reduce in-stent neointima formation, both in the absence and presence of high levels of the proproliferative substance angiotensin II (Ang II). Background Drawbacks of current drug-eluting stents include inhibition of reendothe

  14. Formation of globular clusters induced by external ultraviolet radiation - II. Three-dimensional radiation hydrodynamics simulations

    Science.gov (United States)

    Abe, Makito; Umemura, Masayuki; Hasegawa, Kenji

    2016-12-01

    We explore the possibility of the formation of globular clusters (GCs) under ultraviolet (UV) background radiation. One-dimensional spherical symmetric radiation hydrodynamics (RHD) simulations by Hasegawa et al. have demonstrated that the collapse of low-mass (106-7 M⊙) gas clouds exposed to intense UV radiation can lead to the formation of compact star clusters like GCs if gas clouds contract with supersonic infall velocities. However, three-dimensional effects, such as the anisotropy of background radiation and the inhomogeneity in gas clouds, have not been studied so far. In this paper, we perform three-dimensional RHD simulations in a semicosmological context, and reconsider the formation of compact star clusters in strong UV radiation fields. As a result, we find that although anisotropic radiation fields bring an elongated shadow of neutral gas, almost spherical compact star clusters can be procreated from a `supersonic infall' cloud, since photodissociating radiation suppresses the formation of hydrogen molecules in the shadowed regions and the regions are compressed by UV heated ambient gas. The properties of resultant star clusters match those of GCs. On the other hand, in weak UV radiation fields, dark-matter-dominated star clusters with low stellar density form due to the self-shielding effect as well as the positive feedback by ionizing photons. Thus, we conclude that the `supersonic infall' under a strong UV background is a potential mechanism to form GCs.

  15. Concentration-dependency of beta-lactam-induced filament formation in Gram-negative bacteria.

    NARCIS (Netherlands)

    Buijs, J.; Dofferhoff, A.S.M.; Mouton, J.W.; Wagenvoort, J.H.T.; Meer, J.W.M. van der

    2008-01-01

    Ceftazidime and cefotaxime are beta-lactam antibiotics with dose-related affinities for penicillin-binding protein (PBP)-3 and PBP-1. At low concentrations, these antibiotics inhibit PBP-3, leading to filament formation. Filaments are long strands of non-dividing bacteria that contain enhanced quant

  16. Automobile diesel exhaust particles induce lipid droplet formation in macrophages in vitro

    DEFF Research Database (Denmark)

    Cao, Yi; Jantzen, Kim; Gouveia, Ana Cecilia Damiao

    2015-01-01

    Exposure to diesel exhaust particles (DEP) has been associated with adverse cardiopulmonary health effects, which may be related to dysregulation of lipid metabolism and formation of macrophage foam cells. In this study, THP-1 derived macrophages were exposed to an automobile generated DEP (A...

  17. Glutathione-induced radical formation on lactoperoxidase does not correlate with the enzyme's peroxidase activity.

    Science.gov (United States)

    Bonini, Marcelo G; Siraki, Arno G; Bhattacharjee, Suchandra; Mason, Ronald P

    2007-04-01

    Lactoperoxidase (LPO) is believed to serve as a mediator of host defense against invading pathogens. The protein is more abundant in body fluids such as milk, saliva, and tears. Lactoperoxidase is known to mediate the oxidation of halides and (pseudo)halides in the presence of hydrogen peroxide to reactive intermediates presumably involved in pathogen killing. More recently, LPO has been shown to oxidize a wide diversity of thiol compounds to thiyl free radicals, which ultimately lead to the formation of a protein radical characterized by DMPO-immunospin trapping. In the same study by our group the authors claimed that a consequence of this protein radical formation was the inactivation of LPO (Guo et al., J. Biol. Chem.279:13272-13283; 2004). Here we demonstrate that although thiyl radical formation does lead to LPO radical production, the formation of this radical is unrelated to the enzyme's activity. We suggest the source of this misleading interpretation to be the binding of GSH to ELISA plates, which interferes with ABTS and guaiacol oxidation. In addition, DMPO-GSH-nitrone adducts bind to ELISA plates, leading to ambiguities of interpretation since we have demonstrated that DMPO-GSH nitrone does not bind to LPO, and only LPO-protein-DMPO-nitrone adducts can be detected by Western blot.

  18. Flow induced formation of dual-phase continuity in polymer blends and alloys

    DEFF Research Database (Denmark)

    Lyngaae-Jørgensen, Jørgen; Chtcherbakova, E.A.; Utracki, L.A.

    1997-01-01

    showed that an addition of block copolymer may narrow the volume fraction range where bi-continuous phase structures are formed. Both annealing in the molten stale and shearing history influence the measured phi(cr) for formation of bi-continuous phase structure in amorphous immiscible polymer blends....

  19. Formation Mechanism of Micropores on the Surface of Pure Aluminum Induced by High-Current Pulsed Electron Beam Irradiation

    Institute of Scientific and Technical Information of China (English)

    ZOU Yang; CAI Jie; WAN Ming-Zhen; LV Peng; GUAN Qing-Feng

    2011-01-01

    The mechanism of micropores formed on the surface of polycrystalline pure aluminum under high-current pulsed electron beam (HCPEB) irradiation is explained. It is discovered that dispersed micropores with sizes of 0.1-1μm on the irradiated surface of pure aluminum can be successfully fabricated after HCPEB irradiation. The dominant formation mechanism of the surface micropores should be attributed to the formation of supersaturation vacancies within the near surface during the HCPEB irradiation and the migration of vacancies along gra,in boundaries and/or dislocations towards the irradiated surface. It is expected that the HCPEB technique will become a new method for the rapid synthesis of surface porous materials.%The mechanism of micropores formed on the surface of polycrystalline pure aluminum under high-current pulsed electron beam (HCPEB) irradiation is explained.It is discovered that dispersed micropores with sizes of 0.1-1μm on the irradiated surface of pure aluminum can be successfully fabricated after HCPEB irradiation.The dominant formation mechanism of the surface micropores should be attributed to the formation of supersaturation vacancies within the near surface during the HCPEB irradiation and the migration of vacancies along grain boundaries and/or dislocations towards the irradiated surface.It is expected that the HCPEB technique will become a new method for the rapid synthesis of surface porous materials.High-current pulsed electron beams (HCPEBs)have attracted much attention in the field of material surface modification.[1-7] During the transient bombardment process a high energy (108-109 W·cm-2) is deposited only in a very thin layer (less than tens of micrometers) within a very short time (a few microseconds) and thereby causes ultrafast heating and cooling on the irradiated surface of materials.The dynamic stress fields induced in these processes can induce intense deformation on the material surface.

  20. Laser induced periodic surface structure formation in germanium above laser damage fluence by mid IR femtosecond laser irradiation

    Science.gov (United States)

    Kafka, Kyle; Austin, Drake; Cheng, Jian; Trendafilov, Simeon; Shvets, Gennady; Li, Hui; Yi, Allen; Blaga, Cosmin I.; DiMauro, L. F.; Chowdhury, Enam

    2014-11-01

    Laser induced periodic surface structures (LIPSS) were generated via interaction of multiple 90 femtosecond 1900 - 3600 nm mid IR laser pulses (3 -10,000) on single crystal Ge targets. For specific laser parameters, both low and high frequency LIPSS are found together, which are oriented perpendicular to each other. Study of polarization dependence of LIPSS revealed that orientation and symmetry of interaction could be controlled by rotating polarization of laser pulses. Low frequency LIPSS formation was consistent with surface plasmon coupling of laser pulses with excited Ge.

  1. Dynamic modeling and scaling of nanostructure formation in the lithographically induced self-assembly and self-construction

    Science.gov (United States)

    Wu, Lin; Chou, Stephen Y.

    2003-05-01

    We numerically studied the dynamical formation process and the scaling of the nanostructures in the lithographically induced self-assembly and self-construction of thin polymer films. Our studies show that the period of the self-assembled pillars depends on the ratio between the surface tension force and the electrostatic force. The viscosity of the polymer has no effect on the final pillar shape. When the feature width of the mold is comparable to or smaller than the most unstable disturbance wavelength of the system, the initially self-assembled pillars will merge to form a self-constructed mesa.

  2. Effect of copper on the formation of strain-induced martensite in two austenitic stainless steels AISI 304

    Energy Technology Data Exchange (ETDEWEB)

    Gilapa, Leonidas Cayo Mamani, E-mail: leonidas@ifsc.edu.br [Instituto Federal de Santa Catarina, Rua Pavão, 1337, Bairro Costa e Silva, Joinville, SC CEP 89220-200 (Brazil); Oliveira, Carlos Augusto Silva de, E-mail: carlos.a@ufsc.br [Universidade Federal de Santa Catarina, Campus Universitário Reitor João David Ferreira Lima, Trindade, Florianópolis, SC CEP 88040-970 (Brazil); Silva, Manoel Ribeiro da, E-mail: mrsilva@unifei.edu.br [Universidade Federal de Itajubá, Instituto de Ciências, Itajubá (Brazil)

    2015-01-12

    The transformation of strain-induced martensite in two metastable austenitic stainless steels, AISI 304, with the same basic composition and concentrations of Cu variables was characterized by transmission electron microscopy and magnetic measurements. The deformations to induce the formation of martensite were performed using the test of conformability with Nakajima tooling at room temperature. The results obtained for the various samples showed that the steel with lower content of Cu presented higher degree of magnetization. Also it was observed that the martensite magnetic α′ and paramagnetic ε are formed at the intersection of dislocation, in the grain boundary, inside and at the edge of twinned and the stacking faults in the austenite.

  3. Vortices induced in a stagnation region by wakes - Their incipient formation and effects on heat transfer from cylinders

    Science.gov (United States)

    Nagib, H. M.; Hodson, P. R.

    1977-01-01

    Horseshoe-like vortices, induced by wakes in the stagnation region of bluff bodies, are proposed as an efficient mechanism for augmentation of convective heat transfer. The vortex 'flow module' induced by single or multiple wakes, which had not been observed previously, was first documented and the resulting flow field was studied using various visualization techniques and hot-wire anemometry. In an attempt to understand the driving force behind this flow module, the conditions at which incipient formation of the vortices occurs were investigated. Existence of such a threshold is essential and was hitherto an open question in analytical studies of stability of flow in stagnation region. Finally, effects of the flow module on heat transfer from a cylinder were measured.

  4. Laser-induced periodic surface structures on polymers for formation of gold nanowires and activation of human cells

    Science.gov (United States)

    Barb, R.-A.; Hrelescu, C.; Dong, L.; Heitz, J.; Siegel, J.; Slepicka, P.; Vosmanska, V.; Svorcik, V.; Magnus, B.; Marksteiner, R.; Schernthaner, M.; Groschner, K.

    2014-10-01

    Frequently observed coherent structures in laser-surface processing are ripples, also denoted as laser-induced periodic surface structures (LIPSS). For polyethylene terephthalate (PET) and polystyrene (PS), LIPSS can be induced by irradiation with linearly polarized ns-pulsed UV laser light. Under an angle of incidence of θ, their lateral period is close to the laser wavelength λ divided by ( n eff - sin θ). Here, n eff is the effective refractive index which is 1.32 and 1.23 for PET and PS, respectively. We describe potential applications of LIPSS for alignment and activation of human cells cultivated on polymer substrates, as well as for formation of separated gold nanowires which show pronounced surface plasmon resonances, e.g., at 775 nm for PET.

  5. Host–Guest Chirality Interplay: A Mutually Induced Formation of a Chiral ZMOF and Its Double-Helix Polymer Guests

    KAUST Repository

    Luo, Xiaolong

    2016-01-12

    A novel homochiral zeolite-like metal-organic framework (ZMOF), [(Cu4I4) (dabco)2]·[Cu2(bbimb)]·3DMF (JLU-Liu23, dabco =1,4-diazabicyclo[2.2.2]-octane, H2bbimb =1,3-bis(2-benzimidazol)benzene, DMF = N,N-dimethylformamide), has been successfully constructed to host unprecedented DNA-like [Cu2(bbimb)]n polymers with double-helicity. The host-guest chirality interplay permitted the induced formation of an unusual gyroid MOF with homochirality and helical channels in the framework for the first time, JLU-Liu23. Importantly, the enantiomeric pairs (23P, 23M) can be promoted and isolated in the presence of appropriate chiral inducing agents, affording enantioselective separation of chiral molecules as well as small gas molecules. © 2016 American Chemical Society.

  6. Shiga toxin induces membrane reorganization and formation of long range lipid order

    DEFF Research Database (Denmark)

    Solovyeva, Vita; Johannes, Ludger; Simonsen, Adam Cohen

    2015-01-01

    membrane reordering. When Shiga toxin was added above the lipid chain melting temperature, the toxin interaction with the membrane induced rearrangement and clustering of Gb3 lipids that resulted in the long range order and alignment of lipids in gel domains. The toxin induced redistribution of Gb3 lipids...... microscopy. A content of 1% of glycosphingolipid globotriaosylceramide (Gb3) receptor lipids in a bilayer was used to bind the Shiga toxin B-subunit to the surface of gel domains. Binding of the Shiga toxin B-subunit to lipids led to the modulation of orientational membrane texture in gel domains and induced...... inside gel domains is governed by the temperature at which Shiga toxin was added to the membrane: above or below the phase transition. The temperature is thus one of the critical factors controlling lipid organization and texture in the presence of Shiga toxin. Lipid chain ordering imposed by Shiga toxin...

  7. Formation of polyhedral vesicles and polygonal membrane tubes induced by banana-shaped proteins

    Science.gov (United States)

    Noguchi, Hiroshi

    2015-12-01

    The shape transformations of fluid membranes induced by curved protein rods are studied using meshless membrane simulations. The rod assembly at low rod density induces a flat membrane tube and oblate vesicle. It is found that the polyhedral shapes are stabilized at high rod densities. The discrete shape transition between triangular and buckled discoidal tubes is obtained and their curvature energies are analyzed by a simple geometric model. For vesicles, triangular hosohedron and elliptic-disk shapes are formed in equilibrium, whereas tetrahedral and triangular prism shapes are obtained as metastable states.

  8. Short exposure to paclitaxel induces multipolar spindle formation and aneuploidy through promotion of acentrosomal pole assembly

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    Paclitaxel is a widely used microtubule drug and cancer medicine. Here we report that by short exposure to paclitaxel at a low dose, multipolar spindles were induced in mitotic cells without centrosome amplification. Both TPX2 depletion and Aurora-A overexpression antagonized the multipolarity. Live cell imaging showed that some paclitaxel-treated cells accomplished multipolar cell division and a portion of the daughter cells went on to the next round of mitosis. The surviving cells grew into clones with varied genome content. The results indicated that an aneuploidy population could be induced by short exposure to paclitaxel at a low dose, implicating potential side effects of paclitaxel.

  9. Triple-helix formation induces recombination in mammalian cells via a nucleotide excision repair-dependent pathway.

    Science.gov (United States)

    Faruqi, A F; Datta, H J; Carroll, D; Seidman, M M; Glazer, P M

    2000-02-01

    The ability to stimulate recombination in a site-specific manner in mammalian cells may provide a useful tool for gene knockout and a valuable strategy for gene therapy. We previously demonstrated that psoralen adducts targeted by triple-helix-forming oligonucleotides (TFOs) could induce recombination between tandem repeats of a supF reporter gene in a simian virus 40 vector in monkey COS cells. Based on work showing that triple helices, even in the absence of associated psoralen adducts, are able to provoke DNA repair and cause mutations, we asked whether intermolecular triplexes could stimulate recombination. Here, we report that triple-helix formation itself is capable of promoting recombination and that this effect is dependent on a functional nucleotide excision repair (NER) pathway. Transfection of COS cells carrying the dual supF vector with a purine-rich TFO, AG30, designed to bind as a third strand to a region between the two mutant supF genes yielded recombinants at a frequency of 0.37%, fivefold above background, whereas a scrambled sequence control oligomer was ineffective. In human cells deficient in the NER factor XPA, the ability of AG30 to induce recombination was eliminated, but it was restored in a corrected subline expressing the XPA cDNA. In comparison, the ability of triplex-directed psoralen cross-links to induce recombination was only partially reduced in XPA-deficient cells, suggesting that NER is not the only pathway that can metabolize targeted psoralen photoadducts into recombinagenic intermediates. Interestingly, the triplex-induced recombination was unaffected in cells deficient in DNA mismatch repair, challenging our previous model of a heteroduplex intermediate and supporting a model based on end joining. This work demonstrates that oligonucleotide-mediated triplex formation can be recombinagenic, providing the basis for a potential strategy to direct genome modification by using high-affinity DNA binding ligands.

  10. Lupeol, a bioactive triterpene, prevents tumor formation during 7,12-dimethylbenz(a)anthracene induced oral carcinogenesis.

    Science.gov (United States)

    Palanimuthu, D; Baskaran, N; Silvan, S; Rajasekaran, D; Manoharan, S

    2012-10-01

    The oral cancer chemopreventive efficacy of lupeol, a bioactive triterpene, was assessed by monitoring the tumor incidence and using the status of phase I and II xenobiotic metabolizing enzymes, lipid peroxidation and antioxidants as biochemical end points during 7,12-dimethylbenz(a)anthracene (DMBA) induced hamster buccal pouch carcinogenesis. Oral tumors were developed in the buccal pouch of golden Syrian hamsters by painting with 0.5 % DMBA three times a week for 14 weeks. Well differentiated oral squamous cell carcinoma with marked abnormalities in the status of biochemical markers were noticed in hamsters treated with DMBA alone. Oral administration of lupeol at a dose of 50 mg/kg bw completely inhibited the formation of oral tumors and restored the status of biochemical markers during DMBA induced oral carcinogenesis. The present study thus demonstrates the chemopreventive potential of lupeol in DMBA induced oral carcinogenesis. The chemopreventive potential of lupeol is probably due to its antioxidant or free radical scavenging property and modulating effect on phase I and II xenobiotic metabolizing enzymes in favour of the excretion of carcinogenic metabolites during DMBA induced hamster buccal pouch carcinogenesis.

  11. Administration of a tropomyosin receptor kinase inhibitor attenuates sarcoma-induced nerve sprouting, neuroma formation and bone cancer pain

    Directory of Open Access Journals (Sweden)

    Bloom Aaron P

    2010-12-01

    Full Text Available Abstract Pain often accompanies cancer and most current therapies for treating cancer pain have significant unwanted side effects. Targeting nerve growth factor (NGF or its cognate receptor tropomyosin receptor kinase A (TrkA has become an attractive target for attenuating chronic pain. In the present report, we use a mouse model of bone cancer pain and examine whether oral administration of a selective small molecule Trk inhibitor (ARRY-470, which blocks TrkA, TrkB and TrkC kinase activity at low nm concentrations has a significant effect on cancer-induced pain behaviors, tumor-induced remodeling of sensory nerve fibers, tumor growth and tumor-induced bone remodeling. Early/sustained (initiated day 6 post cancer cell injection, but not late/acute (initiated day 18 post cancer cell injection administration of ARRY-470 markedly attenuated bone cancer pain and significantly blocked the ectopic sprouting of sensory nerve fibers and the formation of neuroma-like structures in the tumor bearing bone, but did not have a significant effect on tumor growth or bone remodeling. These data suggest that, like therapies that target the cancer itself, the earlier that the blockade of TrkA occurs, the more effective the control of cancer pain and the tumor-induced remodeling of sensory nerve fibers. Developing targeted therapies that relieve cancer pain without the side effects of current analgesics has the potential to significantly improve the quality of life and functional status of cancer patients.

  12. High-density formation of Ta nanodot induced by remote hydrogen plasma

    Science.gov (United States)

    Wang, Yaping; Takeuchi, Daichi; Ohta, Akio; Ikeda, Mitsuhisa; Makihara, Katsunori; Miyazaki, Seiichi

    2017-01-01

    We have studied the formation of Ta nanodots (NDs) on thermally grown SiO2/Si by exposing a thin metal layer to a remote H2 plasma (H2-RP) without external heating. Atomic force microscopy (AFM) analyses show that a combination of a Ge (˜30.0 nm)/Ta (˜2.0 nm) bilayer stack with subsequent H2-RP exposure is effective for forming electrically isolated Ta NDs with an areal dot density as high as ˜1011 cm-2, where the Ge layer plays an important role as a barrier layer against the oxidation of the ultrathin Ta layer surface. The change in the chemical structure of the Ge/Ta bilayer stack on SiO2/Si upon Ta ND formation by H2-RP exposure is investigated by hard X-ray photoemission spectroscopy (HAXPES) and X-ray photoelectron spectroscopy (XPS).

  13. Tearing mode formation induced by internal crash events at different β N

    Science.gov (United States)

    Igochine, V.; Classen, I.; Dunne, M.; Gude, A.; Günter, S.; Lackner, K.; McDermott, R. M.; Sertoli, M.; Vezinet, D.; Willensdorfer, M.; Yu, Q.; Zohm, H.; ASDEX Upgrade Team

    2017-03-01

    Tearing mode formation after internal crash events like sawteeth or fishbones is one of the most important MHD processes that results in a big island structure and associated confinement degradation. The process implies magnetic reconnection at the rational surface, which has been investigated in great detail in the ASDEX Upgrade tokamak. Using direct local measurements, it is found that the crash leads to the formation of an ideal kink mode with large saturated amplitude at the resonant surface immediately after the sawtooth crash. This kink mode transforms into a tearing mode on a much longer timescale than the crash itself. The ideal kink mode, formed at the resonant surface after the crash, provides the driving force for the magnetic reconnection. The conversion of the ideal kink mode into a tearing mode after the internal crash is similar for various values of plasma rotation and normalized pressure.

  14. Peptide-induced de novo bone formation after tooth extraction prevents alveolar bone loss in a murine tooth extraction model.

    Science.gov (United States)

    Arai, Yuki; Aoki, Kazuhiro; Shimizu, Yasuhiro; Tabata, Yasuhiko; Ono, Takashi; Murali, Ramachandran; Mise-Omata, Setsuko; Wakabayashi, Noriyuki

    2016-07-05

    Tooth extraction causes bone resorption of the alveolar bone volume. Although recombinant human bone morphogenetic protein 2 (rhBMP-2) markedly promotes de novo bone formation after tooth extraction, the application of high-dose rhBMP-2 may induce side effects, such as swelling, seroma, and an increased cancer risk. Therefore, reduction of the necessary dose of rhBMP-2 which can still obtain sufficient bone mass is necessary by developing a new osteogenic reagent. Recently, we showed that the systemic administration of OP3-4 peptide, which was originally designed as a bone resorption inhibitor, had osteogenic ability both in vitro and in vivo. This study evaluated the ability of the local application of OP3-4 peptide to promote bone formation in a murine tooth extraction model with a very low-dose of BMP. The mandibular incisor was extracted from 10-week-old C57BL6/J male mice and a gelatin hydrogel containing rhBMP-2 with or without OP3-4 peptide (BMP/OP3-4) was applied to the socket of the incisor. Bone formation inside the socket was examined radiologically and histologically at 21 days after the extraction. The BMP/OP3-4-group showed significant bone formation inside the mandibular extraction socket compared to the gelatin-hydrogel-carrier-control group or rhBMP-2-applied group. The BMP/OP3-4-applied mice showed a lower reduction of alveolar bone and fewer osteoclast numbers, suggesting that the newly formed bone inside the socket may prevent resorption of the cortical bone around the extraction socket. Our data revealed that OP3-4 peptide promotes BMP-mediated bone formation inside the extraction socket of mandibular bone, resulting in preservation from the loss of alveolar bone.

