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Sample records for blocks lipopolysaccharide-induced gene

  1. Effects of lipopolysaccharide-induced inflammation on expression of growth-associated genes by corticospinal neurons

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    Lieberman AR

    2006-01-01

    Full Text Available Abstract Background Inflammation around cell bodies of primary sensory neurons and retinal ganglion cells enhances expression of neuronal growth-associated genes and stimulates axonal regeneration. We have asked if inflammation would have similar effects on corticospinal neurons, which normally show little response to spinal cord injury. Lipopolysaccharide (LPS was applied onto the pial surface of the motor cortex of adult rats with or without concomitant injury of the corticospinal tract at C4. Inflammation around corticospinal tract cell bodies in the motor cortex was assessed by immunohistochemistry for OX42 (a microglia and macrophage marker. Expression of growth-associated genes c-jun, ATF3, SCG10 and GAP-43 was investigated by immunohistochemistry or in situ hybridisation. Results Application of LPS induced a gradient of inflammation through the full depth of the motor cortex and promoted c-Jun and SCG10 expression for up to 2 weeks, and GAP-43 upregulation for 3 days by many corticospinal neurons, but had very limited effects on neuronal ATF3 expression. However, many glial cells in the subcortical white matter upregulated ATF3. LPS did not promote sprouting of anterogradely labelled corticospinal axons, which did not grow into or beyond a cervical lesion site. Conclusion Inflammation produced by topical application of LPS promoted increased expression of some growth-associated genes in the cell bodies of corticospinal neurons, but was insufficient to promote regeneration of the corticospinal tract.

  2. Heat stress prevents lipopolysaccharide-induced apoptosis in pulmonary microvascular endothelial cells by blocking calpain/p38 MAPK signalling.

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    Liu, Zhi-Feng; Zheng, Dong; Fan, Guo-Chang; Peng, Tianqing; Su, Lei

    2016-08-01

    Pulmonary microvascular endothelial cells (PMECs) injury including apoptosis plays an important role in the pathogenesis of acute lung injury during sepsis. Our recent study has demonstrated that calpain activation contributes to apoptosis in PMECs under septic conditions. This study investigated how calpain activation mediated apoptosis and whether heat stress regulated calpain activation in lipopolysaccharides (LPS)-stimulated PMECs. In cultured mouse primary PMECs, incubation with LPS (1 μg/ml, 24 h) increased active caspase-3 fragments and DNA fragmentation, indicative of apoptosis. These effects of LPS were abrogated by pre-treatment with heat stress (43 °C for 2 h). LPS also induced calpain activation and increased phosphorylation of p38 MAPK. Inhibition of calpain and p38 MAPK prevented apoptosis induced by LPS. Furthermore, inhibition of calpain blocked p38 MAPK phosphorylation in LPS-stimulated PMECs. Notably, heat stress decreased the protein levels of calpain-1/2 and calpain activities, and blocked p38 MAPK phosphorylation in response to LPS. Additionally, forced up-regulation of calpain-1 or calpain-2 sufficiently induced p38 MAPK phosphorylation and apoptosis in PMECs, both of which were inhibited by heat stress. In conclusion, heat stress prevents LPS-induced apoptosis in PMECs. This effect of heat stress is associated with down-regulation of calpain expression and activation, and subsequent blockage of p38 MAPK activation in response to LPS. Thus, blocking calpain/p38 MAPK pathway may be a novel mechanism underlying heat stress-mediated inhibition of apoptosis in LPS-stimulated endothelial cells.

  3. Dynamic expression of leukocyte innate immune genes in whole blood from horses with lipopolysaccharide-induced acute systemic inflammation

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    Vinther, Anne Mette L.; Skovgaard, Kerstin; Heegaard, Peter M. H.

    2015-01-01

    Background: In horses, insights into the innate immune processes in acute systemic inflammation are limited even though these processes may be highly important for future diagnostic and therapeutic advances in high-mortality disease conditions as the systemic inflammatory response syndrome (SIRS...... expressions in blood leukocytes during equine acute LPS-induced systemic inflammation thoroughly characterized a highly regulated and dynamic innate immune response. These results provide new insights into the molecular mechanisms of equine systemic inflammation.......) and sepsis. Therefore, the aim of this study was to investigate the expression of 31 selected blood leukocyte immune genes in an equine model of acute systemic inflammation to identify significantly regulated genes and to describe their expression dynamics during a 24-h experimental period. Systemic...

  4. Negative feedback regulation of lipopolysaccharide-induced inducible nitric oxide synthase gene expression by heme oxygenase-1 induction in macrophages.

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    Ashino, Takashi; Yamanaka, Rieko; Yamamoto, Masayuki; Shimokawa, Hiroaki; Sekikawa, Kenji; Iwakura, Yoichiro; Shioda, Seiji; Numazawa, Satoshi; Yoshida, Takemi

    2008-04-01

    Heme oxygenase-1 (HO-1) is induced under infectious diseases in macrophages. We performed experiments using various gene deficient mouse-derived macrophages to determine a detailed induction mechanism of HO-1 by lipopolysaccharide (LPS) and the functional role of HO-1 induction in macrophages. LPS (1 microg/mL) maximally induced inducible nitric oxide synthase (iNOS) and HO-1 mRNAs in wild-type (WT) macrophages at 6h and 12h after treatment, respectively, and liberated tumor necrosis factor alpha (TNFalpha) from WT macrophages. LPS also induced iNOS and HO-1 in TNFalpha(-/-) macrophages, but not in iNOS(-/-) macrophages. Interestingly, although LPS strongly induced iNOS, it failed to induce HO-1 almost completely in nuclear-factor erythroid 2-related factor 2 (Nrf2)(-/-) macrophages. The LPS-induced iNOS gene expression was suppressed by pretreatment with HO-1 inducers, hemin and Co-protoporphyrin (CoPP), but not with HO-1 inhibitor, Sn-protoporphyrin in WT macrophages. In the Nrf2(-/-) macrophages, the ability of CoPP to induce HO-1 and its inhibitory effect on the LPS-induced iNOS gene expression were lower than seen in WT macrophages. The present findings suggest that HO-1 is induced via NO-induced nuclear translocation of Nrf2, and the enzymatic function of HO-1 inhibits the overproduction of NO in macrophages.

  5. Comparative effects of the herbal constituent parthenolide (Feverfew on lipopolysaccharide-induced inflammatory gene expression in murine spleen and liver

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    Smolinski Alexa T

    2005-06-01

    Full Text Available Abstract Background Parthenolide, a major sesquiterpene lactone present in extracts of the herb Feverfew, has been investigated for its inhibitory effects on mediators of inflammation, including the proinflammatory cytokines. Although parthenolide's anti-inflammatory effects have been investigated in vitro, little in vivo data are available. Moreover, the molecular mechanisms for these inhibitory effects are not fully understood. The objective of this study was to test the hypothesis that parthenolide suppresses lipopolysaccharide (LPS-induced serum (interleukin IL-6, tumor necrosis factor (TNF-α, IL-1β and cyclooxygenase (COX-2 expression in mice as indicated by reduced splenic and liver mRNA levels. Methods Mice were co-treated i.p. with LPS (1 mg/kg bw and parthenolide (5 mg/kg bw and blood, spleen and liver collected. Serum was analyzed for IL-6, TNF-α and IL-1β by ELISA. Total RNA was extracted from spleen and liver, and real-time RT-PCR was used to determine relative mRNA expression of IL-1β, IL-6, TNF-α and COX-2. Results LPS induced increases in serum IL-6 and TNF-α concentrations with only IL-6 being suppressed in parthenolide-treated mice. Induction of IL-6 mRNA was reduced, TNF-α and COX-2 mRNAs unchanged, and IL-1β mRNA increased in spleens of parthenolide plus LPS co-treated animals compared to LPS-only. No significant differences were observed in inflammatory gene expression between these two groups in liver samples. Overall, mRNA expression of each proinflammatory gene was much higher in spleen when compared to liver. Conclusion In summary, only one gene, IL-6, was modestly suppressed by parthenolide co-exposure which contrasts with many in vitro studies suggesting anti-inflammatory effects of this compound. Also, LPS evoked greater effects in spleen than liver on expression of proinflammatory genes. Further study of the effects of parthenolide and other herbal constituents on inflammatory gene expression using model

  6. Gene expression of the concentration-sensitive sodium channel is suppressed in lipopolysaccharide-induced acute lung injury in mice.

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    Hagiwara, Teruki; Yoshida, Shigeru; Hidaka, Yuji

    2017-04-01

    The concentration-sensitive sodium channel (Na C ) is expressed in alveolar type II epithelial cells and pulmonary microvascular endothelial cells in mouse lungs. We recently reported that Na C contributes to amiloride-insensitive sodium transport in mouse lungs (Respiratory Physiology & Neurobiology, 2016). However, details regarding its physiological role in the lung remain unknown. To examine whether Na C is involved in alveolar fluid clearance during an acute lung injury (ALI), we analyzed the relationship between Na C gene expression in the lung and the development of pulmonary edema in lipopolysaccharide (LPS)-induced ALI mice. LPS-induced ALI mice were prepared by the intratracheal administration of LPS. Bronchoalveolar lavage (BAL) neutrophils and lung water content (LWCs) were used as a marker of ALI and pulmonary edema, respectively. Na C protein production in the lung was detected by immunoblotting and immunofluorescence. The gene expressions of Na C and the epithelial sodium channel (ENaC) of LPS-induced ALI mice were examined by quantitative RT-PCR over a time course of 14 days. The BAL neutrophil count increased until day 2 after LPS administration and had nearly recovered by day 6. LWCs in LPS-induced mice gradually increased until day 8 and had recovered by day 14. The expression of the Na C protein in the lungs of LPS-induced mice dramatically decreased from day 2 to day 6, but recovered by day 8. The mRNA expression of Na C decreased in the lung, as well as those for α-, β-, and γ-ENaC during ALI. Thus, Na C expression is suppressed during the development stage of pulmonary edema and then recovers in the convalescent phase. Our results suggest that suppression of the gene expression of Na C is involved in the development of pulmonary edema in ALI.

  7. Neonatal manipulation of oxytocin prevents lipopolysaccharide-induced decrease in gene expression of growth factors in two developmental stages of the female rat.

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    Bakos, Jan; Lestanova, Zuzana; Strbak, Vladimir; Havranek, Tomas; Bacova, Zuzana

    2014-10-01

    Oxytocin production and secretion is important for early development of the brain. Long-term consequences of manipulation of oxytocin system might include changes in markers of brain plasticity - cytoskeletal proteins and neurotrophins. The aim of the present study was (1) to determine whether neonatal oxytocin administration affects gene expression of nestin, microtubule-associated protein-2 (MAP-2), brain derived neurotrophic factor (BDNF) and nerve growth factor (NGF) in the brain of two developmental stages of rat and (2) to evaluate whether neonatal oxytocin administration protects against lipopolysaccharide (LPS) induced inflammation. Neonatal oxytocin did not prevent a decrease of body weight in the LPS treated animals. Oxytocin significantly increased gene expression of BDNF in the right hippocampus in 21-day and 2-month old rats of both sexes. Gene expression of NGF and MAP-2 significantly increased in males treated with oxytocin. Both, growth factors and intermediate filament-nestin mRNA levels, were reduced in females exposed to LPS. Oxytocin treatment prevented a decrease in the gene expression of only growth factors. In conclusion, neonatal manipulation of oxytocin has developmental and sex-dependent effect on markers of brain plasticity. These results also indicate, that oxytocin may be protective against inflammation particularly in females. Copyright © 2014 Elsevier Ltd. All rights reserved.

  8. Glucocorticoid augments lipopolysaccharide-induced activation of the IκBζ-dependent genes encoding the anti-microbial glycoproteins lipocalin 2 and pentraxin 3.

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    Yamazaki, Soh; Akira, Shizuo; Sumimoto, Hideki

    2015-05-01

    Bacterial lipopolysaccharide (LPS), one of the most potent inducers of inflammation, activates the transcription factor NF-κB to induce expression of both proinflammatory mediators and anti-microbial glycoproteins such as lipocalin 2 (Lcn2) and pentraxin 3 (PTX3) in macrophages. Glucocorticoids are known to inhibit LPS-induced expression of proinflammatory cytokines via glucocorticoid receptor (GR)-mediated transrepression of NF-κB, whereas their effect on induction of anti-microbial effectors has remained to be elucidated. Here we show that the synthetic glucocorticoid dexamethasone (Dex) strongly enhances LPS-induced transcription of Lcn2 and Ptx3, although Dex by itself fails to trigger their transcription. In macrophages deficient in IκBζ (an inducible coactivator of NF-κB), Lcn2 and Ptx3 are not activated by LPS either alone or in combination with Dex. Association of GR as well as Brg1 (a subunit of the chromatin remodelling Swi/Snf complex) with a functional glucocorticoid response element in Lcn2 requires both the costimulation with LPS and the presence of IκBζ. Although Ptx3 does not contain the element, LPS induces recruitment of Dex-liganded GR to NF-κB-binding sites in regulatory regions of Ptx3, an event that does not occur in IκBζ-deficient macrophages. Thus glucocorticoids likely regulate infection-induced inflammation by increasing anti-microbial effectors in an IκBζ-dependent manner, while repressing proinflammatory genes. © The Authors 2014. Published by Oxford University Press on behalf of the Japanese Biochemical Society. All rights reserved.

  9. Lipopolysaccharide-induced M2 to M1 macrophage transformation for IL-12p70 production is blocked by Candida albicans mediated up-regulation of EBI3 expression.

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    Xing-Feng Zheng

    Full Text Available Macrophages are heterogeneous cell populations that are present in all tissues. Macrophages can be divided into classically activated inflammatory macrophages (M1 and alternatively activated anti-inflammatory macrophages (M2. It has been generally accepted that M1 macrophages are polarised in an inflammatory environment to produce pro-inflammatory cytokines, whilst M2 macrophages are involved in anti-inflammation and aid tissue repair in wound healing. Bacterial endotoxin (lipopolysaccharide; LPS is a potent factor in infection, which induces M1 macrophages resulting in higher levels of iNOS, TNFα and IL-12p70 which dictate inflammatory T cell responses. M2 macrophages can be transformed into M1 macrophages following LPS stimulation to promote inflammation. Candida albicans is a commensal fungal microorganism, which has been suggested to induce immune tolerance; however, the mechanism of C. albicans-induced immune tolerance has not been investigated in detail. IL-35 is a recently identified anti-inflammatory cytokine which is a heterodimeric protein consisting of the Epstein-Barr virus-induced gene 3 (EBI3 and IL-12p35. IL-35 shares the protein subunit p35, with IL-12p70. IL-12p70 is the most potent cytokine to induce Th1 responses during inflammation. In this study, we demonstrate that heat-killed C. albicans (HKC strongly suppressed LPS-induced IL-12p70 production in M2 macrophages. Candida albicans induced a high level of EBI3 expression in M2 macrophages, which served as a mechanism for IL-12p70 suppression by competitive binding of the common protein subunit (p35 of IL-35 and IL-12p70. To demonstrate that EBI3 expression had the ability to block IL-12p70 production intracellularly, a Chinese Hamster Ovary (CHO cell line with biscistronic expression of IL-12p40 and p35 was constructed, followed by ectopic over-expression of EBI3. The over-expression of EBI3 in the IL-12p70 producing cell line effectively suppressed IL-12p70 production. IL

  10. SIRT2 ameliorates lipopolysaccharide-induced inflammation in macrophages

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    Lee, Ae Sin; Jung, Yu Jin; Kim, Dal; Nguyen-Thanh, Tung [Department of Internal Medicine, Chonbuk National University Medical School, Jeonju (Korea, Republic of); Kang, Kyung Pyo [Department of Internal Medicine, Chonbuk National University Medical School, Jeonju (Korea, Republic of); Research Institute of Clinical Medicine of Chonbuk National University, Chonbuk National University Hospital, Jeonju (Korea, Republic of); Lee, Sik [Department of Internal Medicine, Chonbuk National University Medical School, Jeonju (Korea, Republic of); Park, Sung Kwang [Department of Internal Medicine, Chonbuk National University Medical School, Jeonju (Korea, Republic of); Research Institute of Clinical Medicine of Chonbuk National University, Chonbuk National University Hospital, Jeonju (Korea, Republic of); Kim, Won, E-mail: kwon@jbnu.ac.kr [Department of Internal Medicine, Chonbuk National University Medical School, Jeonju (Korea, Republic of); Research Institute of Clinical Medicine of Chonbuk National University, Chonbuk National University Hospital, Jeonju (Korea, Republic of)

    2014-08-08

    Highlights: • Knockout of SIRT2 attenuates lipopolysaccharide-induced iNOS expression. • Lipopolysaccharide-induced NO production is decreased in SIRT2 KO macrophage. • SIRT2 deficiency suppresses lipopolysaccharide-induced ROS production in macrophage. • M1-macrophage related factors are decreased in SIRT2 deficient cells. • SIRT2 deficiency decreases lipopolysaccharide-induced activation of NFκB. - Abstract: Introduction: SIRT2 is a NAD(+)-dependent deacetylases and associated with numerous processes such as infection, carcinogenesis, DNA damage and cell cycle regulation. However, the role of SIRT2 in inflammatory process in macrophage remains unclear. Materials and methods: In the present study, we have evaluated the regulatory effects of SIRT2 in lipopolysaccharide (LPS)-stimulated macrophages isolated from SIRT2 knockout (KO) and wild type (WT) mice or Raw264.7 macrophage cells. As inflammatory parameters, expression of inducible nitric oxide synthase (iNOS), the productions of nitric oxide, reactive oxygen species (ROS) and M1-macrophage-related factors were evaluated. We also examined the effects of SIRT2 on activation of nuclear factor-kappaB (NFκB) signaling. Results: SIRT2 deficiency inhibits LPS-induced iNOS mRNA and protein expression in bone marrow derived macrophages. SIRT2-siRNA transfection also suppressed LPS-induced iNOS expression in Raw264.7 macrophage cells. Bone marrow derived macrophages isolated from SIRT2 KO mice produced lower nitric oxide and expressed lower levels of M1-macrophage related markers including iNOS and CD86 in response to LPS than WT mice. Decrease of SIRT2 reduced the LPS-induced reactive oxygen species production. Deficiency of SIRT2 resulted in inhibition of NFκB activation through reducing the phosphorylation and degradation of IκBα. The phosphorylation and nuclear translocation of p65 was significantly decreased in SIRT2-deficient macrophages after LPS stimulation. Discussion: Our data suggested that

  11. Lipopolysaccharide induces IFN-γ production in human NK cells

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    Leonid M Kanevskiy

    2013-01-01

    Full Text Available NK cells have been shown to play a regulatory role in sepsis. According to the current view, NK cells become activated via macrophages or dendritic cells primed by lipopolysaccharide (LPS. Recently TLR4 gene expression was detected in human NK cells suggesting the possibility of a direct action of LPS on NK cells. In this study, effects of LPS on NK cell cytokine production and cytotoxicity were studied using highly purified human NK cells. LPS induced IFN-γ production in the presence of IL-2 in cell populations containing >98% CD56+ cells. Surprisingly, in the same experiments LPS decreased NK cell degranulation. No significant expression of markers related to blood dendritic cells, monocytes or T or B lymphocytes in the NK cell preparations was observed; the portions of HLA-DRbright, CD14+, CD3+ and CD20+ cells amounted to less than 0.1% within the cell populations. No more than 0.2% of NK cells were shown to be slightly positive for surface TLR4 in our experimental system, although intracellular staining revealed moderate amounts of TLR4 inside the NK cell population. These cells were negative for surface CD14, the receptor participating in LPS recognition by TLR4. Incubation of NK cells with IL-2 or/and LPS did not lead to an increase in TLR4 surface expression. TLR4–CD56+ NK cells isolated by cell sorting secreted IFN-γ in response to LPS. Antibody to TLR4 did not block the LPS-induced increase in IFN-γ production. We have also shown that Re-form of LPS lacking outer core oligosaccharide and O-antigen induces less cytokine production in NK cells than full length LPS. We speculate that the polysaccharide fragments of LPS molecule may take part in LPS-induced IFN-γ production by NK cells. Collectively our data suggest the existence of a mechanism of LPS direct action on NK cells distinct from established TLR4-mediated signaling.

  12. Blockade of the N-Methyl-D-Aspartate Glutamate Receptor Ameliorates Lipopolysaccharide-Induced Renal Insufficiency.

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    Lin, Chian-Shiung; Hung, Shun-Fa; Huang, Ho-Shiang; Ma, Ming-Chieh

    2015-01-01

    N-methyl-D-aspartate (NMDA) receptor activation in rat kidney reduces renal perfusion and ultrafiltration. Hypoperfusion-induced ischemia is the most frequent cause of functional insufficiency in the endotoxemic kidney. Here, we used non-hypotensive rat model of lipopolysaccharide-induced endotoxemia to examine whether NMDA receptor hyperfunction contributes to acute kidney injury. Lipopolysaccharide-induced renal damage via increased enzymuria and hemodynamic impairments were ameliorated by co-treatment with the NMDA receptor blocker, MK-801. The NMDA receptor NR1 subunit in the rat kidney mainly co-localized with serine racemase, an enzyme responsible for synthesizing the NMDA receptor co-agonist, D-serine. The NMDA receptor hyperfunction in lipopolysaccharide-treated kidneys was demonstrated by NR1 and serine racemase upregulation, particularly in renal tubules, and by increased D-serine levels. Lipopolysaccharide also induced cell damage in cultured tubular cell lines and primary rat proximal tubular cells. This damage was mitigated by MK-801 and by small interfering RNA targeting NR1. Lipopolysaccharide increased cytokine release in tubular cell lines via toll-like receptor 4. The release of interleukin-1β from these cells are the most abundant. An interleukin-1 receptor antagonist not only attenuated cell death but also abolished lipopolysaccharide-induced NR1 and serine racemase upregulation and increases in D-serine secretion, suggesting that interleukin-1β-mediated NMDA receptor hyperfunction participates in lipopolysaccharide-induced tubular damage. The results of this study indicate NMDA receptor hyperfunction via cytokine effect participates in lipopolysaccharide-induced renal insufficiency. Blockade of NMDA receptors may represent a promising therapeutic strategy for the treatment of sepsis-associated renal failure.

  13. Carbachol ameliorates lipopolysaccharide-induced intestinal epithelial tight junction damage by down-regulating NF-{kappa}{beta} and myosin light-chain kinase pathways

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    Zhang, Ying [Department of Anesthesia, Critical Care Medicine and Emergency Medicine Center, Zhongnan Hospital, Wuhan University, Wuhan 430071, Hubei Province, People' s Republic of China (China); Li, Jianguo, E-mail: 2010lijianguo@sina.cn [Department of Anesthesia, Critical Care Medicine and Emergency Medicine Center, Zhongnan Hospital, Wuhan University, Wuhan 430071, Hubei Province, People' s Republic of China (China)

    2012-11-16

    Highlights: Black-Right-Pointing-Pointer Carbachol reduced the lipopolysaccharide-induced intestinal barrier breakdown. Black-Right-Pointing-Pointer Carbachol ameliorated the lipopolysaccharide-induced ileal tight junction damage. Black-Right-Pointing-Pointer Carbachol prevented the LPS-induced NF-{kappa}{beta} and myosin light-chain kinase activation. Black-Right-Pointing-Pointer Carbachol exerted its beneficial effects in an {alpha}7 nicotinic receptor-dependent manner. -- Abstract: Carbachol is a cholinergic agonist that protects the intestines after trauma or burn injury. The present study determines the beneficial effects of carbachol and the mechanisms by which it ameliorates the lipopolysaccharide (LPS)-induced intestinal barrier breakdown. Rats were injected intraperitoneally with 10 mg/kg LPS. Results showed that the gut barrier permeability was reduced, the ultrastructural disruption of tight junctions (TJs) was prevented, the redistribution of zonula occludens-1 and claudin-2 proteins was partially reversed, and the nuclear factor-kappa beta (NF-{kappa}{beta}) and myosin light-chain kinase (MLCK) activation in the intestinal epithelium were suppressed after carbachol administration in LPS-exposed rats. Pretreatment with the {alpha}7 nicotinic acetylcholine receptor ({alpha}7nAchR) antagonist {alpha}-bungarotoxin blocked the protective action of carbachol. These results suggested that carbachol treatment can protect LPS-induced intestinal barrier dysfunction. Carbachol exerts its beneficial effect on the amelioration of the TJ damage by inhibiting the NF-{kappa}{beta} and MLCK pathways in an {alpha}7nAchR-dependent manner.

  14. Riboflavin attenuates lipopolysaccharide-induced lung injury in rats.

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    Al-Harbi, Naif O; Imam, Faisal; Nadeem, Ahmed; Al-Harbi, Mohammed M; Korashy, Hesham M; Sayed-Ahmed, Mohammed M; Hafez, Mohamed M; Al-Shabanah, Othman A; Nagi, Mahmoud N; Bahashwan, Saleh

    2015-01-01

    Riboflavin (vitamin B2) is an easily absorbed micronutrient with a key role in maintaining health in humans and animals. It is the central component of the cofactors flavin adenine dinucleotide (FAD) and flavin mononucleotide (FMN) and is therefore required by all flavoproteins. Riboflavin also works as an antioxidant by scavenging free radicals. The present study was designed to evaluate the effects of riboflavin against acute lungs injury induced by the administration of a single intranasal dose (20 μg/rat) of lipopolysaccharides (LPS) in experimental rats. Administration of LPS resulted in marked increase in malondialdehyde (MDA) level (p riboflavin in a dose-dependent manner (30 and 100 mg/kg, respectively). Riboflavin (100 mg/kg, p.o.) showed similar protective effects as dexamethasone (1 mg/kg, p.o.). Administration of LPS showed marked cellular changes including interstitial edema, hemorrhage, infiltration of PMNs, etc., which were reversed by riboflavin administration. Histopathological examinations showed normal morphological structures of lungs tissue in the control group. These biochemical and histopathological examination were appended with iNOS and CAT gene expression. The iNOS mRNA expression was increased significantly (p riboflavin significantly (p riboflavin caused a protective effect against LPS-induced ALI. These results suggest that riboflavin may be used to protect against toxic effect of LPS in lungs.