  15. Tanshinol stimulates bone formation and attenuates dexamethasone-induced inhibition of osteogenesis in larval zebrafish

    Directory of Open Access Journals (Sweden)

    Shiying Luo

    2016-01-01

    Conclusion: The present findings suggest that tanshinol prevented decreased osteogenesis in GC-treated larval zebrafish via scavenging ROS and stimulated the expression of osteoblast-specific genes. Tanshinol treatment may be developed as a novel therapeutic approach under recent recognised conditions of GC-induced osteoporosis.

  16. Formation of ring calcium oxalate patterns induced by domains in DPPC Langmuir-Blodgett films

    Institute of Scientific and Technical Information of China (English)

    Yi Ming Liu; Sui Ping Deng; Hui Zheng; Jian Ming Ouyang

    2007-01-01

    The ring patterns of calcium oxalate crystals were induced by domains in Langmuir-Blodgett (LB) films of dipalmitoylpho-sphatidylcholine (DPPC). The result was explained by the defects at the ring boundaries of liquid condensed (LC) and liquid expanded (LE) phases of LB film. These boundaries could provide less free energy and much more nucleating sites for COM crystals.

  17. UV-inducible cellular aggregation of the hyperthermophilic archaeon Sulfolobus solfataricus is mediated by pili formation

    NARCIS (Netherlands)

    Froels, Sabrina; Ajon, Malgorzata; Wagner, Michaela; Teichmann, Daniela; Zolghadr, Behnam; Folea, Mihaela; Boekema, Egbert J.; Driessen, Arnold J. M.; Schleper, Christa; Albers, Sonja-Verena

    2008-01-01

    The hyperthermophilic archaeon Sulfolobus solfataricus has been shown to exhibit a complex transcriptional response to UV irradiation involving 55 genes. Among the strongest UV-induced genes was a putative pili biogenesis operon encoding a potential secretion ATPase, two pre-pilins, a putative trans

  18. Formation of nitric oxide in an industrial burner measured by 2-D laser induced fluorescence

    Energy Technology Data Exchange (ETDEWEB)

    Arnold, A.; Bombach, R.; Kaeppeli, B. [Paul Scherrer Inst. (PSI), Villigen (Switzerland)

    1997-06-01

    We have performed two-dimensional Laser Induced Fluorescence (2-D LIF) measurements of nitric oxide and hydroxyl radical distributions in an industrial burner at atmospheric pressure. The relative 2-D LIF data of NO were set to an absolute scale by calibration with probe sampling combined with gas analysis. (author) 3 figs., 7 refs.

  19. Curcumol suppresses RANKL-induced osteoclast formation by attenuating the JNK signaling pathway

    Energy Technology Data Exchange (ETDEWEB)

    Yu, Mingxiang, E-mail: yu.mingxiang@zs-hospital.sh.cn [Department of Endocrinology and Metabolism, Zhongshan Hospital, Fudan University, Shanghai (China); Chen, Xianying [Department of Endocrinology and Metabolism, Hainan Provincial Nong Ken Hospital, Hainan (China); Lv, Chaoyang [Department of Endocrinology and Metabolism, Zhongshan Hospital, Fudan University, Shanghai (China); Yi, Xilu [Department of Endocrinology and Metabolism, Shanghai Songjiang District Central Hospital, Shanghai (China); Zhang, Yao; Xue, Mengjuan; He, Shunmei [Department of Endocrinology and Metabolism, Zhongshan Hospital, Fudan University, Shanghai (China); Zhu, Guoying [Institute of Radiation Medicine, Fudan University, Shanghai (China); Wang, Hongfu, E-mail: hfwang@shmu.edu.cn [Institute of Radiation Medicine, Fudan University, Shanghai (China)

    2014-05-02

    Highlights: • Curcumol suppresses osteoclasts differentiation in vitro. • Curcumol impairs JNK/AP-1 signaling pathway. • Curcumol may be used for treating osteoclast related diseases. - Abstract: Osteoclasts, derived from hemopoietic progenitors of the monocyte/macrophage lineage, have a unique role in bone resorption, and are considered a potential therapeutic target in the treatment of such pathologic bone diseases as osteoporosis, rheumatoid arthritis, and periodontitis. In the present study, we demonstrate that curcumol, one of the major components of the essential oil of Rhizoma Curcumae, exhibits an inhibitory effect on receptor activator of nuclear factor kappaB ligand (RANKL)-induced osteoclast differentiation with both bone marrow-derived macrophages and RAW264.7 cells in a dose-dependent manner. In addition, RANKL-induced mRNA expression of osteoclast-specific genes, such as tartrate-resistant acid phosphatase, calcitonin receptor, and cathepsin K, is prominently reduced in the presence of curcumol. Furthermore, the molecular mechanism of action was investigated, and curcumol inhibited osteoclastogenesis by specifically impairing RANKL-induced c-Jun N-terminal kinase (JNK)/activator protein-1 (AP-1) signaling, which was further identified in rescue studies by means of anisomycin, a JNK signaling-specific activator. Taken together, these findings suggest that curcumol suppresses RANKL-induced osteoclast differentiation through the JNK/AP-1 signaling pathway, and may be useful as a therapeutic treatment for bone resorption-associated diseases.

  20. Formation of DNA adduct 8-hydroxy-2'-deoxyguanosine induced by man-made mineral fibres.

    Science.gov (United States)

    Leanderson, P; Söderkvist, P; Tagesson, C; Axelson, O

    1988-01-01

    Two man-made mineral fibres, rockwool and glasswool, were found to mediate hydroxylation of deoxyguanosine and calf thymus DNA to form the DNA adduct 8-hydroxy-2'-deoxyguanosine. The modification of the nucleoside is probably mediated by hydroxyl radicals and may play a role in fibre-induced carcinogenesis.

  1. Formation of laser induced periodic surface structures (LIPSS) on Ti upon double fs pulse exposure

    Science.gov (United States)

    Gemini, Laura; Hashida, Masaki; Nishii, Takaya; Miyasaka, Yasuhiro; Inoue, Shunsuke; Limpouch, Jiri; Mocek, Tomas; Sakabe, Shuji

    2015-03-01

    Recently a parametric decay model was proposed in order to foresee LIPSS interspaces, and experimental results are in reasonable agreement. To confirm the possibility assumed by the model of pre-formed plasma generation, Ti surface was irradiated by a femtosecond (fs) laser beam composed by double fs pulses, with a fixed delay of 160 fs. The fluence of the first pulse (FPP), responsible for surface plasma formation, was varied in the range 10-50 mJ cm-2 and always kept below the LIPSS formation threshold fluence (FLIPSS) of Ti for 50-single-shots exposure. The fluence of the delayed pulse (FLP), responsible for LIPSS formation, was varied in the range 60-150 mJ cm-2 and always kept above FLIPSS. Regardless the specific fluence FLP of the delayed pulse, the interspace of the grating structures increases with the increase of FPP, that is the increase of the surface plasma density. This tendency suggests that a variation of the surface plasma density, due to a variation of FPP, actually leads to a modification of the grating features, highlighting the driving role of the first pulse in LIPSS formation. Moreover, we observed that the LIPSS periodicities after double pulse exposures are in quite good agreement with data on LIPSS periodicities after single 160 fs pulse irradiations on Ti surface and with the curve predicted by the parametric decay model. This experimental result suggests that the preformed plasma might be produced in the rising edge of the temporal profile of the laser pulse.

  2. Surface nanostructure formation mechanism of 45 steel induced by supersonic fine particles pombarding

    Institute of Scientific and Technical Information of China (English)

    Dema Ba; Shining Ma; Changqing Li; Fanjun Meng

    2008-01-01

    By means of supersonic fine particles bombarding (SFPB), a nanostruetured surface layer up to 15 μm was fabricated on a 45 steel plate with ferrite and pearlite phases. To reveal the grain refinement mechanism of SFPB-treated 45 steel, microstructure features of various sections in the treated surface were systematically characterized by X-ray diffraction (XRD), scanning electron microscopy (SEM) and transmission electron microscopy (TEM). Grain size increases with an increase of depth from the treated surface. Plastic deformation and grain refinement processes are accompanied by an increase in strain. Plastic deformation in the proeuteetoid ferrite phases has precedence over the pearlite phases. Grain refinement in the ferrite phases involves: the onset of dis-location lines (Dls), dislocation tangles (DTs) and dense dislocation walls (DDWs) in the original grains; the formation of fine la-mellar and roughly equiaxed cells separated by DDWs; by dislocation annihilation and rearrangement, the transformation of DDWS into subboundaries and boundaries and the formation of submicron grains or subgrains; the successive subdivision of grains to finer and finer scale, resulting in the formation of highly misoriented nano-grains. By contrast, eutectoid cementite phase accommodated swain in a sequence as follows: onset of elongated, bended and shear deformation under deformation stress of ferrites, short and thin cementites with a width of about 20-50 nm and discontinuous length were formed. Shorter and thinner cementites were developed into ultra-fine pieces under the action of high density dislocation and strains. At the top surface, some cementites were decomposed under severe plastic deformation. Experimental evidences and analysis indicate that surface nanocrystallization of 45 steel results from dislocation activities, high swains and high strain rate are necessary for the formation of nanocrystallites.

  3. He cluster dynamics in W in the presence of cluster induced formation of He traps

    Science.gov (United States)

    Krasheninnikov, S. I.; Smirnov, R. D.

    2016-02-01

    The theoretical model describing spatiotemporal dynamics of He clusters in tungsten, which takes into account He trap generation associated with the growth of He clusters, is presented. Application of this model to the formation of the layer of nano-bubbles underneath of the surface of thick He irradiated sample, before surface morphology starts to change, gives very good agreement with currently available experimental data. The role of thermophoresis in a long-term evolution of nano-bubble containing structures is discussed.

  4. Paternal cyclophosphamide exposure induces the formation of functional micronuclei during the first zygotic division.

    Directory of Open Access Journals (Sweden)

    Lisanne Grenier

    Full Text Available Paternal exposures to cancer chemotherapeutics or environmental chemicals may have adverse effects on progeny outcome that are manifested in the preimplantation embryo. The objectives of this study were to determine the impact of paternal exposure to cyclophosphamide, an anticancer alkylating agent, on the formation, chromatin origin and function of micronuclei in cleavage stage rat embryos. Male Sprague-Dawley rats were gavaged with saline or cyclophosphamide (6 mg/kg/day for 4 weeks and mated to naturally cycling females to collect pronuclear zygotes and 2 to 8 cell embryos. Micronuclear chromatin structure was characterized using confocal microscopy to detect immunoreactivities for H3K9me3, a marker for maternal chromatin, and lamin B, a nuclear membrane marker. DNA synthesis was monitored using EdU (5-ethynyl-2'-deoxyuridine incorporation. Fertilization by cyclophosphamide-exposed spermatozoa led to a dramatic elevation in micronuclei in cleavage stage embryos (control embryos: 1% to 5%; embryos sired by treated males: 70%. The formation of micronuclei occurred during the first zygotic division and was associated with a subsequent developmental delay. The absence of H3K9me3 indicated that these micronuclei were of paternal origin. The micronuclei had incomplete peri-nuclear and peri-nucleolar lamin B1 membrane formation but incorporated EdU into DNA to the same extent as the main nucleus. The formation of micronuclei in response to the presence of a damaged paternal genome may play a role in increasing the rate of embryo loss that is associated with the use of assisted reproductive technologies, parenthood among cancer survivors, and paternal aging.

  5. Development of a prototype chest digital tomosynthesis (CDT) R/F system with fast image reconstruction using graphics processing unit (GPU) programming

    Science.gov (United States)

    Choi, Sunghoon; Lee, Seungwan; Lee, Haenghwa; Lee, Donghoon; Choi, Seungyeon; Shin, Jungwook; Seo, Chang-Woo; Kim, Hee-Joung

    2017-03-01

    Digital tomosynthesis offers the advantage of low radiation doses compared to conventional computed tomography (CT) by utilizing small numbers of projections ( 80) acquired over a limited angular range. It produces 3D volumetric data, although there are artifacts due to incomplete sampling. Based upon these characteristics, we developed a prototype digital tomosynthesis R/F system for applications in chest imaging. Our prototype chest digital tomosynthesis (CDT) R/F system contains an X-ray tube with high power R/F pulse generator, flat-panel detector, R/F table, electromechanical radiographic subsystems including a precise motor controller, and a reconstruction server. For image reconstruction, users select between analytic and iterative reconstruction methods. Our reconstructed images of Catphan700 and LUNGMAN phantoms clearly and rapidly described the internal structures of phantoms using graphics processing unit (GPU) programming. Contrast-to-noise ratio (CNR) values of the CTP682 module of Catphan700 were higher in images using a simultaneous algebraic reconstruction technique (SART) than in those using filtered back-projection (FBP) for all materials by factors of 2.60, 3.78, 5.50, 2.30, 3.70, and 2.52 for air, lung foam, low density polyethylene (LDPE), Delrin® (acetal homopolymer resin), bone 50% (hydroxyapatite), and Teflon, respectively. Total elapsed times for producing 3D volume were 2.92 s and 86.29 s on average for FBP and SART (20 iterations), respectively. The times required for reconstruction were clinically feasible. Moreover, the total radiation dose from our system (5.68 mGy) was lower than that of conventional chest CT scan. Consequently, our prototype tomosynthesis R/F system represents an important advance in digital tomosynthesis applications.

  6. Single step, pH induced gold nanoparticle chain formation in lecithin/water system.

    Science.gov (United States)

    Sharma, Damyanti

    2013-07-01

    Gold nanoparticle (AuNP) chains have been formed by a single step method in a lecithin/water system where lecithin itself plays the role of a reductant and a template for AuNP chain formation. Two preparative strategies were explored: (1) evaporating lecithin solution with aqueous gold chloride (HAuCl4) at different pHs and (2) dispersing lecithin vesicles in aqueous HAuCl4 solutions of various pHs in the range of 2.5-11.3. In method 1, at initial pH 2.5, 20-50 nm AuNPs are found attached to lecithin vesicles. When pH is raised to 5.5 there are no vesicles present and 20 nm monodisperse particles are found aggregating. Chain formation of fine nanoparticles (3-5 nm) is observed from neutral to basic pH, between 6.5-10.3 The chains formed are hundreds of nanometers to micrometer long and are usually 2-3 nanoparticles wide. On further increasing pH to 11.3, particles form disk-like or raft-like structures. When method (ii) was used a little chain formation was observed. Most of the nanoparticles formed were found either sitting together as raft like structures or scattered on lecithin structures.

  7. Rhodolith formation induced by reef erosion in the Red Sea, Egypt

    Science.gov (United States)

    Piller, W. E.; Rasser, M.

    1996-09-01

    Along the northwestern margin of Safaga Island (Northern Bay of Safaga, Red Sea, Egypt) a small fringing reef (several hundred meters long, up to 2 m high) and small patch reefs are developed due to the local current regime which is favorable for coral growth. Corals and reef rock are encrusted by coralline algae, predominantly by branched Lithophyllum kotschyanum. Owing to destructional processes dominated by sea urchin activities, fragmentation of (1) corals, (2) reef rock, and (3) coralline algae takes place resulting in the formation of almost mono-specific, branched Lithophyllum kotschyanum rhodoliths. Rhodolith formation takes place in various reef environments: (1) in depressions on the reef flat where ellipsoidal rhodoliths develop, with interlocking and fusing branches leading to a coralline algal framework; (2) in discharge channels where smaller elongated rhodoliths occur; (3) in leeward positions between reef flat and seagrass meadows, where a dense belt of spheroidal to ellipsoidal rhodoliths is formed; scattered rhodoliths occur in adjacent seagrass beds. The formation and preservation of rhodoliths requires a complex interplay of destruction, growth, transportation, movement, and stabilization.

  8. Salt stress induces the formation of a novel type of 'pressure wood' in two Populus species.

    Science.gov (United States)

    Janz, Dennis; Lautner, Silke; Wildhagen, Henning; Behnke, Katja; Schnitzler, Jörg-Peter; Rennenberg, Heinz; Fromm, Jörg; Polle, Andrea

    2012-04-01

    • Salinity causes osmotic stress and limits biomass production of plants. The goal of this study was to investigate mechanisms underlying hydraulic adaptation to salinity. • Anatomical, ecophysiological and transcriptional responses to salinity were investigated in the xylem of a salt-sensitive (Populus × canescens) and a salt-tolerant species (Populus euphratica). • Moderate salt stress, which suppressed but did not abolish photosynthesis and radial growth in P. × canescens, resulted in hydraulic adaptation by increased vessel frequencies and decreased vessel lumina. Transcript abundances of a suite of genes (FLA, COB-like, BAM, XET, etc.) previously shown to be activated during tension wood formation, were collectively suppressed in developing xylem, whereas those for stress and defense-related genes increased. A subset of cell wall-related genes was also suppressed in salt-exposed P. euphratica, although this species largely excluded sodium and showed no anatomical alterations. Salt exposure influenced cell wall composition involving increases in the lignin : carbohydrate ratio in both species. • In conclusion, hydraulic stress adaptation involves cell wall modifications reciprocal to tension wood formation that result in the formation of a novel type of reaction wood in upright stems named 'pressure wood'. Our data suggest that transcriptional co-regulation of a core set of genes determines reaction wood composition.

  9. Effect of VPAC1 Blockade on Adipose Tissue Formation and Composition in Mouse Models of Nutritionally Induced Obesity

    Directory of Open Access Journals (Sweden)

    H. Roger Lijnen

    2010-01-01

    Full Text Available Background. The pituitary adenylate cyclase activating polypeptide (PACAP may affect adipogenesis and adipose tissue formation through interaction with its G-protein-coupled receptor VPAC1. Methods. We have used a monoclonal antibody (MAb 23A11 blocking VPAC1 in mouse models of nutritionally induced obesity. Results. Administration of MAb 23A11 (25 mg/kg body weight i.p. twice weekly to 5-week old male C57Bl/6 mice kept on a high-fat diet for 15 weeks had no significant effect on weight gain, nor on subcutaneous (SC or gonadal (GON adipose tissue mass, as compared to the control MAb 1C8. However, adipocyte hypertrophy was observed in SC adipose tissue of MAb 23A11 treated mice. In a second study, 24 weeks old obese mice were treated for 5 weeks with MAb 23A11, without effect on body weight or fat mass, as compared to treatment with MAb 1C8. In addition, MAb 23A11 had no significant effect on glucose tolerance or insulin resistance in lean or obese C57Bl/6 mice. Conclusion. Blocking VPAC1 does not significantly affect adipose tissue formation in mouse models of diet-induced obesity, although it may be associated with mild adipocyte hypertrophy.

  10. Impacts of thermal circulations induced by urbanization on ozone formation in the Pearl River Delta region, China

    Science.gov (United States)

    Li, Mengmeng; Song, Yu; Mao, Zhichun; Liu, Mingxu; Huang, Xin

    2016-02-01

    Thermal circulations induced by urbanization could exert important effects on regional ozone (O3) formation through regulating the chemical transformations and transport of O3 and its precursors. In this study, the Weather Research and Forecasting/Chemistry (WRF/Chem) model combined with remote sensing are used to investigate the impacts of urbanization-induced circulations on O3 formation in the Pearl River Delta (PRD) region, China. The urban heat island (UHI) effect in PRD significantly enhances turbulent mixing and modifies local circulations, i.e., initiates the UHI circulation and strengthens the sea breeze, which in turn cause a detectable decrease of daytime O3 concentration (-1.3 ppb) and an increase of O3 (+5.2 ppb) around the nocturnal rush-hours. The suppressed O3 titration destruction due to NOx dilution into the deeper urban boundary layer (200-400 m) is the main reason for elevated nocturnal O3 levels. In the daytime, however, the upward transport of O3 precursors weakens near-surface O3 photochemical production and conversely enhances upper-level O3 generation. Furthermore, the surface UHI convergence flow and intensified sea breeze act to effectively trap O3 at the suburban and coastal regions.

  11. In vitro platelet activation, aggregation and platelet-granulocyte complex formation induced by surface modified single-walled carbon nanotubes.

    Science.gov (United States)

    Fent, János; Bihari, Péter; Vippola, Minnamari; Sarlin, Essi; Lakatos, Susan

    2015-08-01

    Surface modification of single-walled carbon nanotubes (SWCNTs) such as carboxylation, amidation, hydroxylation and pegylation is used to reduce the nanotube toxicity and render them more suitable for biomedical applications than their pristine counterparts. Toxicity can be manifested in platelet activation as it has been shown for SWCNTs. However, the effect of various surface modifications on the platelet activating potential of SWCNTs has not been tested yet. In vitro platelet activation (CD62P) as well as the platelet-granulocyte complex formation (CD15/CD41 double positivity) in human whole blood were measured by flow cytometry in the presence of 0.1mg/ml of pristine or various surface modified SWCNTs. The effect of various SWCNTs was tested by whole blood impedance aggregometry, too. All tested SWCNTs but the hydroxylated ones activate platelets and promote platelet-granulocyte complex formation in vitro. Carboxylated, pegylated and pristine SWCNTs induce whole blood aggregation as well. Although pegylation is preferred from biomedical point of view, among the samples tested by us pegylated SWCNTs induced far the most prominent activation and a well detectable aggregation of platelets in whole blood.

  12. Ceramide formation is involved in Lactobacillus acidophilus-induced IFN-beta response in dendritic cells

    DEFF Research Database (Denmark)

    Fuglsang, Eva; Henningsen, Louise; Frøkiær, Hanne

    of sphingomyelin to ceramide by acid sphingomyelinase (ASMase) at the outer leaflet of the PM is a key event in endocytosis of gram-positive Lactobacillus acidophilus (L. acidophilus) and the subsequent induction of IFN-beta in DCs and, as the gram-negative Escherichia coli (E. coli) does not induce appreciable...... amounts of IFN-beta, the ASMase activity would affect endocytosis and the ensuing cytokine response of L. acidophilus and E. coli differently. SMase or an inhibitor of ASMase and acid ceramidase, chlorpromazine (CPZ), was added to DCs prior to stimulation with either of the bacteria. Endocytosis...... of fluorescent bacteria +/- FITC-dextran was measured by flow cytometry and gene expression and cytokine response of IFN-beta and IL-12 was measured by qPCR and ELISA, respectively. Addition of SMase increased the uptake of L. acidophilus and L. acidophilus-induced IL-12/IFN-beta but showed no effect...

  13. Kinetics of microstructure formation of high-pressure induced gel from a whey protein isolate

    Energy Technology Data Exchange (ETDEWEB)

    He Jinsong; Yang Hongwei; Zhu Wanpeng [Department of Environmental Science and Engineering, Tsinghua University, Beijing 100084 (China); Mu Taihua, E-mail: mutaihuacaas@126.co [Institute of Agro-Food Science and Technology, Chinese Academy of Agricultural Sciences, Beijing 100094 (China)

    2010-03-01

    The kinetic process of pressure-induced gelation of whey protein isolate (WPI) solutions was studied using in situ light scattering. The relationship of the logarithm of scattered light intensity (I) versus time (t) was linear after the induced time and could be described by the Cahn-Hilliard linear theory. With increasing time, the scattered intensity deviated from the exponential relationship, and the time evolution of the scattered light intensity maximum I{sub m} and the corresponding wavenumber q{sub m} could be described in terms of the power-law relationship as I{sub m}{approx}f{sup {beta}} and q{sub m}{approx}f{sup -}{alpha}, respectively. These results indicated that phase separation occurred during the gelation of WPI solutions under high pressure.