  15. An event-driven approach for studying gene block evolution in bacteria.

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    Ream, David C; Bankapur, Asma R; Friedberg, Iddo

    2015-07-01

    Gene blocks are genes co-located on the chromosome. In many cases, gene blocks are conserved between bacterial species, sometimes as operons, when genes are co-transcribed. The conservation is rarely absolute: gene loss, gain, duplication, block splitting and block fusion are frequently observed. An open question in bacterial molecular evolution is that of the formation and breakup of gene blocks, for which several models have been proposed. These models, however, are not generally applicable to all types of gene blocks, and consequently cannot be used to broadly compare and study gene block evolution. To address this problem, we introduce an event-based method for tracking gene block evolution in bacteria. We show here that the evolution of gene blocks in proteobacteria can be described by a small set of events. Those include the insertion of genes into, or the splitting of genes out of a gene block, gene loss, and gene duplication. We show how the event-based method of gene block evolution allows us to determine the evolutionary rateand may be used to trace the ancestral states of their formation. We conclude that the event-based method can be used to help us understand the formation of these important bacterial genomic structures. The software is available under GPLv3 license on http://github.com/reamdc1/gene_block_evolution.git. Supplementary online material: http://iddo-friedberg.net/operon-evolution © The Author 2015. Published by Oxford University Press.

  16. Dynamic Regulation of Delta-Opioid Receptor in Rat Trigeminal Ganglion Neurons by Lipopolysaccharide-induced Acute Pulpitis.

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    Huang, Jin; Lv, Yiheng; Fu, Yunjie; Ren, Lili; Wang, Pan; Liu, Baozhu; Huang, Keqiang; Bi, Jing

    2015-12-01

    Delta-opioid receptor (DOR) and its endogenous ligands distribute in trigeminal system and play a very important role in modulating peripheral inflammatory pain. DOR activation can trigger p44/42 mitogen-activated protein kinase (ERK1/2) and Akt signaling pathways, which participate in anti-inflammatory and neuroprotective effects. In this study, our purpose was to determine the dynamic changes of DOR in trigeminal ganglion (TG) neurons during the process of acute dental pulp inflammation and elucidate its possible mechanism. Forty rats were used to generate lipopolysaccharide-induced acute pulpitis animal models at 6, 12, and 24 hours and sham-operated groups. Acute pulpitis was confirmed by hematoxylin-eosin staining, and TG neuron activation was determined by anti-c-Fos immunohistochemistry. DOR protein and gene expression in TG was investigated by immunohistochemistry, Western blotting, and real-time polymerase chain reaction, and DOR expression in trigeminal nerves and dental pulp was also determined by immunohistochemistry. To further investigate the mechanism of DOR modulating acute inflammation, the change of pErk1/2 and pAkt in TG was examined by immunohistochemistry. Lipopolysaccharide could successfully induce acute pulpitis and activated TG neurons. Acute pulpitis could dynamically increase DOR protein and gene expression at 6, 12, and 24 hours in TG, and DOR dimerization was significantly increased at 12 and 24 hours. Acute pulpitis also induced the dynamic change of DOR protein in trigeminal nerve and dental pulp. Furthermore, ERK1/2 and Akt signaling pathways were inhibited in TG after acute pulpitis. Increased DOR expression and dimerization may play important roles in peripheral acute inflammatory pain. Copyright © 2015 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.

  17. Methylprednisolone stiffens aortas in lipopolysaccharide-induced chronic inflammation in rats.

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    Ya-Hui Ko

    Full Text Available INTRODUCTION: Glucocorticoids are commonly used as therapeutic agents in many acute and chronic inflammatory and auto-immune diseases. The current study investigated the effects of methylprednisolone (a synthetic glucocorticoid on aortic distensibility and vascular resistance in lipopolysaccharide-induced chronic inflammation in male Wistar rats. METHODS: Chronic inflammation was induced by implanting a subcutaneous slow-release ALZET osmotic pump (1 mg kg(-1 day(-1 lipopolysaccharide for either 2 or 4 weeks. Arterial wave transit time (τ was derived to describe the elastic properties of aortas using the impulse response function of the filtered aortic input impedance spectra. RESULTS: Long-term lipopolysaccharide challenge enhanced the expression of advanced glycation end products (AGEs in the aortas. Lipopolysaccharide also upregulated the inducible form of nitric oxide synthase to produce high levels of nitric oxide (NO, which resulted in vasodilation, as evidenced by the fall in total peripheral resistance (Rp . However, lipopolysaccharide challenge did not influence the elastic properties of aortas, as shown by the unaltered τ. The NO-mediated vascular relaxation may counterbalance the AGEs-induced arterial stiffening so that the aortic distensibility remained unaltered. Treating lipopolysaccharide-challenged rats with methylprednisolone prevented peripheral vasodilation because of its ability to increase Rp . However, methylprednisolone produced an increase in aorta stiffness, as manifested by the significant decline in τ. The diminished aortic distensibility by methylprednisolone paralleled a significant reduction in NO plasma levels, in the absence of any significant changes in AGEs content. CONCLUSION: Methylprednisolone stiffens aortas and elastic arteries in lipopolysaccharide-induced chronic inflammation in rats, for NO activity may be dominant as a counteraction of AGEs.

  18. Sesquiterpenes from Ulmus davidiana var. japonica with the inhibitory effects on lipopolysaccharide-induced nitric oxide production.

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    Kim, Young Choong; Lee, Mi Kyeong; Sung, Sang Hyun; Kim, Seung Hyun

    2007-04-01

    Investigation of antiinflammatory constituents of the stem and root barks of Ulmus davidiana var. japonica resulted in the isolation of three guaiane type sesquiterpenes, torilin, 1-hydroxytorilin, together with a new derivative, (1beta, 7beta, 8beta, 10beta)-1,8,11-trihydroxy-4-guaien-8-angeloyl-3-one named 1-hydroxytorilin A. All the three sesquiterpenes inhibited lipopolysaccharide-induced nitric oxide production in murine microglial BV2 cells.

  19. Differential effect of prostaglandins E1 and E2 on lipopolysaccharide-induced adhesion molecule expression on human monocytes.

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    Takahashi, Hideo K; Iwagaki, Hiromi; Tamura, Ryuji; Katsuno, Goutaro; Xue, Dong; Sugita, Sachi; Mori, Shuji; Yoshino, Tadashi; Tanaka, Noriaki; Nishibori, Masahiro

    2005-04-11

    The effect of prostaglandins E1 and E2 on the 1 ng/ml lipopolysaccharide-induced expression of intercellular adhesion molecule (ICAM)-1, B7.1, B7.2, CD40 and CD40 ligand (CD40L) on monocytes was examined. Prostaglandin E1 suppressed B7.1 and CD40 expression, but prostaglandin E2 did not effect on any type of adhesion molecule expression. Both prostaglandins inhibited tumor necrosis factor (TNF)-alpha production and T-cell proliferation of lipopolysaccharide-treated human peripheral blood mononuclear cells (PBMC). Among prostaglandin E1 receptors (IP/EP1/EP2/EP3/EP4) agonists, ONO-1301, a prostanoid IP-receptor agonist, prevented B7.1 and CD40 expression. ONO-AE1-259-01 a prostanoid EP2-receptor agonist, ONO-AE1-329, a prostanoid EP4-receptor agonist, and ONO-1301 inhibited TNF-alpha production and T-cell proliferation. Moreover, anti-B7.1 and anti-CD40 Abs prevented lipopolysaccharide-induced TNF-alpha production and T-cell proliferation. Therefore, the effect of prostaglandin E1 on TNF-alpha production and T-cell proliferation might depend on the inhibition of B7.1 and CD40 expression, but that of prostaglandin E2 might be independent of adhesion molecules expression. In conclusion, the mechanism responsible for the effect of prostaglandin E1 on lipopolysaccharide-induced responses is distinct from that of prostaglandin E2.

  20. Lipopolysaccharide induces H1 receptor expression and enhances histamine responsiveness in human coronary artery endothelial cells.

    Science.gov (United States)

    Raveendran, Vineesh V; Tan, Xiaoyu; Sweeney, Matthew E; Levant, Beth; Slusser, Joyce; Stechschulte, Daniel J; Dileepan, Kottarappat N

    2011-04-01

    Summary Histamine is a well-recognized modulator of vascular inflammation. We have shown that histamine, acting via H1 receptors (H1R), synergizes lipopolysaccharide (LPS)-induced production of prostaglandin I(2) (PGI(2)), PGE(2) and interleukin-6 (IL-6) by endothelial cells. The synergy between histamine and LPS was partly attributed to histamine -induced expression of Toll-like receptor 4 (TLR4). In this study, we examined whether LPS stimulates the H1R expression in human coronary artery endothelial cells (HCAEC) with resultant enhancement of histamine responsiveness. Incubation of HCAEC with LPS (10-1000 ng/ml) resulted in two-fold to fourfold increases in H1R mRNA expression in a time-dependent and concentration-dependent fashion. In contrast, LPS treatment did not affect H2R mRNA expression. The LPS-induced H1R mRNA expression peaked by 4 hr after LPS treatment and remained elevated above the basal level for 20-24 hr. Flow cytometric and Western blot analyses revealed increased expression of H1R protein in LPS-treated cells. The specific binding of [(3)H]pyrilamine to H1R in membrane proteins from LPS-treated HCAEC was threefold higher than the untreated cells. The LPS-induced H1R expression was mediated through TLR4 as gene silencing by TLR4-siRNA and treatment with a TLR4 antagonist inhibited the LPS effect. When HCAEC were pre-treated with LPS for 24 hr, washed and challenged with histamine, 17-, 10- and 15-fold increases in PGI(2), PGE(2) and IL-6 production, respectively, were noted. Histamine-induced enhancement of the synthesis of PGI(2), PGE(2) and IL-6 by LPS-primed HCAEC was completely blocked by an H1R antagonist. The results demonstrate that LPS, through TLR4 activation, up-regulates the expression and function of H1R and amplifies histamine-induced inflammatory responses in HCAEC. © 2011 The Authors. Immunology © 2011 Blackwell Publishing Ltd.

  1. Amphiphilic block co-polymers: preparation and application in nanodrug and gene delivery.

    Science.gov (United States)

    Xiong, Xiao-Bing; Binkhathlan, Ziyad; Molavi, Ommoleila; Lavasanifar, Afsaneh

    2012-07-01

    Self-assembly of amphiphilic block co-polymers composed of poly(ethylene oxide) (PEO) as the hydrophilic block and poly(ether)s, poly(amino acid)s, poly(ester)s and polypropyleneoxide (PPO) as the hydrophobic block can lead to the formation of nanoscopic structures of different morphologies. These structures have been the subject of extensive research in the past decade as artificial mimics of lipoproteins and viral vectors for drug and gene delivery. The aim of this review is to provide an overview of the synthesis of commonly used amphiphilic block co-polymers. It will also briefly go over some pharmaceutical applications of amphiphilic block co-polymers as "nanodelivery systems" for small molecules and gene therapeutics. Copyright © 2012 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

  2. DNMT1-interacting RNAs block gene specific DNA methylation

    Science.gov (United States)

    Di Ruscio, Annalisa; Ebralidze, Alexander K.; Benoukraf, Touati; Amabile, Giovanni; Goff, Loyal A.; Terragni, Joylon; Figueroa, Maria Eugenia; De Figureido Pontes, Lorena Lobo; Alberich-Jorda, Meritxell; Zhang, Pu; Wu, Mengchu; D’Alò, Francesco; Melnick, Ari; Leone, Giuseppe; Ebralidze, Konstantin K.; Pradhan, Sriharsa; Rinn, John L.; Tenen, Daniel G.

    2013-01-01

    Summary DNA methylation was described almost a century ago. However, the rules governing its establishment and maintenance remain elusive. Here, we present data demonstrating that active transcription regulates levels of genomic methylation. We identified a novel RNA arising from the CEBPA gene locus critical in regulating the local DNA methylation profile. This RNA binds to DNMT1 and prevents CEBPA gene locus methylation. Deep sequencing of transcripts associated with DNMT1 combined with genome-scale methylation and expression profiling extended the generality of this finding to numerous gene loci. Collectively, these results delineate the nature of DNMT1-RNA interactions and suggest strategies for gene selective demethylation of therapeutic targets in disease. PMID:24107992

  3. An allele of the crm gene blocks cyanobacterial circadian rhythms.

    Science.gov (United States)

    Boyd, Joseph S; Bordowitz, Juliana R; Bree, Anna C; Golden, Susan S

    2013-08-20

    The SasA-RpaA two-component system constitutes a key output pathway of the cyanobacterial Kai circadian oscillator. To date, rhythm of phycobilisome associated (rpaA) is the only gene other than kaiA, kaiB, and kaiC, which encode the oscillator itself, whose mutation causes completely arrhythmic gene expression. Here we report a unique transposon insertion allele in a small ORF located immediately upstream of rpaA in Synechococcus elongatus PCC 7942 termed crm (for circadian rhythmicity modulator), which results in arrhythmic promoter activity but does not affect steady-state levels of RpaA. The crm ORF complements the defect when expressed in trans, but only if it can be translated, suggesting that crm encodes a small protein. The crm1 insertion allele phenotypes are distinct from those of an rpaA null; crm1 mutants are able to grow in a light:dark cycle and have no detectable oscillations of KaiC phosphorylation, whereas low-amplitude KaiC phosphorylation rhythms persist in the absence of RpaA. Levels of phosphorylated RpaA in vivo measured over time are significantly altered compared with WT in the crm1 mutant as well as in the absence of KaiC. Taken together, these results are consistent with the hypothesis that the Crm polypeptide modulates a circadian-specific activity of RpaA.

  4. Effects of tylosin, tilmicosin and tulathromycin on inflammatory mediators in bronchoalveolar lavage fluid of lipopolysaccharide-induced lung injury.

    Science.gov (United States)

    Er, Ayse; Yazar, Enver

    2012-12-01

    The aim of this study was to determine the anti-inflammatory effects of macrolides through kinetic parameters in bronchoalveolar lavage fluid (BALF) of lipopolysaccharide-induced lung injury. Rats were divided into four groups: lipopolysaccharide (LPS), LPS + tylosin, LPS + tilmicosin and LPS + tulathromycin. BALF samples were collected at sampling times. TNF, IL-1β, IL-6, IL-10 and 13,14-dihydro-15-keto-prostaglandin F2α (PGM) and C-reactive protein (CRP) were analysed. Area under the curve (AUC) and maximum plasma concentration (Cmax) values of inflammatory mediators were determined by a pharmacokinetic computer programme. When inflammatory mediator concentrations were compared between the LPS group and other groups for each sampling time, the three macrolides had no pronounced depressor effect on cytokine levels, but they depressed PGM and CRP levels. In addition, tylosin and tilmicosin decreased the AUC0-24 level of TNF, while tilmicosin decreased the AUC0-24 level of IL-10. Tylosin and tulathromycin decreased the AUC0-24 of PGM, and all three macrolides decreased the AUC0-24 of CRP. Especially tylosin and tulathromycin may have more expressed anti-inflammatory effects than tilmicosin, via depressing the production of inflammatory mediators in the lung. The AUC may be used for determining the effects of drugs on inflammation. In this study, the antiinflammatory effects of these antibiotics were evaluated with kinetic parameters as a new and different approach.

  5. Aloin Suppresses Lipopolysaccharide-Induced Inflammatory Response and Apoptosis by Inhibiting the Activation of NF-κB

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    Xuan Luo

    2018-02-01

    Full Text Available Numerous herbal-derived natural products are excellent anti-inflammatory agents. Several studies have reported that aloin, the major anthraquinone glycoside obtained from the Aloe species, exhibits anti-inflammatory activity. However, the molecular mechanism of this activity is not well understood. In this report, we found that aloin suppresses lipopolysaccharide-induced pro-inflammatory cytokine secretion and nitric oxide production, and downregulates the expression of tumor necrosis factor alpha (TNF-α, interleukin 6 (IL-6, inducible nitric oxide synthase (iNOS, and cyclooxygenase-2 (COX-2. Aloin inhibits the phosphorylation and acetylation of the NF-κB p65 subunit by suppressing the upstream kinases p38 and Msk1, preventing LPS-induced p65 translocation to the nucleus. We have also shown that aloin inhibits LPS-induced caspase-3 activation and apoptotic cell death. Collectively, these findings suggest that aloin effectively suppresses the inflammatory response, primarily through the inhibition of NF-κB signaling.

  6. Aloin Suppresses Lipopolysaccharide-Induced Inflammatory Response and Apoptosis by Inhibiting the Activation of NF-κB.

    Science.gov (United States)

    Luo, Xuan; Zhang, Haowei; Wei, Xiduan; Shi, Mengjuan; Fan, Ping; Xie, Weidong; Zhang, Yaou; Xu, Naihan

    2018-02-26

    Numerous herbal-derived natural products are excellent anti-inflammatory agents. Several studies have reported that aloin, the major anthraquinone glycoside obtained from the Aloe species, exhibits anti-inflammatory activity. However, the molecular mechanism of this activity is not well understood. In this report, we found that aloin suppresses lipopolysaccharide-induced pro-inflammatory cytokine secretion and nitric oxide production, and downregulates the expression of tumor necrosis factor alpha (TNF-α), interleukin 6 (IL-6), inducible nitric oxide synthase (iNOS), and cyclooxygenase-2 (COX-2). Aloin inhibits the phosphorylation and acetylation of the NF-κB p65 subunit by suppressing the upstream kinases p38 and Msk1, preventing LPS-induced p65 translocation to the nucleus. We have also shown that aloin inhibits LPS-induced caspase-3 activation and apoptotic cell death. Collectively, these findings suggest that aloin effectively suppresses the inflammatory response, primarily through the inhibition of NF-κB signaling.

  7. Escin inhibits lipopolysaccharide-induced inflammation in human periodontal ligament cells.

    Science.gov (United States)

    Liu, Shutai; Wang, Huaizhou; Qiu, Caiqing; Zhang, Jing; Zhang, Taowen; Zhou, Wenjuan; Lu, Zhishan; Rausch-Fan, Xiaohui; Liu, Zhonghao

    2012-11-01

    Periodontitis is a chronic inflammatory disease associated with gram-negative subgingival microflora infection. Accumulating experimental evidence suggests that escin exerts anti-inflammatory and anti-edematous effects. This study was designed to investigate the in vitro effects of escin on the inflammatory reaction of human periodontal ligament cells (hPDLs). hPDLs were stimulated with lipopolysaccharide (LPS). The cells were treated with various concentrations of escin. The viability of hPDLs was evaluated using the MTT method. The expression of Toll-like receptor 2 (TLR2) in hPDLs and the levels of IL-1β, TNF-α and IL-6 in the supernatant were measured. Escin significantly attenuated LPS-induced cytotoxicity in a concentration-dependent manner in hPDLs. Treatment with escin partly blocked the expression of TLR2. Escin also lowered the increase of pro-inflammatory cytokines (IL-1β, TNF-α and IL-6) induced by LPS. The present findings show that escin exerts a protective effect against LPS-induced inflammation in hPDLs. It was also shown that escin is a promising medicine for the treatment of periodontitis.

  8. Lipopolysaccharide-induced multinuclear cells: Increased internalization of polystyrene beads and possible signals for cell fusion

    Energy Technology Data Exchange (ETDEWEB)

    Nakanishi-Matsui, Mayumi, E-mail: nakanim@iwate-med.ac.jp; Yano, Shio; Futai, Masamitsu

    2013-11-01

    Highlights: •LPS induces multinuclear cells from murine macrophage-derived RAW264.7 cells. •Large beads are internalized by cells actively fusing to become multinuclear. •The multinuclear cell formation is inhibited by anti-inflammatory cytokine, IL10. •Signal transduction for cell fusion is different from that for inflammation. -- Abstract: A murine macrophage-derived line, RAW264.7, becomes multinuclear on stimulation with lipopolysaccharide (LPS), an outer membrane component of Gram-negative bacteria. These multinuclear cells internalized more polystyrene beads than mononuclear cells or osteoclasts (Nakanishi-Matsui, M., Yano, S., Matsumoto, N., and Futai, M., 2012). In this study, we analyzed the time courses of cell fusion in the presence of large beads. They were internalized into cells actively fusing to become multinuclear. However, the multinuclear cells once formed showed only low phagocytosis activity. These results suggest that formation of the multinuclear cells and bead internalization took place simultaneously. The formation of multinuclear cells was blocked by inhibitors for phosphoinositide 3-kinase, phospholipase C, calcineurin, and c-Jun N-terminal kinase. In addition, interleukin 6 and 10 also exhibited inhibitory effects. These signaling molecules and cytokines may play a crucial role in the LPS-induced multinuclear cell formation.

  9. Prenylated Flavonoids from Cudrania tricuspidata Suppress Lipopolysaccharide-Induced Neuroinflammatory Activities in BV2 Microglial Cells

    Science.gov (United States)

    Kim, Dong-Cheol; Yoon, Chi-Su; Quang, Tran Hong; Ko, Wonmin; Kim, Jong-Su; Oh, Hyuncheol; Kim, Youn-Chul

    2016-01-01

    In Korea and China, Cudrania tricuspidata Bureau (Moraceae) is an important traditional medicinal plant used to treat lumbago, hemoptysis, and contusions. The C. tricuspidata methanol extract suppressed both production of NO and PGE2 in BV2 microglial cells. Cudraflavanone D (1), isolated from this extract, remarkably suppressed the protein expression of inducible NO synthase and cyclooxygenase-2, and decreased the levels of NO and PGE2 in BV2 microglial cells exposed to lipopolysaccharide. Cudraflavanone D (1) also decreased IL-6, TNF-α, IL-12, and IL-1β production, blocked nuclear translocation of NF-κB heterodimers (p50 and p65) by interrupting the degradation and phosphorylation of inhibitor of IκB-α, and inhibited NF-κB binding. In addition, cudraflavanone D (1) suppressed the phosphorylation of c-Jun N-terminal kinase (JNK) and p38 MAPK pathways. This study indicated that cudraflavanone D (1) can be a potential drug candidate for the cure of neuroinflammation. PMID:26907256

  10. Lipopolysaccharide induces a downregulation of adiponectin receptors in-vitro and in-vivo

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    Alison Hall

    2015-11-01

    Full Text Available Background. Adipose tissue contributes to the inflammatory response through production of cytokines, recruitment of macrophages and modulation of the adiponectin system. Previous studies have identified a down-regulation of adiponectin in pathologies characterised by acute (sepsis and endotoxaemia and chronic inflammation (obesity and type-II diabetes mellitus. In this study, we investigated the hypothesis that LPS would reduce adiponectin receptor expression in a murine model of endotoxaemia and in adipoocyte and myocyte cell cultures.Methods. 25 mg/kg LPS was injected intra-peritoneally into C57BL/6J mice, equivalent volumes of normal saline were used in control animals. Mice were killed at 4 or 24 h post injection and tissues harvested. Murine adipocytes (3T3-L1 and myocytes (C2C12 were grown in standard culture, treated with LPS (0.1 µg/ml–10 µg/ml and harvested at 4 and 24 h. RNA was extracted and qPCR was conducted according to standard protocols and relative expression was calculated.Results. After LPS treatment there was a significant reduction after 4 h in gene expression of adipo R1 in muscle and peri-renal fat and of adipo R2 in liver, peri-renal fat and abdominal wall subcutaneous fat. After 24 h, significant reductions were limited to muscle. Cell culture extracts showed varied changes with reduction in adiponectin and adipo R2 gene expression only in adipocytes.Conclusions. LPS reduced adiponectin receptor gene expression in several tissues including adipocytes. This reflects a down-regulation of this anti-inflammatory and insulin-sensitising pathway in response to LPS. The trend towards base line after 24 h in tissue depots may reflect counter-regulatory mechanisms. Adiponectin receptor regulation differs in the tissues investigated.

  11. Interleukin-1 receptor antagonist protects against lipopolysaccharide induced diaphragm weakness in preterm lambs.

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    Kanakeswary Karisnan

    Full Text Available Chorioamnionitis (inflammation of the fetal membranes is strongly associated with preterm birth and in utero exposure to inflammation significantly impairs contractile function in the preterm lamb diaphragm. The fetal inflammatory response to intra-amniotic (IA lipopolysaccharide (LPS is orchestrated via interleukin 1 (IL-1. We aimed to determine if LPS induced contractile dysfunction in the preterm diaphragm is mediated via the IL-1 pathway. Pregnant ewes received IA injections of recombinant human IL-1 receptor antagonist (rhIL-1ra (Anakinra; 100 mg or saline (Sal 3 h prior to second IA injections of LPS (4 mg or Sal at 119d gestational age (GA. Preterm lambs were killed after delivery at 121d GA (term = 150 d. Muscle fibres dissected from the right hemi-diaphragm were mounted in an in vitro muscle test system for assessment of contractile function. The left hemi-diaphragm was snap frozen for molecular and biochemical analyses. Maximum specific force in lambs exposed to IA LPS (Sal/LPS group was 25% lower than in control lambs (Sal/Sal group; p=0.025. LPS-induced diaphragm weakness was associated with higher plasma IL-6 protein, diaphragm IL-1β mRNA and oxidised glutathione levels. Pre-treatment with rhIL-1ra (rhIL-1ra/LPS ameliorated the LPS-induced diaphragm weakness and blocked systemic and local inflammatory responses, but did not prevent the rise in oxidised glutathione. These findings indicate that LPS induced diaphragm dysfunction is mediated via IL-1 and occurs independently of oxidative stress. Therefore, the IL-1 pathway represents a potential therapeutic target in the management of impaired diaphragm function in preterm infants.

  12. Potential role of an antimicrobial peptide, KLK in inhibiting lipopolysaccharide-induced macrophage inflammation.

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    Pornpimon Jantaruk

    Full Text Available Antimicrobial peptides (AMPs are attractive alternatives to antibiotics. Due to their immune modulatory properties, AMPs are at present emerging as promising agents for controlling inflammatory-mediated diseases. In this study, anti-inflammatory potential of an antimicrobial peptide, KLK (KLKLLLLLKLK and its analogs was evaluated in lipopolysaccharide (LPS-induced RAW 264.7 macrophages. The results herein demonstrated that KLK peptide as well as its analogs significantly inhibited the pro-inflammatory mediator nitric oxide (NO, interleukin-1β (IL-1β and tumor necrosis factor-α (TNF-α production in LPS-stimulated RAW 264.7 macrophages in dose-dependent manners, and such inhibitory effects were not due to direct cytotoxicity. When considering inhibition potency, KLK among the test peptides exhibited the most effective activity. The inhibitory activity of KLK peptide also extended to include suppression of LPS-induced production of prostaglandin E2 (PGE2. KLK significantly decreased mRNA and protein expression of inducible nitric oxide synthase (iNOS and cyclooxygenase-2 (COX-2 as well as mRNA expression of IL-1β and TNF-α. Moreover, KLK inhibited nuclear translocation of nuclear factor-κB (NF-κB p65 and blocked degradation and phosphorylation of inhibitor of κB (IκB. Taken together, these results suggested that the KLK peptide inhibited inflammatory response through the down-regulation of NF-κB mediated activation in macrophages. Since peptide analogs with different amino acid sequences and arrangement were investigated for their anti-inflammatory activities, the residues/structures required for activity were also discussed. Our findings therefore proved anti-inflammatory potential of the KLK peptide and provide direct evidence for therapeutic application of KLK as a novel anti-inflammatory agent.

  13. Improving effect of Sivelestat on lipopolysaccharide-induced lung injury in rats.

    Science.gov (United States)

    Yuan, Qing; Jiang, Yan-Wen; Fang, Qiu-Hong

    2014-09-01

    Sepsis causes neutrophil sequestration in the lung, which leads to acute lung injury (ALI). Neutrophil elastase (NE) is thought to play an important role in the pathogenesis of ALI. This study investigated whether Sivelestat, a specific NE inhibitor, can attenuate ALI induced by lipopolysaccharide (LPS). In vivo, 30 male Wistar rats were divided into three groups (n = 10 each groups) on the basis of the reagent used, which were subjected to LPS injection with or without Sivelestat treatments to induce ALI model. Lung injury was assessed by pulmonary histology, lung wet-weight to dry-weight (W/D) ratio, immunohistochemical analysis of intercellular adhesion molecule-1 (ICAM-1), the number of myeloperoxidase (MPO)-positive cells, and gene expression of ICAM-1. In vitro, pulmonary microvascular endothelial cells (PMVECs) were stimulated with LPS in the presence and absence of Sivelestat; nuclear factor-κB (NF-κB) p65 was measured by immunocytochemistry staining and Western blotting. Infusion of LPS induced lung injury, in vivo, as demonstrated by pulmonary edema with infiltration of neutrophils, the increase in lung W/D ratio, the number of MPO-positive cells and enhanced expression of ICAM-1 and ICAM-1 gene. In vitro, the significant increased release of NF-κB p65 and its subsequent translocation into the nucleus in PMVECs. In contrast, Sivelestat treatment significantly ameliorated the LPS-induced lung injury, as judged by the marked improvement in all these indices. These results indicated that inhibition of NE attenuated LPS-induced lung injury through an inhibition of the inflammatory signaling pathway, besides the direct inhibitory effect on NE. © 2014 APMIS. Published by John Wiley & Sons Ltd.

  14. Peripheral and central mediators of lipopolysaccharide induced suppression of defensive rage behavior in the cat.

    Science.gov (United States)

    Bhatt, S; Bhatt, R S; Zalcman, S S; Siegel, A

    2009-11-10

    Based upon recent findings in our laboratory that cytokines microinjected into the medial hypothalamus or periaqueductal gray (PAG) powerfully modulate defensive rage behavior in cat, the present study determined the effects of peripherally released cytokines following lipopolysaccharide (LPS) challenge upon defensive rage. The study involved initial identification of the effects of peripheral administration of LPS upon defensive rage by electrical stimulation from PAG and subsequent determination of the peripheral and central mechanisms governing this process. The results revealed significant elevation in response latencies for defensive rage from 60 to 300 min, post LPS injection, with no detectable signs of sickness behavior present at 60 min. In contrast, head turning behavior elicited by stimulation of adjoining midbrain sites was not affected by LPS administration, suggesting a specificity of the effects of LPS upon defensive rage. Direct administration of LPS into the medial hypothalamus had no effect on defensive rage, suggesting that the effects of LPS were mediated by peripheral cytokines rather than by any direct actions upon hypothalamic neurons. Complete blockade of the suppressive effects of LPS by peripheral pretreatment with an Anti-tumor necrosis factor-alpha (TNFalpha) antibody but not with an anti- interleukin-1 (IL-1) antibody demonstrated that the effects of LPS were mediated through TNF-alpha rather than through an IL-1 mechanism. A determination of the central mechanisms governing LPS suppression revealed that pretreatment of the medial hypothalamus with PGE(2) or 5-HT(1A) receptor antagonists each completely blocked the suppressive effects of LPS, while microinjections of a TNF-alpha antibody into the medial hypothalamus were ineffective. Microinjections of -Iodo-N-[2-[4-(methoxyphenyl)-1-piperazinyl]ethyl]-N-(2-pyridinyl) benzamide monohydrochloride (p-MPPI) into lateral hypothalamus (to test for anatomical specificity) had no effect upon

  15. A Fermented Whole Grain Prevents Lipopolysaccharides-Induced Dysfunction in Human Endothelial Progenitor Cells

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    Laura Giusti

    2017-01-01

    Full Text Available Endogenous and exogenous signals derived by the gut microbiota such as lipopolysaccharides (LPS orchestrate inflammatory responses contributing to development of the endothelial dysfunction associated with atherosclerosis in obesity, metabolic syndrome, and diabetes. Endothelial progenitor cells (EPCs, bone marrow derived stem cells, promote recovery of damaged endothelium playing a pivotal role in cardiovascular repair. Since healthy nutrition improves EPCs functions, we evaluated the effect of a fermented grain, Lisosan G (LG, on early EPCs exposed to LPS. The potential protective effect of LG against LPS-induced alterations was evaluated as cell viability, adhesiveness, ROS production, gene expression, and NF-kB signaling pathway activation. Our results showed that LPS treatment did not affect EPCs viability and adhesiveness but induced endothelial alterations via activation of NF-kB signaling. LG protects EPCs from inflammation as well as from LPS-induced oxidative and endoplasmic reticulum (ER stress reducing ROS levels, downregulating proinflammatory and proapoptotic factors, and strengthening antioxidant defense. Moreover, LG pretreatment prevented NF-kB translocation from the cytoplasm into the nucleus caused by LPS exposure. In human EPCs, LPS increases ROS and upregulates proinflammatory tone, proapoptotic factors, and antioxidants. LG protects EPCs exposed to LPS reducing ROS, downregulating proinflammatory and proapoptotic factors, and strengthening antioxidant defenses possibly by inhibiting NF-κB nuclear translocation.

  16. Interleukin-10 inhibits lipopolysaccharide induced miR-155 precursor stability and maturation.

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    Sylvia T Cheung

    Full Text Available The anti-inflammatory cytokine interleukin-10 (IL-10 is essential for attenuating the inflammatory response, which includes reducing the expression of pro-inflammatory microRNA-155 (miR-155 in lipopolysaccharide (LPS activated macrophages. miR-155 enhances the expression of pro-inflammatory cytokines such as TNFα and suppresses expression of anti-inflammatory molecules such as SOCS1. Therefore, we examined the mechanism by which IL-10 inhibits miR-155. We found that IL-10 treatment did not affect the transcription of the miR-155 host gene nor the nuclear export of pre-miR-155, but rather destabilized both pri-miR-155 and pre-miR-155 transcripts, as well as interfered with the final maturation of miR-155. This inhibitory effect of IL-10 on miR-155 expression involved the contribution of both the STAT3 transcription factor and the phosphoinositol phosphatase SHIP1. This is the first report showing evidence that IL-10 regulates miRNA expression post-transcriptionally.

  17. Critical role of MKP-1 in lipopolysaccharide-induced osteoclast formation through CXCL1 and CXCL2.

    Science.gov (United States)

    Valerio, Michael S; Herbert, Bethany A; Basilakos, Dimitrios S; Browne, Courtney; Yu, Hong; Kirkwood, Keith L

    2015-01-01

    Osteoclast (OC) progenitors (OCP) have been defined in the bone marrow (BM) as CD3(-)CD45R(B220)(-)GR1(-)CD11b(lo/)(-)CD115(+) (dOCP) and more recently in the peripheral blood (PB) as Lym(-)Ly6G(-)CD11b(+)Ly6C(+). These progenitors respond to stimuli, including LPS from periopathogenic Aggregatibacter actinomycetemcomitans, activating MAPK signaling, resulting in cytokine/chemokine-mediated osteoclastogenesis. Intracellular negative signaling pathways, including MAPK phosphatase-1 (MKP-1, gene Dusp1) deactivate MAPK pathways (p-p38 and p-JNK) and reduce inflammatory cytokines/chemokines. To delineate the role of MKP-1 in chemokine-mediated OC formation using defined OC progenitor populations. Given its role in innate immune inflammatory signaling, we hypothesize that MKP-1 regulates LPS-induced OC formation from BM OCP through deregulated chemokines. BM and PB from WT and Dusp1(-/-) female mice (8-12weeks) was obtained and sorted into defined progenitor populations. BM sorted dOCP were primed with MCSF and RANKL (48h), blocked with vehicle or chemokine blocking antibodies and stimulated with LPS (48-96h). TRAP assay and OC activity were measured for OC formation and activity following treatments. NanoString Array and qPCR were utilized for gene expression analysis. Dusp1(-/-) dOCPs formed more and larger osteoclasts from CD11b(hi) and dOCP compared to matched WT (Pvalidation of target genes revealed that Dusp1 deficient CD11b(+) populations display 1.5-3.5-fold greater expression of CXCL1 and 2-3-fold greater expression of CXCL2 compared to WT in CD11b(hi) and dOCP (Pperiodontal disease. Copyright © 2014 Elsevier Ltd. All rights reserved.

  18. Inhibition of tissue transglutaminase attenuates lipopolysaccharide-induced inflammation in glial cells through AKT/mTOR signal pathway.

    Science.gov (United States)

    Ding, Yirong; Zhang, Ji; Wang, Rui

    2017-05-01

    In view of the facts that tTG protein expression level and its enzyme activity increase in AD brains of both individuals and transgenic animals and compelling evidence of the involvement of inflammation in AD pathogenesis, tTG could be involved in the inflammation responses in the brain. In the present study, we examined the effects of the irreversible and the competitive inhibitor of tTG on the condition of lipopolysaccharide-induced mimic inflammation models in glial cells. Western blot and tTG enzyme activity assay were applied to detect tTG and isopeptide protein levels and tTG enzyme activity. The production of nitric oxide and the expression levels of inducible nitric oxide synthase and cyclooxygenase-2 were determined by Griess Reagents and Western blot respectively to assess anti-inflammatory effects. Moreover, the activation of AKT/mTOR signaling pathway was determined to evaluate the underlying mechanism of anti-inflammatory response. Irreversible and competitive inhibitor of tTG could ameliorate LPS-induced neuroinflammation in glial cells without cytotoxicity. Moreover, AKT/mTOR pathway may be involved in the anti-inflammatory response of tTG inhibitors. Therefore, NTU283 and Cystamine may alleviate inflammatory response in glial cells, probably through, at least partially, inhibiting the activation of AKT/mTOR signaling pathway. Our study provided some clues that tTG inhibitors NTU283 and Cystamine might be potential candidates for the treatments of neuroinflammation-related diseases, although more studies needed for further exploration. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  19. DHA suppresses Prevotella intermedia lipopolysaccharide-induced production of proinflammatory mediators in murine macrophages.

    Science.gov (United States)

    Choi, Eun-Young; Jin, Ji-Young; Choi, Jeom-Il; Choi, In Soon; Kim, Sung-Jo

    2014-04-14

    Several reports have indicated that dietary intake of DHA is associated with lower prevalence of periodontitis. In the present study, we investigated the effect of DHA on the production of proinflammatory mediators in murine macrophage-like RAW264.7 cells stimulated with lipopolysaccharide (LPS) isolated from Prevotella intermedia, a pathogen implicated in inflammatory periodontal disease, and its mechanisms of action. LPS was isolated from lyophilised P. intermedia ATCC 25,611 cells using the standard hot-phenol-water protocol. Culture supernatants were collected and assayed for NO, IL-1β and IL-6. Real-time PCR analysis was carried out to detect the expression of inducible NO synthase (iNOS), IL-1β, IL-6 and haeme oxygenase-1 (HO-1) mRNA. Immunoblot analysis was carried out to quantify the expression of iNOS and HO-1 protein and concentrations of signalling proteins. DNA-binding activities of NF-κB subunits were determined using an ELISA-based assay kit. DHA significantly attenuated the production of NO, IL-1β and IL-6 at both gene transcription and translation levels in P. intermedia LPS-activated RAW264.7 cells. DHA induced the expression of HO-1 in cells treated with P. intermedia LPS. Selective inhibition of HO-1 activity by tin protoporphyrin IX significantly mitigated the inhibitory effects of DHA on LPS-induced NO production. DHA significantly attenuated the phosphorylation of c-Jun N-terminal kinase induced by LPS. In addition, DHA suppressed the transcriptional activity of NF-κB by regulating the nuclear translocation and DNA-binding activity of NF-κB p50 subunit and inhibited the phosphorylation of signal transducer and activator of transcription 1. Further in vivo studies are needed to better evaluate the potential of DHA in humans as a therapeutic agent to treat periodontal disease.

  20. Vitamin D3 pretreatment regulates renal inflammatory responses during lipopolysaccharide-induced acute kidney injury.

    Science.gov (United States)

    Xu, Shen; Chen, Yuan-Hua; Tan, Zhu-Xia; Xie, Dong-Dong; Zhang, Cheng; Zhang, Zhi-Hui; Wang, Hua; Zhao, Hui; Yu, De-Xin; Xu, De-Xiang

    2015-12-22

    Vitamin D receptor (VDR) is highly expressed in human and mouse kidneys. Nevertheless, its functions remain obscure. This study investigated the effects of vitamin D3 (VitD3) pretreatment on renal inflammation during lipopolysaccharide (LPS)-induced acute kidney injury. Mice were intraperitoneally injected with LPS. In VitD3 + LPS group, mice were pretreated with VitD3 (25 μg/kg) at 48, 24 and 1 h before LPS injection. As expected, an obvious reduction of renal function and pathological damage was observed in LPS-treated mice. VitD3 pretreatment significantly alleviated LPS-induced reduction of renal function and pathological damage. Moreover, VitD3 pretreatment attenuated LPS-induced renal inflammatory cytokines, chemokines and adhesion molecules. In addition, pretreatment with 1,25(OH)2D3, the active form of VitD3, alleviated LPS-induced up-regulation of inflammatory cytokines and chemokines in human HK-2 cells, a renal tubular epithelial cell line, in a VDR-dependent manner. Further analysis showed that VitD3, which activated renal VDR, specifically repressed LPS-induced nuclear translocation of nuclear factor kappa B (NF-κB) p65 subunit in the renal tubules. LPS, which activated renal NF-κB, reciprocally suppressed renal VDR and its target gene. Moreover, VitD3 reinforced the physical interaction between renal VDR and NF-κB p65 subunit. These results provide a mechanistic explanation for VitD3-mediated anti-inflammatory activity during LPS-induced acute kidney injury.

  1. Cytokine and acute phase protein gene expression in liver biopsies from dairy cows with a lipopolysaccharide - induced mastitis

    DEFF Research Database (Denmark)

    Vels, J; Røntved, Christine M.; Bjerring, Martin

    2009-01-01

    .1 ± 0.1 vs. log10 2.8 ± 0.1 x 103 cells/mL), heart rate (76 ± 1 vs. 93 ± 1 beats/min), and respiratory rate (32 ± 2 vs. 36 ± 1 breaths/min) in the acute phase of the disease. The LPS treatment upregulated the hepatic expression of TNF- (103 ± 24 vs. 255 ± 18 units), IL-1β (37 ± 23 vs. 296 ± 18 units...

  2. JNK1 Mediates Lipopolysaccharide-Induced CD14 and SR-AI Expression and Macrophage Foam Cell Formation

    Directory of Open Access Journals (Sweden)

    Dong An

    2018-01-01

    Full Text Available Foam cell formation is the key process in the development of atherosclerosis. The uptake of oxidized low-density lipoprotein (oxLDL converts macrophages into foam cells. We recently reported that lipopolysaccharide (LPS-induced foam cell formation is regulated by CD14 and scavenger receptor AI (SR-AI. In this study, we employed pharmaceutical and gene knockdown approaches to determine the upstream molecular mediators, which control LPS-induced foam cell formation. Our results demonstrated that the specific c-Jun N-terminal kinase (JNK pathway inhibitor, SP600125, but neither the specific inhibitor of extracellular signaling-regulated kinase (ERK kinase MEK1/2, U0126, nor the specific inhibitor of p38 MAPK, SB203580, significantly blocks LPS-induced oxLDL uptake, suggesting that the JNK pathway is the upstream mediator of LPS-induced oxLDL uptake/foam cell formation. To address whether JNK pathway mediates LPS-induced oxLDL uptake is due to JNK pathway-regulated CD14 and SR-AI expression, we assessed whether the pharmaceutical inhibitor of JNK influences LPS-induced expression of CD14 and SR-AI. Our results indicate that JNK pathway mediates LPS-induced CD14 and SR-AI expression. To conclusively address the isoform role of JNK family, we depleted JNK isoforms using the JNK isoform-specific siRNA. Our data showed that the depletion of JNK1, but not JNK2 blocked LPS-induced CD14/SR-AI expression and foam cell formation. Taken together, our results reveal for the first time that JNK1 is the key mediator of LPS-induced CD14 and SR-AI expression in macrophages, leading to LPS-induced oxLDL uptake/foam cell formation. We conclude that the novel JNK1/CD14/SR-AI pathway controls macrophage oxLDL uptake/foam cell formation.

  3. Detecting ALK, ROS1 and RET Fusion Genes in Cell Block Samples.

    Science.gov (United States)

    Zhao, Chao; Li, Xuefei; Li, Jiayu; Zhang, Yishi; Ren, Shengxiang; Chen, Xiaoxia; Zhou, Caicun

    2014-06-01

    Whether Cell block (CB) samples are applicable to detect anaplastic lymphoma kinase (ALK), c-ros oncogene 1 (ROS1) and ret proto-oncogene (RET) fusion genes in lung adenocarcinoma is still unknown. In this study, 108 cytological samples that contained lung adenocarcinoma cells were collected, and made into CB. The CB samples all contained at least 30% lung adenocarcinoma cells. In these patients, 48 harbored EGFR mutation. Among the 50 EGFR wild type patients who detected fusion genes, 14 carried EML4-ALK fusion (28%), 2 had TPM3-ROS1 fusion (4%), and 3 harbored KIF5B-RET fusion (6%). No double fusions were found in one sample. Patients with fusion genes were younger than those without fusion genes (p = 0.032), but no significant difference was found in sex and smoking status (p > 0.05). In the thirty-five patients who received first-line chemotherapy, patients with fusion gene positive had disease control rate (DCR) (72.7% VS 50%, p > 0.05) and objective response rate (ORR) (9.1% VS 4.2%, p > 0.05) compared with those having fusion gene negative. The median progression free survival (mPFS) were 4.0 and 2.7 months in patients harbored fusion mutations and wild type, respectively (p > 0.05). We conclude that CB samples could be used to detect ALK, ROS1 and RET fusions in NSCLC. The frequency distribution of three fusion genes is higher in lung adenocarcinoma with wild-type EGFR, compared with unselected NSCLC patient population. Patients with fusion genes positive are younger than those with fusion gene negative, but they had no significantly different PFS in first-line chemotherapy.

  4. Cytokinesis is blocked in mammalian cells transfected with Chlamydia trachomatis gene CT223

    Directory of Open Access Journals (Sweden)

    Weeks Sara K

    2009-01-01

    Full Text Available Abstract Background The chlamydiae alter many aspects of host cell biology, including the division process, but the molecular biology of these alterations remains poorly characterized. Chlamydial inclusion membrane proteins (Incs are likely candidates for direct interactions with host cell cytosolic proteins, as they are secreted to the inclusion membrane and exposed to the cytosol. The inc gene CT223 is one of a sequential set of orfs that encode or are predicted to encode Inc proteins. CT223p is localized to the inclusion membrane in all tested C. trachomatis serovars. Results A plasmid transfection approach was used to examine the function of the product of CT223 and other Inc proteins within uninfected mammalian cells. Fluorescence microscopy was used to demonstrate that CT223, and, to a lesser extent, adjacent inc genes, are capable of blocking host cell cytokinesis and facilitating centromere supranumeracy defects seen by others in chlamydiae-infected cells. Both phenotypes were associated with transfection of plasmids encoding the carboxy-terminal tail of CT223p, a region of the protein that is likely exposed to the cytosol in infected cells. Conclusion These studies suggest that certain Inc proteins block cytokinesis in C. trachomatis-infected cells. These results are consistent with the work of others showing chlamydial inhibition of host cell cytokinesis.

  5. Derepression of the Iroquois Homeodomain Transcription Factor Gene IRX3 Confers Differentiation Block in Acute Leukemia

    Directory of Open Access Journals (Sweden)

    Tim D.D. Somerville

    2018-01-01

    Full Text Available The Iroquois homeodomain transcription factor gene IRX3 is expressed in the developing nervous system, limb buds, and heart, and transcript levels specify obesity risk in humans. We now report a functional role for IRX3 in human acute leukemia. Although transcript levels are very low in normal human bone marrow cells, high IRX3 expression is found in ∼30% of patients with acute myeloid leukemia (AML, ∼50% with T-acute lymphoblastic leukemia, and ∼20% with B-acute lymphoblastic leukemia, frequently in association with high-level HOXA gene expression. Expression of IRX3 alone was sufficient to immortalize hematopoietic stem and progenitor cells (HSPCs in myeloid culture and induce lymphoid leukemias in vivo. IRX3 knockdown induced terminal differentiation of AML cells. Combined IRX3 and Hoxa9 expression in murine HSPCs impeded normal T-progenitor differentiation in lymphoid culture and substantially enhanced the morphologic and phenotypic differentiation block of AML in myeloid leukemia transplantation experiments through suppression of a terminal myelomonocytic program. Likewise, in cases of primary human AML, high IRX3 expression is strongly associated with reduced myelomonocytic differentiation. Thus, tissue-inappropriate derepression of IRX3 contributes significantly to the block in differentiation, which is the pathognomonic feature of human acute leukemias.

  6. Alternative splicing, a new target to block cellular gene expression by poliovirus 2A protease

    Energy Technology Data Exchange (ETDEWEB)

    Alvarez, Enrique, E-mail: ealvarez@cbm.uam.es [Centro de Biologia Molecular Severo Ochoa (CSIC-UAM), Nicolas Cabrera, 1 Universidad Autonoma de Madrid, Cantoblanco, 28049 Madrid (Spain); Castello, Alfredo; Carrasco, Luis; Izquierdo, Jose M. [Centro de Biologia Molecular Severo Ochoa (CSIC-UAM), Nicolas Cabrera, 1 Universidad Autonoma de Madrid, Cantoblanco, 28049 Madrid (Spain)

    2011-10-14

    Highlights: {yields} Novel role for poliovirus 2A protease as splicing modulator. {yields} Poliovirus 2A protease inhibits the alternative splicing of pre-mRNAs. {yields} Poliovirus 2A protease blocks the second catalytic step of splicing. -- Abstract: Viruses have developed multiple strategies to interfere with the gene expression of host cells at different stages to ensure their own survival. Here we report a new role for poliovirus 2A{sup pro} modulating the alternative splicing of pre-mRNAs. Expression of 2A{sup pro} potently inhibits splicing of reporter genes in HeLa cells. Low amounts of 2A{sup pro} abrogate Fas exon 6 skipping, whereas higher levels of protease fully abolish Fas and FGFR2 splicing. In vitro splicing of MINX mRNA using nuclear extracts is also strongly inhibited by 2A{sup pro}, leading to accumulation of the first exon and the lariat product containing the unspliced second exon. These findings reveal that the mechanism of action of 2A{sup pro} on splicing is to selectively block the second catalytic step.

  7. Histone deacetylase inhibitors restore IL-10 expression in lipopolysaccharide-induced cell inflammation and reduce IL-1β and IL-6 production in breast silicone implant in C57BL/6J wild-type murine model.

    Science.gov (United States)

    Di Liddo, Rosa; Valente, Sergio; Taurone, Samanta; Zwergel, Clemens; Marrocco, Biagina; Turchetta, Rosaria; Conconi, Maria Teresa; Scarpa, Carlotta; Bertalot, Thomas; Schrenk, Sandra; Mai, Antonello; Artico, Marco

    2016-01-20

    Among epigenetic enzymes, histone deacetylases (HDACs) are responsible for regulating the expression of an extensive array of genes by reversible deacetylation of nuclear histones as well as a large number of non-histone proteins. Initially proposed for cancer therapy, recently the interest for HDAC inhibitors (HDACi) as orally active, safe, and anti-inflammatory agents is rising due to their ability in reducing the severity of inflammatory and autoimmune diseases. In particular, selective HDAC3, HDAC6, and HDAC8 inhibitors have been described to downregulate the expression of pro-inflammatory cytokines (TNF-α, TGF-β, IL-1β, and IL-6). Herein, using KB31, C2C12, and 3T3-J2 cell lines, we demonstrated that, under lipopolysaccharide-induced in vitro inflammation, HDAC3/6/8 inhibitor MC2625 and HDAC6-selective inhibitor MC2780 were effective at a concentration of 30 ng/mL to downregulate mRNA expression of pro-inflammatory cytokines (IL-1β and IL-6) and to promote the transcription of IL-10 gene, without affecting the cell viability. Afterwards, we investigated by immunohistochemistry the activity of MC2625 and MC2780 at a concentration of 60 ng/kg animal weight to regulate silicone-triggered immune response in C57BL/6J female mice. Our findings evidenced the ability of such inhibitors to reduce host inflammation in silicone implants promoting a thickness reduction of peri-implant fibrous capsule, upregulating IL-10 expression, and reducing the production of both IL-1β and IL-6. These results underline the potential application of MC2625 and MC2780 in inflammation-related diseases.

  8. NLRP3 inflammasome activation in D-galactosamine and lipopolysaccharide-induced acute liver failure: role of heme oxygenase-1.

    Science.gov (United States)

    Kim, Seok-Joo; Lee, Sun-Mee

    2013-12-01

    D-Galactosamine (GalN) and lipopolysaccharide (LPS) are commonly used to study mechanisms of hepatic malfunction that result in hepatic inflammation and subsequent fulminant hepatic failure. Inflammasomes are intracellular multiprotein complexes that in response to cellular danger signals trigger the biological maturation of proinflammatory cytokines. Heme oxygenase-1 (HO-1) is a cytoprotective enzyme that induces anti-inflammatory and antioxidant activity against oxidative cellular stress. This study examined activation of the NACHT, LRR, and PYD domain-containing protein 3 (NLRP3) inflammasome in GalN/LPS-induced hepatic injury and the role of HO-1 in the signaling pathways of inflammasome. Mice (C57BL/6) were pretreated twice with hemin (HO-1 inducer, 30 mg/kg) and zinc protoporphyrin (ZnPP; HO-1 inhibitor, 10mg/kg) at 12 and 2h before GalN (800 mg/kg)/LPS (40 μg/kg) administration. HO-1 induction with hemin reversed the lethality induced by GalN/LPS administration, and ZnPP pretreatment blocked this change. Lipid peroxidation markedly increased after GalN/LPS treatment, whereas glutathione content decreased in the GalN/LPS group. These changes were attenuated by hemin, but ZnPP reversed the effects of hemin. Serum levels of tumor necrosis factor-α (TNF-α) and interleukin (IL)-1β increased after GalN/LPS treatment; these increases were attenuated by hemin. Hepatic mRNA levels of TNF-α, IL-1β, and NLRP3 increased after GalN/LPS treatment, and hemin attenuated increases in TNF-α and IL-1β. After GalN/LPS treatment, the hepatic expression of NLRP3, ASC, and caspase-1 (p10) was increased. In immunoprecipitation studies, hemin attenuated the interaction of NLRP3 with ASC and caspase-1. GalN/LPS induced expression of the thioredoxin-interacting protein (TXNIP) gene and the interaction between NLRP3 and TXNIP; again, hemin attenuated these effects. The effects of hemin were reversed by ZnPP. Our findings suggest that activation of the NLRP3 inflammasome leads

  9. 3'-RACE Amplification of Aminopeptidase N Gene from Anopheles stephensi Applicable in Transmission Blocking Vaccines.