  14. Axonal lesion-induced microglial proliferation and microglial cluster formation in the mouse

    DEFF Research Database (Denmark)

    Dissing-Olesen, L; Ladeby, R; Nielsen, Helle Hvilsted;

    2007-01-01

    Microglia are innate immune cells and form the first line of defense of the CNS. Proliferation is a key event in the activation of microglia in acute pathology, and has been extensively characterized in rats, but not in mice. In this study we investigated axonal-lesion-induced microglial...... proliferation and surface antigen expression in C57BL/6 mice. Transection of the entorhino-dentate perforant path projection results in an anterograde axonal and a dense terminal degeneration that induces a region-specific activation of microglia in the dentate gyrus. Time-course analysis showed activation...... and the proliferation marker bromodeoxyuridine, injected 1 h prior to perfusion, showed that lesion-reactive microglia accounted for the vast majority of proliferating cells. Microglia proliferated as soon as 24 h after lesion and 25% of all microglial cells were proliferating 3 days post-lesion. Immunofluorescence...

  15. Kinetics of microstructure formation of high-pressure induced gel from a whey protein isolate

    Science.gov (United States)

    He, Jin-Song; Yang, Hongwei; Zhu, Wanpeng; Mu, Tai-Hua

    2010-03-01

    The kinetic process of pressure-induced gelation of whey protein isolate (WPI) solutions was studied using in situ light scattering. The relationship of the logarithm of scattered light intensity (I) versus time (t) was linear after the induced time and could be described by the Cahn-Hilliard linear theory. With increasing time, the scattered intensity deviated from the exponential relationship, and the time evolution of the scattered light intensity maximum Im and the corresponding wavenumber qm could be described in terms of the power-law relationship as Im~fβ and qm~f-α, respectively. These results indicated that phase separation occurred during the gelation of WPI solutions under high pressure.

  16. Arsenic-induced micronuclei formation in mammalian cells and its counteraction by tea.

    Science.gov (United States)

    Sinha, Dona; Roy, Madhumita; Siddiqi, Maqsood; Bhattacharya, Rathin K

    2005-01-01

    The Gangetic plain of West Bengal, India, has been engulfed by a disastrous environmental calamity of arsenic contamination of the ground water. Chronic arsenic toxicity caused by drinking arsenic-contaminated water has been one of the worst health hazards gradually affecting nine districts of West Bengal since the early 1980s. Over and above hyperpigmentation and keratosis,weakness, burning sensation of the eyes, swelling of the legs, liver fibrosis, chronic lung disease, gangrene of the toes, neuropathy, and skin cancer are other manifestations. Induction of cancer is frequently associated with DNA damage, changes in ploidy of cells, and non-random chromosome aberrations. Counteraction of these genotoxic and cytogenetic abnormalities with natural dietary polyphenols could be a useful strategy to combat arsenic-induced DNA damage and thereby cancer. A review of the literature showed that it is the antioxidant property of tea polyphenols that affords protection against various types of cancer. The present study was conducted to investigate whether the extracts of green tea and black tea (Darjeeling and Assam) as well as their polyphenols could ameliorate this arsenic-induced genotoxicity. The normal mammalian cell culture derived from male Chinese hamster lung fibroblast cells (V79) was used as the test system to assess the genotoxicity by micronucleus assay. The results showed that both green tea and black tea extracts have equal potential in modulating the arsenic-induced genotoxicity. This effect was perhaps induced by the constituent polyphenols present in green and black tea. In addition, the repair activity of the damaged cells was enhanced when treated with these tea extracts and their polyphenols. Thus, tea and its polyphenols may have a promising role in counteracting the devastating effects of arsenic.

  17. Anhydride-functional silane immobilized onto titanium surfaces induces osteoblast cell differentiation and reduces bacterial adhesion and biofilm formation

    Energy Technology Data Exchange (ETDEWEB)

    Godoy-Gallardo, Maria, E-mail: maria.godoy.gallardo@upc.edu [Biomaterials, Biomechanics and Tissue Engineering Group, Department of Materials Science and Metallurgy, Technical University of Catalonia (UPC), ETSEIB, Av. Diagonal 647, 08028 Barcelona (Spain); Centre for Research in NanoEngineering (CRNE) — UPC, C/ Pascual i Vila 15, 08028 Barcelona (Spain); Guillem-Marti, Jordi, E-mail: jordi.guillem.marti@upc.edu [Biomaterials, Biomechanics and Tissue Engineering Group, Department of Materials Science and Metallurgy, Technical University of Catalonia (UPC), ETSEIB, Av. Diagonal 647, 08028 Barcelona (Spain); Centre for Research in NanoEngineering (CRNE) — UPC, C/ Pascual i Vila 15, 08028 Barcelona (Spain); Sevilla, Pablo, E-mail: psevilla@euss.es [Department of Mechanics, Escola Universitària Salesiana de Sarrià (EUSS), C/ Passeig de Sant Bosco, 42, 08017 Barcelona (Spain); Manero, José M., E-mail: jose.maria.manero@upc.edu [Biomaterials, Biomechanics and Tissue Engineering Group, Department of Materials Science and Metallurgy, Technical University of Catalonia (UPC), ETSEIB, Av. Diagonal 647, 08028 Barcelona (Spain); Centre for Research in NanoEngineering (CRNE) — UPC, C/ Pascual i Vila 15, 08028 Barcelona (Spain); Gil, Francisco J., E-mail: francesc.xavier.gil@upc.edu [Biomaterials, Biomechanics and Tissue Engineering Group, Department of Materials Science and Metallurgy, Technical University of Catalonia (UPC), ETSEIB, Av. Diagonal 647, 08028 Barcelona (Spain); Centre for Research in NanoEngineering (CRNE) — UPC, C/ Pascual i Vila 15, 08028 Barcelona (Spain); and others

    2016-02-01

    Bacterial infection in dental implants along with osseointegration failure usually leads to loss of the device. Bioactive molecules with antibacterial properties can be attached to titanium surfaces with anchoring molecules such as silanes, preventing biofilm formation and improving osseointegration. Properties of silanes as molecular binders have been thoroughly studied, but research on the biological effects of these coatings is scarce. The aim of the present study was to determine the in vitro cell response and antibacterial effects of triethoxysilypropyl succinic anhydride (TESPSA) silane anchored on titanium surfaces. X-ray photoelectron spectroscopy confirmed a successful silanization. The silanized surfaces showed no cytotoxic effects. Gene expression analyses of Sarcoma Osteogenic (SaOS-2) osteoblast-like cells cultured on TESPSA silanized surfaces reported a remarkable increase of biochemical markers related to induction of osteoblastic cell differentiation. A manifest decrease of bacterial adhesion and biofilm formation at early stages was observed on treated substrates, while favoring cell adhesion and spreading in bacteria–cell co-cultures. Surfaces treated with TESPSA could enhance a biological sealing on implant surfaces against bacteria colonization of underlying tissues. Furthermore, it can be an effective anchoring platform of biomolecules on titanium surfaces with improved osteoblastic differentiation and antibacterial properties. - Highlights: • TESPSA silane induces osteoblast differentiation. • TESPSA reduces bacterial adhesion and biofilm formation. • TESPSA is a promising anchoring platform of biomolecules onto titanium.

  18. Amelioration of cold injury-induced cortical brain edema formation by selective endothelin ETB receptor antagonists in mice.

    Directory of Open Access Journals (Sweden)

    Shotaro Michinaga

    Full Text Available Brain edema is a potentially fatal pathological condition that often occurs in stroke and head trauma. Following brain insults, endothelins (ETs are increased and promote several pathophysiological responses. This study examined the effects of ETB antagonists on brain edema formation and disruption of the blood-brain barrier in a mouse cold injury model (Five- to six-week-old male ddY mice. Cold injury increased the water content of the injured cerebrum, and promoted extravasation of both Evans blue and endogenous albumin. In the injury area, expression of prepro-ET-1 mRNA and ET-1 peptide increased. Intracerebroventricular (ICV administration of BQ788 (ETB antagonist, IRL-2500 (ETB antagonist, or FR139317 (ETA antagonist prior to cold injury significantly attenuated the increase in brain water content. Bolus administration of BQ788, IRL-2500, or FR139317 also inhibited the cold injury-induced extravasation of Evans blue and albumin. Repeated administration of BQ788 and IRL-2500 beginning at 24 h after cold injury attenuated both the increase in brain water content and extravasation of markers. In contrast, FR139317 had no effect on edema formation when administrated after cold injury. Cold injury stimulated induction of glial fibrillary acidic protein-positive reactive astrocytes in the injured cerebrum. Induction of reactive astrocytes after cold injury was attenuated by ICV administration of BQ788 or IRL-2500. These results suggest that ETB receptor antagonists may be an effective approach to ameliorate brain edema formation following brain insults.

  19. Pathogen-induced conditioning of the primary xylem vessels - a prerequisite for the formation of bacterial emboli by Pectobacterium atrosepticum.

    Science.gov (United States)

    Gorshkov, V Y; Daminova, A G; Mikshina, P V; Petrova, O E; Ageeva, M V; Salnikov, V V; Gorshkova, T A; Gogolev, Y V

    2016-07-01

    Representatives of Pectobacterium genus are some of the most harmful phytopathogens in the world. In the present study, we have elucidated novel aspects of plant-Pectobacterium atrosepticum interactions. This bacterium was recently demonstrated to form specific 'multicellular' structures - bacterial emboli in the xylem vessels of infected plants. In our work, we showed that the process of formation of these structures includes the pathogen-induced reactions of the plant. The colonisation of the plant by P. atrosepticum is coupled with the release of a pectic polysaccharide, rhamnogalacturonan I, into the vessel lumen from the plant cell wall. This polysaccharide gives rise to a gel that serves as a matrix for bacterial emboli. P. atrosepticum-caused infection involves an increase of reactive oxygen species (ROS) levels in the vessels, creating the conditions for the scission of polysaccharides and modification of plant cell wall composition. Both the release of rhamnogalacturonan I and the increase in ROS precede colonisation of the vessels by bacteria and occur only in the primary xylem vessels, the same as the subsequent formation of bacterial emboli. Since the appearance of rhamnogalacturonan I and increase in ROS levels do not hamper the bacterial cells and form a basis for the assembly of bacterial emboli, these reactions may be regarded as part of the susceptible response of the plant. Bacterial emboli thus represent the products of host-pathogen integration, since the formation of these structures requires the action of both partners.

  20. Salt-induced vesicle formation from single anionic surfactant SDBS and its mixture with LSB in aqueous solution.

    Science.gov (United States)

    Zhai, Limin; Zhao, Mei; Sun, Dejun; Hao, Jingcheng; Zhang, Lungjun

    2005-03-31

    Vesicles can be formed spontaneously in aqueous solution of a single anionic surfactant sodium dodecyl benzenesulfonate (SDBS) just under the inducement of salt, which makes the formation of vesicle much easier and simpler. The existence of vesicles was demonstrated by TEM image using the negative-staining method. The mechanism of the formation may be attributed to the compression of salt on the electric bilayer of the surfactant headgroups, which alters the packing parameter of the surfactant. The addition of the zwitterionic surfactant lauryl sulfonate betaine (LSB) makes the vesicles more stable, expands the range of formation and vesicle size, and reduces the polydispersity of the vesicles. The vesicle region was presented in a pseudoternary diagram of SDBS/LSB/brine. The variations of vesicle size with the salinity and mixing ratios, as well as the surfactant concentration, were determined using the dynamic light scattering method. It is found that the vesicle size is independent of the surfactant concentration but subject to the salinity and the mixing ratio of the two surfactants.

  1. Matrix metalloproteinases regulate the formation of dendritic spine head protrusions during chemically induced long-term potentiation.

    Directory of Open Access Journals (Sweden)

    Zsuzsanna Szepesi

    Full Text Available Dendritic spines are are small membranous protrusions that extend from neuronal dendrites and harbor the majority of excitatory synapses. Increasing evidence has shown that matrix metalloproteinases (MMPs, a family of extracellularly acting and Zn(2+-dependent endopeptidases, are able to rapidly modulate dendritic spine morphology. Spine head protrusions (SHPs are filopodia-like processes that extend from the dendritic spine head, representing a form of postsynaptic structural remodeling in response to altered neuronal activity. Herein, we show that chemically induced long-term potentiation (cLTP in dissociated hippocampal cultures upregulates MMP-9 activity that controls the formation of SHPs. Blocking of MMPs activity or microtubule dynamics abolishes the emergence of SHPs. In addition, autoactive recombinant MMP-9, promotes the formation of SHPs in organotypic hippocampal slices. Furthermore, spines with SHPs gained postsynaptic α-amino-3-hydroxyl-5-methyl-4-isoxazole propionic acid (AMPA receptors upon cLTP and the synaptic delivery of AMPA receptors was controlled by MMPs. The present results strongly imply that MMP-9 is functionally involved in the formation of SHPs and the control of postsynaptic receptor distribution upon cLTP.

  2. Red mud (RM)-Induced enhancement of iron plaque formation reduces arsenic and metal accumulation in two wetland plant species.

    Science.gov (United States)

    Yang, J X; Guo, Q J; Yang, J; Zhou, X Y; Ren, H Y; Zhang, H Z; Xu, R X; Wang, X D; Peters, M; Zhu, G X; Wei, R F; Tian, L Y; Han, X K

    2016-01-01

    Human activities have resulted in arsenic (As) and heavy metals accumulation in paddy soils in China. Phytoremediation has been suggested as an effective and low-cost method to clean up contaminated soils. A combined soil-sand pot experiment was conducted to investigate the influence of red mud (RM) supply on iron plaque formation and As and heavy metal accumulation in two wetland plant species (Cyperus alternifolius Rottb., Echinodorus amazonicus Rataj), using As and heavy metals polluted paddy soil combined with three rates of RM application (0, 2%, 5%). The results showed that RM supply significantly decreased As and heavy metals accumulation in shoots of the two plants due to the decrease of As and heavy metal availability and the enhancement of the formation of iron plaque on the root surface and in the rhizosphere. Both wetland plants supplied with RM tended to have more Fe plaque, higher As and heavy metals on roots and in their rhizospheres, and were more tolerant of As and heavy metal toxicity. The results suggest that RM-induced enhancement of the formation of iron plaque on the root surface and in the rhizosphere of wetland plants may be significant for remediation of soils contaminated with As and heavy metals.

  3. ATP Is Required and Advances Cytokine-Induced Gap Junction Formation in Microglia In Vitro

    Directory of Open Access Journals (Sweden)

    Pablo J. Sáez

    2013-01-01

    Full Text Available Microglia are the immune cells in the central nervous system. After injury microglia release bioactive molecules, including cytokines and ATP, which modify the functional state of hemichannels (HCs and gap junction channels (GJCs, affecting the intercellular communication via extracellular and intracellular compartments, respectively. Here, we studied the role of extracellular ATP and several cytokines as modulators of the functional state of microglial HCs and GJCs using dye uptake and dye coupling techniques, respectively. In microglia and the microglia cell line EOC20, ATP advanced the TNF-α/IFN-γ-induced dye coupling, probably through the induction of IL-1β release. Moreover, TNF-α/IFN-γ, but not TNF-α plus ATP, increased dye uptake in EOC20 cells. Blockade of Cx43 and Panx1 HCs prevented dye coupling induced by TNF-α/IFN-γ, but not TNF-α plus ATP. In addition, IL-6 prevented the induction of dye coupling and HC activity induced by TNF-α/IFN-γ in EOC20 cells. Our data support the notion that extracellular ATP affects the cellular communication between microglia through autocrine and paracrine mechanisms, which might affect the timing of immune response under neuroinflammatory conditions.

  4. Increase in norepinephrine-induced formation of phosphatidic acid in rat vas deferens after denervation.

    Science.gov (United States)

    Takenawa, T; Masaki, T; Goto, K

    1983-01-01

    Surgical denervation of rat vas deferens causes supersensitivity in that the tissue sensitivity and the maximum response to a variety of agonists increase. To understand the molecular mechanism of supersensitivity in smooth muscle, norepinephrine(NE)-induced alteration in phospholipid metabolism was studied using control and denervated vasa deferentia. When the tissue was stimulated by NE, only [32P]Pi incorporation into phosphatidic acid(PA) was increased in proportion to the increase in NE concentration without any significant effect on that into other phospholipids. This PA labeling was significantly accelerated by denervation. In the denervated tissue, PA labeling was stimulated by lower concentrations of NE and the maximum response to NE was increased compared to the control. The breakdown of phosphatidylinositol 4-monophosphate(DPI) and phosphatidylinositol 4,5-diphosphate (TPI) was also accelerated by NE. But the influence of denervation on this NE-induced DPI and TPI was not marked. Therefore, it is likely that denervation clearly enhanced NE-induced PA labeling without an appreciable effect on that of the other phospholipids. Furthermore, the absolute amount of PA was also increased by NE, and this increase was exaggerated by denervation. Considering that PA can behave as a Ca2+ ionophore in the plasma membrane, these results suggest that the stimulated accumulation of PA plays an important role in receptor-linked supersensitivity in smooth muscle.

  5. Novel Peptide for Attenuation of Hyperoxia-induced Disruption of Lung Endothelial Barrier and Pulmonary Edema via Modulating Peroxynitrite Formation*

    Science.gov (United States)

    Kondrikov, Dmitry; Gross, Christine; Black, Stephen M.; Su, Yunchao

    2014-01-01

    Pulmonary damages of oxygen toxicity include vascular leakage and pulmonary edema. We have previously reported that hyperoxia increases the formation of NO and peroxynitrite in lung endothelial cells via increased interaction of endothelial nitric oxide (eNOS) with β-actin. A peptide (P326TAT) with amino acid sequence corresponding to the actin binding region of eNOS residues 326–333 has been shown to reduce the hyperoxia-induced formation of NO and peroxynitrite in lung endothelial cells. In the present study, we found that exposure of pulmonary artery endothelial cells to hyperoxia (95% oxygen and 5% CO2) for 48 h resulted in disruption of monolayer barrier integrity in two phases, and apoptosis occurred in the second phase. NOS inhibitor NG-nitro-l-arginine methyl ester attenuated the endothelial barrier disruption in both phases. Peroxynitrite scavenger uric acid did not affect the first phase but ameliorated the second phase of endothelial barrier disruption and apoptosis. P326TAT inhibited hyperoxia-induced disruption of monolayer barrier integrity in two phases and apoptosis in the second phase. More importantly, injection of P326TAT attenuated vascular leakage, pulmonary edema, and endothelial apoptosis in the lungs of mice exposed to hyperoxia. P326TAT also significantly reduced the increase in eNOS-β-actin association and protein tyrosine nitration. Together, these results indicate that peptide P326TAT ameliorates barrier dysfunction of hyperoxic lung endothelial monolayer and attenuates eNOS-β-actin association, peroxynitrite formation, endothelial apoptosis, and pulmonary edema in lungs of hyperoxic mice. P326TAT can be a novel therapeutic agent to treat or prevent acute lung injury in oxygen toxicity. PMID:25315770

  6. Knockout of the 15 kDa selenoprotein protects against chemically-induced aberrant crypt formation in mice.

    Directory of Open Access Journals (Sweden)

    Petra A Tsuji

    Full Text Available Evidence suggests that selenium has cancer preventive properties that are largely mediated through selenoproteins. Our previous observations demonstrated that targeted down-regulation of the 15 kDa selenoprotein (Sep15 in murine colon cancer cells resulted in the reversal of the cancer phenotype. The present study investigated the effect of Sep15 knockout in mice using a chemically-induced colon cancer model. Homozygous Sep15 knockout mice, and wild type littermate controls were given four weekly subcutaneous injections of azoxymethane (10 mg/kg. Sep15 knockout mice developed significantly (p<0.001 fewer aberrant crypt foci than controls demonstrating that loss of Sep15 protects against aberrant crypt foci formation. Dietary selenium above adequate levels did not significantly affect aberrant crypt foci formation in Sep15 knockout mice. To investigate molecular targets affected by loss of Sep15, gene expression patterns in colonic mucosal cells of knockout and wild type mice were examined using microarray analysis. Subsequent analyses verified that guanylate binding protein-1 (GBP-1 mRNA and protein expression were strongly upregulated in Sep15 knockout mice. GBP-1, which is expressed in response to interferon-γ, is considered to be an activation marker during inflammatory diseases, and up-regulation of GBP-1 in humans has been associated with a highly significant, increased five-year survival rate in colorectal cancer patients. In agreement with these studies, we observed a higher level of interferon-γ in plasma of Sep15 knockout mice. Overall, our results demonstrate for the first time, that Sep15 knockout mice are protected against chemically-induced aberrant crypt foci formation and that Sep15 appears to have oncogenic properties in colon carcinogenesis in vivo.

  7. Plant stanols induce intestinal tumor formation by up-regulating Wnt and EGFR signaling in Apc Min mice.

    Science.gov (United States)

    Marttinen, Maija; Päivärinta, Essi; Storvik, Markus; Huikko, Laura; Luoma-Halkola, Heli; Piironen, Vieno; Pajari, Anne-Maria; Mutanen, Marja

    2013-01-01

    The rate of APC mutations in the intestine increases in middle-age. At the same period of life, plant sterol and stanol enriched functional foods are introduced to diet to lower blood cholesterol. This study examined the effect of plant stanol enriched diet on intestinal adenoma formation in the Apc(Min) mouse. Apc(Min) mice were fed 0.8% plant stanol diet or control diet for nine weeks. Cholesterol, plant sterols and plant stanols were analyzed from the caecum content and the intestinal mucosa. Levels of β-catenin, cyclin D1, epidermal growth factor receptor (EGFR) and extracellular signal-regulated kinase 1/2 (ERK1/2) were measured from the intestinal mucosa by Western blotting. Gene expression was determined from the intestinal mucosa using Affymetrix and the data were analyzed for enriched categories and pathways. Plant stanols induced adenoma formation in the small intestine, however, the adenoma size was not affected. We saw increased levels of nuclear β-catenin, phosphorylated β-catenin (Ser675 and Ser552), nuclear cyclin D1, total and phosphorylated EGFR and phosphorylated ERK1/2 in the intestinal mucosa after plant stanol feeding. The Affymetrix data demonstrate that several enzymes of cholesterol synthesis pathway were up-regulated, although the cholesterol level in the intestinal mucosa was not altered. We show that plant stanols induce adenoma formation by activating Wnt and EGFR signaling. EGFR signaling seems to have promoted β-catenin phosphorylation and its translocation into the nucleus, where the expression of cyclin D1 was increased. Up-regulated cholesterol synthesis may partly explain the increased EGFR signaling in the plant stanol-fed mice.