    Science.gov (United States)

    Bokharaei, Hanieh; Raz, Abbasali; Zakeri, Sedigheh; Djadid, Navid Dinparast

    2012-07-01

    Because of the lack of an effective and economical control strategy against malaria (the most devastating infectious disease in developing countries) Transmission-Blocking Vaccines (TBVs) concept has been raised in recent years, promising a more efficient way to malaria control. TBVs aim at interfering and/or blocking pathogen development within the vector, halting transmission to non-infected vertebrate host. Aminopeptidase N (APN) is one of the most potent proteins in parasite development in Anopheles malaria vectors, which is strongly co-localized with human malaria parasites in the mosquito midgut epithelium. Therefore, Aminopeptidase N is one of the best choices for a new TBV. In this study for the first time we used 3'-RACE to amplify APN gene in Anopheles stephensi (An.stephensi), a major malaria vector in Iran, Indian subcontinent up to China by using different sets of primers including exon junction, conserved and specific region primers. Full length of APN was sequenced stepwise, which could be applied in designing a new regional TBV and act as an essential component of malaria elimination program in An.stephensi distribution areas. Primers design and method modification should be set up exactly in approach based amplifications. From results we came to this conclusion that that 3'-RACE could be applied to amplified key regions which are beyond reach.

  10. Bigelovii A Protects against Lipopolysaccharide-Induced Acute Lung Injury by Blocking NF-κB and CCAAT/Enhancer-Binding Protein δ Pathways

    Directory of Open Access Journals (Sweden)

    Chunguang Yan

    2016-01-01

    Full Text Available Optimal methods are applied to acute lung injury (ALI and the acute respiratory distress syndrome (ARDS, but the mortality rate is still high. Accordingly, further studies dedicated to identify novel therapeutic approaches to ALI are urgently needed. Bigelovii A is a new natural product and may exhibit anti-inflammatory activity. Therefore, we sought to investigate its effect on lipopolysaccharide- (LPS- induced ALI and the underlying mechanisms. We found that LPS-induced ALI was significantly alleviated by Bigelovii A treatment, characterized by reduction of proinflammatory mediator production, neutrophil infiltration, and lung permeability. Furthermore, Bigelovii A also downregulated LPS-stimulated inflammatory mediator expressions in vitro. Moreover, both NF-κB and CCAAT/enhancer-binding protein δ (C/EBPδ activation were obviously attenuated by Bigelovii A treatment. Additionally, phosphorylation of both p38 MAPK and ERK1/2 (upstream signals of C/EBPδ activation in response to LPS challenge was also inhibited by Bigelovii A. Therefore, Bigelovii A could attenuate LPS-induced inflammation by suppression of NF-κB, inflammatory mediators, and p38 MAPK/ERK1/2—C/EBPδ, inflammatory mediators signaling pathways, which provide a novel theoretical basis for the possible application of Bigelovii A in clinic.

  11. Senataxin Mutation Reveals How R-Loops Promote Transcription by Blocking DNA Methylation at Gene Promoters.

    Science.gov (United States)

    Grunseich, Christopher; Wang, Isabel X; Watts, Jason A; Burdick, Joshua T; Guber, Robert D; Zhu, Zhengwei; Bruzel, Alan; Lanman, Tyler; Chen, Kelian; Schindler, Alice B; Edwards, Nancy; Ray-Chaudhury, Abhik; Yao, Jianhua; Lehky, Tanya; Piszczek, Grzegorz; Crain, Barbara; Fischbeck, Kenneth H; Cheung, Vivian G

    2018-02-01

    R-loops are three-stranded nucleic acid structures found abundantly and yet often viewed as by-products of transcription. Studying cells from patients with a motor neuron disease (amyotrophic lateral sclerosis 4 [ALS4]) caused by a mutation in senataxin, we uncovered how R-loops promote transcription. In ALS4 patients, the senataxin mutation depletes R-loops with a consequent effect on gene expression. With fewer R-loops in ALS4 cells, the expression of BAMBI, a negative regulator of transforming growth factor β (TGF-β), is reduced; that then leads to the activation of the TGF-β pathway. We uncovered that genome-wide R-loops influence promoter methylation of over 1,200 human genes. DNA methyl-transferase 1 favors binding to double-stranded DNA over R-loops. Thus, in forming R-loops, nascent RNA blocks DNA methylation and promotes further transcription. Hence, our results show that nucleic acid structures, in addition to sequences, influence the binding and activity of regulatory proteins. Copyright © 2017 Elsevier Inc. All rights reserved.

  12. Cytomegalovirus selectively blocks antigen processing and presentation of its immediate-early gene product.

    Science.gov (United States)

    Gilbert, M J; Riddell, S R; Plachter, B; Greenberg, P D

    1996-10-24

    Recognition of virus-infected cells by CD8+ cytotoxic T lymphocytes requires that the viral proteins be processed into peptides, the derived peptides transported into the endoplasmic reticulum and inserted into the binding groove of a major histocompatibility complex class I molecule, and the antigenic complex exported to the cell surface. However, viral pathogens can disrupt this process and interfere with immune recognition. These mechanisms may be vital to large viruses such as human cytomegalovirus (CMV), which causes persistent infection despite producing over 200 potentially antigenic proteins during the sequential immediate-early, early and late phases of viral gene expression. Products of CMV early-phase gene expression can globally block class I presentation and prevent recognition of infected cells by cytotoxic T lymphocytes, but an essential viral transcription factor, the 72K principal immediate-early protein, is abundantly expressed before this blockade. However, only a few host CD8+ cytotoxic T lymphocytes specific for immediate-early protein are present in seropositive individuals, and these lyse CMV-infected cells poorly. Here we demonstrate selective abrogation of immediate-early peptide presentation by a CMV matrix protein with associated kinase activity and suggest that modification of a viral protein can result in limiting access to the processing machinery and evasion of cytotoxic-T-cell recognition.

  13. AWRK6, A Synthetic Cationic Peptide Derived from Antimicrobial Peptide Dybowskin-2CDYa, Inhibits Lipopolysaccharide-Induced Inflammatory Response

    Directory of Open Access Journals (Sweden)

    Qiuyu Wang

    2018-02-01

    Full Text Available Lipopolysaccharides (LPS are major outer membrane components of Gram-negative bacteria and produce strong inflammatory responses in animals. Most antibiotics have shown little clinical anti-endotoxin activity while some antimicrobial peptides have proved to be effective in blocking LPS. Here, the anti-LPS activity of the synthetic peptide AWRK6, which is derived from antimicrobial peptide dybowskin-2CDYa, has been investigated in vitro and in vivo. The positively charged α-helical AWRK6 was found to be effective in blocking the binding of LBP (LPS binding protein with LPS in vitro using ELISA. In a murine endotoxemia model, AWRK6 offered satisfactory protection efficiency against endotoxemia death, and the serum levels of LPS, IL-1β, IL-6, and TNF-α were found to be attenuated using ELISA. Further, histopathological analysis suggested that AWRK6 could improve the healing of liver and lung injury in endotoxemia mice. The results of real-time PCR and Western blotting showed that AWRK6 significantly reversed LPS-induced TLR4 overexpression and IκB depression, as well as the enhanced IκB phosphorylation. Additionally, AWRK6 did not produce any significant toxicity in vivo and in vitro. In summary, AWRK6 showed efficacious protection from LPS challenges in vivo and in vitro, by blocking LPS binding to LBP, without obvious toxicity, providing a promising strategy against LPS-induced inflammatory responses.

  14. Production of Polyclonal Antiobies to a Recombinant Potato Mop-top Virus Non-structural Triple Gene Block Protein l

    Czech Academy of Sciences Publication Activity Database

    Čeřovská, Noemi; Filigarová, Marie; Pečenková, Tamara

    2006-01-01

    Roč. 154, - (2006), s. 422-427 ISSN 0931-1785 R&D Projects: GA ČR GA522/04/1329 Institutional research plan: CEZ:AV0Z50380511 Keywords : Potato mop-top virus * recombinant protein * triple gene block * polyclonal antibodies Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 0.817, year: 2006

  15. Carbon monoxide induced PPARγ SUMOylation and UCP2 block inflammatory gene expression in macrophages.

    Directory of Open Access Journals (Sweden)

    Arvand Haschemi

    Full Text Available Carbon monoxide (CO dampens pro-inflammatory responses in a peroxisome proliferator-activated receptor-γ (PPARγ and p38 mitogen-activated protein kinase (MAPK dependent manner. Previously, we demonstrated that CO inhibits lipopolysaccharide (LPS-induced expression of the proinflammatory early growth response-1 (Egr-1 transcription factor in macrophages via activation of PPARγ. Here, we further characterize the molecular mechanisms by which CO modulates the activity of PPARγ and Egr-1 repression. We demonstrate that CO enhances SUMOylation of PPARγ which we find was attributed to mitochondrial ROS generation. Ectopic expression of a SUMOylation-defective PPARγ-K365R mutant partially abolished CO-mediated suppression of LPS-induced Egr-1 promoter activity. Expression of a PPARγ-K77R mutant did not impair the effect of CO. In addition to PPARγ SUMOylation, CO-activated p38 MAPK was responsible for Egr-1 repression. Blocking both CO-induced PPARγ SUMOylation and p38 activation, completely reversed the effects of CO on inflammatory gene expression. In primary macrophages isolated form C57/BL6 male mice, we identify mitochondrial ROS formation by CO as the upstream trigger for the observed effects on Egr-1 in part through uncoupling protein 2 (UCP2. Macrophages derived from bone marrow isolated from Ucp2 gene Knock-Out C57/BL6 mice (Ucp2(-/-, produced significantly less ROS with CO exposure versus wild-type macrophages. Moreover, absence of UCP2 resulted in a complete loss of CO mediated Egr-1 repression. Collectively, these results indentify p38 activation, PPARγ-SUMOylation and ROS formation via UCP2 as a cooperative system by which CO impacts the inflammatory response.

  16. Dual RNA sequencing reveals the expression of unique transcriptomic signatures in lipopolysaccharide-induced BV-2 microglial cells.

    Directory of Open Access Journals (Sweden)

    Amitabh Das

    Full Text Available Microglial cells become rapidly activated through interactions with pathogens, and the persistent activation of these cells is associated with various neurodegenerative diseases. Previous studies have investigated the transcriptomic signatures in microglia or macrophages using microarray technologies. However, this method has numerous restrictions, such as spatial biases, uneven probe properties, low sensitivity, and dependency on the probes spotted. To overcome this limitation and identify novel transcribed genes in response to LPS, we used RNA Sequencing (RNA-Seq to determine the novel transcriptomic signatures in BV-2 microglial cells. Sequencing assessment and quality evaluation showed that approximately 263 and 319 genes (≥ 1.5 log2-fold, such as cytokines and chemokines, were strongly induced after 2 and 4 h, respectively, and the induction of several genes with unknown immunological functions was also observed. Importantly, we observed that previously unidentified transcription factors (TFs (irf1, irf7, and irf9, histone demethylases (kdm4a and DNA methyltransferases (dnmt3l were significantly and selectively expressed in BV-2 microglial cells. The gene expression levels, transcription start sites (TSS, isoforms, and differential promoter usage revealed a complex pattern of transcriptional and post-transcriptional gene regulation upon infection with LPS. In addition, gene ontology, molecular networks and pathway analyses identified the top significantly regulated functional classification, canonical pathways and network functions at each activation status. Moreover, we further analyzed differentially expressed genes to identify transcription factor (TF motifs (-950 to +50 bp of the 5' upstream promoters and epigenetic mechanisms. Furthermore, we confirmed that the expressions of key inflammatory genes as well as pro-inflammatory mediators in the supernatants were significantly induced in LPS treated primary microglial cells. This

  17. An Optimal Mean Based Block Robust Feature Extraction Method to Identify Colorectal Cancer Genes with Integrated Data.

    Science.gov (United States)

    Liu, Jian; Cheng, Yuhu; Wang, Xuesong; Zhang, Lin; Liu, Hui

    2017-08-17

    It is urgent to diagnose colorectal cancer in the early stage. Some feature genes which are important to colorectal cancer development have been identified. However, for the early stage of colorectal cancer, less is known about the identity of specific cancer genes that are associated with advanced clinical stage. In this paper, we conducted a feature extraction method named Optimal Mean based Block Robust Feature Extraction method (OMBRFE) to identify feature genes associated with advanced colorectal cancer in clinical stage by using the integrated colorectal cancer data. Firstly, based on the optimal mean and L 2,1 -norm, a novel feature extraction method called Optimal Mean based Robust Feature Extraction method (OMRFE) is proposed to identify feature genes. Then the OMBRFE method which introduces the block ideology into OMRFE method is put forward to process the colorectal cancer integrated data which includes multiple genomic data: copy number alterations, somatic mutations, methylation expression alteration, as well as gene expression changes. Experimental results demonstrate that the OMBRFE is more effective than previous methods in identifying the feature genes. Moreover, genes identified by OMBRFE are verified to be closely associated with advanced colorectal cancer in clinical stage.

  18. Induction of heme oxygenas-1 attenuates NLRP3 inflammasome activation in lipopolysaccharide-induced mastitis in mice.

    Science.gov (United States)

    Xiaoyu, Hu; Si, Hongbin; Li, Shumin; Wang, Wenqing; Guo, Jian; Li, Yanyi; Cao, Yongguo; Fu, Yunhe; Zhang, Naisheng

    2017-11-01

    Mastitis is one of most prevalent production disease in dairy herds worldwide, and is responsible for enormous economic losses. Heme oxygenase-1 (HO-1) is a cytoprotective enzyme, which is involved in the response to oxidative stress and inflammatory response. The purpose of this study was to detect the protective effect of HO-1 on LPS-induced mastitis in mice. BALB/c mice were pretreated with hemin (HO-1 inducer) and zinc protoporphyrin (ZnPP; HO-1 inhibitor) at 2h before LPS stimulation. The results showed that the mammary gland damage, production of inflammatory cytokines IL-1β, and MPO activity in mammary gland tissues were significantly reduced after pretreated with hemin compared with the group of LPS stimulation only. However, ZnPP reversed the effects of hemin. Furthermore, we found that the levels of ROS and NLRP3 inflammasome were increased after LPS stimulation. The increases were inhibited by hemin and the inhibition of hemin on ROS production and NLRP3 inflammasome activation were blocked by ZnPP. In addition, the results showed that hemin reduced the expression of thioredoxin-interacting protein (TXNIP) induced by LPS, and ZnPP attenuated these changes. In conclusion, the results suggested that overproduction of HO-1 may inhibit the activation of NLRP3 inflammasome and the expression of TXNIP. Induction of HO-1 may be served as a promising method against mastitis induced by LPS. Copyright © 2017 Elsevier B.V. All rights reserved.

  19. Anti-inflammatory effects of linalool in RAW 264.7 macrophages and lipopolysaccharide-induced lung injury model.

    Science.gov (United States)

    Huo, Meixia; Cui, Xiurui; Xue, Jiangdong; Chi, Gefu; Gao, Ruijie; Deng, Xuming; Guan, Shuang; Wei, Jingyuan; Soromou, Lanan Wassy; Feng, Haihua; Wang, Dacheng

    2013-03-01

    Inflammation, characterized by redness, swelling, pain and a sensation of heat, is one of the body's self-defense systems. Although the inflammation response has an important role in host survival, it also leads to chronic inflammatory diseases. Linalool is a natural compound of the essential oils in several aromatic plants species. It possesses anti-inflammatory, antinociceptive, and other bioactive properties. In the present study, we investigated the protective effects of linalool on inflammation in lipopolysaccharide (LPS)-stimulated RAW 264.7 cells and an LPS-induced in vivo lung injury model. We evaluated the effects of linalool on LPS-induced production of inflammatory mediators in Raw 264.7 murine macrophages by enzyme-linked immunosorbent assay and Western blot. To confirm the anti-inflammatory activity of linalool in vivo, we induced an acute lung injury in an LPS-induced mouse model. Linalool attenuated the production of LPS-induced tumor necrosis-α and interleukin-6 both in vitro and in vivo. Furthermore, phosphorylation of IκBα protein, p38, c-Jun terminal kinase, and extracellular signal-regulated kinase in LPS-stimulated RAW 264.7 cells was blocked by linalool. Our in vivo study also found that linalool attenuated lung histopathologic changes in mouse models. The results suggest that linalool inhibits inflammation both in vitro and in vivo, and may be a potential therapeutic candidate for the treatment of inflammatory diseases. Copyright © 2013 Elsevier Inc. All rights reserved.

  20. Acanthopanax trifoliatus inhibits lipopolysaccharide-induced inflammatory response in vitro and in vivo

    Directory of Open Access Journals (Sweden)

    Tzu-Mei Chien

    2015-10-01

    Full Text Available Acanthopanax trifoliatus is a well-known herb that is used for the treatment of bruising, neuralgia, impotence, and gout in Taiwan. This herb exhibits multifunctional activities, including anticancer, anti-inflammation, and antioxidant effects. This paper investigated the in vitro and in vivo anti-inflammatory effect of A. trifoliatus. High-performance liquid chromatography analysis established the fingerprint chromatogram of the ethyl acetate fraction of A. trifoliatus (EAAT. The anti-inflammatory effect of EAAT was detected using lipopolysaccharide (LPS stimulation of the mouse macrophage cell line RAW264.7 in vitro and LPS-induced lung injury in vivo. The effects of EAAT on LPS-induced production of inflammatory mediators in RAW264.7 murine macrophages and the mouse model were measured using enzyme-linked immunosorbent assay and Western blot. EAAT attenuated the production of LPS-induced nitric oxide (NO, tumor necrosis factor-alpha, interleukin-1β (IL-1β, and IL-6 in vitro and in vivo. Pretreatment with EAAT markedly reduced LPS-induced histological alterations in lung tissues. Furthermore, EAAT significantly reduced the number of total cells and protein concentration levels in the bronchoalveolar lavage fluid. Western blotting test results revealed that EAAT blocked protein expression of inducible NO synthase, cyclooxygenase-2, phosphorylation of Nuclear factor-kappa-B Inhibitor alpha (IκB-α protein, and mitogen-activated protein kinases in LPS-stimulated RAW264.7 cells as well as LPS-induced lung injury. This study suggests that A. trifoliatus may be a potential therapeutic candidate for the treatment of inflammatory diseases.

  1. Effects of betaine on lipopolysaccharide-induced memory impairment in mice and the involvement of GABA transporter 2

    Directory of Open Access Journals (Sweden)

    Miwa Masaya

    2011-11-01

    Full Text Available Abstract Background Betaine (glycine betaine or trimethylglycine plays important roles as an osmolyte and a methyl donor in animals. While betaine is reported to suppress expression of proinflammatory molecules and reduce oxidative stress in aged rat kidney, the effects of betaine on the central nervous system are not well known. In this study, we investigated the effects of betaine on lipopolysaccharide (LPS-induced memory impairment and on mRNA expression levels of proinflammatory molecules, glial markers, and GABA transporter 2 (GAT2, a betaine/GABA transporter. Methods Mice were continuously treated with betaine for 13 days starting 1 day before they were injected with LPS, or received subacute or acute administration of betaine shortly before or after LPS injection. Then, their memory function was evaluated using Y-maze and novel object recognition tests 7 and 10-12 days after LPS injection (30 μg/mouse, i.c.v., respectively. In addition, mRNA expression levels in hippocampus were measured by real-time RT-PCR at different time points. Results Repeated administration of betaine (0.163 mmol/kg, s.c. prevented LPS-induced memory impairment. GAT2 mRNA levels were significantly increased in hippocampus 24 hr after LPS injection, and administration of betaine blocked this increase. However, betaine did not affect LPS-induced increases in levels of mRNA related to inflammatory responses. Both subacute administration (1 hr before, and 1 and 24 hr after LPS injection and acute administration (1 hr after LPS injection of betaine also prevented LPS-induced memory impairment in the Y-maze test. Conclusions These data suggest that betaine has protective effects against LPS-induced memory impairment and that prevention of LPS-induced changes in GAT2 mRNA expression is crucial to this ameliorating effect.

  2. Black tea extract prevents lipopolysaccharide-induced NF-κB signaling and attenuates dextran sulfate sodium-induced experimental colitis

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    Cho Sung-Bum

    2011-10-01

    Full Text Available Abstract Background Black tea has been shown to elicit anti-oxidant, anti-carcinogenic, anti-inflammatory and anti-mutagenic properties. In this study, we investigated the impact of black tea extract (BTE on lipopolysaccharide (LPS-induced NF-κB signaling in bone marrow derived-macrophages (BMM and determined the therapeutic efficacy of this extract on colon inflammation. Methods The effect of BTE on LPS-induced NF-κB signaling and pro-inflammatory gene expression was evaluated by RT-PCR, Western blotting, immunofluorescence and electrophoretic mobility shift assay (EMSA. The in vivo efficacy of BTE was assessed in mice with 3% dextran sulfate sodium (DSS-induced colitis. The severity of colitis was measured by weight loss, colon length and histologic scores. Results LPS-induced IL-12p40, IL-23p19, IL-6 and IL-1β mRNA expressions were inhibited by BTE. LPS-induced IκBα phosphorylation/degradation and nuclear translocation of NF-κB/p65 were blocked by BTE. BTE treatment blocked LPS-induced DNA-binding activity of NF-κB. BTE-fed, DSS-exposed mice showed the less weight loss, longer colon length and lower histologic score compared to control diet-fed, DSS-exposed mice. DSS-induced IκBα phosphorylation/degradation and phosphorylation of NF-κB/p65 were blocked by BTE. An increase of cleaved caspase-3 and poly (ADP-ribose polymerase (PARP in DSS-exposed mice was blocked by BTE. Conclusions These results indicate that BTE attenuates colon inflammation through the blockage of NF-κB signaling and apoptosis in DSS-induced experimental colitis model.

  3. Lipopolysaccharide induces the migration of human dental pulp cells by up-regulating miR-146a.

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    Wang, Min-Ching; Hung, Pei-Shih; Tu, Hsi-Feng; Shih, Wen-Yu; Li, Wan-Chun; Chang, Kuo-Wei

    2012-12-01

    MicroRNAs are small noncoding RNAs that play crucial roles in regulating normal and pathologic functions. Bacterial lipopolysaccharide (LPS) is one of the key regulators of pulpal pathogenesis. This study investigated how LPS regulates microRNA expression and affects the phenotype of human dental pulp cells (DPCs). Primary DPCs were established and immortalized to achieve immortalized DPCs (I-DPCs). DPCs and I-DPCs were treated with LPS and examined to identify changes in microRNA expression, cell proliferation, and cell migration. Quantitative reverse-transcriptase polymerase chain reaction was used to detect changes in gene expression. Exogenous miR-146a expression was performed transfection with pre-mir-146a mimic. Knockdown of interleukin receptor-associated kinase (IRAK1) and tumor necrosis factor receptor-associated factor 6 (TRAF6) expression was performed by small interference oligonucleotide transfection. Western blot analysis was used to detect changes in the expression of the IRAK1 and TRAF6 proteins. The differentiation of DPCs was induced by osteogenic medium. I-DPCs had a higher level of human telomerase reverse transcriptase gene than the parental DPCs. Up-regulation of miR-146a expression and an increase in migration was induced by LPS treatment of DPCs and I-DPCs. Exogenous miR-146a expression increased the migration of DPCs and I-DPCs and down-regulated the expression of IRAK1 and TRAF6. Knockdown of IRAK1 and/or TRAF6 increased the migration of DPCs. The results suggested that LPS is able to increase the migration of DPCs by modulating the miR-146a-TRAF6/IRAK1 regulatory cascade. Copyright © 2012 American Association of Endodontists. All rights reserved.

  4. Lipopolysaccharide-induced weakness in the preterm diaphragm is associated with mitochondrial electron transport chain dysfunction and oxidative stress.

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    Yong Song

    Full Text Available Diaphragmatic contractility is reduced in preterm lambs after lipopolysaccharide (LPS exposure in utero. The mechanism of impaired fetal diaphragm contractility after LPS exposure is unknown. We hypothesise that in utero exposure to LPS induces a deficiency of mitochondrial complex activity and oxidative damage in the fetal diaphragm. To test this hypothesis, we used a well-established preterm ovine model of chorioamnionitis: Pregnant ewes received intra-amniotic (IA saline or 10 mg LPS, at 2 d or 7 d prior to surgical delivery at 121 d GA (term = 150 d. The fetus was killed humanely immediately after delivery for tissue sampling. Mitochondrial fractions were prepared from the isolated diaphragm and mitochondrial electron transfer chain activities were evaluated using enzymatic assays. Oxidative stress was investigated by quantifying mitochondrial oxidative protein levels and determining antioxidant gene and protein (catalase, superoxide dismutase 2 and glutathione peroxidase 1 expression. The activity of the erythroid 2-related factor 2 (Nrf2-mediated antioxidant signalling pathway was examined by quantifying the Nrf2 protein content of cell lysate and nuclear extract. A 2 d LPS exposure in utero significantly decreased electron transfer chain complex II and IV activity (p<0.05. A 7 d LPS exposure inhibited superoxide dismutase 2 and catalase expression at gene and protein levels, and Nrf2 pathway activity (p<0.05 compared with control and 2 d LPS groups, respectively. Diaphragm mitochondria accumulated oxidised protein after a 7 d LPS exposure. We conclude that intrauterine exposure to LPS induces mitochondrial oxidative stress and electron chain dysfunction in the fetal diaphragm, that is further exacerbated by impairment of the antioxidant signalling pathway and decreased antioxidant activity.

  5. Lipopolysaccharide-induced blood-brain barrier disruption: roles of cyclooxygenase, oxidative stress, neuroinflammation, and elements of the neurovascular unit.