  8. Titanium dioxide nanoparticles induce oxidative stress and DNA-adduct formation but not DNA-breakage in human lung cells

    Directory of Open Access Journals (Sweden)

    Schins Roel PF

    2009-06-01

    Full Text Available Abstract Titanium dioxide (TiO2, also known as titanium (IV oxide or anatase, is the naturally occurring oxide of titanium. It is also one of the most commercially used form. To date, no parameter has been set for the average ambient air concentration of TiO2 nanoparticles (NP by any regulatory agency. Previously conducted studies had established these nanoparticles to be mainly non-cyto- and -genotoxic, although they had been found to generate free radicals both acellularly (specially through photocatalytic activity and intracellularly. The present study determines the role of TiO2-NP (anatase, ∅ in vitro. For comparison, iron containing nanoparticles (hematite, Fe2O3, ∅ 2-NP did not induce DNA-breakage measured by the Comet-assay in both cell types. Generation of reactive oxygen species (ROS was measured acellularly (without any photocatalytic activity as well as intracellularly for both types of particles, however, the iron-containing NP needed special reducing conditions before pronounced radical generation. A high level of DNA adduct formation (8-OHdG was observed in IMR-90 cells exposed to TiO2-NP, but not in cells exposed to hematite NP. Our study demonstrates different modes of action for TiO2- and Fe2O3-NP. Whereas TiO2-NP were able to generate elevated amounts of free radicals, which induced indirect genotoxicity mainly by DNA-adduct formation, Fe2O3-NP were clastogenic (induction of DNA-breakage and required reducing conditions for radical formation.

  9. Effect of treatment with phenobarbital and stiripentol on carbamazepine-induced teratogenicity and reactive metabolite formation.

    Science.gov (United States)

    Finnell, R H; Bennett, G D; Slattery, J T; Amore, B M; Bajpai, M; Levy, R H

    1995-12-01

    A model using SWV mice was developed to investigate the mechanistic basis of carbamazepine (CBZ)-related fetotoxicity. Drug administration was initiated prior to conception and continued until day 18 of gestation. The incidence of malformation was 33% following CBZ exposure (1,500 mg/kg/day), compared with a 5% incidence in pair-fed control animals (P stiripentol (STP; a cytochrome P-450 inhibitor) (300 mg/kg/day) decreased the incidence of malformations produced by CBZ (1,500 mg/kg/day) from 33% to 16.7% (P < 0.05). The effect of PB administration on the binding of 14C in maternal and fetal tissue was assessed in dams that received CBZ (1,000 mg/kg/day) with or without PB (45 mg/kg/day) or STP (300 mg/kg/day) chronically and a single i.p. dose of 14C-CBZ on day 12 of gestation. In all instances, binding was greatest in maternal liver, then in the placenta, fetal head and body, and maternal thigh muscle. In all tissues, PB caused a two-to threefold increase in binding, compared with binding in mice exposed to CBZ alone. STP administration decreased protein adduct formation only in maternal liver. The binding of 14C was also assessed in hepatic microsomes prepared from female mice exposed to CBZ and PB or STP as in the in vivo study of 14C binding. The extent of irreversible binding was 67% greater in microsomes prepared from mice pretreated with PB and CBZ than with CBZ alone, while STP resulted in only 21% inhibition of 14C adduct formation (P < 0.05). The results are consistent with the formation of a chemically reactive teratogenic metabolite of CBZ in mice by cytochrome(s) P-450.

  10. Induced sclerotium formation exposes new bioactive metabolites from Aspergillus sclerotiicarbonarius

    DEFF Research Database (Denmark)

    Petersen, Lene Maj; Frisvad, Jens Christian; Knudsen, Peter Boldsen

    2015-01-01

    Sclerotia are known to be fungal survival structures, and induction of sclerotia may prompt production of otherwise undiscovered metabolites. Aspergillus sclerotiicarbonarius (IBT 28362) was investigated under sclerotium producing conditions, which revealed a highly altered metabolic profile. Four...... new compounds were isolated from cultivation under sclerotium formation conditions and their structures elucidated using different analytical techniques (HRMS, UV, 1D and 2D NMR). This included sclerolizine, an alkylated and oxidized pyrrolizine, the new emindole analog emindole SC and two new....... These results demonstrate induction of sclerotia as an alternative way of triggering otherwise silent biosynthetic pathways in filamentous fungi for the discovery of novel bioactive secondary metabolites....

  11. Modelling the formation of nanostructures on metal surface induced by femtosecond laser ablation

    Energy Technology Data Exchange (ETDEWEB)

    Djouder, M. [Laboratoire de Physique et Chimie Quantique, Universite Mouloud Mammeri de Tizi-ouzou, BP 17 RP, 15000 Tizi-Ouzou (Algeria); Itina, T.E. [Laboratoire Hubert Curien, UMR CNRS 5516/Universite Jean Monnet, 18 rue de Professeur Benoit Lauras, 42000 Saint-Etienne (France); Deghiche, D. [Laboratoire de Physique et Chimie Quantique, Universite Mouloud Mammeri de Tizi-ouzou, BP 17 RP, 15000 Tizi-Ouzou (Algeria); Lamrous, O., E-mail: omarlamrous@mail.ummto.dz [Laboratoire de Physique et Chimie Quantique, Universite Mouloud Mammeri de Tizi-ouzou, BP 17 RP, 15000 Tizi-Ouzou (Algeria)

    2012-01-15

    We employ the particle-in-cell method to simulate the mechanisms of femtosecond (fs) laser interactions with a metallic target. The theoretical approach considers the solid as a gas of free electrons in a lattice of immobile ions and the laser fluences close to the ablation threshold. At first moments of the interaction, our simulations mapped out different nanostructures. We carefully characterized the rippling phase and found that its morphology is dependent on the distribution of the electron density and the period of the ripples depends on the laser intensity. The simulation method provides new insights into the mechanisms that are responsible for surface grating formation.

  12. Gel Formation in Polymers Undergoing Radiation-Induced Crosslinking and Scission

    DEFF Research Database (Denmark)

    Handlos, V. N.; Singer, Klaus Albert Julius

    1976-01-01

    A study was made of the solubility of irradiated polyethylene. The experimental data were treated according to the Saito-Inokuti theory for gel formation in polymers exposed to ionizing radiation. Among other things, this theory is based upon the molecular weight distribution of the unirradiated...... polymer; in the present work, the actual distributions were determined by high-temperature gel permeation chromatography and corrected for long-chain branching. Under these circumstances, good agreement between theory and experimental data was obtained, which allowed the determination of the radiation...... yield of main-chain scission and crosslinking....

  13. Rovibrational Formation of Ultracold NaH Molecules Induced by an Ultrashort Laser Pulse

    Institute of Scientific and Technical Information of China (English)

    SU Qian-Zhen; YU Jie; NIU Ying-Yu; CONG Shu-Lin

    2010-01-01

    @@ The formation of the NaH molecule from unaligned ultracold atoms via photoassociation (PA) is theoretically investigated by numerically solving the time-dependent Schr(o)dinger equation including the vibrational and rotational degrees of freedom.The PA processes via one- and two-photon excitations are described.The calculated results show that the associated molecule can be prepared to a desired rovibrational state of the ground electronic state for Nail.Compared with the one-photon association probability,the two-photon association probability is obviously enhanced.

  14. UV-Induced prevention of biofilm formation inside medical tubes and catheters

    DEFF Research Database (Denmark)

    Pedersen, Jens Kristian Mølgaard; Nielsen, Kristian; Bang, Ole

    2014-01-01

    risk connected withthe use of medical tubes and catheters is the direct cause of more than 60% of all infections acquired inEuropean hospitals. Once formed, the biofilm is generally very tough to suppress by either the body’simmunity system or by use of antibiotics, which may even favor the population...... of multi resistant bacteriacultures. Prevention of biofilm formation inside the tube or catheter, without risk of developing multiresistance, may be achieved by creating a UV-exposed environment in the interior. This may be realized bytransforming the tube itself into an optical waveguide supporting UV...

  15. Quantifying Signaling-Induced Reorientation of TCR's During Immunological Synapse Formation

    Energy Technology Data Exchange (ETDEWEB)

    Moss, W C; Irvine, D J; Davis, M M; Krummel, M F

    2002-10-17

    Productive T cell recognition of antigen-presenting cells (APCs) is normally accompanied by the formation of a cell-cell contact called the 'immunological synapse.' Our understanding of the steps leading up to this formation has been limited by the absence of tools for analyzing 3D surfaces and surface distributions as they change over time. Here we use a 3D fluorescence quantitation method to show that T cell receptors are recruited in bulk within the first minute after the onset of activation and with velocities ranging from 0.04 to 0.1 {micro}m/s; a speed significantly greater than unrestricted diffusion. Our method reveals a second feature of this reorientation: a conformational change as the T cell pushes more total membrane into the interface creating a larger contact area for additional receptors. Analysis of individual T cell receptor velocities using a single-particle tracking method confirms our velocity measurement. This method should permit the quantitation of other dynamic membrane events and the associated movement of cell-surface molecules.

  16. Bar-induced central star formation as revealed by integral field spectroscopy from CALIFA

    CERN Document Server

    Lin, Lin; He, Yanqin; Xiao, Ting; Wang, Enci

    2016-01-01

    We investigate the recent star formation history (SFH) in the inner region of 57 nearly face-on spiral galaxies selected from the Calar Alto Legacy Integral Field Area (CALIFA) survey. For each galaxy we use the integral field spectroscopy from CALIFA to obtain two-dimensional maps and radial profiles of three parameters that are sensitive indicators of the recent SFH: the 4000\\AA\\ break (D$_n$(4000)), and the equivalent width of H$\\delta$ absorption (EW(H$\\delta_A$)) and H$\\alpha$ emission (EW(H$\\alpha$)). We have also performed photometric decomposition of bulge/bar/disk components based on SDSS optical image. We identify a class of 17 "turnover" galaxies whose central region present significant drop in D$_n$(4000), and most of them correspondingly show a central upturn in EW(H$\\delta_A$) and EW(H$\\alpha$). This indicates that the central region of the turnover galaxies has experienced star formation in the past 1-2 Gyr, which makes the bulge younger and more star-forming than surrounding regions. We find a...

  17. Cytokines induced neutrophil extracellular traps formation: implication for the inflammatory disease condition.

    Directory of Open Access Journals (Sweden)

    Ravi S Keshari

    Full Text Available Neutrophils (PMNs and cytokines have a critical role to play in host defense and systemic inflammatory response syndrome (SIRS. Neutrophil extracellular traps (NETs have been shown to extracellularly kill pathogens, and inflammatory potential of NETs has been shown. Microbial killing inside the phagosomes or by NETs is mediated by reactive oxygen and nitrogen species (ROS/RNS. The present study was undertaken to assess circulating NETs contents and frequency of NETs generation by isolated PMNs from SIRS patients. These patients displayed significant augmentation in the circulating myeloperoxidase (MPO activity and DNA content, while PMA stimulated PMNs from these patients, generated more free radicals and NETs. Plasma obtained from SIRS patients, if added to the PMNs isolated from healthy subjects, enhanced NETs release and free radical formation. Expressions of inflammatory cytokines (IL-1β, TNFα and IL-8 in the PMNs as well as their circulating levels were significantly augmented in SIRS subjects. Treatment of neutrophils from healthy subjects with TNFα, IL-1β, or IL-8 enhanced free radicals generation and NETs formation, which was mediated through the activation of NADPH oxidase and MPO. Pre-incubation of plasma from SIRS with TNFα, IL-1β, or IL-8 antibodies reduced the NETs release. Role of IL-1β, TNFα and IL-8 thus seems to be involved in the enhanced release of NETs in SIRS subjects.

  18. MAB4-induced auxin sink generates local auxin gradients in Arabidopsis organ formation.

    Science.gov (United States)

    Furutani, Masahiko; Nakano, Yasukazu; Tasaka, Masao

    2014-01-21

    In Arabidopsis, leaves and flowers form cyclically in the shoot meristem periphery and are triggered by local accumulations of the plant hormone auxin. Auxin maxima are established by the auxin efflux carrier PIN-formed1 (PIN1). During organ formation, two distinct types of PIN1 polarization occur. First, convergence of PIN1 polarity in the surface of the meristem creates local auxin peaks. Second, basipetal PIN1 polarization causes auxin to move away from the surface in the middle of an incipient organ primordium, thought to contribute to vascular formation. Several mathematical models have been developed in attempts to explain the PIN1 localization pattern. However, the molecular mechanisms that control these dynamic changes are unknown. Here, we show that loss-of-function in the MACCHI-BOU 4 (MAB4) family genes, which encode nonphototropic hypocotyl 3-like proteins and regulate PIN endocytosis, cause deletion of basipetal PIN1 polarization, resulting in extensive auxin accumulation all over the meristem surface from lack of a sink for auxin. These results indicate that the MAB4 family genes establish inward auxin transport from the L1 surface of incipient organ primordia by basipetal PIN1 polarization, and that this behavior is essential for the progression of organ development. Furthermore, the expression of the MAB4 family genes depends on auxin response. Our results define two distinct molecular mechanisms for PIN1 polarization during organ development and indicate that an auxin response triggers the switching between these two mechanisms.

  19. Formation of H3O+ from alcohols and ethers induced by intense laser fields.

    Science.gov (United States)

    Shirota, Tatsuro; Mano, Narutoshi; Tsuge, Masashi; Hoshina, Kennosuke

    2010-03-15

    The processes of H(3)O(+) production from alcohols (ethanol, 2-propanol, 1-propanol, 2-butanol) and ethers (diethyl ether and ethyl methyl ether), and their deuterium-substituted species, by intense laser fields (800 nm, 100 fs, approximately 1 x 10(14) W/cm) were investigated through time-of-flight (TOF) mass spectrometry. H(3)O(+) formation was observed for all these compounds except for ethyl methyl ether. From the analysis of TOF signals of H((3-n))D(n)O(+) (n = 0, 1, 2, and 3) that have expanding tails with increasing flight time, it has been confirmed that the reaction proceeds through metastable dissociation from the intermediate species C(2)H((5-m))D(m)O(+)(m = 0-5). The common shape of the H((3-n))D(n)O(+) signal profiles contains two major distributions in the time constant, i.e., fast and slow components of production. Ab initio calculations for the isomers and transition states of C(2)H(5)O(+) were also performed, and the observed H((3-n))D(n)O(+) production mechanism has been discussed. In addition, a stable isomer having a complex structure and two isomerization pathways were discovered to contribute to the H(3)O(+) formation process.

  20. The formation and decay of superheavy nuclei produced in sup 4 sup 8 Ca-induced reactions

    CERN Document Server

    Kumar, S; Gupta, R K; Münzenberg, G; Scheid, W

    2003-01-01

    The formation of superheavy nuclei in sup 4 sup 8 Ca+ sup 2 sup 3 sup 2 Th, sup 2 sup 3 sup 8 U, sup 2 sup 4 sup 2 sup , sup 2 sup 4 sup 4 Pu and sup 2 sup 4 sup 8 Cm reactions and their subsequent decay are studied within the quantum mechanical fragmentation theory (QMFT) and the QMFT-based preformed cluster decay model (PCM) of Gupta and collaborators. According to QMFT, all these sup 4 sup 8 Ca-induced reactions are cold fusion reactions with relative excitation energies larger than those for the Pb-induced cold fusion reactions and smaller than those for the lighter beam, i.e. Mg, Si or S-induced hot fusion reactions. The same reactions were first suggested by Gupta et al in 1977 on the basis of QMFT, and this study re-establishes the same result. In fact, for such heavy isotopes of Z = 110 to 116, sup 5 sup 0 Ca is shown to be a better beam for cold fusion, but sup 5 sup 0 Ca is a radioactive nucleus. The alpha-decay half-lives of these nuclei after 3n and/or 4n evaporations, i.e. of the evaporation resi...

  1. Presynaptically released Cbln1 induces dynamic axonal structural changes by interacting with GluD2 during cerebellar synapse formation.

    Science.gov (United States)

    Ito-Ishida, Aya; Miyazaki, Taisuke; Miura, Eriko; Matsuda, Keiko; Watanabe, Masahiko; Yuzaki, Michisuke; Okabe, Shigeo

    2012-11-08

    Differentiation of pre- and postsynaptic sites is coordinated by reciprocal interaction across synaptic clefts. At parallel fiber (PF)-Purkinje cell (PC) synapses, dendritic spines are autonomously formed without PF influence. However, little is known about how presynaptic structural changes are induced and how they lead to differentiation of mature synapses. Here, we show that Cbln1 released from PFs induces dynamic structural changes in PFs by a mechanism that depends on postsynaptic glutamate receptor delta2 (GluD2) and presynaptic neurexin (Nrx). Time-lapse imaging in organotypic culture and ultrastructural analyses in vivo revealed that Nrx-Cbln1-GluD2 signaling induces PF protrusions that often formed circular structures and encapsulated PC spines. Such structural changes in PFs were associated with the accumulation of synaptic vesicles and GluD2, leading to formation of mature synapses. Thus, PF protrusions triggered by Nrx-Cbln1-GluD2 signaling may promote bidirectional maturation of PF-PC synapses by a positive feedback mechanism.

  2. Phloroglucinol protects retinal pigment epithelium and photoreceptor against all-trans-retinal-induced toxicity and inhibits A2E formation.

    Science.gov (United States)

    Cia, David; Cubizolle, Aurélie; Crauste, Céline; Jacquemot, Nathalie; Guillou, Laurent; Vigor, Claire; Angebault, Claire; Hamel, Christian P; Vercauteren, Joseph; Brabet, Philippe

    2016-09-01

    Among retinal macular diseases, the juvenile recessive Stargardt disease and the age-related degenerative disease arise from carbonyl and oxidative stresses (COS). Both stresses originate from an accumulation of all-trans-retinal (atRAL) and are involved in bisretinoid formation by condensation of atRAL with phosphatidylethanolamine (carbonyl stress) in the photoreceptor and its transformation into lipofuscin bisretinoids (oxidative stress) in the retinal pigment epithelium (RPE). As atRAL and bisretinoid accumulation contribute to RPE and photoreceptor cell death, our goal is to select powerful chemical inhibitors of COS. Here, we describe that phloroglucinol, a natural phenolic compound having anti-COS properties, protects both rat RPE and mouse photoreceptor primary cultures from atRAL-induced cell death and reduces hydrogen peroxide (H2 O2 )-induced damage in RPE in a dose-dependent manner. Mechanistic analyses demonstrate that the protective effect encompasses decrease in atRAL-induced intracellular reactive oxygen species and free atRAL levels. Moreover, we show that phloroglucinol reacts with atRAL to form a chromene adduct which prevents bisretinoid A2E synthesis in vitro. Taken together, these data show that the protective effect of phloroglucinol correlates with its ability to trap atRAL and to prevent its further transformation into deleterious bisretinoids. Phloroglucinol might be a good basis to develop efficient therapeutic derivatives in the treatment of retinal macular diseases.

  3. Mycobacterium tuberculosis-Induced Polarization of Human Macrophage Orchestrates the Formation and Development of Tuberculous Granulomas In Vitro.

    Directory of Open Access Journals (Sweden)

    Zikun Huang

    Full Text Available The tuberculous granuloma is an elaborately organized structure and one of the main histological hallmarks of tuberculosis. Macrophages, which are important immunologic effector and antigen-presenting cells, are the main cell type found in the tuberculous granuloma and have high plasticity. Macrophage polarization during bacterial infection has been elucidated in numerous recent studies; however, macrophage polarization during tuberculous granuloma formation and development has rarely been reported. It remains to be clarified whether differences in the activation status of macrophages affect granuloma formation. In this study, the variation in macrophage polarization during the formation and development of tuberculous granulomas was investigated in both sections of lung tissues from tuberculosis patients and an in vitro tuberculous granuloma model. The roles of macrophage polarization in this process were also investigated. Mycobacterium tuberculosis (M. tuberculosis infection was found to induce monocyte-derived macrophage polarization. In the in vitro tuberculous granuloma model, macrophage transformation from M1 to M2 was observed over time following M. tuberculosis infection. M2 macrophages were found to predominate in both necrotic and non-necrotic granulomas from tuberculosis patients, while both M1 and M2 polarized macrophages were found in the non-granulomatous lung tissues. Furthermore, it was found that M1 macrophages promote granuloma formation and macrophage bactericidal activity in vitro, while M2 macrophages inhibit these effects. The findings of this study provide insights into the mechanism by which M. tuberculosis circumvents the host immune system as well as a theoretical foundation for the development of novel tuberculosis therapies based on reprogramming macrophage polarization.

  4. Neutrino Signal of Collapse-induced Thermonuclear Supernovae: The Case for Prompt Black Hole Formation in SN 1987A

    Science.gov (United States)

    Blum, Kfir; Kushnir, Doron

    2016-09-01

    Collapse-induced thermonuclear explosion (CITE) may explain core-collapse supernovae (CCSNe). We analyze the neutrino signal in CITE and compare it to the neutrino burst of SN 1987A. For strong (≳ {10}51 erg) CCSNe, such as SN 1987A, CITE predicts a proto-neutron star (PNS) accretion phase lasting up to a few seconds that is cut off by black hole (BH) formation. The neutrino luminosity can later be revived by accretion disk emission after a dead time of a few to a few tens of seconds. In contrast, the neutrino mechanism for CCSNe predicts a short (≲s) PNS accretion phase, followed by slowly declining PNS cooling luminosity. We repeat statistical analyses used in the literature to interpret the neutrino mechanism, and apply them to CITE. The first 1-2 s of the neutrino burst are equally compatible with CITE and with the neutrino mechanism. However, the data points toward a luminosity drop at t = 2-3 s, which is in some tension with the neutrino mechanism but can be naturally attributed to BH formation in CITE. The occurrence of neutrino signal events at 5 s suggests that, within CITE, the accretion disk formed by that time. We perform two-dimensional numerical simulations showing that CITE may be able to accommodate this disk formation time while reproducing the ejected 56Ni mass and ejecta kinetic energy within factors of 2-3 of observations. We estimate the accretion disk neutrino luminosity, finding it to be on the low side but compatible with the data to a factor of 10. Given comparable uncertainties in the disk luminosity simulation, we conclude that direct BH formation may have occurred in SN 1987A.