    Science.gov (United States)

    Banks, William A; Gray, Alicia M; Erickson, Michelle A; Salameh, Therese S; Damodarasamy, Mamatha; Sheibani, Nader; Meabon, James S; Wing, Emily E; Morofuji, Yoichi; Cook, David G; Reed, May J

    2015-11-25

    Disruption of the blood-brain barrier (BBB) occurs in many diseases and is often mediated by inflammatory and neuroimmune mechanisms. Inflammation is well established as a cause of BBB disruption, but many mechanistic questions remain. We used lipopolysaccharide (LPS) to induce inflammation and BBB disruption in mice. BBB disruption was measured using (14)C-sucrose and radioactively labeled albumin. Brain cytokine responses were measured using multiplex technology and dependence on cyclooxygenase (COX) and oxidative stress determined by treatments with indomethacin and N-acetylcysteine. Astrocyte and microglia/macrophage responses were measured using brain immunohistochemistry. In vitro studies used Transwell cultures of primary brain endothelial cells co- or tri-cultured with astrocytes and pericytes to measure effects of LPS on transendothelial electrical resistance (TEER), cellular distribution of tight junction proteins, and permeability to (14)C-sucrose and radioactive albumin. In comparison to LPS-induced weight loss, the BBB was relatively resistant to LPS-induced disruption. Disruption occurred only with the highest dose of LPS and was most evident in the frontal cortex, thalamus, pons-medulla, and cerebellum with no disruption in the hypothalamus. The in vitro and in vivo patterns of LPS-induced disruption as measured with (14)C-sucrose, radioactive albumin, and TEER suggested involvement of both paracellular and transcytotic pathways. Disruption as measured with albumin and (14)C-sucrose, but not TEER, was blocked by indomethacin. N-acetylcysteine did not affect disruption. In vivo, the measures of neuroinflammation induced by LPS were mainly not reversed by indomethacin. In vitro, the effects on LPS and indomethacin were not altered when brain endothelial cells (BECs) were cultured with astrocytes or pericytes. The BBB is relatively resistant to LPS-induced disruption with some brain regions more vulnerable than others. LPS-induced disruption appears is

  6. A computational model of lipopolysaccharide-induced nuclear factor kappa B activation: a key signalling pathway in infection-induced preterm labour.

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    Gemma C Sharp

    Full Text Available Preterm birth is the single biggest cause of significant neonatal morbidity and mortality, and the incidence is rising. Development of new therapies to treat and prevent preterm labour is seriously hampered by incomplete understanding of the molecular mechanisms that initiate labour at term and preterm. Computational modelling provides a new opportunity to improve this understanding. It is a useful tool in (i identifying gaps in knowledge and informing future research, and (ii providing the basis for an in silico model of parturition in which novel drugs to prevent or treat preterm labour can be "tested". Despite their merits, computational models are rarely used to study the molecular events initiating labour. Here, we present the first attempt to generate a dynamic kinetic model that has relevance to the molecular mechanisms of preterm labour. Using published data, we model an important candidate signalling pathway in infection-induced preterm labour: that of lipopolysaccharide (LPS -induced activation of Nuclear Factor kappa B. This is the first model of this pathway to explicitly include molecular interactions upstream of Nuclear Factor kappa B activation. We produced a formalised graphical depiction of the pathway and built a kinetic model based on ordinary differential equations. The kinetic model accurately reproduced published in vitro time course plots of Lipopolysaccharide-induced Nuclear Factor kappa B activation in mouse embryo fibroblasts. In this preliminary work we have provided proof of concept that it is possible to build computational models of signalling pathways that are relevant to the regulation of labour, and suggest that models that are validated with wet-lab experiments have the potential to greatly benefit the field.

  7. A computational model of lipopolysaccharide-induced nuclear factor kappa B activation: a key signalling pathway in infection-induced preterm labour.

    Science.gov (United States)

    Sharp, Gemma C; Ma, Hongwu; Saunders, Philippa T K; Norman, Jane E

    2013-01-01

    Preterm birth is the single biggest cause of significant neonatal morbidity and mortality, and the incidence is rising. Development of new therapies to treat and prevent preterm labour is seriously hampered by incomplete understanding of the molecular mechanisms that initiate labour at term and preterm. Computational modelling provides a new opportunity to improve this understanding. It is a useful tool in (i) identifying gaps in knowledge and informing future research, and (ii) providing the basis for an in silico model of parturition in which novel drugs to prevent or treat preterm labour can be "tested". Despite their merits, computational models are rarely used to study the molecular events initiating labour. Here, we present the first attempt to generate a dynamic kinetic model that has relevance to the molecular mechanisms of preterm labour. Using published data, we model an important candidate signalling pathway in infection-induced preterm labour: that of lipopolysaccharide (LPS) -induced activation of Nuclear Factor kappa B. This is the first model of this pathway to explicitly include molecular interactions upstream of Nuclear Factor kappa B activation. We produced a formalised graphical depiction of the pathway and built a kinetic model based on ordinary differential equations. The kinetic model accurately reproduced published in vitro time course plots of Lipopolysaccharide-induced Nuclear Factor kappa B activation in mouse embryo fibroblasts. In this preliminary work we have provided proof of concept that it is possible to build computational models of signalling pathways that are relevant to the regulation of labour, and suggest that models that are validated with wet-lab experiments have the potential to greatly benefit the field.

  8. Autophagy involved in lipopolysaccharide-induced foam cell formation is mediated by adipose differentiation-related protein.

    Science.gov (United States)

    Feng, Xuyang; Yuan, Yuan; Wang, Chao; Feng, Jun; Yuan, Zuyi; Zhang, Xiumin; Sui, Wen; Hu, Peizhen; Zheng, Pengfei; Ye, Jing

    2014-01-09

    Autophagy is an essential process for breaking down macromolecules and aged/damaged cellular organelles to maintain cellular energy balance and cellular nutritional status. The idea that autophagy regulates lipid metabolism is an emerging concept with important implications for atherosclerosis. However, the potential role of autophagy and its relationship with lipid metabolism in foam cell formation remains unclear. In this study, we found that autophagy was involved in the lipopolysaccharide (LPS)-induced the formation of foam cells and was at least partially dependent on adipose differentiation-related protein (ADRP). Foam cell formation was evaluated by Oil red O staining. Autophagic activity was determined by immunofluorescence and Western blotting. ADRP gene expression of ADRP was examined by real-time PCR (RT-PCR). The protein expression of ADRP and LC3 was measured using Western blotting analysis. Intracellular cholesterol and triglyceride levels in foam cells were quantitatively measured by enzymatic colorimetric assays. LPS promoted foam cell formation by inducing lipid accumulation in macrophages. The activation of autophagy with rapamycin (Rap) decreased intracellular cholesterol and triglyceride levels, whereas the inhibition of autophagy with 3-methyladenine (3MA) enhanced the accumulation of lipid droplets. Overexpression of ADRP alone increased the formation of foam cells and consequently autophagic activity. In contrast, the inhibitory effects of ADRP activity with siRNA suppressed the activation of autophagy. Taken together, we propose a novel role for ADRP in the regulation of macrophage autophagy during LPS stimulation. We defined a new molecular pathway in which LPS-induced foam cell formation is regulated through autophagy. These findings facilitate the understanding of the role of autophagy in the development of atherosclerosis.

  9. Induction of heme oxygenase-1 attenuates lipopolysaccharide-induced cyclooxygenase-2 expression in mouse brain endothelial cells

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    Yang Chuen-Mao

    2010-11-01

    Full Text Available Abstract Background Prostaglandin E2 (PGE2, an arachidonic acid metabolite converted by cyclooxygenase-2 (COX-2, plays important roles in the regulation of endothelial functions in response to bacterial infection. The enzymatic activity of COX-2 can be down-regulated by heme oxygenase-1 (HO-1 induction. However, the mechanisms underlying HO-1 modulating COX-2 protein expression are not known. Objective The aim of the present study was to investigate whether the up-regulation of HO-1 regulates COX-2 expression induced by lipopolysaccharide (LPS, an endotoxin produced by Gram negative bacteria, in mouse brain endothelial cells (bEnd.3 Methods Cultured bEnd.3 cells were used to investigate LPS-induced COX-2 expression and PGE2 production. Cobalt protoporphyrin IX (CoPP, an HO-1 inducer, infection with a recombinant adenovirus carried with HO-1 gene (Adv-HO-1, or zinc protoporphyrin (ZnPP, an HO-1 inhibitor was used to stimulate HO-1 induction or inhibit HO-1 activity. The expressions of COX-2 and HO-1 were evaluated by western blotting. PGE2 levels were detected by an enzyme-linked immunoassay. Hemoglobin (a chelator of carbon monoxide, CO, one of metabolites of HO-1 and CO-RM2 (a CO releasing molecule were used to investigate the mechanisms of HO-1 regulating COX-2 expression. Results We found that LPS-induced COX-2 expression and PGE2 production were mediated through NF-κB (p65 via activation of Toll-like receptor 4 (TLR4. LPS-induced COX-2 expression was inhibited by HO-1 induction by pretreatment with CoPP or infection with Adv-HO-1. This inhibitory effect of HO-1 was reversed by pretreatment with either ZnPP or hemoglobin. Pretreatment with CO-RM2 also inhibited TLR4/MyD88 complex formation, NF-κB (p65 activation, COX-2 expression, and PGE2 production induced by LPS. Conclusions We show here a novel inhibition of HO-1 on LPS-induced COX-2/PGE2 production in bEnd.3. Our results reinforce the emerging role of cerebral endothelium-derived HO-1

  10. Horizontal gene transfer from macrophages to ischemic muscles upon delivery of naked DNA with Pluronic block copolymers.

    Science.gov (United States)

    Mahajan, Vivek; Gaymalov, Zagit; Alakhova, Daria; Gupta, Richa; Zucker, Irving H; Kabanov, Alexander V

    2016-01-01

    Intramuscular administration of plasmid DNA (pDNA) with non-ionic Pluronic block copolymers increases gene expression in injected muscles and lymphoid organs. We studied the role of immune cells in muscle transfection upon inflammation. Local inflammation in murine hind limb ischemia model (MHLIM) drastically increased DNA, RNA and expressed protein levels in ischemic muscles injected with pDNA/Pluronic. The systemic inflammation (MHLIM or peritonitis) also increased expression of pDNA/Pluronic in the muscles. When pDNA/Pluronic was injected in ischemic muscles the reporter gene, Green Fluorescent Protein (GFP) co-localized with desmin(+) muscle fibers and CD11b(+) macrophages (MØs), suggesting transfection of MØs along with the muscle cells. P85 enhanced (∼ 4 orders) transfection of MØs with pDNA in vitro. Moreover, adoptively transferred MØs were shown to pass the transgene to inflamed muscle cells in MHLIM. Using a co-culture of myotubes (MTs) and transfected MØs expressing a reporter gene under constitutive (cmv-luciferase) or muscle specific (desmin-luciferase) promoter we demonstrated that P85 enhances horizontal gene transfer from MØ to MTs. Therefore, MØs can play an important role in muscle transfection with pDNA/Pluronic during inflammation, with both inflammation and Pluronic contributing to the increased gene expression. pDNA/Pluronic has potential for therapeutic gene delivery in muscle pathologies that involve inflammation. Copyright © 2015 Elsevier Ltd. All rights reserved.

  11. Well-defined block copolymers for gene delivery to dendritic cells: probing the effect of polycation chain-length.

    Science.gov (United States)

    Tang, Rupei; Palumbo, R Noelle; Nagarajan, Lakshmi; Krogstad, Emily; Wang, Chun

    2010-03-03

    The development of safe and efficient polymer carriers for DNA vaccine delivery requires mechanistic understanding of structure-function relationship of the polymer carriers and their interaction with antigen-presenting cells. Here we have synthesized a series of diblock copolymers with well-defined chain-length using atom transfer radical polymerization and characterized the influence of polycation chain-length on the physico-chemical properties of the polymer/DNA complexes as well as the interaction with dendritic cells. The copolymers consist of a hydrophilic poly(ethylene glycol) block and a cationic poly(aminoethyl methacrylate) (PAEM) block. The average degree of polymerization (DP) of the PAEM block was varied among 19, 39, and 75, with nearly uniform distribution. With increasing PAEM chain-length, polyplexes formed by the diblock copolymers and plasmid DNA had smaller average particle size and showed higher stability against electrostatic destabilization by salt and heparin. The polymers were not toxic to mouse dendritic cells (DCs) and only displayed chain-length-dependent toxicity at a high concentration (1mg/mL). In vitro gene transfection efficiency and polyplex uptake in DCs were also found to correlate with chain-length of the PAEM block with the longer polymer chain favoring transfection and cellular uptake. The polyplexes induced a modest up-regulation of surface markers for DC maturation that was not significantly dependent on PAEM chain-length. Finally, the polyplex prepared from the longest PAEM block (DP of 75) achieved an average of 20% enhancement over non-condensed anionic dextran in terms of uptake by DCs in the draining lymph nodes 24h after subcutaneous injection into mice. Insights gained from studying such structurally well-defined polymer carriers and their interaction with dendritic cells may contribute to improved design of practically useful DNA vaccine delivery systems. Copyright 2009 Elsevier B.V. All rights reserved.

  12. Sensitivity of spiral ganglion neurons to damage caused by mobile phone electromagnetic radiation will increase in lipopolysaccharide-induced inflammation in vitro model.

    Science.gov (United States)

    Zuo, Wen-Qi; Hu, Yu-Juan; Yang, Yang; Zhao, Xue-Yan; Zhang, Yuan-Yuan; Kong, Wen; Kong, Wei-Jia

    2015-05-29

    it could cause the changes of cellular ultrastructure at special SAR 4.0 W/kg when cells are in fragile or micro-damaged condition. It seems that the sensitivity of SGN to damage caused by mobile phone electromagnetic radiation will increase in a lipopolysaccharide-induced inflammation in vitro model.

  13. Inhibitory monoclonal antibodies against mouse proteases raised in gene-deficient mice block proteolytic functions in vivo

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    Ida Katrine Lund

    2012-06-01

    Full Text Available Identification of targets for cancer therapy requires the understanding of the in vivo roles of proteins, which can be derived from studies using gene-targeted mice. An alternative strategy is the administration of inhibitory monoclonal antibodies (mAbs, causing acute disruption of the target protein function(s. This approach has the advantage of being a model for therapeutic targeting. mAbs for use in mouse models can be obtained through immunization of gene-deficient mice with the autologous protein. Such mAbs react with both species-specific epitopes and epitopes conserved between species. mAbs against proteins involved in extracellular proteolysis, including plasminogen activators (uPA, tPA, their inhibitor PAI-1, the uPA receptor (uPAR, two matrix metalloproteinases (MMP9 and MMP14, as well as the collagen internalization receptor uPARAP, have been developed. The inhibitory mAbs against uPA and uPAR block plasminogen activation and thereby hepatic fibrinolysis in vivo. Wound healing, another plasmin-dependent process, is delayed by an inhibitory mAb against uPA in the adult mouse. Thromboembolism can be inhibited by anti-PAI-1 mAbs in vivo. In conclusion, function-blocking mAbs are well-suited for targeted therapy in mouse models of different diseases, including cancer.

  14. Hap2, a novel gene in Babesia bigemina is expressed in tick stages, and specific antibodies block zygote formation

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    Minerva Camacho-Nuez

    2017-11-01

    Full Text Available Abstract Background Bovine babesiosis is a tick-borne disease caused by the protozoan parasites of the genus Babesia. In their host vector, Babesia spp. undergo sexual reproduction. Therefore, the development of sexual stages and the subsequent formation of the zygote are essential for the parasite to invade the intestinal cells of the vector tick and continue its life-cycle. HAP2/GCS1 is a protein identified in plants, protozoan parasites and other organisms that has an important role during membrane fusion in fertilization processes. The identification and characterization of HAP-2 protein in Babesia would be very significant to understand the biology of the parasite and to develop a transmission-blocking vaccine in the future. Results To isolate and sequence the hap2 gene DNA from an infected bovine with Babesia bigemina was purified. The hap2 gene was amplified, cloned and sequenced. The sequences of hap2 from four geographically different strains showed high conservation at the amino acid level, including the typical structure with a signal peptide and the HAP2/GSC domain. Antisera anti-HAP2 against the conserved extracellular region of the HAP2 amino acid sequence were obtained from rabbits. The expression of hap2 in the host and vector tissues was analyzed by using semi-quantitative RT-PCR, and the protein was examined by western blot and immunofluorescence. Based on the RT-PCR and WB results, HAP2 is expressed in both, sexual stages induced in vitro, and in infected ticks as well. We did not detect any expression in asexual erythrocytic stages of B. bigemina, relevantly anti-HAP2 specific antibodies were able to block zygotes formation in vitro. Conclusion Babesia bigemina HAP2 is expressed only in tick-infecting stages, and specific antibodies block zygote formation. Further studies regarding the function of HAP2 during tick infection may provide new insights into the molecular mechanisms of sexual reproduction of the parasite.

  15. Hap2, a novel gene in Babesia bigemina is expressed in tick stages, and specific antibodies block zygote formation.

    Science.gov (United States)

    Camacho-Nuez, Minerva; Hernández-Silva, Diego Josimar; Castañeda-Ortiz, Elizabeth Jacqueline; Paredes-Martínez, María Elena; Rocha-Martínez, Marisol Karina; Alvarez-Sánchez, María Elizbeth; Mercado-Curiel, Ricardo Francisco; Aguilar-Tipacamu, Gabriela; Mosqueda, Juan

    2017-11-13

    Bovine babesiosis is a tick-borne disease caused by the protozoan parasites of the genus Babesia. In their host vector, Babesia spp. undergo sexual reproduction. Therefore, the development of sexual stages and the subsequent formation of the zygote are essential for the parasite to invade the intestinal cells of the vector tick and continue its life-cycle. HAP2/GCS1 is a protein identified in plants, protozoan parasites and other organisms that has an important role during membrane fusion in fertilization processes. The identification and characterization of HAP-2 protein in Babesia would be very significant to understand the biology of the parasite and to develop a transmission-blocking vaccine in the future. To isolate and sequence the hap2 gene DNA from an infected bovine with Babesia bigemina was purified. The hap2 gene was amplified, cloned and sequenced. The sequences of hap2 from four geographically different strains showed high conservation at the amino acid level, including the typical structure with a signal peptide and the HAP2/GSC domain. Antisera anti-HAP2 against the conserved extracellular region of the HAP2 amino acid sequence were obtained from rabbits. The expression of hap2 in the host and vector tissues was analyzed by using semi-quantitative RT-PCR, and the protein was examined by western blot and immunofluorescence. Based on the RT-PCR and WB results, HAP2 is expressed in both, sexual stages induced in vitro, and in infected ticks as well. We did not detect any expression in asexual erythrocytic stages of B. bigemina, relevantly anti-HAP2 specific antibodies were able to block zygotes formation in vitro. Babesia bigemina HAP2 is expressed only in tick-infecting stages, and specific antibodies block zygote formation. Further studies regarding the function of HAP2 during tick infection may provide new insights into the molecular mechanisms of sexual reproduction of the parasite.

  16. An upstream promoter element blocks the reverse transcription of the mouse insulin-degrading enzyme gene.

    Science.gov (United States)

    Zhang, Lang; Ding, Qingyang; Wang, Pan; Wang, Zhao

    2013-01-04

    Despite the prevalence of bidirectional promoters among the mammalian genomes, the majority of promoters are unidirectional. The mechanism through which unidirectional promoters are prevented from reverse transcription remains to be clarified. Here we investigate the transcriptional directionality of the mouse insulin-degrading enzyme (IDE) promoter, which contains a CpG island and has dispersed transcription initiation sites. Although IDE is unidirectionally transcribed according to its genomic context, the basic promoter region of mouse IDE has bidirectional transcriptional properties. The region between -219 and +133 of mouse IDE relative to its first transcription initiation site has bidirectional transcriptional activities, but the region between -350 and +133 can only be transcribed from the normal direction, implying that an upstream promoter element locating between -350 and -219 blocks the reverse transcription of mouse IDE. We further mapped this upstream promoter element to the region between -243 and -287. Promoter mutation analysis showed that the upstream promoter element contains two functional sub-regions. In conclusion, we identified an upstream promoter element which blocks the reverse transcription of mouse IDE. Our studies are suggestive for the transcriptional mechanism of bidirectional promoters in mammalian genomes. Crown Copyright © 2012. Published by Elsevier Inc. All rights reserved.

  17. Gene expression changes in rat prostate after activation or blocking of the androgen and estrogen receptor

    DEFF Research Database (Denmark)

    Nellemann, Christine Lydia; Dalgaard, Majken; Holst, Bjørn

    2005-01-01

    responsive genes (complement C3, ER alpha, ER beta, AR, TRPM-2, PBPC3, ODC, and IGF-1 mRNA) was analyzed in rat ventral prostate by real time RT-PCR. Administration of estradiol benzoate (EB) to castrated testosterone-treated rats had no effect on reproductive organ weights or gene expression levels...... and the anti-estrogen, ICI 182780, only affected ODC expression. Therefore, estrogenic or anti-estrogenic compounds would not be expected to seriously affect the outcome of a Hershberger test. However, EB given alone to castrated rats resulted in various effects. EB increased seminal vesicle weight, an effect....... These data indicate that estrogens have various effects in castrated male rats and that expression of several genes is under multi-hormonal control in the ventral prostate. However, interactions between estrogens and androgens do not play a major role in the Hershberger assay, as simultaneous TP...

  18. Melatonin inhibits Prevotella intermedia lipopolysaccharide-induced production of nitric oxide and interleukin-6 in murine macrophages by suppressing NF-κB and STAT1 activity.

    Science.gov (United States)

    Choi, Eun-Young; Jin, Ji-Young; Lee, Ju-Youn; Choi, Jeom-Il; Choi, In Soon; Kim, Sung-Jo

    2011-03-01

    Although a range of biological and pharmacological activities of melatonin have been reported, little is known about its potential anti-inflammatory efficacy in periodontal disease. In this study, we investigated the effects of melatonin on the production of inflammatory mediators by murine macrophages stimulated with lipopolysaccharide (LPS) from Prevotella intermedia, a major cause of inflammatory reactions in the periodontium, and sought to determine the underlying mechanisms of action. Melatonin suppressed the production of nitric oxide (NO) and interleukin-6 (IL-6) at both gene transcription and translation levels in P. intermedia LPS-activated RAW264.7 cells. P. intermedia LPS-induced NF-κB-dependent luciferase activity was significantly inhibited by melatonin. Melatonin did not reduce NF-κB transcriptional activity at the level of IκB-α degradation. Melatonin blocked NF-κB signaling through the inhibition of nuclear translocation and DNA-binding activity of NF-κB p50 subunit and suppressed STAT1 signaling. Although further research is required to clarify the detailed mechanism of action, we conclude that melatonin may contribute to blockade of the host-destructive processes mediated by these two proinflammatory mediators and could be a highly efficient modulator of host response in the treatment of inflammatory periodontal disease. © 2010 The Authors. Journal of Pineal Research © 2010 John Wiley & Sons A/S.

  19. Western diet induces colonic nitrergic myenteric neuropathy and dysmotility in mice via saturated fatty acid- and lipopolysaccharide-induced TLR4 signalling.

    Science.gov (United States)

    Reichardt, François; Chassaing, Benoit; Nezami, Behtash Ghazi; Li, Ge; Tabatabavakili, Sahar; Mwangi, Simon; Uppal, Karan; Liang, Bill; Vijay-Kumar, Matam; Jones, Dean; Gewirtz, Andrew T; Srinivasan, Shanthi

    2017-03-01

    A high-fat diet (60% kcal from fat) is associated with motility disorders inducing constipation and loss of nitrergic myenteric neurons in the proximal colon. Gut microbiota dysbiosis, which occurs in response to HFD, contributes to endotoxaemia. High levels of lipopolysaccharide lead to apoptosis in cultured myenteric neurons that express Toll-like receptor 4 (TLR4). Consumption of a Western diet (WD) (35% kcal from fat) for 6 weeks leads to gut microbiota dysbiosis associated with altered bacterial metabolites and increased levels of plasma free fatty acids. These disorders precede the nitrergic myenteric cell loss observed in the proximal colon. Mice lacking TLR4 did not exhibit WD-induced myenteric cell loss and dysmotility. Lipopolysaccharide-induced in vitro enteric neurodegeneration requires the presence of palmitate and may be a result of enhanced NO production. The present study highlights the critical role of plasma saturated free fatty acids that are abundant in the WD with respect to driving enteric neuropathy and colonic dysmotility. The consumption of a high-fat diet (HFD) is associated with myenteric neurodegeneration, which in turn is associated with delayed colonic transit and constipation. We examined the hypothesis that an inherent increase in plasma free fatty acids (FFA) in the HFD together with an HFD-induced alteration in gut microbiota contributes to the pathophysiology of these disorders. C57BL/6 mice were fed a Western diet (WD) (35% kcal from fat enriched in palmitate) or a purified regular diet (16.9% kcal from fat) for 3, 6, 9 and 12 weeks. Gut microbiota dysbiosis was investigated by fecal lipopolysaccharide (LPS) measurement and metabolomics (linear trap quadrupole-Fourier transform mass spectrometer) analysis. Plasma FFA and LPS levels were assessed, in addition to colonic and ileal nitrergic myenteric neuron quantifications and motility. Compared to regular diet-fed control mice, WD-fed mice gained significantly more weight

  20. p27KIP1 blocks cyclin E-dependent transactivation of cyclin A gene expression

    DEFF Research Database (Denmark)

    Zerfass-Thome, K; Schulze, A; Zwerschke, W

    1997-01-01

    Cyclin E is necessary and rate limiting for the passage of mammalian cells through the G1 phase of the cell cycle. Control of cell cycle progression by cyclin E involves cdk2 kinase, which requires cyclin E for catalytic activity. Expression of cyclin E/cdk2 leads to an activation of cyclin A gene...... expression, as monitored by reporter gene constructs derived from the human cyclin A promoter. Promoter activation by cyclin E/cdk2 requires an E2F binding site in the cyclin A promoter. We show here that cyclin E/cdk2 kinase can directly bind to E2F/p107 complexes formed on the cyclin A promoter-derived E2F...... binding site, and this association is controlled by p27KIP1, most likely through direct protein-protein interaction. These observation suggest that cyclin E/cdk2 associates with E2F/p107 complexes in late G1 phase, once p27KIP1 has decreased below a critical threshold level. Since a kinase-negative mutant...

  1. Eupatolide inhibits lipopolysaccharide-induced COX-2 and iNOS expression in RAW264.7 cells by inducing proteasomal degradation of TRAF6.