  5. Hypochlorite-induced damage to plasma and proteins: formation of nitrogen-centred radicals and their role in protein oxidation

    Energy Technology Data Exchange (ETDEWEB)

    Hawkins, C.L.; Davies, M.J. [Heart Research Institute, Camperdown, NSW (Australia)

    1998-12-31

    The respiratory burst of activated phagocyte cells results in the generation of hypochlorite (HOCl) via the release of the hydrogen peroxide and the enzyme myeloperoxidase. Little information is available about the mechanisms and intermediates involved in these reactions. Electron paramagnetic resonance (EPR) spectroscopy with spin trapping has been employed to identify radicals formed in fresh human plasma and isolated proteins and peptides on treatment with HOCI. Reaction of plasma with HOCI in the presence of a spin trap gives broad, anisotropic radical adducts consistent with the formation of large, slowly-tumbling, protein-derived radicals. The identity of the plasma-derived radical adducts was investigated further by the incubation of the pre-formed adducts with the non-specific proteolytic enzyme pronase. This treatment gave sharper, signals consistent with the release of more mobile, low-molecular-weight spin adducts from the initial protein-derived adducts. The hyperfine couplings of these sharper signals are characteristic of the formation of nitrogen-centred radical adducts. Similar or identical species are observed on treatment with isolated human serum albumin, suggesting that this is a major site of HOCI-induced oxidation. Reaction of HOCI-treated plasma or isolated proteins/peptides with excess methionine eliminates radical formation, consistent with lysine-derived chloramines (via homolysis or heterolysis of N-CI bonds) being the radical source. The effect of HOCI on the structural integrity of the plasma proteins was investigated by SDS-PAGE. It was demonstrated that incubation of HOCI-treated plasma or proteins, after removal of excess oxidant, resulted in a time- and HOCI-dependent fragmentation of the proteins. No evidence was obtained for the presence of either discrete fragments or aggregated material. This suggests that the reaction of HOCI with plasma proteins results in the formation of a large number of random fragments. Treatment with

  6. Tidal current-induced formation——storm-induced change——tidal current-induced recovery——Interpretation of depositional dynamics of formation and evolution of radial sand ridges on the Yellow Sea seafloor

    Institute of Scientific and Technical Information of China (English)

    张长宽; 张东生; 张君伦; 王震

    1999-01-01

    The results of simulated tidal current field, wave field and storm-induced current field are employed to interpret the depositional dynamic mechanism of formation and evolution of the radial sand ridges on the Yellow Sea seafloor. The anticlockwise rotary tidal wave to the south of Shandong Peninsula meets the following progressive tidal wave from the South Yellow Sea, forming a radial current field outside Jianggang. This current field provides a necessary dynamic condition for the formation and existence of the radial sand ridges on the Yellow Sea seafloor. The results of simulated "old current field (holocene)" show that there existed a convergent-divergent tidal zone just outside the palaeo-Yangtze River estuary where a palaeo-underwater accumulation was developed. The calculated results from wave models indicate that the wave impact on the topography, under the condition of high water level and strong winds, is significant. The storm current induced by typhoons landing in the Yangtze River estuary

  7. Initiation and termination of DNA replication during S phase in relation to cyclins D1, E and A, p21WAF1, Cdt1 and the p12 subunit of DNA polymerase δ revealed in individual cells by cytometry.

    Science.gov (United States)

    Darzynkiewicz, Zbigniew; Zhao, Hong; Zhang, Sufang; Lee, Marietta Y W T; Lee, Ernest Y C; Zhang, Zhongtao

    2015-05-20

    During our recent studies on mechanism of the regulation of human DNA polymerase δ in preparation for DNA replication or repair, multiparameter imaging cytometry as exemplified by laser scanning cytometry (LSC) has been used to assess changes in expression of the following nuclear proteins associated with initiation of DNA replication: cyclin A, PCNA, Ki-67, p21(WAF1), DNA replication factor Cdt1 and the smallest subunit of DNA polymerase δ, p12. In the present review, rather than focusing on Pol δ, we emphasize the application of LSC in these studies and outline possibilities offered by the concurrent differential analysis of DNA replication in conjunction with expression of the nuclear proteins. A more extensive analysis of the data on a correlation between rates of EdU incorporation, likely reporting DNA replication, and expression of these proteins, is presently provided. New data, specifically on the expression of cyclin D1 and cyclin E with respect to EdU incorporation as well as on a relationship between expression of cyclin A vs. p21(WAF1) and Ki-67 vs. Cdt1, are also reported. Of particular interest is the observation that this approach makes it possible to assess the temporal sequence of degradation of cyclin D1, p21(WAF1), Cdt1 and p12, each with respect to initiation of DNA replication and with respect to each other. Also the sequence or reappearance of these proteins in G2 after termination of DNA replication is assessed. The reviewed data provide a more comprehensive presentation of potential markers, whose presence or absence marks the DNA replicating cells. Discussed is also usefulness of these markers as indicators of proliferative activity in cancer tissues that may bear information on tumor progression and have a prognostic value.

  8. FORMATION AND MICROSTRUCTURE OF POLYETHYLENE MICROPOROUS MEMBRANES THROUGH THERMALLY INDUCED PHASE SEPARATION

    Institute of Scientific and Technical Information of China (English)

    LI Wenjun; YUAN Youxin; CABASSO,Israel

    1995-01-01

    Microporous membranes of low-high density polyethylene and their blends were prepared by thermally-induced phase separation of polymer/long-aliphatic chain alcohol (diluent)mixtures.The microstructures of this particular membrane, which depends on the diluent properties,polymer concentration and cooling rate, were observed by scanning electron microscopy."Beehive-type,"leafy-like, and lacy porous structure morphologies can be formed,depending on the blend composition and phase separation conditions, which were discussed by the polymer and diluent crystallization processes.

  9. Shock formation induced by poloidal flow and its effects on the edge stability in tokamaks

    Science.gov (United States)

    Seol, Jaechun; Shaing, Kerchung; Aydemir, Ahmet

    2016-10-01

    In the high confinement mode of tokamaks, magnitude of the radial electric field increases at the edge. Thus, the poloidal flow inside the transport barrier can be sonic when the edge pressure gradient is not steep enough to make the poloidal flow subsonic. When the poloidal Mach number is close to unity, a shock appears in the low field side and causes a large density perturbation. In this study, we describe a shock induced by the sonic poloidal plasma flow. Then, an entropy production across the shock is calculated. Finally, we introduce a simple model for Type III edge localized modes using the poloidal density variation driven by the sonic poloidal flow.

  10. Propylene glycol and contact-lens solutions containing this diol induce pseudocyst formation in acanthamoebae.

    Science.gov (United States)

    Kliescikova, Jarmila; Kulda, Jaroslav; Nohynkova, Eva

    2011-01-01

    Propylene glycol used as an ophthalmic demulcent in certain contact-lens care systems has been included recently among factors responsible for increasing Acanthamoeba keratitis. In this study, we provide evidence that propylene glycol as well as examined contact-lens solutions containing it induce rapid differentiation of acanthamoebae into pseudocysts. The partial resistance of the pseudocysts and their reversibility to viable trophozoites even after 24-h exposure to the contact-lens solutions indicate a potential risk of infection to contact-lens users.

  11. Participation of oxygen and carbon in formation of oxidation-induced stacking faults in monocrystalline silicon

    Directory of Open Access Journals (Sweden)

    Иван Федорович Червоный

    2015-11-01

    Full Text Available It is experimentally established, that density of oxidation-induced stacking faults (OISF in the boron doped monocrystalline silicon plates, that above, than it is more relation of oxygen atoms concentration to carbon atoms concentration in them.On research results of geometry of OISF rings in the different sections of single-crystal geometry of areas is reconstructed with their different closeness. At adjustment of the growing modes of single-crystals of silicon the increase of output of suitable product is observed

  12. NF-kB activity-dependent P-selectin involved in ox-LDL-induced foam cell formation in U937 cell

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Yi, E-mail: wangyi2004a@126.com [Department of Cardiology, Shanghai First People' s Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200080 (China); Wang, Xiang; Sun, Minghui; Zhang, Zhenyu; Cao, Heng; Chen, Xiaoqing [Department of Cardiology, Shanghai First People' s Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200080 (China)

    2011-08-05

    Highlights: {yields} Ox-LDL induced foam cell formation in the human U937 promonocytic cell line in a dose- and time-dependent manner. {yields} Ox-LDL induced expression of P-selectin through degradation of IkBa and augment of NF-kB activity and protein level during macrophage-derived foam cell formation. {yields} P-selectin and NF-kB may be identified as pivotal regulators of ox-LDL-induced foam cell formation. {yields} Therapy based on the inhibition of P-selectin and NF-kB may complement conventional treatments to prevent atherosclerosis. -- Abstract: Oxidized low-density lipoprotein (ox-LDL) plays a critical role in regulation of atherosclerosis. However, little is known about the role of Nuclear factor kB (NF-kB) activity-dependent P-selectin in ox-LDL-induced foam cell formation during atherosclerosis. In this study, we first investigated ox-LDL induced foam cell formation in the human U937 promonocytic cell line in a dose- and time-dependent manner. Treatment of U937 cells with ox-LDL increased lipid accumulation as well as intracellular cholesterol content. Next, a comparative analysis of gene expression profiling using cDNA microarray and Real-time-PCR indicated that ox-LDL exposure induced, in three treated groups, an extremely marked increase in the mRNA level of P-selectin. Protein levels of P-selectin and its upstream regulators IkBa and NF-kB showed that NF-kB pathway is involved in the ox-LDL-induced foam cell formation. Finally, overexpression of NF-kB significantly accelerated, whereas, inhibition of NF-kB with siRNA remarkably attenuated ox-LDL-induced macrophage-derived foam cell formation. It was concluded that the activity of NF-kB is augmented during macrophage-derived foam cell formation. Activation of NF-kB increased, whereas, inhibition of NF-kB decreased ox-LDL-induced P-selectin expression and lipid accumulation in macrophages, suggesting ox-LDL induced expression of P-selectin through degradation of IkBa and activation of NF-kB in the

  13. (-)-Rhazinilam and the diphenylpyridazinone NSC 613241: Two compounds inducing the formation of morphologically similar tubulin spirals but binding apparently to two distinct sites on tubulin.

    Science.gov (United States)

    Bai, Ruoli; Hamel, Ernest

    2016-08-15

    The most potent microtubule assembly inhibitor of newer diphenylpyridazinone derivatives examined was NSC 613241. Because NSC 613241 and (-)-rhazinilam also induce the formation of similar 2-filament spirals, these aberrant reactions were compared. Spiral formation with both compounds was enhanced by GTP and inhibited by GDP and by 15 other inhibitors of microtubule assembly. Similarly, microtubule assembly induced by paclitaxel or laulimalide is enhanced by GTP and inhibited by GDP and assembly inhibitors, but neither [(3)H]NSC 613241 nor [(3)H](-)-rhazinilam bound to microtubules or inhibited the binding of [(3)H]paclitaxel or [(3)H]peloruside A to microtubules. Differences in the pitch of aberrant polymers were found: NSC 613241-induced and (-)-rhazinilam-induced spirals had average repeats of 85 and 79-80 nm, respectively. We found no binding of [(3)H]NSC 613241 or [(3)H](-)-rhazinilam to αβ-tubulin dimer, but both compounds were incorporated into the polymers they induced in substoichiometric reactions, with as little as 0.1-0.2 mol compound/mol of tubulin, and no cross-inhibition by NSC 613241 or (-)-rhazinilam into spirals occurred. Under reaction conditions where neither compound induced spiral formation, both compounds together synergistically induced substantial spiral formation. We conclude that (-)-rhazinilam and NSC 613241 bind to different sites on tubulin that differ from binding sites for other antitubulin agents.

  14. Complement-induced thrombus formation on the surface of poly(N-vinylpyrrolidone)-grafted polyethylene.

    Science.gov (United States)

    Fukumura, H; Hayashi, K; Yoshikawa, S; Miya, M; Yamamoto, N; Yamashita, I

    1987-01-01

    The role of complement activation in thrombogenesis was investigated on the surface of hydrophilic monomer-graft copolymerized polyethylene (PE) tubes. N-vinylpyrrolidone (NVP)-grafted tubes activated in an in vitro complement system of canine serum; but no activation occurred in 2-hydroxyethyl methacrylate (HEMA)-grafted tubes. The relative patent time for NVP-grafted tubes implanted in canine peripheral veins was shorter than that for HEMA-grafted tubes and adhesion of numerous leucocytes was observed on the luminal surfaces of the NVP-grafted tubes. Decomplementation by prior administration of cobra venom factor elongated the relative patent time for NVP-grafted tubes only and also inhibited the adhesion of leucocytes onto them. These results suggest that the complement activation participates in thrombus formation on the polymer surfaces in canine veins.

  15. Bioprinting by laser-induced forward transfer for tissue engineering applications: jet formation modeling

    Energy Technology Data Exchange (ETDEWEB)

    Mezel, C; Hallo, L [Centre Lasers Intenses et Applications, UMR 5107 Universite Bordeaux 1-CNRS-CEA, 33405 Talence, Cedex (France); Souquet, A; Guillemot, F, E-mail: mezel@celia.u-bordeaux1.f [Institut National de la Sante et de la Recherche Medicale, Universite Bordeaux 2 - UMR 577, 146 Rue Leo Saignat, 33076 Bordeaux Cedex (France)

    2010-03-15

    In this paper, a nanosecond LIFT process is analyzed both from experimental and modeling points of view. Experimental results are first presented and compared to simple estimates obtained from physical analysis, i.e. energy balance, jump relations and analytical pocket dynamics. Then a self-consistent 2D axisymmetric modeling strategy is presented. It is shown that data accessible from experiments, i.e. jet diameter and velocity, can be reproduced. Moreover, some specific mechanisms involved in the rear-surface deformation and jet formation may be described by some scales of hydrodynamic process, i.e. shock waves propagation and expansion waves, as a consequence of the laser heating. It shows that the LIFT process is essentially driven by hydrodynamics and thermal transfer, and that a coupled approach including self-consistent laser energy deposition, heating by thermal conduction and specific models for matter is required.

  16. Bioprinting by laser-induced forward transfer for tissue engineering applications: jet formation modeling.

    Science.gov (United States)

    Mézel, C; Souquet, A; Hallo, L; Guillemot, F

    2010-03-01

    In this paper, a nanosecond LIFT process is analyzed both from experimental and modeling points of view. Experimental results are first presented and compared to simple estimates obtained from physical analysis, i.e. energy balance, jump relations and analytical pocket dynamics. Then a self-consistent 2D axisymmetric modeling strategy is presented. It is shown that data accessible from experiments, i.e. jet diameter and velocity, can be reproduced. Moreover, some specific mechanisms involved in the rear-surface deformation and jet formation may be described by some scales of hydrodynamic process, i.e. shock waves propagation and expansion waves, as a consequence of the laser heating. It shows that the LIFT process is essentially driven by hydrodynamics and thermal transfer, and that a coupled approach including self-consistent laser energy deposition, heating by thermal conduction and specific models for matter is required.

  17. Vortex formation in protoplanetary discs induced by the vertical shear instability

    CERN Document Server

    Richard, Samuel; Umurhan, Orkan M

    2016-01-01

    We present the results of 2D and 3D hydrodynamic simulations of idealized protoplanetary discs that examine the formation and evolution of vortices by the vertical shear instability (VSI). In agreement with recent work, we find that discs with radially decreasing temperature profiles and short thermal relaxation time-scales, are subject to the axisymmetric VSI. In three dimensions, the resulting velocity perturbations give rise to quasi-axisymmetric potential vorticity perturbations that break-up into discrete vortices, in a manner that is reminiscent of the Rossby wave instability. Discs with very short thermal evolution time-scales (i.e. {\\tau}<0.1 local orbit periods) develop strong vorticity perturbations that roll up into vortices that have small aspect ratios ({\\chi}<2) and short lifetimes (~ a few orbits). Longer thermal time-scales give rise to vortices with larger aspect ratios (6<{\\chi}<10), and lifetimes that depend on the entropy gradient. A steeply decreasing entropy profile leads to ...

  18. Modeling of Ni Diffusion Induced Austenite Formation in Ferritic Stainless Steel Interconnects

    DEFF Research Database (Denmark)

    Chen, Ming; Molin, Sebastian; Zhang, L.

    2015-01-01

    Ferritic stainless steel interconnect plates are widely used in planar solid oxide fuel cell (SOFC) or electrolysis cell (SOEC) stacks. During stack production and operation, nickel from the Ni/YSZ fuel electrode or from the Ni contact component diffuses into the IC plate, causing transformation...... of the ferritic phase into an austenitic phase in the interface region. This is accompanied with changes in volume and in mechanical and corrosion properties of the IC plates. In this work, kinetic modeling of the inter-diffusion between Ni and FeCr based ferritic stainless steel was conducted, using the CALPHAD...... approach with the DICTRA software. The kinetics of inter-diffusion and austenite formation was explored in full detail, as functions of layer thickness, temperature, time, and steel composition. The simulation was further validated by comparing with experimental results. Growth of the austenite phase...

  19. Molecular Dynamics Simulation of Water Pore Formation in Lipid Bilayer Induced by Shock Waves

    Science.gov (United States)

    Koshiyama, Ken-ichiro; Kodama, Tetsuya; Yano, Takeru; Fujikawa, Shigeo

    2006-05-01

    Water molecule penetration into a bilayer hydrophobic region with a shock wave impulse has been investigated using molecular dynamics simulations [Koshiyama et al., AIP Conference Proceedings, 754, 104-106, (2005)]. Here we report results of simulation of spontaneous water pore formation in a bilayer that contains water molecules in the hydrophobic region in an initial state. The bilayers of 128 DPPC lipid and 3655 water molecules with insertion of 392, 784, and 1176 water molecules in the hydrophobic region are simulated. A water pore is spontaneously formed when 1176 water molecules exist in the hydrophobic region. The water pore diameter is estimated to be c.a. 1.9 nm, which is three times larger than that of 5-fluorouracil (5FU) used in cancer treatment.

  20. Deuterium-induced nanostructure formation on tungsten exposed to high-flux plasma

    Energy Technology Data Exchange (ETDEWEB)

    Xu, H.Y., E-mail: donaxu@163.com [Key Laboratory of Advanced Materials, Department of Materials Science and Engineering, Tsinghua University, Beijing 100084 (China); Science and Technology on Surface Physics and Chemistry Laboratory, Mianyang, Sichuan 621907 (China); De Temmerman, G. [FOM Institute DIFFER, Dutch Institute For Fundamental Energy Research, Ass. EURATOM-FOM, Trilateral Euregio Cluster, Postbus 1207, 3430BE Nieuwegein (Netherlands); ITER Organization, Route de Vinon-sur-Verdon CS 90046-13067, St Paul Lez Durance Cedex (France); Luo, G.-N. [Institute of Plasma Physics, Chinese Academy of Sciences, Hefei, Anhui 230031 (China); Jia, Y.Z.; Yuan, Y.; Fu, B.Q.; Godfrey, A. [Key Laboratory of Advanced Materials, Department of Materials Science and Engineering, Tsinghua University, Beijing 100084 (China); Liu, W., E-mail: liuw@mail.tsinghua.edu.cn [Key Laboratory of Advanced Materials, Department of Materials Science and Engineering, Tsinghua University, Beijing 100084 (China)

    2015-08-15

    Surface topography of polycrystalline tungsten (W) have been examined after exposure to a low-energy (38 eV/D), high-flux (∼1.1–1.5 × 10{sup 24} m{sup −2} s{sup −1}) deuterium plasma in the Pilot-PSI linear plasma device. The methods used were scanning electron microscopy (SEM), transmission electron microscopy (TEM), positron annihilation Doppler broadening (PADB) and grazing incident X-ray diffraction (GI-XRD). After exposure to high flux D plasma, blisters and nanostructures are formed on the W surface. Generation of defects was evidenced by PADB, while high stress and mixture of phases were detected in depth of 50 nm by GI-XRD. TEM observation revealed fluctuations and disordered microstructure on the outmost surface layer. Based on these results, surface reconstruction is considered as a possible mechanism for the formation of defects and nanostructures.

  1. Formation of coastline features by large-scale instabilities induced by high-angle waves.

    Science.gov (United States)

    Ashton, A; Murray, A B; Arnault, O

    2001-11-15

    Along shore sediment transport that is driven by waves is generally assumed to smooth a coastline. This assumption is valid for small angles between the wave crest lines and the shore, as has been demonstrated in shoreline models. But when the angle between the waves and the shoreline is sufficiently large, small perturbations to a straight shoreline will grow. Here we use a numerical model to investigate the implications of this instability mechanism for large-scale morphology over long timescales. Our simulations show growth of coastline perturbations that interact with each other to produce large-scale features that resemble various kinds of natural landforms, including the capes and cuspate forelands observed along the Carolina coast of southeastern North America. Wind and wave data from this area support our hypothesis that such an instability mechanism could be responsible for the formation of shoreline features at spatial scales up to hundreds of kilometres and temporal scales up to millennia.

  2. Polymer Wall Formation Using Liquid-Crystal/Polymer Phase Separation Induced on Patterned Polyimide Films

    Science.gov (United States)

    Murashige, Takeshi; Fujikake, Hideo; Sato, Hiroto; Kikuchi, Hiroshi; Kurita, Taiichiro; Sato, Fumio

    2004-12-01

    We could form lattice-shaped polymer walls in a liquid crystal (LC) layer through the thermal phase separation of an LC/polystyrene solution between substrates with polyimide films etched by short-wavelength ultraviolet irradiation using a photomask. The LC wetting difference between the polyimide and substrate surfaces caused the coalescence of growing LC droplets on patterned polyimide films with the progress of phase separation. Consequently, polymer walls were formed on substrate surface areas without polyimide films. The shape of the polymer wall formed became sharp with the use of rubbed polyimide films because the nucleation of growing LC droplets concentrated on the patterned polyimide films. It is thought that the increase in the alignment order of LC molecules in the solution near the rubbed polyimide films promotes the formation of LC molecular aggregation, which becomes the growth nuclei of LC droplets.

  3. Dichotomous-noise-induced pattern formation in a reaction-diffusion system

    Science.gov (United States)

    Das, Debojyoti; Ray, Deb Shankar

    2013-06-01

    We consider a generic reaction-diffusion system in which one of the parameters is subjected to dichotomous noise by controlling the flow of one of the reacting species in a continuous-flow-stirred-tank reactor (CSTR) -membrane reactor. The linear stability analysis in an extended phase space is carried out by invoking Furutzu-Novikov procedure for exponentially correlated multiplicative noise to derive the instability condition in the plane of the noise parameters (correlation time and strength of the noise). We demonstrate that depending on the correlation time an optimal strength of noise governs the self-organization. Our theoretical analysis is corroborated by numerical simulations on pattern formation in a chlorine-dioxide-iodine-malonic acid reaction-diffusion system.

  4. Anaerobic bacteria grow within Candida albicans biofilms and induce biofilm formation in suspension cultures.

    Science.gov (United States)

    Fox, Emily P; Cowley, Elise S; Nobile, Clarissa J; Hartooni, Nairi; Newman, Dianne K; Johnson, Alexander D

    2014-10-20

    The human microbiome contains diverse microorganisms, which share and compete for the same environmental niches. A major microbial growth form in the human body is the biofilm state, where tightly packed bacterial, archaeal, and fungal cells must cooperate and/or compete for resources in order to survive. We examined mixed biofilms composed of the major fungal species of the gut microbiome, Candida albicans, and each of five prevalent bacterial gastrointestinal inhabitants: Bacteroides fragilis, Clostridium perfringens, Escherichia coli, Klebsiella pneumoniae, and Enterococcus faecalis. We observed that biofilms formed by C. albicans provide a hypoxic microenvironment that supports the growth of two anaerobic bacteria, even when cultured in ambient oxic conditions that are normally toxic to the bacteria. We also found that coculture with bacteria in biofilms induces massive gene expression changes in C. albicans, including upregulation of WOR1, which encodes a transcription regulator that controls a phenotypic switch in C. albicans, from the "white" cell type to the "opaque" cell type. Finally, we observed that in suspension cultures, C. perfringens induces aggregation of C. albicans into "mini-biofilms," which allow C. perfringens cells to survive in a normally toxic environment. This work indicates that bacteria and C. albicans interactions modulate the local chemistry of their environment in multiple ways to create niches favorable to their growth and survival.

  5. Polycation-induced benzoperylene probe excimer formation and the ratiometric detection of heparin and heparinase.

    Science.gov (United States)

    Yang, Meiding; Chen, Jian; Zhou, Huipeng; Li, Wenying; Wang, Yan; Li, Juanmin; Zhang, Cuiyun; Zhou, Chuibei; Yu, Cong

    2016-01-15

    A benzoperylene probe excimer emission in an aqueous buffer solution is observed for the first time, and a novel ratiometric fluorescence method based on the probe excimer emission for the sensitive detection of heparin and heparinase is demonstrated. A negatively charged benzoperylene derivative, 6-(benzo[ghi]perylene-1,2-dicarboxylic imide-yl)hexanoic acid (BPDI), was employed. A polycation, poly(diallyldimethylammonium) chloride (poly-DDA), could induce aggregation of BPDI through noncovalent interactions. A decrease of BPDI monomer emission and a simultaneous increase of BPDI excimer emission were observed. Upon the addition of heparin, the strong binding between heparin and poly-DDA caused release of BPDI monomer molecules, and an excimer-monomer emission signal transition was detected. However, after the enzymatic hydrolysis of heparin by heparinase, heparin was hydrolyzed into small fragments, which weakened the competitive binding of heparin to poly-DDA. Poly-DDA induced aggregation of BPDI, and a monomer-excimer emission signal transition was detected. Our assay is simple, rapid, inexpensive, sensitive and selective, which could facilitate the heparin and heparinase related biochemical and biomedical research.

  6. Demarcation laser photocoagulation induced retinal necrosis and rupture resulting in large retinal tear formation.

    Science.gov (United States)

    Quezada, Carlos; Pieramici, Dante J; Matsui, Rodrigo; Rabena, Melvin; Graue, Federico

    2015-06-01

    Retinal tears after laser photocoagulation are a rare complication that occurs after intense laser. It is talked about among retina specialist occurring particularly at the end of a surgical case while applying endophotocoagulation; to the best our knowledge, there are no reports in the literature of a large retinal tear induced after attempted in-office demarcation laser photocoagulation (DLP) that simulated a giant retinal tear. DLP has been employed in the management of selected cases of macula sparring rhegmatogenous retinal detachment (RRD). Even though extension of the retinal detachment through the "laser barrier" is considered a failure of treatment, few complications have been described with the use of this less invasive retinal detachment repair technique. We describe a case of a high myopic woman who initially was treated with demarcation laser photocoagulation for an asymptomatic retinal detachment associated with a single horseshoe tear and a full thickness large retinal tear was created where the laser was placed. Intense laser photocoagulation resulted in abrupt laser induced retinal necrosis and rupture creating this large retinal break. Proper laser technique should reduce the risks associated with this procedure.

  7. Shear-Induced Amyloid Formation in the Brain: I. Potential Vascular and Parenchymal Processes.

    Science.gov (United States)

    Trumbore, Conrad N

    2016-09-06

    Shear distortion of amyloid-beta (Aβ) solutions accelerates amyloid cascade reactions that may yield different toxic oligomers than those formed in quiescent solutions. Recent experiments indicate that cerebrospinal fluid (CSF) and interstitial fluid (ISF) containing Aβ flow through narrow brain perivascular pathways and brain parenchyma. This paper suggests that such flow causes shear distortion of Aβ molecules involving conformation changes that may be one of the initiating events in the etiology of Alzheimer's disease. Aβ shearing can occur in or around brain arteries and arterioles and is suggested as the origin of cerebral amyloid angiopathy deposits in cerebrovascular walls. Comparatively low flow rates of ISF within the narrow extracellular spaces (ECS) of the brain parenchyma are suggested as a possible initiating factor in both the formation of neurotoxic Aβ42 oligomers and amyloid fibrils. Aβ42 in slow-flowing ISF can gain significant shear energy at or near the walls of tortuous brain ECS flow paths, promoting the formation of a shear-distorted, excited state hydrophobic Aβ42* conformation. This Aβ42* molecule could possibly be involved in one of two paths, one involving rapid adsorption to a brain membrane surface, ultimately forming neurotoxic oligomers on membranes, and the other ultimately forming plaque within the ECS flow pathways. Rising Aβ concentrations combined with shear at or near critical brain membranes are proposed as contributing factors to Alzheimer's disease neurotoxicity. These hypotheses may be applicable in other neurodegenerative diseases, including tauopathies and alpha-synucleinopathies, in which shear-distorted proteins also may form in the brain ECS.

  8. Detecção dos genes codificantes da toxina CDT, e pesquisa de fatores que influenciam na produção de hemolisinas em amostras de Campylobacter jejuni de origem avícola

    OpenAIRE

    Michele M. Trindade; Gustavo Perdoncini; Sierra-Arguello,Yuli M.; Maristela Lovato; Anderlise Borsoi; Vladimir P. Nascimento

    2015-01-01

    Resumo: Membros termofílicos do gênero Campylobacter são reconhecidos como importantes enteropatógenos para o ser humano e animais. A grande diversidade ecológica destes micro-organismos em diferentes habitats tais como água, animais e alimentos predispõem ao aparecimento de novos fatores de virulência. Este trabalho teve por objetivo detectar os genes codificantes da Toxina Distensiva Citoletal (CDT) por meio da técnica de PCR, pesquisar a atividade de hemolisinas e a influência de soluções ...

  9. H-NST induces LEE expression and the formation of attaching and effacing lesions in enterohemorrhagic Escherichia coli.

    Directory of Open Access Journals (Sweden)

    Jonathan A Levine

    Full Text Available Enteropathogenic E. coli (EPEC and enterohemorrhagic E. coli are important causes of morbidity and mortality worldwide. These enteric pathogens contain a type III secretion system (T3SS responsible for the attaching and effacing (A/E lesion phenotype. The T3SS is encoded by the locus of enterocyte effacement (LEE pathogenicity island. The H-NS-mediated repression of LEE expression is counteracted by Ler, the major activator of virulence gene expression in A/E pathogens. A regulator present in EPEC, H-NST, positively affects expression of H-NS regulon members in E. coli K-12, although the effect of H-NST on LEE expression and virulence of A/E pathogens has yet-to-be determined.We examine the effect of H-NST on LEE expression and A/E lesion formation on intestinal epithelial cells. We find that H-NST positively affects the levels of LEE-encoded proteins independently of ler and induces A/E lesion formation. We demonstrate H-NST binding to regulatory regions of LEE1 and LEE3, the first report of DNA-binding by H-NST. We characterize H-NST mutants substituted at conserved residues including Ala16 and residues Arg60 and Arg63, which are part of a potential DNA-binding domain. The single mutants A16V, A16L, R60Q and the double mutant R60Q/R63Q exhibit a decreased effect on LEE expression and A/E lesion formation. DNA mobility shift assays reveal that these residues are important for H-NST to bind regulatory LEE DNA targets. H-NST positively affects Ler binding to LEE DNA in the presence of H-NS, and thereby potentially helps Ler displace H-NS bound to DNA.H-NST induces LEE expression and A/E lesion formation likely by counteracting H-NS-mediated repression. We demonstrate that H-NST binds to DNA and identify arginine residues that are functionally important for DNA-binding. Our study suggests that H-NST provides an additional means for A/E pathogens to alleviate repression of virulence gene expression by H-NS to promote virulence capabilities.

  10. Erosive arthritis and hepatic granuloma formation induced by peptidoglycan polysaccharide in rats is aggravated by prasugrel treatment.

    Directory of Open Access Journals (Sweden)

    Analia E Garcia

    Full Text Available Administration of the thienopyridine P2Y12 receptor antagonist, clopidogrel, increased the erosive arthritis induced by peptidoglycan polysaccharide (PG-PS in rats or by injection of the arthritogenic K/BxN serum in mice. To determine if the detrimental effects are caused exclusively by clopidogrel, we evaluated prasugrel, a third-generation thienopyridine pro-drug, that contrary to clopidogrel is mostly metabolized into its active metabolite in the intestine. Prasugrel effects were examined on the PG-PS-induced arthritis rat model. Erosive arthritis was induced in Lewis rats followed by treatment with prasugrel for 21 days. Prasugrel treated arthritic animals showed a significant increase in the inflammatory response, compared with untreated arthritic rats, in terms of augmented macroscopic joint diameter associated with significant signs of inflammation, histomorphometric measurements of the hind joints and elevated platelet number. Moreover, fibrosis at the pannus, assessed by immunofluorescence of connective tissue growth factor, was increased in arthritic rats treated with prasugrel. In addition to the arthritic manifestations, hepatomegaly, liver granulomas and giant cell formation were observed after PG-PS induction and even more after prasugrel exposure. Cytokine plasma levels of IL-1 beta, IL-6, MIP1 alpha, MCP1, IL-17 and RANTES were increased in arthritis-induced animals. IL-10 plasma levels were significantly decreased in animals treated with prasugrel. Overall, prasugrel enhances inflammation in joints and liver of this animal model. Since prasugrel metabolites inhibit neutrophil function ex-vivo and the effects of both clopidogrel and prasugrel metabolites on platelets are identical, we conclude that the thienopyridines metabolites might exert non-platelet effects on other immune cells to aggravate inflammation.

  11. S100A7-downregulation inhibits epidermal growth factor-induced signaling in breast cancer cells and blocks osteoclast formation.

    Directory of Open Access Journals (Sweden)

    Vikram Paruchuri

    Full Text Available S100A7 is a small calcium binding protein, which has been shown to be differentially expressed in psoriatic skin lesions, as well as in squamous cell tumors of the skin, lung and breast. Although its expression has been correlated to HER+ high-grade tumors and to a high risk of progression, the molecular mechanisms of these S100A7-mediated tumorigenic effects are not well known. Here, we showed for the first time that epidermal growth factor (EGF induces S100A7 expression in both MCF-7 and MDA-MB-468 cell lines. We also observed a decrease in EGF-directed migration in shRNA-downregulated MDA-MB-468 cell lines. Furthermore, our signaling studies revealed that EGF induced simultaneous EGF receptor phosphorylation at Tyr1173 and HER2 phosphorylation at Tyr1248 in S100A7-downregulated cell lines as compared to the vector-transfected controls. In addition, reduced phosphorylation of Src at tyrosine 416 and p-SHP2 at tyrosine 542 was observed in these downregulated cell lines. Further studies revealed that S100A7-downregulated cells had reduced angiogenesis in vivo based on matrigel plug assays. Our results also showed decreased tumor-induced osteoclastic resorption in an intra-tibial bone injection model involving SCID mice. S100A7-downregulated cells had decreased osteoclast number and size as compared to the vector controls, and this decrease was associated with variations in IL-8 expression in in vitro cell cultures. This is a novel report on the role of S100A7 in EGF-induced signaling in breast cancer cells and in osteoclast formation.

  12. Interconnection of salt-induced hydrophobic compaction and secondary structure formation depends on solution conditions: revisiting early events of protein folding at single molecule resolution.

    Science.gov (United States)

    Haldar, Shubhasis; Chattopadhyay, Krishnananda

    2012-03-30

    What happens in the early stage of protein folding remains an interesting unsolved problem. Rapid kinetics measurements with cytochrome c using submillisecond continuous flow mixing devices suggest simultaneous formation of a compact collapsed state and secondary structure. These data seem to indicate that collapse formation is guided by specific short and long range interactions (heteropolymer collapse). A contrasting interpretation also has been proposed, which suggests that the collapse formation is rapid, nonspecific, and a trivial solvent related compaction, which could as well be observed by a homopolymer (homopolymer collapse). We address this controversy using fluorescence correlation spectroscopy (FCS), which enables us to monitor the salt-induced compaction accompanying collapse formation and the associated time constant directly at single molecule resolution. In addition, we follow the formation of secondary structure using far UV CD. The data presented here suggest that both these models (homopolymer and heteropolymer) could be applicable depending on the solution conditions. For example, the formation of secondary structure and compact state is not simultaneous in aqueous buffer. In aqueous buffer, formation of the compact state occurs through a two-state co-operative transition following heteropolymer formalism, whereas secondary structure formation takes place gradually. In contrast, in the presence of urea, a compaction of the protein radius occurs gradually over an extended range of salt concentration following homopolymer formalism. The salt-induced compaction and the formation of secondary structure take place simultaneously in the presence of urea.

  13. Evaporation-induced formation of fractal-like structures from nanofluids.

    Science.gov (United States)

    Crivoi, Alexandru; Duan, Fei

    2012-01-28

    After the nanofluids are fully dried, the self-assembled nanoparticles can form various structures on the substrate. The fractal-like patterns are among them. The two-dimensional Kinetic Monte Carlo model is developed to predict the drying patterns of the nanofluids in an open domain, where the dewetting front shrinks from the edge toward the center. The simulation reveals that the initially dispersed particles can be deposited into an isotropic branched structure which remains frozen after full evaporation of the base fluid. The well-developed fractal-like particle aggregates are different from the fractal cavities obtained in the previous closed domain simulation. The present prediction of the fractal particle aggregation is verified by the experiments with the water-based nanofluids. The images taken using a scanning electron microscope prove that the evaporation-induced branched microstructures are formed by the nanoparticles as the water is totally dried.

  14. Numerical Simulation of Shear-Horizontal-Wave-Induced Electromagnetic Field in Borehole Surrounded by Porous Formation

    Institute of Scientific and Technical Information of China (English)

    CUI Zhi-Wen; WANG Ke-Xie; SUN Jian-Cuo; ZHU Zheng-Ya; YAO Gui-Jin; HU Heng-Shan

    2007-01-01

    Seismoelectric field excited by purely torsional loading applied directJy to the borehole wall is considered.A brief formulation and some computed waveforms show the advantage of using shear-horizontal (SH) transverseelectric(TE) seismoelectric waves logging to measure shear velocity in a fluid-saturated porous lormation.By assuming that the acoustic field is not influenced by its induced electromagnetic field due to seismoelectric effect,the coupling governing equations for electromagnetic field are reduced to Maxwell equations with a propagation current source.It is shown that this simplification is valid and the borehole seismoelectric conversion effcient is mainly dependent on the electrokinetic coupling coeffcient.The receivers to detect the conversion electromagnetic field and to obtain shear veloeity can be set in the borehole fluid in the SH-TE seismoelectric wave log.

  15. Sucrose-induced analgesia during early life modulates adulthood learning and memory formation.

    Science.gov (United States)

    Nuseir, Khawla Q; Alzoubi, Karem H; Alabwaini, Jehad; Khabour, Omar F; Kassab, Manal I

    2015-06-01

    This study is aimed at examining the long-term effects of chronic pain during early life (postnatal day 0 to 8weeks), and intervention using sucrose, on cognitive functions during adulthood in rats. Pain was induced in rat pups via needle pricks of the paws. Sucrose solution or paracetamol was administered for analgesia before the paw prick. Control groups include tactile stimulation to account for handling and touching the paws, and sucrose alone was used. All treatments were started on day one of birth and continued for 8weeks. At the end of the treatments, behavioral studies were conducted to test the spatial learning and memory using radial arm water maze (RAWM), as well as pain threshold via foot-withdrawal response to a hot plate apparatus. Additionally, the hippocampus was dissected, and blood was collected. Levels of neurotrophins (BDNF, IGF-1 and NT-3) and endorphins were assessed using ELISA. The results show that chronic noxious stimulation resulted in comparable foot-withdrawal latency between noxious and tactile groups. On the other hand, pretreatment with sucrose or paracetamol increased pain threshold significantly both in naive rats and noxiously stimulated rats (Psucrose treatment prevented such impairment (PSucrose significantly increased serum levels of endorphin and enkephalin. Chronic pain decreased levels of BDNF in the hippocampus and this decrease was prevented by sucrose and paracetamol treatments. Hippocampal levels of NT-3 and IGF-1 were not affected by any treatment. In conclusion, chronic pain induction during early life induced short memory impairment, and pretreatment with sucrose prevented this impairment via mechanisms that seem to involve BDNF. As evident in the results, sucrose, whether alone or in the presence of pre-noxious stimulation, increases pain threshold in such circumstances; most likely via a mechanism that involves an increase in endogenous opioids.

  16. Formation of rutile fasciculate zone induced by sunlight irradiation at room temperature and its hemocompatibility

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Xuan-Hui; Zheng, Xiang; Cheng, Yuan [School of Chemical Engineering and Materials Science, Zhejiang University of Technology, Hangzhou 310014 (China); Li, Guo-Hua, E-mail: nanozjut@zjut.edu.cn [School of Chemical Engineering and Materials Science, Zhejiang University of Technology, Hangzhou 310014 (China); State Key Laboratory Breeding Base of Green Chemistry Synthesis Technology, Zhejiang University of Technology, Hangzhou 310014 (China); Research Center of Nanoscience and Technology, Zhejiang University of Technology, Hangzhou 310014 (China); Chen, Xiao-Ping, E-mail: chxp@zjut.edu.cn [School of Biological and Environmental Engineering, Zhejiang University of Technology, Hangzhou 310014 (China); Zheng, Jian-Hui [School of Biological and Environmental Engineering, Zhejiang University of Technology, Hangzhou 310014 (China)

    2013-08-01

    The fasciculate zone of phase pure rutile was fabricated under sunlight irradiation at room temperature, using titanium tetrachloride as a sole precursor. The crystal phase, morphology and microstructure, and optical absorption behavior of the samples were characterized by X-ray Diffraction, High-Resolution Transmission Electron Microscope (HRTEM) and UV–vis Diffuse Reflectance Spectra (DRS), respectively. XRD results show that the crystal phase of the sample is composed of rutile only, and a lattice distortion displays in the crystallite of the sample. HRTEM results show that the morphology of rutile particle is fasciculate zone constituted of nanoparticles with a diameter of 4–7 nm, and these particles grow one by one and step by step. The pattern of the selected area electron diffraction of the sample is Kikuchi type, which can be attributed to the predominant orientation growth of rutile nanoparticles along [001] induced by sunlight irradiation. DRS results show that the absorption threshold of the sample is 415 nm, corresponding to the band gap energy of 2.99 eV, which is lower than the band gap energy of rutile, 3.03 eV. Blood compatibility measurement shows that the sample has no remarkable effect on hemolytic and coagulation activity. The percent hemolysis of red blood cells is less than 5% even treated with a big dosage of the fasciculate rutile and under UV irradiation, and there are no obvious changes of plasma recalcification time after the rutile treatment. Thus, the novel structure of rutile fasciculate has low potential toxicity for blood and is hemocompatibility safe. Highlights: • A novel approach to fabricate the fasciculate zone of phase pure rutile • The fasciculate grows from a particle to nanorod and to fasciculate, step by step. • A preferred orientation growth induced by sunlight irradiation in the fasciculate • The rutile fasciculate is low toxicity for blood and is hemocompatibility safe.

  17. Bacterially Induced Dolomite Formation in the Presence of Sulfate Ions under Aerobic Conditions

    Science.gov (United States)

    Sanchez-Roman, M.; McKenzie, J. A.; Vasconcelos, C.; Rivadeneyra, M.

    2005-12-01

    The origin of dolomite remains a long-standing enigma in sedimentary geology because, although thermodynamically favorable, precipitation of dolomite from modern seawater does not occur. Experiments conducted at elevated temperatures (200 oC) indicated that the presence of small concentrations of sulfate ions inhibits the transformation of calcite to dolomite [1]. Indeed, sulfate ions appeared to inhibit dolomite formation above 2 mM concentration (versus 28 mM in modern seawater). Recently, culture experiments have demonstrated that sulfate-reducing bacteria mediate the precipitation of dolomite at Earth surface conditions in the presence of sustained sulfate ion concentrations [2,3]. Additionally, in a number of modern hypersaline environments, dolomite forms from solutions with high sulfate ion concentrations (2 to 70 times seawater). These observations suggest that the experimentally observed sulfate-ion inhibition [1] may not apply to all ancient dolomite formation. Here, we report aerobic culture experiments conducted at low temperatures (25 and 35 oC) and variable sulfate ion concentrations (0, 0.5, 1 and 2 x seawater values) using moderately halophilic bacteria, Halomonas meridiana. After an incubation period of 15 days, experiments at 35 oC with variable sulfate ion concentrations (0, 0.5 x and seawater values) contained crystals of Ca-dolomite and stochiometric dolomite. The experiment at 35 oC with 2 x seawater sulfate ion concentration produced dolomite crystals after 20 days of incubation. In a parallel set of experiments at 25 oC, precipitation of dolomite was observed after 25 days of incubation in cultures with variable sulfate ion concentrations (0, 0.5 x and seawater values). In the culture with 2 x seawater sulfate ion concentration, dolomite crystals were observed after 30 days. Our study demonstrates that halophilic bacteria (or heterotrophic microorganisms), which do not require sulfate ions for metabolism, can mediate dolomite precipitation

  18. Antiviral Innate Immune Response Interferes with the Formation of Replication-Associated Membrane Structures Induced by a Positive-Strand RNA Virus

    Directory of Open Access Journals (Sweden)

    Diede Oudshoorn

    2016-12-01

    Full Text Available Infection with nidoviruses like corona- and arteriviruses induces a reticulovesicular network of interconnected endoplasmic reticulum (ER-derived double-membrane vesicles (DMVs and other membrane structures. This network is thought to accommodate the viral replication machinery and protect it from innate immune detection. We hypothesized that the innate immune response has tools to counteract the formation of these virus-induced replication organelles in order to inhibit virus replication. Here we have investigated the effect of type I interferon (IFN treatment on the formation of arterivirus-induced membrane structures. Our approach involved ectopic expression of arterivirus nonstructural proteins nsp2 and nsp3, which induce DMV formation in the absence of other viral triggers of the interferon response, such as replicating viral RNA. Thus, this setup can be used to identify immune effectors that specifically target the (formation of virus-induced membrane structures. Using large-scale electron microscopy mosaic maps, we found that IFN-β treatment significantly reduced the formation of the membrane structures. Strikingly, we also observed abundant stretches of double-membrane sheets (a proposed intermediate of DMV formation in IFN-β-treated samples, suggesting the disruption of DMV biogenesis. Three interferon-stimulated gene products, two of which have been reported to target the hepatitis C virus replication structures, were tested for their possible involvement, but none of them affected membrane structure formation. Our study reveals the existence of a previously unknown innate immune mechanism that antagonizes the viral hijacking of host membranes. It also provides a solid basis for further research into the poorly understood interactions between the innate immune system and virus-induced replication structures.

  19. Coal induced production of a rhamnolipid biosurfactant by Pseudomonas stutzeri, isolated from the formation water of Jharia coalbed.

    Science.gov (United States)

    Singh, Durgesh Narain; Tripathi, Anil Kumar

    2013-01-01

    A strain of Pseudomonas stutzeri was isolated form an enrichment of perchlorate reducing bacteria from the formation water collected from an Indian coalbed which solubilized coal and produced copious amount of biosurfactant when coal was added to the medium. It produced maximum biosurfactant with lignite coal followed by olive oil and soybean oil which was able to emulsify several aromatic hydrocarbons including kerosene oil, diesel oil, hexane, toluene etc. Haemolytic test, growth inhibition of Bacillus subtilis and FTIR analysis showed rhamnolipid nature of the biosurfactant. The stability of the coal induced biosurfactant in pH range of 4-8 and up to 25% NaCl concentration and 100 °C temperature suggests that due to its ability to produce biosurfactant and solubilize coal P. stutzeri may be useful in the coalbed for in situ biotransformation of coal into methane and in the bioremediation of PAHs from oil contaminated sites including marine environments.