    Science.gov (United States)

    Lee, Jongkyu; Tae, Nara; Lee, Jung Joon; Kim, Taeho; Lee, Jeong-Hyung

    2010-06-25

    Inula britannica is a traditional medicinal plant used to treat bronchitis, digestive disorders, and inflammation in Eastern Asia. Here, we identified eupatolide, a sesquiterpene lactone from I. britannica, as an inhibitor of cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) expression. Eupatolide inhibited the production of nitric oxide (NO) and prostaglandin E(2) (PGE(2)) as well as iNOS and COX-2 protein expression in lipopolysaccharide (LPS)-stimulated RAW264.7 cells. Eupatolide dose-dependently decreased the mRNA levels and the promoter activities of COX-2 and iNOS in LPS-stimulated RAW264.7 cells. Moreover, eupatolide significantly suppressed the LPS-induced expression of nuclear factor-kappa B (NF-kappaB) and activator protein-1 (AP-1) reporter genes. Pretreatment of eupatolide inhibited LPS-induced phosphorylation and degradation of I kappaB alpha, and phosphorylation of RelA/p65 on Ser-536 as well as the activation of mitogen-activated protein kinases (MAPKs) and Akt in LPS-stimulated RAW264.7 cells. Eupatolide induced proteasomal degradation of tumor necrosis factor receptor-associated factor-6 (TRAF6), and subsequently inhibited LPS-induced TRAF6 polyubiquitination. These results suggest that eupatolide blocks LPS-induced COX-2 and iNOS expression at the transcriptional level through inhibiting the signaling pathways such as NF-kappaB and MAPKs via proteasomal degradation of TRAF6. Taken together, eupatolide may be a novel anti-inflammatory agent that induces proteasomal degradation of TRAF6, and a valuable compound for modulating inflammatory conditions. (c) 2010 Elsevier B.V. All rights reserved.

  2. Carbon monoxide-releasing molecule-3 suppresses Prevotella intermedia lipopolysaccharide-induced production of nitric oxide and interleukin-1β in murine macrophages.

    Science.gov (United States)

    Choi, Eun-Young; Choe, So-Hui; Hyeon, Jin-Yi; Choi, Jeom-Il; Choi, In Soon; Kim, Sung-Jo

    2015-10-05

    This study was performed to analyze the effect of carbon monoxide (CO)-releasing molecule-3 (CORM-3) in alleviating the production of proinflammatory mediators in macrophages treated with lipopolysaccharide (LPS) from Prevotella intermedia, a pathogen associated with periodontal disease, and its possible mechanisms of action. LPS was isolated using the hot phenol-water method. Culture supernatants were assayed for nitric oxide (NO) and interleukin-1β (IL-1β). Gene expression was quantified by real-time PCR, and protein expression by immunoblotting. DNA-binding activities of NF-κB subunits were determined using an ELISA-based kit. CORM-3 suppressed the production of inducible NO synthase (iNOS)-derived NO and IL-1β at both gene transcription and translation levels in P. intermedia LPS-activated RAW264.7 cells. CORM-3 enhanced heme oxygenase-1 (HO-1) expression in cells stimulated with P. intermedia LPS, and inhibition of HO-1 activity by SnPP notably reversed the suppressive effect of CORM-3 on LPS-induced production of NO. LPS-induced phosphorylation of p38 and JNK was not affected by CORM-3. CORM-3 did not influence P. intermedia LPS-induced degradation of IκB-α. Instead, nuclear translocation of NF-κB p65 and p50 subunits was blocked by CORM-3 in LPS-treated cells. In addition, CORM-3 reduced LPS-induced p65 and p50 binding to DNA. Besides, CORM-3 significantly suppressed P. intermedia LPS-induced phosphorylation of STAT1. Overall, this study indicates that CORM-3 suppresses the production of NO and IL-1β in P. intermedia LPS-activated murine macrophages via HO-1 induction and inhibition of NF-κB and STAT1 pathways. The modulation of host inflammatory response by CORM-3 would be an attractive therapeutic approach to attenuate the progression of periodontal disease. Copyright © 2015 Elsevier B.V. All rights reserved.

  3. Combined cocaine hydrolase gene transfer and anti-cocaine vaccine synergistically block cocaine-induced locomotion.

    Directory of Open Access Journals (Sweden)

    Marilyn E Carroll

    Full Text Available Mice and rats were tested for reduced sensitivity to cocaine-induced hyper-locomotion after pretreatment with anti-cocaine antibody or cocaine hydrolase (CocH derived from human butyrylcholinesterase (BChE. In Balb/c mice, direct i.p. injection of CocH protein (1 mg/kg had no effect on spontaneous locomotion, but it suppressed responses to i.p. cocaine up to 80 mg/kg. When CocH was injected i.p. along with a murine cocaine antiserum that also did not affect spontaneous locomotion, there was no response to any cocaine dose. This suppression of locomotor activity required active enzyme, as it was lost after pretreatment with iso-OMPA, a selective BChE inhibitor. Comparable results were obtained in rats that developed high levels of CocH by gene transfer with helper-dependent adenoviral vector, and/or high levels of anti-cocaine antibody by vaccination with norcocaine hapten conjugated to keyhole limpet hemocyanin (KLH. After these treatments, rats were subjected to a locomotor sensitization paradigm involving a "training phase" with an initial i.p. saline injection on day 1 followed by 8 days of repeated cocaine injections (10 mg/kg, i.p.. A 15-day rest period then ensued, followed by a final "challenge" cocaine injection. As in mice, the individual treatment interventions reduced cocaine-stimulated hyperactivity to a modest extent, while combined treatment produced a greater reduction during all phases of testing compared to control rats (with only saline pretreatment. Overall, the present results strongly support the view that anti-cocaine vaccine and cocaine hydrolase vector treatments together provide enhanced protection against the stimulatory actions of cocaine in rodents. A similar combination therapy in human cocaine users might provide a robust therapy to help maintain abstinence.

  4. Combined Cocaine Hydrolase Gene Transfer and Anti-Cocaine Vaccine Synergistically Block Cocaine-Induced Locomotion

    Science.gov (United States)

    Carroll, Marilyn E.; Zlebnik, Natalie E.; Anker, Justin J.; Kosten, Thomas R.; Orson, Frank M.; Shen, Xiaoyun; Kinsey, Berma; Parks, Robin J.; Gao, Yang; Brimijoin, Stephen

    2012-01-01

    Mice and rats were tested for reduced sensitivity to cocaine-induced hyper-locomotion after pretreatment with anti-cocaine antibody or cocaine hydrolase (CocH) derived from human butyrylcholinesterase (BChE). In Balb/c mice, direct i.p. injection of CocH protein (1 mg/kg) had no effect on spontaneous locomotion, but it suppressed responses to i.p. cocaine up to 80 mg/kg. When CocH was injected i.p. along with a murine cocaine antiserum that also did not affect spontaneous locomotion, there was no response to any cocaine dose. This suppression of locomotor activity required active enzyme, as it was lost after pretreatment with iso-OMPA, a selective BChE inhibitor. Comparable results were obtained in rats that developed high levels of CocH by gene transfer with helper-dependent adenoviral vector, and/or high levels of anti-cocaine antibody by vaccination with norcocaine hapten conjugated to keyhole limpet hemocyanin (KLH). After these treatments, rats were subjected to a locomotor sensitization paradigm involving a “training phase" with an initial i.p. saline injection on day 1 followed by 8 days of repeated cocaine injections (10 mg/kg, i.p.). A 15-day rest period then ensued, followed by a final “challenge" cocaine injection. As in mice, the individual treatment interventions reduced cocaine-stimulated hyperactivity to a modest extent, while combined treatment produced a greater reduction during all phases of testing compared to control rats (with only saline pretreatment). Overall, the present results strongly support the view that anti-cocaine vaccine and cocaine hydrolase vector treatments together provide enhanced protection against the stimulatory actions of cocaine in rodents. A similar combination therapy in human cocaine users might provide a robust therapy to help maintain abstinence. PMID:22912888

  5. [Mobile ISCR elements: structure, functions, and role in the emergence, increasing and spreading of blocks of bacterial genes of multiple antibiotic resistance].

    Science.gov (United States)

    Il'ina, T S

    2012-01-01

    The recently discovered method of horizontal distribution of bacterial genes with atypical ISCR sequences is reviewed using an example of drug resistance genes. The adjacent DNA segment mobilization is provided by the transposition of such elements, including rolling circle replication, formation of autonomous nonreplicable circular structures, and homological recombination. The gene distribution capacity with the ISCR elements is more significant than the capacity of transposons and integrons, thereby providing formation of groups of mobile genes, including antibiotic-resistance genes of pathogenic bacteria. The structure and functions of the ISCR elements were discussed together with their similarity and dissimilarity with the group of IS91-similar elements and their role in the emergence of blocks of bacterial genes encoding of multiple antibiotic resistance and their contribution to evolution of bacterial and plasmid genes.

  6. Efficient bacterial expression of recombinant potato mop-top virus non-structural triple gene block protein 1 modified by progressive deletion of its N-terminus

    Czech Academy of Sciences Publication Activity Database

    Pečenková, Tamara; Filigarová, Marie; Čeřovská, Noemi

    2005-01-01

    Roč. 41, - (2005), s. 128-135 ISSN 1046-5928 R&D Projects: GA ČR GA522/04/1329 Institutional research plan: CEZ:AV0Z50380511 Keywords : Protein expression * Potato mop-top virus * Triple gene block Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 1.553, year: 2005

  7. Characterization and mapping of a shattering mutant in rice that corresponds to a block of domestication genes.

    Science.gov (United States)

    Ji, Hyeon-So; Chu, Sang-Ho; Jiang, Wenzhu; Cho, Young-Il; Hahn, Jang-Ho; Eun, Moo-Young; McCouch, Susan R; Koh, Hee-Jong

    2006-06-01

    Easy shattering reduces yield due to grain loss during harvest in cereals. Shattering is also a hindrance in breeding programs that use wild accessions because the shattering habit is often linked to desirable traits. We characterized a shattering mutant line of rice, Hsh, which was derived from a nonshattering japonica variety, Hwacheong, by N-methyl-N-nitrosourea (MNU) treatment. The breaking tensile strength (BTS) of the grain pedicel was measured using a digital force gauge to evaluate the degree of shattering of rice varieties at 5, 10, 15, 20, 25, 30, 35, and 40 days after heading (DAH). The BTS of Hwacheong did not decrease with increasing DAH, maintaining a level of 180-240 gf, while that of Hsh decreased greatly during 10-20 DAH and finally stabilized at 50 gf. Optical microscopy revealed that Hsh had a well-developed abscission layer similar to the wild rice Oryza nivara (accession IRGC105706), while Hwacheong did not produce an abscission layer, indicating that the shattering of Hsh was caused by differentiation of the abscission layer. On the basis of the BTS value and morphology of the abscission layer of F(1) plants and segregation data in F(2) populations, it was concluded that the easy shattering of Hsh was controlled by the single recessive gene sh-h. The gene sh-h was determined to be located on rice chromosome 7 by bulked segregant analysis. Using 14 SSR markers on rice chromosome 7, the gene sh-h was mapped between the flanking markers RM8262 and RM7161 at distances of 1.6 and 2.0 cM, respectively. An SSR marker Rc17 cosegregated with the gene sh-h. The locus sh-h for shattering was tightly linked to the Rc locus conferring red pericarp, as well as a QTL qSD(s)-7-1 for seed dormancy, implying that this region might represent a domestication block in the evolutionary pathway of rice.

  8. A highly conserved gene island of three genes on chromosome 3B of hexaploid wheat: diverse gene function and genomic structure maintained in a tightly linked block

    Directory of Open Access Journals (Sweden)

    Ma Wujun

    2010-05-01

    Full Text Available Abstract Background The complexity of the wheat genome has resulted from waves of retrotransposable element insertions. Gene deletions and disruptions generated by the fast replacement of repetitive elements in wheat have resulted in disruption of colinearity at a micro (sub-megabase level among the cereals. In view of genomic changes that are possible within a given time span, conservation of genes between species tends to imply an important functional or regional constraint that does not permit a change in genomic structure. The ctg1034 contig completed in this paper was initially studied because it was assigned to the Sr2 resistance locus region, but detailed mapping studies subsequently assigned it to the long arm of 3B and revealed its unusual features. Results BAC shotgun sequencing of the hexaploid wheat (Triticum aestivum cv. Chinese Spring genome has been used to assemble a group of 15 wheat BACs from the chromosome 3B physical map FPC contig ctg1034 into a 783,553 bp genomic sequence. This ctg1034 sequence was annotated for biological features such as genes and transposable elements. A three-gene island was identified among >80% repetitive DNA sequence. Using bioinformatics analysis there were no observable similarity in their gene functions. The ctg1034 gene island also displayed complete conservation of gene order and orientation with syntenic gene islands found in publicly available genome sequences of Brachypodium distachyon, Oryza sativa, Sorghum bicolor and Zea mays, even though the intergenic space and introns were divergent. Conclusion We propose that ctg1034 is located within the heterochromatic C-band region of deletion bin 3BL7 based on the identification of heterochromatic tandem repeats and presence of significant matches to chromodomain-containing gypsy LTR retrotransposable elements. We also speculate that this location, among other highly repetitive sequences, may account for the relative stability in gene order and

  9. Actin Cytoskeleton and Golgi Involvement in Barley stripe mosaic virus Movement and Cell Wall Localization of Triple Gene Block Proteins

    Directory of Open Access Journals (Sweden)

    Hyoun-Sub Lim

    2013-03-01

    Full Text Available Barley stripe mosaic virus (BSMV induces massive actin filament thickening at the infection front of infected Nicotiana benthamiana leaves. To determine the mechanisms leading to actin remodeling, fluorescent protein fusions of the BSMV triple gene block (TGB proteins were coexpressed in cells with the actin marker DsRed: Talin. TGB ectopic expression experiments revealed that TGB3 is a major elicitor of filament thickening, that TGB2 resulted in formation of intermediate DsRed:Talin filaments, and that TGB1 alone had no obvious effects on actin filament structure. Latrunculin B (LatB treatments retarded BSMV cell-to-cell movement, disrupted actin filament organization, and dramatically decreased the proportion of paired TGB3 foci appearing at the cell wall (CW. BSMV infection of transgenic plants tagged with GFP-KDEL exhibited membrane proliferation and vesicle formation that were especially evident around the nucleus. Similar membrane proliferation occurred in plants expressing TGB2 and/or TGB3, and DsRed: Talin fluorescence in these plants colocalized with the ER vesicles. TGB3 also associated with the Golgi apparatus and overlapped with cortical vesicles appearing at the cell periphery. Brefeldin A treatments disrupted Golgi and also altered vesicles at the CW, but failed to interfere with TGB CW localization. Our results indicate that actin cytoskeleton interactions are important in BSMV cell-to-cell movement and for CW localization of TGB3.

  10. Homology blocks of Plasmodium falciparum var genes and clinically distinct forms of severe malaria in a local population.

    Science.gov (United States)

    Rorick, Mary M; Rask, Thomas S; Baskerville, Edward B; Day, Karen P; Pascual, Mercedes

    2013-11-06

    The primary target of the human immune response to the malaria parasite Plasmodium falciparum, P. falciparum erythrocyte membrane protein 1 (PfEMP1), is encoded by the members of the hyper-diverse var gene family. The parasite exhibits antigenic variation via mutually exclusive expression (switching) of the ~60 var genes within its genome. It is thought that different variants exhibit different host endothelial binding preferences that in turn result in different manifestations of disease. Var sequences comprise ancient sequence fragments, termed homology blocks (HBs), that recombine at exceedingly high rates. We use HBs to define distinct var types within a local population. We then reanalyze a dataset that contains clinical and var expression data to investigate whether the HBs allow for a description of sequence diversity corresponding to biological function, such that it improves our ability to predict disease phenotype from parasite genetics. We find that even a generic set of HBs, which are defined for a small number of non-local parasites: capture the majority of local sequence diversity; improve our ability to predict disease severity from parasite genetics; and reveal a previously hypothesized yet previously unobserved parasite genetic basis for two forms of severe disease. We find that the expression rates of some HBs correlate more strongly with severe disease phenotypes than the expression rates of classic var DBLα tag types, and principal components of HB expression rate profiles further improve genotype-phenotype models. More specifically, within the large Kenyan dataset that is the focus of this study, we observe that HB expression differs significantly for severe versus mild disease, and for rosetting versus impaired consciousness associated severe disease. The analysis of a second much smaller dataset from Mali suggests that these HB-phenotype associations are consistent across geographically distant populations, since we find evidence suggesting

  11. Identification of Putative Ortholog Gene Blocks Involved in Gestant and Lactating Mammary Gland Development: A Rodent Cross-Species Microarray Transcriptomics Approach

    Science.gov (United States)

    Rodríguez-Cruz, Maricela; Coral-Vázquez, Ramón M.; Hernández-Stengele, Gabriel; Sánchez, Raúl; Salazar, Emmanuel; Sanchez-Muñoz, Fausto; Encarnación-Guevara, Sergio; Ramírez-Salcedo, Jorge

    2013-01-01

    The mammary gland (MG) undergoes functional and metabolic changes during the transition from pregnancy to lactation, possibly by regulation of conserved genes. The objective was to elucidate orthologous genes, chromosome clusters and putative conserved transcriptional modules during MG development. We analyzed expression of 22,000 transcripts using murine microarrays and RNA samples of MG from virgin, pregnant, and lactating rats by cross-species hybridization. We identified 521 transcripts differentially expressed; upregulated in early (78%) and midpregnancy (89%) and early lactation (64%), but downregulated in mid-lactation (61%). Putative orthologous genes were identified. We mapped the altered genes to orthologous chromosomal locations in human and mouse. Eighteen sets of conserved genes associated with key cellular functions were revealed and conserved transcription factor binding site search entailed possible coregulation among all eight block sets of genes. This study demonstrates that the use of heterologous array hybridization for screening of orthologous gene expression from rat revealed sets of conserved genes arranged in chromosomal order implicated in signaling pathways and functional ontology. Results demonstrate the utilization power of comparative genomics and prove the feasibility of using rodent microarrays to identification of putative coexpressed orthologous genes involved in the control of human mammary gland development. PMID:24288657

  12. Amphiphilic star block copolymers as gene carrier Part I: Synthesis via ATRP using calix[4]resorcinarene-based initiators and characterization

    Energy Technology Data Exchange (ETDEWEB)

    Zheng, Anna; Xue, Yan; Wei, Dafu [Shanghai Key Laboratory of Advanced Polymeric Materials, Key Laboratory for Ultrafine Materials of Ministry of Education, School of Materials Science and Engineering, East China University of Science and Technology, Shanghai 200237 (China); Guan, Yong, E-mail: yguan@ecust.edu.cn [Shanghai Key Laboratory of Advanced Polymeric Materials, Key Laboratory for Ultrafine Materials of Ministry of Education, School of Materials Science and Engineering, East China University of Science and Technology, Shanghai 200237 (China); Xiao, Huining [Department of Chemical Engineering, University of New Brunswick, Fredericton, New Brunswick, Canada E3B 5A3 (Canada)

    2013-01-01

    In this work, a cationic star polymer [poly(2-dimethylamino)ethyl methacrylate (PDMAEMA)] was prepared via atom transfer radical polymerization (ATRP), using brominated calix[4]resorcinarene as an initiator. Hydrophobic moieties, methyl methacrylate (MMA) and butyl acrylate (BA), were further incorporated via 'one-pot' method. Well-defined eight-armed star block copolymers bearing hydrophilic blocks inside and hydrophobic blocks outside were synthesized. The molecular weight, particle size, electrophoretic mobility and apparent charge density were determined by gel permeation chromatography (GPC), dynamic light scattering (DLS), phase analysis light scattering (PALS) and colloidal titration, respectively. The zeta potentials and apparent charge densities of the products exhibited the characteristics of polyelectrolyte. The incorporation of hydrophobic moieties generated electrostatic screening effect. The as-synthesized amphiphilic star copolymer is promising as a thermo-sensitive gene carrier for gene therapy. Highlights: Black-Right-Pointing-Pointer Amphiphilic cationic star block copolymers with well-controlled structures were prepared via ATRP. Black-Right-Pointing-Pointer The molecular structures and properties of the initiator and copolymers were systematically characterized. Black-Right-Pointing-Pointer The products exhibited the positive charged character, and hydrophobic moieties generated electrostatic screening effect.

  13. Complexation of AB+, AB+C, ACB+, and A(B+-stat-C) block copolymer micelles with poly(styrene sulfonate) as models for tunable gene delivery vectors

    Science.gov (United States)

    Laaser, Jennifer; Jiang, Yaming; Lohmann, Elise; Reineke, Theresa; Lodge, Timothy

    We investigate the complexation of poly(styrene sulfonate) with micelles with mixed cationic/hydrophilic coronas as models for tunable gene delivery vectors. The micelles are self-assembled from AB+, AB+C, ACB+, and A(B+-stat-C) block polymer architectures, where the hydrophobic A blocks (poly(styrene)) form the micelle cores, and the cationic B blocks (poly(dimethylamino ethyl methacrylate)) and hydrophilic, nonionic C blocks (poly(poly(ethylene glycol) methyl ether methacrylate)) form the coronas. We find that hydrophilic units do not change the colloidal stability of the complexes, and complexes based on all four micelle architectures form broad, multimodal size distributions. While complexes based on the AB+, AB+C, and ACB+polymer architectures are kinetically trapped at low ionic strength, however, those based on the A(B+-stat-C) architecture rapidly rearrange into single-micelle complexes when the linear polyanion is in excess. This suggests that the randomly-placed hydrophilic units break up the ion pairing between the cationic and anionic chains and promote formation of over-charged complexes. Design of the micelle architecture may thus provide a powerful way control the structure and stability of micelle-polyelectrolyte complexes for gene delivery applications.

  14. COX-2–prostacyclin signaling through endothelial nitric oxide is not necessary for lipopolysaccharide-induced hypotension and bradycardia in conscious unrestrained mice

    DEFF Research Database (Denmark)

    Stæhr, Mette

    caused a concomitant decrease in mean arterial blood pressure (MAP) and heart rate (HR) that was significant after 2-3h and sustained through the experiment (8h). The LPS-induced changes in MAP and HR were not different from control in COX-2-/- mice and in eNOS-/- mice. Intravenous infusion...... of a prostacyclin receptor (IP) antagonist, (BR5064, 0.1 mg/kg bolus followed by infusion at a rate of 0.005 mg/kg/h for 8 h), effectively blocked the hypotensive effect of an IP agonist (beraprost 20 µg/kg), but did not attenuate the LPS-induced decrease in MAP and HR. LPS decreased eNOS mRNA level in liver...

  15. Side-chain amino-acid-based pH-responsive self-assembled block copolymers for drug delivery and gene transfer.

    Science.gov (United States)

    Kumar, Sonu; Acharya, Rituparna; Chatterji, Urmi; De, Priyadarsi

    2013-12-10

    Developing safe and effective nanocarriers for multitype of delivery system is advantageous for several kinds of successful biomedicinal therapy with the same carrier. In the present study, we have designed amino acid biomolecules derived hybrid block copolymers which can act as a promising vehicle for both drug delivery and gene transfer. Two representative natural chiral amino acid-containing (l-phenylalanine and l-alanine) vinyl monomers were polymerized via reversible addition-fragmentation chain transfer (RAFT) process in the presence of monomethoxy poly(ethylene glycol) based macro-chain transfer agents (mPEGn-CTA) for the synthesis of well-defined side-chain amino-acid-based amphiphilic block copolymers, monomethoxy poly(ethylene glycol)-b-poly(Boc-amino acid methacryloyloxyethyl ester) (mPEGn-b-P(Boc-AA-EMA)). The self-assembled micellar aggregation of these amphiphilic block copolymers were studied by fluorescence spectroscopy, atomic force microscopy (AFM) and scanning electron microscopy (SEM). Potential applications of these hybrid polymers as drug carrier have been demonstrated in vitro by encapsulation of nile red dye or doxorubicin drug into the core of the micellar nanoaggregates. Deprotection of side-chain Boc- groups in the amphiphilic block copolymers subsequently transformed them into double hydrophilic pH-responsive cationic block copolymers having primary amino groups in the side-chain terminal. The DNA binding ability of these cationic block copolymers were further investigated by using agarose gel retardation assay and AFM. The in vitro cytotoxicity assay demonstrated their biocompatible nature and these polymers can serve as "smart" materials for promising bioapplications.

  16. Voluntary exercise blocks Western diet-induced gene expression of the chemokines CXCL10 and CCL2 in the prefrontal cortex.

    Science.gov (United States)

    Carlin, Jesse L; Grissom, Nicola; Ying, Zhe; Gomez-Pinilla, Fernando; Reyes, Teresa M

    2016-11-01

    Obesity increases inflammation, both peripherally and centrally, and exercise can ameliorate some of the negative health outcomes associated with obesity. Within the brain, the effect of obesity on inflammation has been well characterized in the hypothalamus and hippocampus, but has been relatively understudied in other brain regions. The current study was designed to address two primary questions; (1) whether western diet (high fat/high sucrose) consumption would increase markers of inflammation in the prefrontal cortex and (2) whether concurrent voluntary wheel running would ameliorate any inflammation. Adult male mice were exposed to a western diet or a control diet for 8weeks. Concurrently, half the animals were given running wheels in their home cages, while half did not have access to wheels. At the conclusion of the study, prefrontal cortex was removed and expression of 18 proinflammatory genes was assayed. Expression of a number of proinflammatory molecules was upregulated by consumption of the western diet. For two chemokines, chemokine (C-C motif) ligand 2 (CCL2) and C-X-C motif chemokine 10 (CXCL10), voluntary exercise blocked the increase in the expression of these genes. Cluster analysis confirmed that the majority of the tested genes were upregulated by western diet, and identified another small cluster of genes that were downregulated by either diet or exercise. These data identify a proinflammatory phenotype within the prefrontal cortex of mice fed a western diet, and indicate that chemokine induction can be blocked by voluntary exercise. Copyright © 2016 Elsevier Inc. All rights reserved.