  20. Formation of femtosecond laser induced surface structures on silicon: Insights from numerical modeling and single pulse experiments

    Energy Technology Data Exchange (ETDEWEB)

    Derrien, T.J.-Y., E-mail: thibault.derrien@lp3.univ-mrs.fr [Lasers, Plasmas and Photonic Processes Laboratory (LP3), UMR 6182 CNRS - Universite de la Mediterranee, Parc Scientifique et Technologique de Luminy, 163 Avenue de luminy - C. 917, 13288 Marseille cedex 9 (France); Torres, R.; Sarnet, T.; Sentis, M. [Lasers, Plasmas and Photonic Processes Laboratory (LP3), UMR 6182 CNRS - Universite de la Mediterranee, Parc Scientifique et Technologique de Luminy, 163 Avenue de luminy - C. 917, 13288 Marseille cedex 9 (France); Itina, T.E. [Hubert Curien laboratory (LaHC), UMR 5516 CNRS - Universite Jean Monnet, Bat. F, 18 rue du Professeur Benoit Lauras, 42000, Saint Etienne (France)

    2012-09-15

    Highlights: Black-Right-Pointing-Pointer Theoretical conditions for exciting SPP in Si are verified. Black-Right-Pointing-Pointer SPP model explains why a seed is needed to produce single shot ripples. Black-Right-Pointing-Pointer Two regimes of ripples are identified and explained by numerical simulations. Black-Right-Pointing-Pointer The presented results have a strong correlation with experiments. - Abstract: Laser induced periodic surface structures (LIPSS) are formed by multiple irradiation of femtosecond laser on a silicon target. In this paper, we focus and discuss the surface plasmon polariton mechanism by an analysis of transient phase-matching conditions in Si on the basis of a single pulse experiment and numerical simulations. Two regimes of ripple formation mechanisms at low number of shots are identified and detailed. Correlation of numerical and experimental results is good.

  1. Formation of laser-induced periodic surface structures (LIPSS) on tool steel by multiple picosecond laser pulses of different polarizations

    Science.gov (United States)

    Gregorčič, Peter; Sedlaček, Marko; Podgornik, Bojan; Reif, Jürgen

    2016-11-01

    Laser-induced periodic surface structures (LIPSS) are produced on cold work tool steel by irradiation with a low number of picosecond laser pulses. As expected, the ripples, with a period of about 90% of the laser wavelength, are oriented perpendicular to the laser polarization. Subsequent irradiation with the polarization rotated by 45° or 90° results in a corresponding rotation of the ripples. This is visible already with the first pulse and becomes almost complete - erasing the previous orientation - after as few as three pulses. The phenomenon is not only observed for single-spot irradiation but also for writing long coherent traces. The experimental results strongly defy the role of surface plasmon-polaritons as the predominant key to LIPSS formation.

  2. OH-radical induced degradation of hydroxybenzoic- and hydroxycinnamic acids and formation of aromatic products-A gamma radiolysis study

    Energy Technology Data Exchange (ETDEWEB)

    Krimmel, Birgit; Swoboda, Friederike [University of Vienna, Department of Nutritional Sciences, Section Radiation Biology (Austria); Solar, Sonja, E-mail: sonja.solar@univie.ac.a [University of Vienna, Department of Nutritional Sciences, Section Radiation Biology (Austria); Reznicek, Gottfried [Department of Pharmacognosy, Althanstrasse 14, A-1090 Vienna (Austria)

    2010-12-15

    The OH-radical induced degradation of hydroxybenzoic acids (HBA), hydroxycinnamic acids (HCiA) and methoxylated derivatives, as well as of chlorogenic acid and rosmarinic acid was studied by gamma radiolysis in aerated aqueous solutions. Primary aromatic products resulting from an OH-radical attachment to the ring (hydroxylation), to the position occupied by the methoxyl group (replacement -OCH{sub 3} by -OH) as well as to the propenoic acid side chain of the cinnamic acids (benzaldehyde formations) were analysed by HPLC-UV and LC-ESI-MS. A comparison of the extent of these processes is given for 3,4-dihydroxybenzoic acid, vanillic acid, isovanillic acid, syringic acid, cinnamic acid, 4-hydroxycinnamic acid, caffeic acid, ferulic acid, isoferulic acid, chlorogenic acid, and rosmarinic acid. For all cinnamic acids and derivatives benzaldehydes were significant oxidation products. With the release of caffeic acid from chlorogenic acid the cleavage of a phenolic glycoside could be demonstrated. Reaction mechanisms are discussed.

  3. OH-radical induced degradation of hydroxybenzoic- and hydroxycinnamic acids and formation of aromatic products—A gamma radiolysis study

    Science.gov (United States)

    Krimmel, Birgit; Swoboda, Friederike; Solar, Sonja; Reznicek, Gottfried

    2010-12-01

    The OH-radical induced degradation of hydroxybenzoic acids (HBA), hydroxycinnamic acids (HCiA) and methoxylated derivatives, as well as of chlorogenic acid and rosmarinic acid was studied by gamma radiolysis in aerated aqueous solutions. Primary aromatic products resulting from an OH-radical attachment to the ring (hydroxylation), to the position occupied by the methoxyl group (replacement -OCH 3 by -OH) as well as to the propenoic acid side chain of the cinnamic acids (benzaldehyde formations) were analysed by HPLC-UV and LC-ESI-MS. A comparison of the extent of these processes is given for 3,4-dihydroxybenzoic acid, vanillic acid, isovanillic acid, syringic acid, cinnamic acid, 4-hydroxycinnamic acid, caffeic acid, ferulic acid, isoferulic acid, chlorogenic acid, and rosmarinic acid. For all cinnamic acids and derivatives benzaldehydes were significant oxidation products. With the release of caffeic acid from chlorogenic acid the cleavage of a phenolic glycoside could be demonstrated. Reaction mechanisms are discussed.

  4. Hubble Space Telescope Observations of Accretion-Induced Star Formation in the Tadpole Galaxy Kiso 5639

    CERN Document Server

    Elmegreen, Debra Meloy; Almeida, Jorge Sanchez; Munoz-Tunon, Casiana; Mendez-Abreu, Jairo; Gallagher, John S; Rafelski, Marc; Filho, Mercedes; Ceverino, Daniel

    2016-01-01

    The tadpole galaxy Kiso 5639 has a slowly rotating disk with a drop in metallicity at its star-forming head, suggesting that star formation was triggered by the accretion of metal-poor gas. We present multi-wavelength HST WFC3 images of UV through I band plus Halpha to search for peripheral emission and determine the properties of various regions. The head has a mass in young stars of ~10^6 Mo and an ionization rate of 6.4x10^51 s^{-1}, equivalent to ~2100 O9-type stars. There are four older star-forming regions in the tail, and an underlying disk with a photometric age of ~1 Gyr. The mass distribution function of 61 star clusters is a power law with a slope of -1.73+-0.51. Fourteen young clusters in the head are more massive than 10^4 Mo, suggesting a clustering fraction of 30%-45%. Wispy filaments of Halpha emission and young stars extend away from the galaxy. Shells and holes in the head HII region could be from winds and supernovae. Gravity from the disk should limit the expansion of the HII region, altho...

  5. High Magnetic Field-Induced Formation of Banded Microstructures in Lamellar Eutectic Alloys During Directional Solidification

    Science.gov (United States)

    Li, Xi; Fautrelle, Yves; Gagnoud, Annie; Ren, Zhongming; Moreau, Rene

    2016-08-01

    The influences of high magnetic field (up to 12 T) on the morphology of Pb-Sn and Al-Al2Cu lamellar eutectics during directional solidification were investigated. The experimental results indicate that, along with a decrease in eutectic spacing, the banded structure forms at lower growth speeds under high magnetic field and the band spacing decreases as the magnetic field increases. Moreover, the application of a magnetic field enriches the Cu solute in the liquid ahead of the liquid/solid interface during directional solidification of an Al-Al2Cu eutectic alloy. The effects of high magnetic field on the eutectic points of non-ferromagnetic alloys and the stress acting on the eutectic lamellae during directional solidification have been studied. Both thermodynamic evaluation and DTA measurements reveal that the high magnetic field has a negligible effect on the eutectic points of non-ferromagnetic alloys. However, the high magnetic field caused an increase of the nucleation temperature and undercooling. The numerical results indicate that a considerable stress is produced on the eutectic lamellae during directional solidification under high magnetic field. The formation of a banded structure in a lamellar eutectic during directional solidification under high magnetic field may be attributed to both the buildup of the solute in the liquid ahead of the liquid/solid interface and the stress acting on the eutectic lamellae.

  6. Formation of helium induced nanostructure ‘fuzz’ on various tungsten grades

    Science.gov (United States)

    Baldwin, M. J.; Doerner, R. P.

    2010-09-01

    The response of a variety of W material grades to nanostructure 'fuzz' formation is explored. W targets are exposed to He or D 2-0.2He plasmas in PISCES-B at 900-1320 K to below sputter threshold He + ions of energy 25-60 eV for up to 2.2 × 10 4 s. SEM and XPS reveal nanoscopic reorganization of the W surface to a layer of 'fuzz' of porosity ˜90% as determined by a 'fuzz' removal/weight loss method. The variability of 'fuzz' growth is examined at 1120 K for 1 h durations: SR, SC and doped W grades - La 2O 3 (1% wt.), Re (5% and 10% wt.), and TiC (1.5% wt.) developed 2-3 μm thick 'fuzz' layers, while a VPS grade developed a layer 4 μm thick. An RC grade revealed additional 'fuzz' at deep (>100 μm) grain boundaries. However, heat treatment up to 1900 K produced reintegration of 'fuzz' with the bulk and He release at ˜1000 K and ˜1400-1800 K due to depopulation from vacancy complexes.

  7. Formation of helium induced nanostructure 'fuzz' on various tungsten grades

    Energy Technology Data Exchange (ETDEWEB)

    Baldwin, M.J., E-mail: mbaldwin@ferp.ucsd.ed [Center for Energy Research and Department of Mechanical and Aerospace Engineering, University of California-San Diego, 9500 Gilman Dr., La Jolla, CA 92093-0417 (United States); Doerner, R.P. [Center for Energy Research and Department of Mechanical and Aerospace Engineering, University of California-San Diego, 9500 Gilman Dr., La Jolla, CA 92093-0417 (United States)

    2010-09-30

    The response of a variety of W material grades to nanostructure 'fuzz' formation is explored. W targets are exposed to He or D{sub 2}-0.2He plasmas in PISCES-B at 900-1320 K to below sputter threshold He{sup +} ions of energy 25-60 eV for up to 2.2 x 10{sup 4} s. SEM and XPS reveal nanoscopic reorganization of the W surface to a layer of 'fuzz' of porosity {approx}90% as determined by a 'fuzz' removal/weight loss method. The variability of 'fuzz' growth is examined at 1120 K for 1 h durations: SR, SC and doped W grades - La{sub 2}O{sub 3} (1% wt.), Re (5% and 10% wt.), and TiC (1.5% wt.) developed 2-3 {mu}m thick 'fuzz' layers, while a VPS grade developed a layer 4 {mu}m thick. An RC grade revealed additional 'fuzz' at deep (>100 {mu}m) grain boundaries. However, heat treatment up to 1900 K produced reintegration of 'fuzz' with the bulk and He release at {approx}1000 K and {approx}1400-1800 K due to depopulation from vacancy complexes.

  8. The formation of brown adipose tissue induced by transgenic over-expression of PPARγ2.

    Science.gov (United States)

    Zhou, Ying; Yang, Jinzeng; Huang, Jinliang; Li, Ting; Xu, Dequan; Zuo, Bo; Hou, Liming; Wu, Wangjun; Zhang, Lin; Xia, Xiaoliang; Ma, Zhiyuan; Ren, Zhuqing; Xiong, Yuanzhu

    2014-04-18

    Brown adipose tissue (BAT) is specialized to dissipate energy as heat, therefore reducing fat deposition and counteracting obesity. Brown adipocytes arise from myoblastic progenitors during embryonic development by the action of transcription regulator PRDM16 binding to PPARγ, which promotes BAT-like phenotype in white adipose tissue. To investigate the capability of converting white adipose tissue to BAT or browning by PPARγ in vivo, we generated transgenic mice with over-expressed PPARγ2. The transgenic mice showed strong brown fat features in subcutaneous fat in morphology and histology. To provide molecular evidences on browning characteristics of the adipose tissue, we employed quantitative real-time PCR to determine BAT-specific gene expressions. The transgenic mice had remarkably elevated mRNA level of UCP1, Elovl3, PGC1α and Cebpα in subcutaneous fat. Compared with wild-type mice, UCP1 protein levels were increased significantly in transgenic mice. ATP concentration was slightly decreased in the subcutaneous fat of transgenic mice. Western blotting analysis also confirmed that phosphorylated AMPK and ACC proteins were significantly (P<0.01) increased in the transgenic mice. Therefore, this study demonstrated that over-expression of PPARγ2 in skeletal muscle can promote conversion of subcutaneous fat to brown fat formation, which can have beneficial effects on increasing energy metabolisms and combating obesity.

  9. The formation of green rust induced by tropical river biofilm components

    Energy Technology Data Exchange (ETDEWEB)

    Jorand, F., E-mail: jorand@pharma.uhp-nancy.fr [Laboratoire de Chimie Physique et Microbiologie pour l' Environnement (LCPME) UMR 7564, CNRS-Nancy-Universite, Institut Jean Barriol, 405 rue de Vandoeuvre, F-54600 Villers-les Nancy (France); Zegeye, A. [Laboratoire de Chimie Physique et Microbiologie pour l' Environnement (LCPME) UMR 7564, CNRS-Nancy-Universite, Institut Jean Barriol, 405 rue de Vandoeuvre, F-54600 Villers-les Nancy (France); Ghanbaja, J. [Service Commun de Microscopies Electroniques et Microanalyses X (SCMEM), Nancy-Universite, Bvd des Aiguillettes, BP 239, 54506, Vandoeuvre-les-Nancy (France); Abdelmoula, M. [Laboratoire de Chimie Physique et Microbiologie pour l' Environnement (LCPME) UMR 7564, CNRS-Nancy-Universite, Institut Jean Barriol, 405 rue de Vandoeuvre, F-54600 Villers-les Nancy (France)

    2011-06-01

    In the Sinnamary Estuary (French Guiana), a dense red biofilm grows on flooded surfaces. In order to characterize the iron oxides in this biofilm and to establish the nature of secondary minerals formed after anaerobic incubation, we conducted solid analysis and performed batch incubations. Elemental analysis indicated a major amount of iron as inorganic compartment along with organic matter. Solid analysis showed the presence of two ferric oxides ferrihydrite and lepidocrocite. Bacteria were abundant and represented more than 10{sup 11} cells g{sup -1} of dry weight among which iron reducers were revealed. Optical and electronic microscopy analysis revealed than the bacteria were in close vicinity of the iron oxides. After anaerobic incubations with exogenous electron donors, the biofilm's ferric material was reduced into green rust, a Fe{sup II}-Fe{sup III} layered double hydroxide. This green rust remained stable for several years. From this study and previous reports, we suggest that ferruginous biofilms should be considered as a favorable location for GR biomineralization when redox conditions and electron donors availability are gathered. - Research highlights: {yields} Characterization of ferruginous biofilm components by solid analysis methods. {yields} Lepidocrocite and ferrihydrite were the main iron oxides. {yields} Anaerobic incubation of biofilm with electron donors produced green rust. {yields} Biofilm components promote the formation of the green rust. {yields} Ferruginous biofilm could contribute to the natural mercury attenuation.

  10. Hyperthermia-induced micronucleus formation in a human keratinocyte cell line

    Energy Technology Data Exchange (ETDEWEB)

    Hintzsche, Henning; Riese, Thorsten [Universitaet Wuerzburg, Institut fuer Pharmakologie und Toxikologie, Versbacher Str. 9, 97078 Wuerzburg (Germany); Stopper, Helga, E-mail: Stopper@toxi.uni-wuerzburg.de [Universitaet Wuerzburg, Institut fuer Pharmakologie und Toxikologie, Versbacher Str. 9, 97078 Wuerzburg (Germany)

    2012-10-15

    Elevated temperature can cause biological effects in vitro and in vivo. Many studies on effects of hypo- and hyperthermia have been conducted, but only few studies systematically investigated the formation of genomic damage in the micronucleus test in human cells in vitro as a consequence of different temperatures. In the present study, HaCaT human keratinocytes were exposed to different temperatures from 37 Degree-Sign C to 42 Degree-Sign C for 24 h in a regular cell culture incubator. Micronucleus frequency as a marker of genomic damage was elevated in a temperature-dependent and statistically significant manner. Apoptosis occurred at temperatures of 39 Degree-Sign C or higher. Cell proliferation was unaffected up to 40 Degree-Sign C and decreased at 41 Degree-Sign C and 42 Degree-Sign C. Expression of the heat shock protein Hsp70 was elevated, particularly at temperatures of 40 Degree-Sign C and higher. These findings are in agreement with several in vivo studies and some in vitro studies looking at single, specific temperatures, but a systematically investigated temperature-dependent increase of genomic damage in human keratinocytes in vitro is demonstrated for the first time here.

  11. Evaluation of heterotopic bone formation induced by squalane and bone morphogenetic protein composite.

    Science.gov (United States)

    Kawakami, T; Kawai, T; Takei, N; Kise, T; Eda, S; Urist, M R

    1997-04-01

    Bone morphogenetic protein is an important molecule whose bioactivity depends on the carrier. Squalane is used in the formulation of various kinds of cosmetics because it is easily emulsified and has the property of spreading well. Thus, squalane might be effective as a bone morphogenetic protein delivery system. As a test for this possibility, gelatin capsules containing squalane and bone morphogenetic protein (bovine derived partially purified) composite were implanted under the hind-quarter perimuscular membrane of ddY mice. Control capsules containing only bone morphogenetic protein were used for controls. The implants were radiographically and histologically examined at 1 to 4 weeks after the operation. According to the radiographic analysis, squalane and bone morphogenetic protein composite and bone morphogenetic protein only control specimens formed widespread heterotopic bone tissues. The amount of heterotopic bone formation in the composite experimental specimens was approximately 40% greater than that in the controls. Histologic examination of experimental and control specimens revealed varying amounts of perichondral ossification by 2 weeks. By 3 and 4 weeks, the bone deposits were colonized by hematopoietic bone marrow. Squalane was effective for the slow local release of bone morphogenetic protein. Furthermore, the squalane and bone morphogenetic protein composite was a reliable osteoinductive biomaterial.

  12. Diversification of seed arrangement induced by ovule rotation and septum formation in Leguminosae.

    Science.gov (United States)

    Endo, Yasuhiko; Ohashi, Hiroyoshi

    2009-09-01

    The plants of Leguminosae, which comprises 731 genera, bear monocarpellary flowers. The fruit, known as a pod, generally contains a row of seeds, and the internal structure appears to be simple. In Leguminosae, the seeds are generally arranged longitudinally along the suture of the pod but, in a few genera, namely, Cassia, Indigofera, and Senna, they are arranged transversely. Transverse seed arrangement facilitates the accommodation of a considerable number of seeds and has been considered to be established by rotation of seeds during development. We studied the development both these patterns of seed arrangement, i.e., longitudinal and transverse, in Senna and Indigofera in order to elucidate the structural changes occurring in ovaries (or pods) and determine the forces responsible for rotation of ovules (or seeds) by dissecting ovaries and pods at different developmental stages. Our results showed that at an early developmental stage the ovules were obliquely oriented or transversely arranged; later, the direction of their growth was restricted by the ovary walls or neighboring ovules, and therefore the obliquely oriented ovules rotated inward or outward. Thus, it was clarified that the processes involved in the formation of the internal structure of pods are regulated in a complex manner.

  13. Rheological properties and formation mechanism of DC electric fields induced konjac glucomannan-tungsten gels.

    Science.gov (United States)

    Wang, Lixia; Jiang, Yaoping; Lin, Youhui; Pang, Jie; Liu, Xiang Yang

    2016-05-20

    Konjac glucomannan-tungsten (KGM-T) hydrogel of electrochemical reversibility was successfully produced under DC electric fields in the presence of sodium tungstate. The structure and the effects of sodium tungstate concentration, KGM concentration, voltage and electric processing time on the rheological properties of the gels were investigated. pH experiments showed that KGM sol containing Na2WO4·2H2O in the vicinity of the positive electrode became acidic and the negative electrode basic after the application of DC electric fields. Under acid conditions, WO4(2-) ions transformed into isopoly-tungstic acid ions. FTIR and Raman studies indicated that isopoly-tungstic acid ions absorbed on KGM molecular chain and cross-linked with -OH groups at C-6 position on sugar units of KGM. Frequency sweep data showed with increasing sodium tungstate concentration, voltage, and electric processing time, the viscoelastic moduli, i.e., the storage and the loss moduli of the gel increased, whereas an increase in KGM concentration led to a decrease in gel viscoelastic moduli. The temperature sweep measurements indicated the obtained gel exhibited high thermal stability. Finally, the mechanism of gel formation was proposed. Our work may pave the way to use DC electric fields for the design and development of KGM gels as well as polysaccharide gels.

  14. Copper induced hollow carbon nanospheres by arc discharge method: controlled synthesis and formation mechanism

    Science.gov (United States)

    Hu, Rui; Alexandru Ciolan, Mihai; Wang, Xiangke; Nagatsu, Masaaki

    2016-08-01

    Hollow carbon nanospheres with controlled morphologies were synthesized via the copper-carbon direct current arc discharge method by alternating the concentrations of methane in the reactant gas mixture. A self-healing process to keep the structural integrity of encapsulated graphitic shells was evolved gradually by adding methane gas from 0% to 20%. The outer part of the coated layers expanded and hollow nanospheres grew to be large fluffy ones with high methane concentrations from 30% to 50%. A self-repairing function by the reattachment of broken graphitic layers initiated from near-electrode space to distance was also distinctly exhibited. By comparing several comparable metals (e.g. copper, silver, gold, zinc, iron and nickel)-carbon arc discharge products, a catalytic carbon-encapsulation mechanism combined with a core-escaping process has been proposed. Specifically, on the basis of the experimental results, copper could be applied as a unique model for both the catalysis of graphitic encapsulation and as an adequate template for the formation of hollow nanostructures.

  15. Negative Regulation of Leptin-induced Reactive Oxygen Species (ROS) Formation by Cannabinoid CB1 Receptor Activation in Hypothalamic Neurons.