  17. Ulinastatin suppresses lipopolysaccharide induced neuro-inflammation through the downregulation of nuclear factor-κB in SD rat hippocampal astrocyte

    Energy Technology Data Exchange (ETDEWEB)

    Li, Yuting; Zhao, Lei; Fu, Huiqun [Department of Anesthesiology, Xuanwu Hospital, Capital Medical University, 100053 Beijing (China); Wu, Yan [Department of Anatomy, Capital Medical University, 100069 Beijing (China); Wang, Tianlong, E-mail: litingliting258@163.com [Department of Anesthesiology, Xuanwu Hospital, Capital Medical University, 100053 Beijing (China)

    2015-03-20

    Astrocyte activation plays a pivotal role in neuroinflammation, which contributes to neuronal damage, so the inhibition of astrocyte activation may alleviate the progression of neurodegeneration. Recent studies have proved that urinary trypsin inhibitor ulinastatin could inhibit NF-kB activation. In our study, the inhibitory effects of ulinastatin on the production of pro-inflammatory mediators were investigated in lipopolysaccharide (LPS)-reduced primary astrocyte. Our results showed that ulinastatin significantly inhibited LPS-induced astrogliosis, which is measured by MTT and BrdU. Ulinastatin decreased the production of pro-inflammatory cytokines, such as TNF-α, IL-6, IL-1β, it significantly decreased both the mRNA and the protein levels of these pro-inflammatory cytokines and also increased the protein levels of IκB-α binded to NF-κB, which blocked NF-κB translocation to the nucleus and prevented its activity. Our results suggest that ulinastatin is able to inhibit neuroinflammation by interfering with NF-κB signaling. The study provides direct evidence of potential therapy methods of ulinastatin for the treatment of neuroinflammatory diseases. - Highlights: • The anti-inflammatory effect of UTI on hippocampal astrocyte. • UTI showed protective effect on neuroinflammation by the downregulation of NF-κB. • UTI led to expression of cytokines decreased in concentration and time dependence.

  18. Inhibition of c-Jun-N-terminal kinase increases cardiac peroxisome proliferator-activated receptor alpha expression and fatty acid oxidation and prevents lipopolysaccharide-induced heart dysfunction.

    Science.gov (United States)

    Drosatos, Konstantinos; Drosatos-Tampakaki, Zoi; Khan, Raffay; Homma, Shunichi; Schulze, P Christian; Zannis, Vassilis I; Goldberg, Ira J

    2011-10-21

    Septic shock results from bacterial infection and is associated with multi-organ failure, high mortality, and cardiac dysfunction. Sepsis causes both myocardial inflammation and energy depletion. We hypothesized that reduced cardiac energy production is a primary cause of ventricular dysfunction in sepsis. The JNK pathway is activated in sepsis and has also been implicated in impaired fatty acid oxidation in several tissues. Therefore, we tested whether JNK activation inhibits cardiac fatty acid oxidation and whether blocking JNK would restore fatty acid oxidation during LPS treatment. LPS treatment of C57BL/6 mice and adenovirus-mediated activation of the JNK pathway in cardiomyocytes inhibited peroxisome proliferator-activated receptor α expression and fatty acid oxidation. Surprisingly, none of the adaptive responses that have been described in other types of heart failure, such as increased glucose utilization, reduced αMHC:βMHC ratio or induction of certain microRNAs, occurred in LPS-treated mice. Treatment of C57BL/6 mice with a general JNK inhibitor (SP600125) increased fatty acid oxidation in mice and a cardiomyocyte-derived cell line. JNK inhibition also prevented LPS-mediated reduction in fatty acid oxidation and cardiac dysfunction. Inflammation was not alleviated in LPS-treated mice that received the JNK inhibitor. We conclude that activation of JNK signaling reduces fatty acid oxidation and prevents the peroxisome proliferator-activated receptor α down-regulation that occurs with LPS.

  19. Clinical significance of proliferation, apoptosis and senescence of nasopharyngeal cells by the simultaneously blocking EGF, IGF-1 receptors and Bcl-xl genes

    Energy Technology Data Exchange (ETDEWEB)

    Dai, Guodong [Anatomy and Embryology, Wuhan University School of Medicine, Wuhan, Hubei 430071 (China); Peng, Tao; Zhou, Xuhong [Department of Otolaryngology-Head and Neck Surgery, Zhongnan Hospital of Wuhan University, Wuhan 430071 (China); Zhu, Jun; Kong, Zhihua; Ma, Li; Xiong, Zhi [Anatomy and Embryology, Wuhan University School of Medicine, Wuhan, Hubei 430071 (China); Yuan, Yulin, E-mail: yuanyulin19620120@126.com [Anatomy and Embryology, Wuhan University School of Medicine, Wuhan, Hubei 430071 (China)

    2013-11-01

    Highlight: •Construction of shRNA segments expression vectors is valid by the investigation of RT-PCR for IGF1R, EGFR and Bcl-xl mRNA and protein expression. •Studies have suggested that the vectors in blocking these genes of the growth factor receptors and anti- apoptosis is capable of breaking the balance of tumor growth so that tumor trend apoptosis and senescence. •Simultaneously blocking multiple genes that are abnormally expressed may be more effective in treating cancer cells than silencing a single gene. -- Abstract: Background: In previous work, we constructed short hairpin RNA (shRNA) expression plasmids that targeted human EGF and IGF-1 receptors messenger RNA, respectively, and demonstrated that these vectors could induce apoptosis of human nasopharyngeal cell lines (CNE2) and inhibit ligand-induced pAkt and pErk activation. Method: We have constructed multiple shRNA expression vectors of targeting EGFR, IGF1R and Bcl-xl, which were transfected to the CNE2 cells. The mRNA expression was assessed by RT-PCR. The growth of the cells, cell cycle progression, apoptosis of the cells, senescent tumor cells and the proteins of EGFR, IGF1R and Bcl-xl were analyzed by MTT, flow cytometry, cytochemical therapy or Western blot. Results: In group of simultaneously blocking EGFR, IGF1R and Bcl-xl genes, the mRNA of EGFR, IGF1R and Bcl-xl expression was decreased by (66.66 ± 3.42)%, (73.97 ± 2.83)% and (64.79 ± 2.83)%, and the protein expressions was diminished to (67.69 ± 4.02)%, (74.32 ± 2.30)%, and (60.00 ± 3.34)%, respectively. Meanwhile, the cell apoptosis increased by 65.32 ± 0.18%, 65.16 ± 0.25% and 55.47 ± 0.45%, and senescent cells increased by 1.42 ± 0.15%, 2.26 ± 0.15% and 3.22 ± 0.15% in the second, third and fourth day cultures, respectively. Conclusions: Simultaneously blocking EGFR, IGF1R and Bcl-xl genes is capable of altering the balance between proliferating versus apoptotic and senescent cells in the favor of both of apoptosis and

  20. The cysteine residues at the C-terminal tail of Bamboo mosaic virus triple gene block protein 2 are critical for efficient plasmodesmata localization of protein 1 in the same block.

    Science.gov (United States)

    Ho, Tsai-Ling; Lee, Hsiang-Chi; Chou, Yuan-Lin; Tseng, Yang-Hao; Huang, Wei-Cheng; Wung, Chiung-Hua; Lin, Na-Sheng; Hsu, Yau-Heiu; Chang, Ban-Yang

    2017-01-15

    The movement of some plant viruses are accomplished by three proteins encoded by a triple gene block (TGB). The second protein (TGBp2) in the block is a transmembrane protein. This study was aimed to unravel the mechanism underlying the relatively inefficient cell-to-cell movement of Bamboo mosaic virus (BaMV) caused by amino acid substitutions for the three Cys residues, Cys-109, Cys-112 and Cys-119, at the C-terminal tail of TGBp2. Results from confocal microscopy revealed that substitutions of the three Cys residues of TGBp2, especially Cys-109 and Cys-112, would reduce the efficiency of TGBp2- and TGBp3-dependent PD localization of TGBp1. Moreover, there is an additive effect of the substitutions on reducing the efficiency of PD localization of TGBp1. These results indicate that the Cys residues in the C-terminal tail region of TGBp2 participate in the TGBp2- and TGBp3-dependent PD localization of TGBp1, and thus influence the cell-to-cell movement capability of BaMV. Copyright © 2016 Elsevier Inc. All rights reserved.

  1. Effect of nitric oxide-releasing derivative of indomethacin on Prevotella intermedia lipopolysaccharide-induced production of proinflammatory mediators in murine macrophages.

    Science.gov (United States)

    Choe, So-Hui; Choi, Eun-Young; Hyeon, Jin-Yi; Choi, In Soon; Kim, Sung-Jo

    2017-10-14

    The purpose of this study was to investigate the influences of NCX 2121, a nitric oxide (NO)-releasing derivative of indomethacin, upon the generation of proinflammatory mediators using murine macrophages activated by lipopolysaccharide (LPS) isolated from Prevotella intermedia, which is one of the pathogens implicated in periodontal diseases. Inducible NO synthase (iNOS)-derived NO, IL-1β and IL-6 as well as their relevant mRNA were significantly attenuated by NCX 2121 in RAW264.7 cells activated by P. intermedia LPS. NCX 2121 was much more effective than the parental compound indomethacin in reducing these proinflammatory mediators. NCX 2121 triggered induction of heme oxygenase-1 (HO-1) in cells exposed to P. intermedia LPS, and its inhibitory influence upon P. intermedia LPS-elicited NO generation was notably blocked by SnPP treatment. NCX 2121 attenuated NF-κB-dependent SEAP release induced by P. intermedia LPS. NCX 2121 did not display inhibitory action towards IκB-α degradation triggered by LPS. Instead, it significantly diminished nuclear translocation as well as DNA-binding action of NF-κB p50 subunit elicited by P. intermedia LPS. Further, NCX 2121 significantly up-regulated SOCS1 mRNA expression in cells challenged with P. intermedia LPS. In summary, NCX 2121 down-regulates P. intermedia LPS-elicited generation of NO, IL-1β and IL-6 in murine macrophages in a mechanism that involves anti-inflammatory HO-1 induction as well as decrement of NF-κB activation, which may be associated with SOCS1 expression. NCX 2121 may have potential benefits as a host immunomodulatory agent for the therapy of periodontal disease. Copyright © 2017 Elsevier Inc. All rights reserved.

  2. Inhibition of Phosphodiesterase 4 by FCPR03 Alleviates Lipopolysaccharide-Induced Depressive-Like Behaviors in Mice: Involvement of p38 and JNK Signaling Pathways

    Directory of Open Access Journals (Sweden)

    Hui Yu

    2018-02-01

    Full Text Available Inflammatory responses induced by peripheral administration of lipopolysaccharide (LPS triggers depressive-like behavioral syndrome in rodents. Inhibition of phosphodiesterase 4 (PDE4 produces a robust anti-inflammatory effect in inflammatory cells. Unfortunately, archetypal PDE4 inhibitors cause intolerable gastrointestinal side-effects, such as vomiting and nausea. N-isopropyl-3-(cyclopropylmethoxy-4-difluoromethoxy benzamide (FCPR03 is a novel, selective PDE4 inhibitor with little, or no, emetic potency. Our previous studies show that FCPR03 is effective in attenuating neuroinflammation in mice treated with LPS. However, whether FCPR03 could exert antidepressant-like effect induced by LPS is largely unknown. In the present study, mice injected intraperitoneally (i.p. with LPS was established as an in vivo animal model of depression. The antidepressant-like activities of FCPR03 were evaluated using a tail suspension test, forced swimming test, and sucrose preference test. We demonstrated that administration of FCPR03 (1 mg/kg produced antidepressant-like effects in mice challenged by LPS, as evidenced by decreases in the duration of immobility in the forced swim and tail suspension tests, while no significant changes in locomotor activity were observed. FCPR03 also increased sucrose preference in mice treated with LPS. In addition, treatment with FCPR03 abolished the downregulation of brain-derived neurotrophic factor induced by LPS and decreased the level of corticosterone in plasma. Meanwhile, periphery immune challenge by LPS induced enhanced phosphorylation of p38-mitogen activated protein kinase (p38 and c-Jun N-terminal kinase (JNK in both the cerebral cortex and hippocampus in mice. Interestingly, treatment with FCPR03 significantly blocked the role of LPS and reduced the levels of phosphorylated p38 and JNK. Collectively, these results indicate that FCPR03 shows antidepressant-like effects in mice challenged by LPS, and the p38/JNK

  3. The Neurokinin-1 Receptor Contributes to the Early Phase of Lipopolysaccharide-Induced Fever via Stimulation of Peripheral Cyclooxygenase-2 Protein Expression in Mice

    Directory of Open Access Journals (Sweden)

    Eszter Pakai

    2018-02-01

    Full Text Available Neurokinin (NK signaling is involved in various inflammatory processes. A common manifestation of systemic inflammation is fever, which is usually induced in animal models with the administration of bacterial lipopolysaccharide (LPS. A role for the NK1 receptor was shown in LPS-induced fever, but the underlying mechanisms of how the NK1 receptor contributes to febrile response, especially in the early phase, have remained unknown. We administered LPS (120 µg/kg, intraperitoneally to mice with the Tacr1 gene, i.e., the gene encoding the NK1 receptor, either present (Tacr1+/+ or absent (Tacr1−/− and measured their thermoregulatory responses, serum cytokine levels, tissue cyclooxygenase-2 (COX-2 expression, and prostaglandin (PG E2 concentration. We found that the LPS-induced febrile response was attenuated in Tacr1−/− compared to their Tacr1+/+ littermates starting from 40 min postinfusion. The febrigenic effect of intracerebroventricularly administered PGE2 was not suppressed in the Tacr1−/− mice. Serum concentration of pyrogenic cytokines did not differ between Tacr1−/− and Tacr1+/+ at 40 min post-LPS infusion. Administration of LPS resulted in amplification of COX-2 mRNA expression in the lungs, liver, and brain of the mice, which was statistically indistinguishable between the genotypes. In contrast, the LPS-induced augmentation of COX-2 protein expression was attenuated in the lungs and tended to be suppressed in the liver of Tacr1−/− mice compared with Tacr1+/+ mice. The Tacr1+/+ mice responded to LPS with a significant surge of PGE2 production in the lungs, whereas Tacr1−/− mice did not. In conclusion, the NK1 receptor is necessary for normal fever genesis. Our results suggest that the NK1 receptor contributes to the early phase of LPS-induced fever by enhancing COX-2 protein expression in the periphery. These findings advance the understanding of the crosstalk between NK signaling and the “cytokine-COX-2

  4. Suppression of lipopolysaccharide-induced of inducible nitric oxide synthase and cyclooxygenase-2 by Sanguis Draconis, a dragon's blood resin, in RAW 264.7 cells.

    Science.gov (United States)

    Choy, Cheuk-Sing; Hu, Chien-Ming; Chiu, Wen-Ta; Lam, Carlos-Shu Kei; Ting, Yih; Tsai, Shin-Han; Wang, Tzu-Chien

    2008-02-12

    Sanguis Draconis (SD) is a kind of dragon's blood resin that is obtained from Daemomorops draco (Palmae). It is used in traditional medicine and has shown anti-inflammatory activity in some diseases. In this study, we examined the effects of Sanguis Dranonis ethanol extract (SDEE) on LPS-induced inflammation using RAW 264.7 cells. Our data indicated that SDEE inhibits LPS-stimulated NO, PGE2, IL-1 beta and TNF-alpha release, and iNOS and COX-2 expression. Furthermore, SDEE suppressed the LPS-induced p65 expression of NF-kappa B, which was associated with the inhibition of I kappa B-alpha degradation. We also found that the expression of HO-1 was significantly increased in RAW 264.7 cells by SDEE. These results suggest among possibilities of anti-inflammation that SDEE inhibits the production of NO and PGE2 by the down-regulation of iNOS and COX-2 gene expression via the suppression of NF-kappaB (p65) activation. SDEE can induce HO-1 over-expression in macrophage cells, which indicates that it may possess antioxidant properties. This result means that SEDD its anti-inflammatory effects in macrophages may be through a novel mechanism that involves the action of HO-1. Thus, SD could provide a potential therapeutic approach for inflammation-associated disorders.

  5. Arctigenin inhibits lipopolysaccharide-induced iNOS expression in RAW264.7 cells through suppressing JAK-STAT signal pathway.

    Science.gov (United States)

    Kou, Xianjuan; Qi, Shimei; Dai, Wuxing; Luo, Lan; Yin, Zhimin

    2011-08-01

    Arctigenin has been demonstrated to have an anti-inflammatory function, but the precise mechanisms of its action remain to be fully defined. In the present study, we determined the effects of arctigenin on lipopolysaccharide (LPS)-induced production of proinflammatory mediators and the underlying mechanisms involved in RAW264.7 cells. Our results indicated that arctigenin exerted its anti-inflammatory effect by inhibiting ROS-dependent STAT signaling through its antioxidant activity. Arctigenin also significantly reduced the phosphorylation of STAT1 and STAT 3 as well as JAK2 in LPS-stimulated RAW264.7 cells. The inhibitions of STAT1 and STAT 3 by arctigenin prevented their translocation to the nucleus and consequently inhibited expression of iNOS, thereby suppressing the expression of inflammation-associated genes, such as IL-1β, IL-6 and MCP-1, whose promoters contain STAT-binding elements. However, COX-2 expression was slightly inhibited at higher drug concentrations (50 μM). Our data demonstrate that arctigenin inhibits iNOS expression via suppressing JAK-STAT signaling pathway in macrophages. Crown Copyright © 2011. Published by Elsevier B.V. All rights reserved.

  6. Allium hookeri root extract exerts anti-inflammatory effects by nuclear factor-κB down-regulation in lipopolysaccharide-induced RAW264.7 cells.

    Science.gov (United States)

    Jang, Ja-Young; Lee, Min-Jung; You, Bo-Ram; Jin, Jong-Sik; Lee, Sung-Hyen; Yun, Ye-Rang; Kim, Hyun Ju

    2017-02-23

    Allium hookeri (AH) is widely consumed as a vegetable and herbal medicine in southeastern Asia. AH has been reported antioxidant, antimicrobial, improvement of bone health and antidiabetic effects. In the present study, we investigated the inhibitory effect of a methanol extract of AH root (AHE) on inflammatory response in lipopolysaccharide (LPS)-induced RAW264.7 cells. Initially, characterization of organic sulfur compounds in AHE was determined using high performance liquid chromatography-electrospray ionization-mass spectrometry (HPLC-ESI-MS). Cells were incubated with LPS and AHE for 24 h. The productions of nitric oxide (NO), reactive oxygen species (ROS), and inflammation-related cytokines were examined. Gene and protein expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) were assessed by polymerase chain reaction and Western blotting. Key factor, nuclear factor kappa B (NF-κB) was also determined. AHE contained organosulfur compounds such as alliin and S-allylcysteine by HPLC-ESI-MS. AHE significantly inhibited NO, ROS, and cytokines production in LPS-induced RAW264.7 cells. In addition, AHE treatment inhibited iNOS and COX-2 mRNA and protein levels, leading to a decrease in iNOS-derived NO level. Furthermore, NF-κB activation was, at least in part, suppressed by AHE treatment. Our data suggest that AHE treatment inhibits the inflammation condition through suppression of iNOS and COX-2 expression via NF-κB down-regulation.

  7. 14-3-3γ regulates cell viability and milk fat synthesis in lipopolysaccharide-induced dairy cow mammary epithelial cells.

    Science.gov (United States)

    Liu, Lixin; Zhang, L I; Lin, Y E; Bian, Yanjie; Gao, Xuejun; Qu, B O; Li, Qingzhang

    2016-04-01

    Our previous study demonstrated that 14-3-3γ overexpression was able to inhibit the production of lipopolysaccharide (LPS)-induced cytokines in dairy cow mammary epithelial cells (DCMECs) by inhibiting the activation of nuclear factor-κB (NF-κB) signaling pathways. However, the association between 14-3-3γ overexpression and milk fat synthesis in LPS-induced DCMECs remains unclear. Therefore, the present study investigated the effect of 14-3-3γ on cell viability and milk fat synthesis in LPS-induced DCMECs. The results of the MTT assay and lactate dehydrogenase activity assay demonstrated that 14-3-3γ overexpression was able to attenuate LPS-induced cytotoxicity in DCMECs, and increase the viability of the cells. In addition, the results of reverse transcription-quantitative polymerase chain reaction suggested that mRNA expression levels of genes associated with milk fat synthesis, including sterol regulatory element binding protein (SREBP1), peroxisome proliferator-activated receptor-γ (PPARG), cluster of differentiation 36, acetyl-coA carboxylase (ACC), fatty acid synthase (FAS) and fatty acid binding protein-3, were significantly upregulated in cells overexpressing the 14-3-3γ protein. In addition, as compared with the LPS-treated group, the activities of FAS and ACC were significantly increased. Furthermore, western blotting demonstrated that 14-3-3γ overexpression enhanced the protein expression levels of phosphorylated SREBP1 and PPARG. These results suggested that high levels of 14-3-3γ protein were able to attenuate LPS-induced cell damage and promote milk fat synthesis in LPS-induced DCMECs by increasing the cell viability and upregulating the expression levels of transcription factors associated with milk fat synthesis.

  8. Ghrelin protects against palmitic acid or lipopolysaccharide-induced hepatocyte apoptosis through inhibition of MAPKs/iNOS and restoration of Akt/eNOS pathways.

    Science.gov (United States)

    Mao, Yuqing; Wang, Jianbo; Yu, Fujun; Li, Zhengyang; Li, Huanqing; Guo, Chuanyong; Fan, Xiaoming

    2016-12-01

    Ghrelin has been shown to exert various biological functions. However, the effect and mechanism of ghrelin on PA- or LPS-induced liver injury remains unknown. Normal human hepatocyte lines (LO2 and 7701) were pretreated with ghrelin (10 -8 M) for 30min before stimulation with lipopolysaccharide (LPS) or palmitic acid (PA). The proliferation and apoptosis of cells were detected with CCK8, Hoechst staining and flow cytometric analysis. Levels of NO of cell supernatants were examined by enzyme-linked immunosorbent assay (ELISA). The protein levels and mRNA of target genes of endothelial NOS (eNOS) and inducible NOS (iNOS) were measured by western blotting, immunofluorescence and quantitative real-time polymerase chain reaction (qRT-PCR). The expression of Bax, Bcl2, caspase 3, p-Akt, p-P38 and p-JNK were detected by western blotting. Results of CCK8, Hoechst staining and flow cytometric analysis showed that ghrelin-pretreatment attenuated LPS- or PA- induced cellular proliferation inhibition and apoptosis induction. ELISA results revealed that ghrelin pretreatment reduced levels of NO of cell supernatants (Pghrelin- pretreated group were significantly reduced compared with LPS- or PA- treated group, while protein levels of eNOS were restored by ghrelin pretreatment. Results of qRT-PCR showed that mRNA levels of Bax, iNOS were reduced by ghrelin pretreatment, while levels of mRNA of Bcl2 and eNOS were increased (Pghrelin pretreatment, while the protein levels of p-JNK, p-P38 and caspase 3 were reduced. The restoration of eNOS could be reversed by an Akt inhibitor. Ghrelin pretreatment attenuated LPS- or PA-induced hepatocyte apoptosis, which may least partly via inhibition of mitogen-activated protein kinases (MAPKs)/iNOS and restoration of Akt/eNOS pathways. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  9. Population Blocks.

    Science.gov (United States)

    Smith, Martin H.

    1992-01-01

    Describes an educational game called "Population Blocks" that is designed to illustrate the concept of exponential growth of the human population and some potential effects of overpopulation. The game material consists of wooden blocks; 18 blocks are painted green (representing land), 7 are painted blue (representing water); and the remaining…

  10. Keap1 silencing boosts lipopolysaccharide-induced transcription of interleukin 6 via activation of nuclear factor κB in macrophages

    Energy Technology Data Exchange (ETDEWEB)

    Lv, Peng [Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing (China); Institute for Chemical Safety Sciences, The Hamner Institutes for Health Sciences, 6 Davis Drive, Research Triangle Park, NC 27709 (United States); Xue, Peng; Dong, Jian [Institute for Chemical Safety Sciences, The Hamner Institutes for Health Sciences, 6 Davis Drive, Research Triangle Park, NC 27709 (United States); Peng, Hui [Institute for Chemical Safety Sciences, The Hamner Institutes for Health Sciences, 6 Davis Drive, Research Triangle Park, NC 27709 (United States); Evaluation and Research Center for Toxicology, Institute of Disease Control and Prevention, Academy of Military Medical Sciences (China); Clewell, Rebecca [Institute for Chemical Safety Sciences, The Hamner Institutes for Health Sciences, 6 Davis Drive, Research Triangle Park, NC 27709 (United States); Wang, Aiping [Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing (China); Wang, Yue [Institute for Medical Device Standardization Administration, National Institutes for Food and Drug Control, Beijing (China); Peng, Shuangqing [Evaluation and Research Center for Toxicology, Institute of Disease Control and Prevention, Academy of Military Medical Sciences (China); Qu, Weidong [Key Laboratory of the Public Health Safety, Ministry of Education, School of Public Health, Fudan University, Shanghai (China); Zhang, Qiang; Andersen, Melvin E. [Institute for Chemical Safety Sciences, The Hamner Institutes for Health Sciences, 6 Davis Drive, Research Triangle Park, NC 27709 (United States); Pi, Jingbo, E-mail: jpi@thehamner.org [Institute for Chemical Safety Sciences, The Hamner Institutes for Health Sciences, 6 Davis Drive, Research Triangle Park, NC 27709 (United States)

    2013-11-01

    Interleukin-6 (IL6) is a multifunctional cytokine that regulates immune and inflammatory responses. Multiple transcription factors, including nuclear factor κB (NF-κB) and nuclear factor E2-related factor 2 (Nrf2), regulate IL6 transcription. Kelch-like ECH-associated protein 1 (Keap1) is a substrate adaptor protein for the Cullin 3-dependent E3 ubiquitin ligase complex, which regulates the degradation of many proteins, including Nrf2 and IκB kinase β (IKKβ). Here, we found that stable knockdown of Keap1 (Keap1-KD) in RAW 264.7 (RAW) mouse macrophages and human monocyte THP-1 cells significantly increased expression of Il6, and Nrf2-target genes, under basal and lipopolysaccharide (LPS, 0.001–0.1 μg/ml)-challenged conditions. However, Nrf2 activation alone, by tert-butylhydroquinone treatment of RAW cells, did not increase expression of Il6. Compared to cells transduced with scrambled non-target negative control shRNA, Keap1-KD RAW cells showed enhanced protein levels of IKKβ and increased expression and phosphorylation of NF-κB p65 under non-stressed and LPS-treated conditions. Because the expression of Il6 in Keap1-KD RAW cells was significantly attenuated by silencing of Ikkβ, but not Nrf2, it appears that stabilized IKKβ is responsible for the enhanced transactivation of Il6 in Keap1-KD cells. This study demonstrated that silencing of Keap1 in macrophages boosts LPS-induced transcription of Il6 via NF-κB activation. Given the importance of IL6 in the inflammatory response, the Keap1–IKKβ–NF-κB pathway may be a novel target for treatment and prevention of inflammation and associated disorders. - Highlights: • Knockdown of Keap1 increases expression of Il6 in macrophages. • Silencing of Keap1 results in protein accumulation of IKKβ and NF-κB p65. • Induction of Il6 resulting from Keap1 silencing is attributed to NF-κB activation.