    Science.gov (United States)

    Palomba, Letizia; Silvestri, Cristoforo; Imperatore, Roberta; Morello, Giovanna; Piscitelli, Fabiana; Martella, Andrea; Cristino, Luigia; Di Marzo, Vincenzo

    2015-05-29

    The adipocyte-derived, anorectic hormone leptin was recently shown to owe part of its regulatory effects on appetite-regulating hypothalamic neuropeptides to the elevation of reactive oxygen species (ROS) levels in arcuate nucleus (ARC) neurons. Leptin is also known to exert a negative regulation on hypothalamic endocannabinoid levels and hence on cannabinoid CB1 receptor activity. Here we investigated the possibility of a negative regulation by CB1 receptors of leptin-mediated ROS formation in the ARC. Through pharmacological and molecular biology experiments we report data showing that leptin-induced ROS accumulation is 1) blunted by arachidonyl-2'-chloroethylamide (ACEA) in a CB1-dependent manner in both the mouse hypothalamic cell line mHypoE-N41 and ARC neuron primary cultures, 2) likewise blocked by a peroxisome proliferator-activated receptor-γ (PPAR-γ) agonist, troglitazone, in a manner inhibited by T0070907, a PPAR-γ antagonist that also inhibited the ACEA effect on leptin, 3) blunted under conditions of increased endocannabinoid tone due to either pharmacological or genetic inhibition of endocannabinoid degradation in mHypoE-N41 and primary ARC neuronal cultures from MAGL(-/-) mice, respectively, and 4) associated with reduction of both PPAR-γ and catalase activity, which are reversed by both ACEA and troglitazone. We conclude that CB1 activation reverses leptin-induced ROS formation and hence possibly some of the ROS-mediated effects of the hormone by preventing PPAR-γ inhibition by leptin, with subsequent increase of catalase activity. This mechanism might underlie in part CB1 orexigenic actions under physiopathological conditions accompanied by elevated hypothalamic endocannabinoid levels.

  16. The costae presenting in high-temperature-induced vestigial wings of Drosophila: implications for anterior wing margin formation

    Indian Academy of Sciences (India)

    Daxiang Yang

    2007-01-01

    It has long been noted that high temperature produces great variation in wing forms of the vestigial mutant of Drosophila. Most of the wings have defects in the wing blade and partially formed wing margin, which are the result of autonomous cell death in the presumptive wing blade or costal region of the wing disc. The vestigial gene ($vg$) and the interaction of Vg protein with other gene products are well understood. With this biochemical knowledge, reinvestigations of the high-temperature-induced vestigial wings and the elucidation of the molecular mechanism underlying the large-scale variation of the wing forms may provide insight into further understanding of development of the wing of Drosophila. As a first step of such explorations, I examined high-temperature-induced (29°C) vestigial wings. In the first part of this paper, I provide evidences to show that the proximal and distal costae in these wings exhibit regular and continuous variation, which suggests different developmental processes for the proximal and distal costal sections. Judging by the costae presenting in the anterior wing margin, I propose that the proximal and distal costal sections are independent growth units. The genes that regulate formation of the distal costal section also strongly affect proliferation of cells nearby; however, the same phenomenon has not been found in the proximal costal section. The distal costal section seems to be an extension of the radius vein. vestigial, one of the most intensely researched temperature-sensitive mutations, is a good candidate for the study of marginal vein formation. In the second part of the paper, I regroup the wing forms of these wings, chiefly by comparison of venation among these wings, and try to elucidate the variation of the wing forms according to the results of previous work and the conclusions reached in the first part of this paper, and provide clues for further researches.

  17. The single-giant unilamellar vesicle method reveals lysenin-induced pore formation in lipid membranes containing sphingomyelin.

    Science.gov (United States)

    Alam, Jahangir Md; Kobayashi, Toshihide; Yamazaki, Masahito

    2012-06-26

    Lysenin is a sphingomyelin (SM)-binding pore-forming toxin. To reveal the interaction of lysenin with lipid membranes, we investigated lysenin-induced membrane permeation of a fluorescent probe, calcein, through dioleoylphosphatidylcholine(DOPC)/SM, DOPC/SM/cholesterol(chol), and SM/chol membranes, using the single-giant unilamellar vesicle (GUV) method. The results clearly show that lysenin formed pores in all the membranes, through which membrane permeation of calcein occurred without disruption of GUVs. The membrane permeation began stochastically, and the membrane permeability coefficient increased over time to reach a maximum, steady value, Ps, which persisted for a long time(100--500 s), indicating that the pore concentration increases over time and finally reaches its steady value, NP s . The Ps values increased as the SM/lysenin ratio decreased, and at low concentrations of lysenin, the Ps values of SM/DOPC/chol (42/30/28)GUVs were much larger than those of SM/DOPC (58/42) GUVs. The dependence of Ps on the SM/lysenin ratio for these membranes was almost the same as that of the fraction of sodium dodecyl sulfate (SDS)-resistant lysenin oligomers, indicating that NP s increases as the SDS-resistant oligomer fraction increases. On the other hand, lysenin formed pores in GUVs of SM/chol(60/40) membrane, which is in a homogeneous liquid-ordered phase, indicating that the phase boundary is not necessary for pore formation. The Ps values of SM/chol (60/40) GUVs were smaller than those of SM/DOPC/chol (42/30/28) GUVs even though the SDS-resistant oligomer fractions were similar for both membranes, suggesting that not all of the oligomers can convert into a pore. On the basis of these results, we discuss the elementary processes of lysenin-induced pore formation.

  18. Modification of linear prepolymers to tailor heterogeneous network formation through photo-initiated Polymerization-Induced Phase Separation.

    Science.gov (United States)

    Szczepanski, Caroline R; Stansbury, Jeffrey W

    2015-07-23

    Polymerization-induced phase separation (PIPS) was studied in ambient photopolymerizations of triethylene glycol dimethacrylate (TEGDMA) modified by poly(methyl methacrylate) (PMMA). The molecular weight of PMMA and the rate of network formation (through incident UV-irradiation) were varied to influence both the promotion of phase separation through increases in overall free energy, as well as the extent to which phase development occurs during polymerization through diffusion prior to network gelation. The overall free energy of the polymerizing system increases with PMMA molecular weight, such that PIPS is promoted thermodynamically at low loading levels (5 wt%) of a higher molecular weight PMMA (120 kDa), while a higher loading level (20 wt%) is needed to induce PIPS with lower PMMA molecular weight (11 kDa), and phase separation was not promoted at any loading level tested of the lowest molecular weight PMMA (1 kDa). Due to these differences in overall free energy, systems modified by PMMA (11 kDa) underwent phase separation via Nucleation and Growth, and systems modified by PMMA (120 kDa), followed the Spinodal Decomposition mechanism. Despite differences in phase structure, all materials form a continuous phase rich in TEGDMA homopolymer. At high irradiation intensity (Io=20mW/cm(2)), the rate of network formation prohibited significant phase separation, even when thermodynamically preferred. A staged curing approach, which utilizes low intensity irradiation (Io=300µW/cm(2)) for the first ~50% of reaction to allow phase separation via diffusion, followed by a high intensity flood-cure to achieve a high degree of conversion, was employed to form phase-separated networks with reduced polymerization stress yet equivalent final conversion and modulus.

  19. Formation of Nanostructures in Severely Deformed High-Strength Steel Induced by High-Frequency Ultrasonic Impact Treatment

    Science.gov (United States)

    Dutta, R. K.; Malet, L.; Gao, H.; Hermans, M. J. M.; Godet, S.; Richardson, I. M.

    2015-02-01

    Surface modification by the generation of a nanostructured surface layer induced via ultrasonic impact treatment was performed at the weld toe of a welded high-strength quenched and tempered structural steel, S690QL1 (Fe-0.16C-0.2Si-0.87Mn-0.33Cr-0.21Mo (wt pct)). Such high-frequency peening techniques are known to improve the fatigue life of welded components. The nanocrystallized structure as a function of depth from the top-treated surface was characterized via a recently developed automated crystal orientation mapping in transmission electron microscopy. Based on the experimental observations, a grain refinement mechanism induced by plastic deformation during the ultrasonic impact treatment is proposed. It involves the formation of low-angle misoriented lamellae displaying a high density of dislocations followed by the subdivision of microbands into blocks and the resulting formation of polygonal submicronic grains. These submicronic grains further breakdown into nano grains. The results show the presence of retained austenite even after severe surface plastic deformation. The average grain size of the retained austenite and martensite is 17 and 35 nm, respectively. The in-grain deformation mechanisms are different in larger and smaller grains. Larger grains show long-range lattice rotations, while smaller grains show plastic deformation through grain rotation. Also the smaller nano grains exhibit the presence of short-range disorder. Surface nanocrystallization also leads to an increased fraction of low angle and low energy coincident site lattice boundaries especially in the smaller grains ( nm).

  20. Tetanus Toxin Hc Fragment Induces the Formation of Ceramide Platforms and Protects Neuronal Cells against Oxidative Stress.

    Directory of Open Access Journals (Sweden)

    Roger Cubí

    Full Text Available Tetanus toxin (TeTx is the protein, synthesized by the anaerobic bacteria Clostridium tetani, which causes tetanus disease. TeTx gains entry into target cells by means of its interaction with lipid rafts, which are membrane domains enriched in sphingomyelin and cholesterol. However, the exact mechanism of host membrane binding remains to be fully established. In the present study we used the recombinant carboxyl terminal fragment from TeTx (Hc-TeTx, the domain responsible for target neuron binding, showing that Hc-TeTx induces a moderate but rapid and sustained increase in the ceramide/sphingomyelin ratio in primary cultures of cerebellar granule neurons and in NGF-differentiated PC12 cells, as well as induces the formation of ceramide platforms in the plasma membrane. The mentioned increase is due to the promotion of neutral sphingomyelinase activity and not to the de novo synthesis, since GW4869, a specific neutral sphingomyelinase inhibitor, prevents neutral sphingomyelinase activity increase and formation of ceramide platforms. Moreover, neutral sphingomyelinase inhibition with GW4869 prevents Hc-TeTx-triggered signaling (Akt phosphorylation, as well as the protective effect of Hc-TeTx on PC12 cells subjected to oxidative stress, while siRNA directed against nSM2 prevents protection by Hc-TeTx of NSC-34 cells against oxidative insult. Finally, neutral sphingomyelinase activity seems not to be related with the internalization of Hc-TeTx into PC12 cells. Thus, the presented data shed light on the mechanisms triggered by TeTx after membrane binding, which could be related with the events leading to the neuroprotective action exerted by the Hc-TeTx fragment.

  1. Nanosecond pulsed electric fields induce poly(ADP-ribose) formation and non-apoptotic cell death in HeLa S3 cells.

    Science.gov (United States)

    Morotomi-Yano, Keiko; Akiyama, Hidenori; Yano, Ken-ichi

    2013-08-30

    Nanosecond pulsed electric fields (nsPEFs) have recently gained attention as effective cancer therapy owing to their potency for cell death induction. Previous studies have shown that apoptosis is a predominant mode of nsPEF-induced cell death in several cell lines, such as Jurkat cells. In this study, we analyzed molecular mechanisms for cell death induced by nsPEFs. When nsPEFs were applied to Jurkat cells, apoptosis was readily induced. Next, we used HeLa S3 cells and analyzed apoptotic events. Contrary to our expectation, nsPEF-exposed HeLa S3 cells exhibited no molecular signs of apoptosis execution. Instead, nsPEFs induced the formation of poly(ADP-ribose) (PAR), a hallmark of necrosis. PAR formation occurred concurrently with a decrease in cell viability, supporting implications of nsPEF-induced PAR formation for cell death. Necrotic PAR formation is known to be catalyzed by poly(ADP-ribose) polymerase-1 (PARP-1), and PARP-1 in apoptotic cells is inactivated by caspase-mediated proteolysis. Consistently, we observed intact and cleaved forms of PARP-1 in nsPEF-exposed and UV-irradiated cells, respectively. Taken together, nsPEFs induce two distinct modes of cell death in a cell type-specific manner, and HeLa S3 cells show PAR-associated non-apoptotic cell death in response to nsPEFs.

  2. B lymphocytes induce the formation of follicular dendritic cell clusters in a lymphotoxin alpha-dependent fashion.

    Science.gov (United States)

    Fu, Y X; Huang, G; Wang, Y; Chaplin, D D

    1998-04-06

    Lymphotoxin (LT)alpha is expressed by activated T cells, especially CD4(+) T helper type 1 cells, and by activated B and natural killer cells, but the functions of this molecule in vivo are incompletely defined. We have previously shown that follicular dendritic cell (FDC) clusters and germinal centers (GCs) are absent from the peripheral lymphoid tissues of LTalpha-deficient (LTalpha-/-) mice. LTalpha-/- mice produce high levels of antigen-specific immunoglobulin (Ig)M, but very low levels of IgG after immunization with sheep red blood cells. We show here that LTalpha-expressing B cells are essential for the recovery of primary, secondary, and memory humoral immune responses in LTalpha-/- mice. It is not necessary for T cells to express LTalpha to support these immune functions. Importantly, LTalpha-expressing B cells alone are essential and sufficient for the formation of FDC clusters. Once these clusters are formed by LTalpha-expressing B cells, then LTalpha-deficient T cells can interact with B cells to generate GCs and productive class-switched antibody responses. Thus, B cells themselves provide an essential signal that induces and maintains the lymphoid microenvironment essential for GC formation and class-switched Ig responses.

  3. Laser induced periodic surface structure formation in germanium by strong field mid IR laser solid interaction at oblique incidence.

    Science.gov (United States)

    Austin, Drake R; Kafka, Kyle R P; Trendafilov, Simeon; Shvets, Gennady; Li, Hui; Yi, Allen Y; Szafruga, Urszula B; Wang, Zhou; Lai, Yu Hang; Blaga, Cosmin I; DiMauro, Louis F; Chowdhury, Enam A

    2015-07-27

    Laser induced periodic surface structures (LIPSS or ripples) were generated on single crystal germanium after irradiation with multiple 3 µm femtosecond laser pulses at a 45° angle of incidence. High and low spatial frequency LIPSS (HSFL and LSFL, respectively) were observed for both s- and p-polarized light. The measured LSFL period for p-polarized light was consistent with the currently established LIPSS origination model of coupling between surface plasmon polaritons (SPP) and the incident laser pulses. A vector model of SPP coupling is introduced to explain the formation of s-polarized LSFL away from the center of the damage spot. Additionally, a new method is proposed to determine the SPP propagation length from the decay in ripple depth. This is used along with the measured LSFL period to estimate the average electron density and Drude collision time of the laser-excited surface. Finally, full-wave electromagnetic simulations are used to corroborate these results while simultaneously offering insight into the nature of LSFL formation.

  4. Heat-induced formation of mepiquat by decarboxylation of pipecolic acid and its betaine derivative. Part 1: Model system studies.

    Science.gov (United States)

    Yuan, Yuan; Tarres, Adrienne; Bessaire, Thomas; Stadler, Richard H; Delatour, Thierry

    2017-07-15

    This study describes, for the first time, the role of pipecolic acid betaine and pipecolic acid, naturally present in some foods, in the formation of the plant growth regulator N,N-dimethylpiperidinium (mepiquat) under dry thermal conditions. The formation of mepiquat and intermediate compounds was investigated in model systems using high performance liquid chromatography-quadrupole/time-of-flight mass spectrometry. Mepiquat is released with a yield of up to 0.66mol% after thermal treatment (>150°C) of pipecolic acid betaine. Similar conversion rates are attained with the congener piperidine-2-carboxylic acid (dl-pipecolic acid), albeit in the presence of alkylating agents, such as choline, glycine betaine or trigonelline, that are fairly widespread in food crops. These new pathways to mepiquat indicate that the occurrence of low levels of this thermally induced compound is probably more widespread in processed foods than initially suspected (see Part 2 of this study on the occurrence of mepiquat in selected foodstuffs).

  5. Effects of Cold Rolling and Strain-Induced Martensite Formation in a SAF 2205 Duplex Stainless Steel

    Science.gov (United States)

    Breda, Marco; Brunelli, Katya; Grazzi, Francesco; Scherillo, Antonella; Calliari, Irene

    2015-02-01

    Duplex stainless steels (DSSs) are biphasic steels having a ferritic-austenitic microstructure that allows them to combine good mechanical and corrosion-resistance properties. However, these steels are sensitive to microstructural modifications, such as ferrite decomposition at high temperatures and the possibility of strain-induced martensite (SIM) formation from cold-worked austenite, which can significantly alter their interesting features. In the present work, the effects of cold rolling on the developed microstructural features in a cold-rolled SAF 2205 DSS and the onset of martensitic transformation are discussed. The material was deformed at room temperature from 3 to 85 pct thickness reduction, and several characterization techniques (scanning and transmission electron microscopy, X-ray diffraction, hardness measurements, and time-of-flight-neutron diffraction) were employed in order to fully describe the microstructural behavior of the steel. Despite the low stacking fault energy of DSS austenite, which contributed to SIM formation, the steel was found to be more stable than other stainless steel grades, such as AISI 304L. Rolling textures were similar to those pertaining to single-phase materials, but the presence of the biphasic (Duplex) microstructure imposed deformation constraints that affected the developed microstructural features, owing to phases interactions. Moreover, even if an intensification of the strain field in austenite was revealed, retarded SIM transformation kinetics and lower martensite amounts with respect to AISI 304L were observed.

  6. DNase I and proteinase K impair Listeria monocytogenes biofilm formation and induce dispersal of pre-existing biofilms.

    Science.gov (United States)

    Nguyen, Uyen T; Burrows, Lori L

    2014-09-18

    Current sanitation methods in the food industry are not always sufficient for prevention or dispersal of Listeria monocytogenes biofilms. Here, we determined if prevention of adherence or dispersal of existing biofilms could occur if biofilm matrix components were disrupted enzymatically. Addition of DNase during biofilm formation reduced attachment (biofilms with 100μg/ml of DNase for 24h induced incomplete biofilm dispersal, with biofilm remaining compared to control. In contrast, addition of proteinase K completely inhibited biofilm formation, and 72h biofilms-including those grown under stimulatory conditions-were completely dispersed with 100μg/ml proteinase K. Generally-regarded-as-safe proteases bromelain and papain were less effective dispersants than proteinase K. In a time course assay, complete dispersal of L. monocytogenes biofilms from both polystyrene and type 304H food-grade stainless steel occurred within 5min at proteinase K concentrations above 25μg/ml. These data confirm that both DNA and proteins are required for L. monocytogenes biofilm development and maintenance, and that these components of the biofilm matrix can be targeted for effective prevention and removal of biofilms.

  7. Hyperlipidemia induced by high-fat diet enhances dentin formation and delays dentin mineralization in mouse incisor.

    Science.gov (United States)

    Ye, Xin; Zhang, Jin; Yang, Pishan

    2016-10-01

    Dyslipidemia has become a serious health problem in children and adolescents worldwide for its high prevalence. Since hard tissues of permanent teeth form mainly during this period and lipids are actively involved in tooth development, the effects of hyperlipidemia on dental tissue formation and mineralization need to be illustrated. In this study, hyperlipidemia model was established in mice fed with high-fat diet (HFD). Micro-CT and histomorphological analyses were performed on the mandibular bones to assess the morphological changes of the mandibular incisor and first molar. After 4 weeks of HFD feeding, mice had significantly elevated serum lipid levels compared with mice fed with control diet. After 8 weeks, the mandibular incisor presented significantly increased dentin thickness and decreased diameter of pulp cavity in HFD-fed mice compared with control diet-fed mice, while its gross morphology and enamel thickness were not altered. In the mandibular first molar, dentin thickness of root did not show difference between the two groups. Histological section showed that mandibular incisor of HFD-fed mice manifested a wider predentin region and a lower mineral apposition rate compared with that of the control mice. In conclusion, hyperlipidemia induced by HFD feeding enhances dentin formation and delays dentin mineralization in the developing mouse incisor.

  8. c-Myc Enhances Sonic Hedgehog-Induced Medulloblastoma Formation from Nestin-Expressing Neural Progenitors in Mice

    Directory of Open Access Journals (Sweden)

    Ganesh Rao

    2003-05-01

    Full Text Available Medulloblastomas are malignant brain tumors that arise in the cerebella of children. The presumed cellsof-origin are undifferentiated precursors of granule neurons that occupy the external granule layer (EGL of the developing cerebellum. The overexpression of proteins that normally stimulate proliferation of neural progenitor cells may initiate medulloblastoma formation. Two known mitogens for neural progenitors are the c-Myc oncoprotein and Sonic hedgehog (Shh, a crucial determinant of embryonic pattern formation in the central nervous system. We modeled the ability of c-Myc and Shh to induce medulloblastoma in mice using the RCAS/tv-a system, which allows postnatal gene transfer and expression in a cell type-specific manner. We targeted the expression of Shh and c-Myc to nestin-expressing neural progenitor cells by injecting replication-competent ALV splice acceptor (RCAS vectors into the cerebella of newborn mice. Following injection with RCAS-Shh alone, 3/32 (9% mice developed medulloblastomas and 5/32 showed multifocal hyperproliferation of the EGL, possibly a precursor stage of medulloblastoma. Following injection with RCAS-Shh plus RCAS-Myc, 9/39 (23% mice developed medulloblastomas. We conclude that nestin-expressing neural progenitors, present in the cerebellum at birth, can act as the cells-of-origin for medulloblastoma, and that c-Myc cooperates with Shh to enhance tumorigenicity.

  9. Enhanced activity of ADP glucose pyrophosphorylase and formation of starch induced by Azospirillum brasilense in Chlorella vulgaris.

    Science.gov (United States)

    Choix, Francisco J; Bashan, Yoav; Mendoza, Alberto; de-Bashan, Luz E

    2014-05-10

    ADP-glucose pyrophosphorylase (AGPase) regulates starch biosynthesis in higher plants and microalgae. This study measured the effect of the bacterium Azospirillum brasilense on AGPase activity in the freshwater microalga Chlorella vulgaris and formation of starch. This was done by immobilizing both microorganisms in alginate beads, either replete with or deprived of nitrogen or phosphorus and all under heterotrophic conditions, using d-glucose or Na-acetate as the carbon source. AGPase activity during the first 72h of incubation was higher in C. vulgaris when immobilized with A. brasilense. This happened simultaneously with higher starch accumulation and higher carbon uptake by the microalgae. Either carbon source had similar effects on enzyme activity and starch accumulation. Starvation either by N or P had the same pattern on AGPase activity and starch accumulation. Under replete conditions, the population of C. vulgaris immobilized alone was higher than when immobilized together, but under starvation conditions A. brasilense induced a larger population of C. vulgaris. In summary, adding A. brasilense enhanced AGPase activity, starch formation, and mitigation of stress in C. vulgaris.

  10. 5-Azacytidine Induces Anoikis, Inhibits Mammosphere Formation and Reduces Metalloproteinase 9 Activity in MCF-7 Human Breast Cancer Cells

    Directory of Open Access Journals (Sweden)

    Hsueh-Wei Chang

    2014-03-01

    Full Text Available Cancer stem cells are a subset of cancer cells that initiate the growth of tumors. Low levels of cancer stem cells also exist in established cancer cell lines, and can be enriched in serum-free tumorsphere cultures. Since cancer stem cells have been reported to be resilient to common chemotherapeutic drugs in comparison to regular cancer cells, screening for compounds selectively targeting cancer stem cells may provide an effective therapeutic strategy. We found that 5-azacytidine (5-AzaC selectively induced anoikis of MCF-7 in suspension cultures with an EC50 of 8.014 µM, and effectively inhibited tumorsphere formation, as well as the migration and matrix metalloproteinases-9 (MMP-9 activity of MCF-7 cells. Furthermore, 5-AzaC and radiation collaboratively inhibited MCF-7 tumorsphere formation at clinically relevant radiation doses. Investigating the underlying mechanism may provide insight into signaling pathways crucial for cancer stem cell survival and pave the way to novel potential therapeutic targets.

  11. Copper inducing Aβ42 rather than Aβ40 nanoscale oligomer formation is the key process for Aβ neurotoxicity.

    Science.gov (United States)

    Jin, Lu; Wu, Wei-Hui; Li, Qiu-Ye