  11. Expression of nodule-specific genes in alfalfa root nodules blocked at an early stage of development.

    NARCIS (Netherlands)

    Dickstein, R.; Bisseling, T.; Reinhold, V.N.; Ausubel, F.M.

    1988-01-01

    To help dissect the molecular basis of the Rhizobium-legume symbiosis, we used in vitro translation and Northern blot analysis of nodule RNA to examine alfalfa-specific genes (nodulins) expressed in two types of developmentally defective root nodules elicited by Rhizobium meliloti. Fix- nodules were

  12. Inhibitory Monoclonal Antibodies against Mouse Proteases Raised in Gene-Deficient Mice Block Proteolytic Functions in vivo

    DEFF Research Database (Denmark)

    Lund, Ida K; Rasch, Morten G; Ingvarsen, Signe

    2012-01-01

    Identification of targets for cancer therapy requires the understanding of the in vivo roles of proteins, which can be derived from studies using gene-targeted mice. An alternative strategy is the administration of inhibitory monoclonal antibodies (mAbs), causing acute disruption of the target...... protein function(s). This approach has the advantage of being a model for therapeutic targeting. mAbs for use in mouse models can be obtained through immunization of gene-deficient mice with the autologous protein. Such mAbs react with both species-specific epitopes and epitopes conserved between species....... mAbs against proteins involved in extracellular proteolysis, including plasminogen activators urokinase plasminogen activator (uPA), tissue-type plasminogen activator (tPA), their inhibitor PAI-1, the uPA receptor (uPAR), two matrix metalloproteinases (MMP9 and MMP14), as well as the collagen...

  13. Leveraging two-way probe-level block design for identifying differential gene expression with high-density oligonucleotide arrays.

    Science.gov (United States)

    Barrera, Leah; Benner, Chris; Tao, Yong-Chuan; Winzeler, Elizabeth; Zhou, Yingyao

    2004-04-20

    To identify differentially expressed genes across experimental conditions in oligonucleotide microarray experiments, existing statistical methods commonly use a summary of probe-level expression data for each probe set and compare replicates of these values across conditions using a form of the t-test or rank sum test. Here we propose the use of a statistical method that takes advantage of the built-in redundancy architecture of high-density oligonucleotide arrays. We employ parametric and nonparametric variants of two-way analysis of variance (ANOVA) on probe-level data to account for probe-level variation, and use the false-discovery rate (FDR) to account for simultaneous testing on thousands of genes (multiple testing problem). Using publicly available data sets, we systematically compared the performance of parametric two-way ANOVA and the nonparametric Mack-Skillings test to the t-test and Wilcoxon rank-sum test for detecting differentially expressed genes at varying levels of fold change, concentration, and sample size. Using receiver operating characteristic (ROC) curve comparisons, we observed that two-way methods with FDR control on sample sizes with 2-3 replicates exhibits the same high sensitivity and specificity as a t-test with FDR control on sample sizes with 6-9 replicates in detecting at least two-fold change. Our results suggest that the two-way ANOVA methods using probe-level data are substantially more powerful tests for detecting differential gene expression than corresponding methods for probe-set level data.

  14. Leveraging two-way probe-level block design for identifying differential gene expression with high-density oligonucleotide arrays

    Directory of Open Access Journals (Sweden)

    Tao Yong-Chuan

    2004-04-01

    Full Text Available Abstract Background To identify differentially expressed genes across experimental conditions in oligonucleotide microarray experiments, existing statistical methods commonly use a summary of probe-level expression data for each probe set and compare replicates of these values across conditions using a form of the t-test or rank sum test. Here we propose the use of a statistical method that takes advantage of the built-in redundancy architecture of high-density oligonucleotide arrays. Results We employ parametric and nonparametric variants of two-way analysis of variance (ANOVA on probe-level data to account for probe-level variation, and use the false-discovery rate (FDR to account for simultaneous testing on thousands of genes (multiple testing problem. Using publicly available data sets, we systematically compared the performance of parametric two-way ANOVA and the nonparametric Mack-Skillings test to the t-test and Wilcoxon rank-sum test for detecting differentially expressed genes at varying levels of fold change, concentration, and sample size. Using receiver operating characteristic (ROC curve comparisons, we observed that two-way methods with FDR control on sample sizes with 2–3 replicates exhibits the same high sensitivity and specificity as a t-test with FDR control on sample sizes with 6–9 replicates in detecting at least two-fold change. Conclusions Our results suggest that the two-way ANOVA methods using probe-level data are substantially more powerful tests for detecting differential gene expression than corresponding methods for probe-set level data.

  15. Suaeda japonica Makino Attenuates Lipopolysaccharide- Induced ...

    African Journals Online (AJOL)

    HP

    oxidant and anti-neuro-inflammatory activities of Suaeda japonica ... obesity and diabetes [2]. Recently, S. japonica has been used as functional food ..... nitric oxide synthase inhibitors and arginase competition for L-arginine utilization. Cell Mol Life.

  16. Suaeda japonica Makino Attenuates Lipopolysaccharide- Induced ...

    African Journals Online (AJOL)

    ... kappa-B (NF-êB)-dependent. Conclusion: Our findings imply that SJE may be a potential therapeutic agent in regulating microgliamediated neuroinflammatory responses observed in several neurodegenerative diseases. Keywords: Suaeda japonica, Antioxidant activity, Anti-inflammatory activity, Microglial Cells, iNOS, ...

  17. Hara on lipopolysaccharide-induced neuroinflammation

    African Journals Online (AJOL)

    factors that can trigger neuroinflammation (1). Astrocytes, microglia, and even neurons are all crucial players in maintaining tissue homeostasis, and in times of ..... pathway for cell to cell communication, leading to neuroinflammation. In this study, it was observed that IJE significantly suppressed iNOS protein production in ...

  18. Inhibition of lipopolysaccharide-induced neuroinflammatory events ...

    African Journals Online (AJOL)

    tetrazolium bromide (MTT) assay. Lipopolysaccharide (LPS) is used to activate BV-2 microglia. Nitric oxide (NO) levels were measured using Griess assay. Inducible NO synthase (iNOS) expressional levels were measured by Western blot analysis.

  19. Inhibition of Lipopolysaccharide-Induced Neuroinflammatory Events ...

    African Journals Online (AJOL)

    mL) with an IC50 value of 0.08 μg/mL. Conclusion: Data from this study indicate that CCP extract attenuates neuroinflammatory responses in. LPS-activated BV-2 microglia by inhibiting excessive production of pro-inflammatory mediators such ...

  20. Protective Effects of Pretreatment with Quercetin Against Lipopolysaccharide-Induced Apoptosis and the Inhibition of Osteoblast Differentiation via the MAPK and Wnt/β-Catenin Pathways in MC3T3-E1 Cells

    Directory of Open Access Journals (Sweden)

    Chun Guo

    2017-10-01

    Full Text Available Background/Aims: Quercetin, a flavonoid found in onions and other vegetables, has potential inhibitory effects on bone resorption in vivo and in vitro. In our previous study, we found that quercetin treatment reversed lipopolysaccharide (LPS-induced inhibition of osteoblast differentiation through the mitogen-activated protein kinase (MAPK pathway in MC3T3-E1 cells. In this study, we investigated the underlying mechanisms of pretreatment with quercetin on apoptosis and the inhibition of osteoblast differentiation in MC3T3-E1 cells induced by LPS. Methods: MC3T3-E1 osteoblasts were treated with quercetin for 2 h; cells were then incubated with LPS in the presence of quercetin for the indicated times. Cell viability was measured using the Cell Counting Kit-8 (CCK-8 assay, and cell apoptosis was evaluated using Hoechst 33258 staining. The mRNA expression levels of osteoblast-specific genes, Bax and caspase-3 were determined by real-time quantitative polymerase chain reaction (qPCR. Protein levels of osteoblast-specific genes, caspase-3, Bax, cytochrome c, Bcl-2, Bcl-XL, phosphorylated MAPKs and Wnt/β-catenin were measured using Western blot assays. The MAPK and Wnt/β-catenin signalling pathways were blocked prior to pretreatment with quercetin. Results: Pretreatment with quercetin significantly restored LPS-suppressed bone mineralization and the mRNA and protein expression levels of osteoblast-specific genes such as Osterix (OSX, runt-related transcription factor 2 (Runx2, alkaline phosphatase (ALP and osteocalcin (OCN in a dose-dependent manner. Pretreatment with quercetin also inhibited osteoblast apoptosis, significantly restored the down-regulated expression of Bcl-2 and Bcl-XL and decreased the upregulated expression of caspase-3, Bax, and cytochrome c in MC3T3-E1 cells induced by LPS. Furthermore, pretreatment with quercetin not only decreased the abundance of phosphorylated p38 MAPK and increased the abundance of phosphorylated

  1. Novel Cocaine Vaccine Linked to a Disrupted Adenovirus Gene Transfer Vector Blocks Cocaine Psychostimulant and Reinforcing Effects

    OpenAIRE

    Wee, Sunmee; Hicks, Martin J; De, Bishnu P; Rosenberg, Jonathan B; Moreno, Amira Y; Kaminsky, Stephen M; Janda, Kim D; Crystal, Ronald G; Koob, George F

    2011-01-01

    Immunotherapy is a promising treatment for drug addiction. However, insufficient immune responses to vaccines in most subjects pose a challenge. In this study, we tested the efficacy of a new cocaine vaccine (dAd5GNE) in antagonizing cocaine addiction-related behaviors in rats. This vaccine used a disrupted serotype 5 adenovirus (Ad) gene transfer vector coupled to a third-generation cocaine hapten, termed GNE (6-(2R,3S)-3-(benzoyloxy)-8-methyl-8-azabicyclo [3.2.1] octane-2-carboxamido-hexano...

  2. Cardiac fibroblast transcriptome analyses support a role for interferogenic, profibrotic, and inflammatory genes in anti-SSA/Ro-associated congenital heart block.

    Science.gov (United States)

    Clancy, Robert M; Markham, Androo J; Jackson, Tanisha; Rasmussen, Sara E; Blumenberg, Miroslav; Buyon, Jill P

    2017-09-01

    The signature lesion of SSA/Ro autoantibody-associated congenital heart block (CHB) is fibrosis and a macrophage infiltrate, supporting an experimental focus on cues influencing the fibroblast component. The transcriptomes of human fetal cardiac fibroblasts were analyzed using two complementary approaches. Cardiac injury conditions were simulated in vitro by incubating human fetal cardiac fibroblasts with supernatants from macrophages transfected with the SSA/Ro-associated noncoding Y ssRNA. The top 10 upregulated transcripts in the stimulated fibroblasts reflected a type I interferon (IFN) response [e.g., IFN-induced protein 44-like (IFI44L), of MX dynamin-like GTPase (MX)1, MX2, and radical S -adenosyl methionine domain containing 2 (Rsad2)]. Within the fibrotic pathway, transcript levels of endothelin-1 (EDN1), phosphodiesterase (PDE)4D, chemokine (C-X-C motif) ligand (CXCL)2, and CXCL3 were upregulated, while others, including adenomedullin, RAP guanine nucleotide exchange factor 3 (RAPGEF3), tissue inhibitor of metalloproteinase (TIMP)1, TIMP3, and dual specificity phosphatase 1, were downregulated. Agnostic Database for Annotation, Visualization and Integrated Discovery analysis revealed a significant increase in inflammatory genes, including complement C3A receptor 1 (C3AR1), F2R-like thrombin/trypsin receptor 3, and neutrophil cytosolic factor 2. In addition, stimulated fibroblasts expressed high levels of phospho-MADS box transcription enhancer factor 2 [a substrate of MAPK5 (ERK5)], which was inhibited by BIX-02189, a specific inhibitor of ERK5. Translation to human disease leveraged an unprecedented opportunity to interrogate the transcriptome of fibroblasts freshly isolated and cell sorted without stimulation from a fetal heart with CHB and a matched healthy heart. Consistent with the in vitro data, five IFN response genes were among the top 10 most highly expressed transcripts in CHB fibroblasts. In addition, the expression of matrix-related genes

  3. Restricted Gene Flow for Gadus macrocephalus from Yellow Sea Based on Microsatellite Markers: Geographic Block of Tsushima Current

    Directory of Open Access Journals (Sweden)

    Na Song

    2016-03-01

    Full Text Available The Pacific cod Gadus macrocephalus is a demersal, economically important fish in the family Gadidae. Population genetic differentiation of Pacific cod was examined across its northwestern Pacific range by screening variation of eight microsatellite loci in the present study. All four populations exhibited high genetic diversity. Pairwise fixation index (Fst suggested a moderate to high level of genetic differentiation among populations. Population of the Yellow Sea (YS showed higher genetic difference compared to the other three populations based on the results of pairwise Fst, three-dimensional factorial correspondence analysis (3D-FCA and STRUCTURE, which implied restricted gene flow among them. Wilcoxon signed rank tests suggested no significant heterozygosity excess and no recent genetic bottleneck events were detected. Microsatellite DNA is an effective molecular marker for detecting the phylogeographic pattern of Pacific cod, and these Pacific cod populations should be three management units.

  4. Notch signaling and proneural genes work together to control the neural building blocks for the initial scaffold in the hypothalamus

    Science.gov (United States)

    Ware, Michelle; Hamdi-Rozé, Houda; Dupé, Valérie

    2014-01-01

    The vertebrate embryonic prosencephalon gives rise to the hypothalamus, which plays essential roles in sensory information processing as well as control of physiological homeostasis and behavior. While patterning of the hypothalamus has received much attention, initial neurogenesis in the developing hypothalamus has mostly been neglected. The first differentiating progenitor cells of the hypothalamus will give rise to neurons that form the nucleus of the tract of the postoptic commissure (nTPOC) and the nucleus of the mammillotegmental tract (nMTT). The formation of these neuronal populations has to be highly controlled both spatially and temporally as these tracts will form part of the ventral longitudinal tract (VLT) and act as a scaffold for later, follower axons. This review will cumulate and summarize the existing data available describing initial neurogenesis in the vertebrate hypothalamus. It is well-known that the Notch signaling pathway through the inhibition of proneural genes is a key regulator of neurogenesis in the vertebrate central nervous system. It has only recently been proposed that loss of Notch signaling in the developing chick embryo causes an increase in the number of neurons in the hypothalamus, highlighting an early function of the Notch pathway during hypothalamus formation. Further analysis in the chick and mouse hypothalamus confirms the expression of Notch components and Ascl1 before the appearance of the first differentiated neurons. Many newly identified proneural target genes were also found to be expressed during neuronal differentiation in the hypothalamus. Given the critical role that hypothalamic neural circuitry plays in maintaining homeostasis, it is particularly important to establish the targets downstream of this Notch/proneural network. PMID:25520625

  5. Blocking signaling at the level of GLI regulates downstream gene expression and inhibits proliferation of canine osteosarcoma cells.

    Directory of Open Access Journals (Sweden)

    Mehdi Hayat Shahi

    Full Text Available The Hedgehog-GLI signaling pathway is active in a variety of human malignancies and is known to contribute to the growth and survival of human osteosarcoma cells. In this study, we examined the expression and regulation of GLI transcription factors in multiple canine osteosarcoma cell lines and analyzed the effects of inhibiting GLI with GANT61, a GLI-specific inhibitor. Compared with normal canine osteoblasts, real-time PCR showed that GLI1 and GLI2 were highly expressed in two out of three cell lines and correlated with downstream target gene expression of PTCH1and PAX6. Treatment of canine osteosarcoma cells with GANT61 resulted in decreased expression of GLI1, GLI2, PTCH1, and PAX6. Furthermore, GANT61 inhibited proliferation and colony formation in all three canine osteosarcoma cell lines. The finding that GLI signaling activity is present and active in canine osteosarcoma cells suggests that spontaneously arising osteosarcoma in dogs might serve as a good model for future preclinical testing of GLI inhibitors.

  6. Cytokine-dependent and–independent gene expression changes and cell cycle block revealed in Trypanosoma cruzi-infected host cells by comparative mRNA profiling

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    Burleigh Barbara A

    2009-05-01

    Full Text Available Abstract Background The requirements for growth and survival of the intracellular pathogen Trypanosoma cruzi within mammalian host cells are poorly understood. Transcriptional profiling of the host cell response to infection serves as a rapid read-out for perturbation of host physiology that, in part, reflects adaptation to the infective process. Using Affymetrix oligonucleotide array analysis we identified common and disparate host cell responses triggered by T. cruzi infection of phenotypically diverse human cell types. Results We report significant changes in transcript abundance in T. cruzi-infected fibroblasts, endothelial cells and smooth muscle cells (2852, 2155 and 531 genes respectively; fold-change ≥ 2, p-value T. cruzi-infected fibroblasts and endothelial cells transwell plates were used to distinguish cytokine-dependent and -independent gene expression profiles. This approach revealed the induction of metabolic and signaling pathways involved in cell proliferation, amino acid catabolism and response to wounding as common themes in T. cruzi-infected cells. In addition, the downregulation of genes involved in mitotic cell cycle and cell division predicted that T. cruzi infection may impede host cell cycle progression. The observation of impaired cytokinesis in T. cruzi-infected cells, following nuclear replication, confirmed this prediction. Conclusion Metabolic pathways and cellular processes were identified as significantly altered at the transcriptional level in response to T. cruzi infection in a cytokine-independent manner. Several of these alterations are supported by previous studies of T. cruzi metabolic requirements or effects on the host. However, our methods also revealed a T. cruzi-dependent block in the host cell cycle, at the level of cytokinesis, previously unrecognized for this pathogen-host cell interaction.

  7. Novel Cocaine Vaccine Linked to a Disrupted Adenovirus Gene Transfer Vector Blocks Cocaine Psychostimulant and Reinforcing Effects

    Science.gov (United States)

    Wee, Sunmee; Hicks, Martin J; De, Bishnu P; Rosenberg, Jonathan B; Moreno, Amira Y; Kaminsky, Stephen M; Janda, Kim D; Crystal, Ronald G; Koob, George F

    2012-01-01

    Immunotherapy is a promising treatment for drug addiction. However, insufficient immune responses to vaccines in most subjects pose a challenge. In this study, we tested the efficacy of a new cocaine vaccine (dAd5GNE) in antagonizing cocaine addiction-related behaviors in rats. This vaccine used a disrupted serotype 5 adenovirus (Ad) gene transfer vector coupled to a third-generation cocaine hapten, termed GNE (6-(2R,3S)-3-(benzoyloxy)-8-methyl-8-azabicyclo [3.2.1] octane-2-carboxamido-hexanoic acid). Three groups of rats were immunized with dAd5GNE. One group was injected with 3H-cocaine, and radioactivity in the blood and brain was determined. A second group was tested for cocaine-induced locomotor sensitization. A third group was examined for cocaine self-administration, extinction, and reinstatement of responding for cocaine. Antibody titers were determined at various time-points. In each experiment, we added a control group that was immunized with dAd5 without a hapten. The vaccination with dAd5GNE produced long-lasting high titers (>105) of anti-cocaine antibodies in all of the rats. The vaccination inhibited cocaine-induced hyperlocomotor activity and sensitization. Vaccinated rats acquired cocaine self-administration, but they showed less motivation to self-administer cocaine under a progressive-ratio schedule than control rats. When cocaine was not available in a session, control rats exhibited ‘extinction burst' responding, whereas vaccinated rats did not. Moreover, when primed with cocaine, vaccinated rats did not reinstate responding, suggesting a blockade of cocaine-seeking behavior. These data strongly suggest that our dAd5GNE vector-based vaccine may be effective in treating cocaine abuse and addiction. PMID:21918504

  8. Blocking the PI3K/AKT Pathway Enhances Mammalian Reovirus Replication by Repressing IFN-stimulated Genes

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    Jin eTian

    2015-09-01

    Full Text Available Many host cellular signaling pathways were activated and exploited by virus infection for more efficient replication. The PI3K/Akt pathway has recently attracted considerable interest due to its role in regulating virus replication. This study demonstrated for the first time that the mammalian reovirus strains Masked Palm Civet/China/2004 (MPC/04 and Bat/China/2003 (B/03 can induce transient activation of the PI3K/Akt pathway early in infection in vitro. When UV-treated, both viruses activated PI3K/Akt signaling, indicating that the virus/receptor interaction was sufficient to activate PI3K/Akt. Reovirus virions can use both clathrin- and caveolae-mediated endocytosis, but only chlorpromazine, a specific inhibitor of clathrin-mediated endocytosis, or siRNA targeting clathrin suppressed Akt phosphorylation. We also identified the upstream molecules of the PI3K pathway. Virus infection induced phosphorylation of focal adhesion kinase (FAK but not Gab1, and blockage of FAK phosphorylation suppressed Akt phosphorylation. Blockage of PI3K/Akt activation increased virus RNA synthesis and viral yield. We also found that reovirus infection activated the IFN-stimulated response element (ISRE in an interferon-independent manner and up-regulated IFN-stimulated genes (ISGs via the PI3K/Akt/EMSY pathway. Suppression of PI3K/Akt activation impaired the induction of ISRE and down-regulated the expression of ISGs. Overexpression of ISG15 and Viperin inhibited virus replication, and knockdown of either enhanced virus replication. Collectively, these results demonstrate that PI3K/Akt activated by mammalian reovirus serves as a pathway for sensing and then inhibiting virus replication/infection.

  9. Transglutaminase 2 gene ablation protects against renal ischemic injury by blocking constant NF-κB activation

    International Nuclear Information System (INIS)

    Kim, Dae-Seok; Kim, Bora; Tahk, Hongmin; Kim, Dong-Hyun; Ahn, Eu-Ree; Choi, Changsun; Jeon, Yoon; Park, Seo Young; Lee, Ho; Oh, Seung Hyun; Kim, Soo-Youl

    2010-01-01

    Research highlights: → No acute renal tubular necrotic lesions were found in TGase2 -/- mice with ischemic kidney injury. → NF-κB activation is reduced in TGase2 -/- mice with ischemic kidney injury. → Hypoxic stress did not increase NF-κB activity in MEFs from TGase2 -/- mice. → COX-2 induction is suppressed in TGase2 -/- mice with ischemic kidney injury. -- Abstract: Transglutaminase 2 knockout (TGase2 -/- ) mice show significantly reduced inflammation with decreased myofibroblasts in a unilateral ureteral obstruction (UUO) model, but the mechanism remains to be clarified. Nuclear factor-κB (NF-κB) activation plays a major role in the progression of inflammation in an obstructive nephropathy model. However, the key factors extending the duration of NF-κB activation in UUO are not known. In several inflammatory diseases, we and others recently found that TGase 2 plays a key role in extending NF-κB activation, which contributes to the pathogenesis of disease. In the current study, we found that NF-κB activity in mouse embryogenic fibroblasts (MEFs) from TGase2 -/- mice remained at the control level while the NF-κB activity of wild-type (WT) MEFs was highly increased under hypoxic stress. Using the obstructive nephropathy model, we found that NF-κB activity remained at the control level in TGase2 -/- mouse kidney tissues, as measured by COX-2 expression, but was highly increased in WT tissues. We conclude that TGase 2 gene ablation reduces the duration of NF-κB activation in ischemic injury.

  10. The human major histocompatibility complex class II HLA-DRB1 and HLA-DQA1 genes are separated by a CTCF-binding enhancer-blocking element.

    Science.gov (United States)

    Majumder, Parimal; Gomez, Jorge A; Boss, Jeremy M

    2006-07-07

    The human major histocompatibility complex class II (MHC-II) region encodes a cluster of polymorphic heterodimeric glycoproteins HLA-DR, -DQ, and -DP that functions in antigen presentation. Separated by approximately 44 kb of DNA, the HLA-DRB1 and HLA-DQA1 encode MHC-II proteins that function in separate MHC-II heterodimers and are diametrically transcribed. A region of high acetylation located in the intergenic sequences between HLA-DRB1 and HLA-DQA1 was discovered and termed XL9. The peak of acetylation coincided with sequences that bound the insulator protein CCCTC-binding factor as determined by chromatin immunoprecipitations and in vitro DNA binding studies. XL9 was also found to be associated with the nuclear matrix. The activity of the XL9 region was examined and found to be a potent enhancer-blocking element. These results suggest that the XL9 region may have evolved to separate the transcriptional units of the HLA-DR and HLA-DQ genes.

  11. Pepino mosaic virus triple gene block protein 1 (TGBp1) interacts with and increases tomato catalase 1 activity to enhance virus accumulation.

    Science.gov (United States)

    Mathioudakis, Matthaios M; Veiga, Rita S L; Canto, Tomas; Medina, Vicente; Mossialos, Dimitris; Makris, Antonios M; Livieratos, Ioannis

    2013-08-01

    Various plant factors are co-opted by virus elements (RNA, proteins) and have been shown to act in pathways affecting virus accumulation and plant defence. Here, an interaction between Pepino mosaic virus (PepMV) triple gene block protein 1 (TGBp1; p26) and tomato catalase 1 (CAT1), a crucial enzyme in the decomposition of toxic hydrogen peroxide (H₂O₂), was identified using the yeast two-hybrid assay, and confirmed via an in vitro pull-down assay and bimolecular fluorescent complementation (BiFC) in planta. Each protein was independently localized within loci in the cytoplasm and nuclei, sites at which their interaction had been visualized by BiFC. Following PepMV inoculation, CAT mRNA and protein levels in leaves were unaltered at 0, 3 and 6 days (locally) and 8 days (systemically) post-inoculation; however, leaf extracts from the last two time points contained increased CAT activity and lower H₂O₂ evels. Overexpression of PepMV p26 in vitro and in planta conferred the same effect, suggesting an additional involvement of TGBp1 in potexvirus pathogenesis. The accumulation of PepMV genomic and subgenomic RNAs and the expression of viral coat protein in noninoculated (systemic) leaves were reduced significantly in CAT-silenced plants. It is postulated that, during PepMV infection, a p26-CAT1 interaction increases H₂O₂ cavenging, thus acting as a negative regulator of plant defence mechanisms to promote PepMV infections. © 2013 BSPP AND JOHN WILEY & SONS LTD.

  12. Isorhamnetin inhibits Prevotella intermedia lipopolysaccharide-induced production of interleukin-6 in murine macrophages via anti-inflammatory heme oxygenase-1 induction and inhibition of nuclear factor-κB and signal transducer and activator of transcription 1 activation.

    Science.gov (United States)

    Jin, J Y; Choi, E Y; Park, H R; Choi, J I; Choi, I S; Kim, S J

    2013-12-01

    Interleukin-6 (IL-6) is a key proinflammatory cytokine that has been considered to be important in the pathogenesis of periodontal disease. Therefore, host-modulatory agents directed at inhibiting IL-6 appear to be beneficial in terms of attenuating periodontal disease progression and potentially improving disease susceptibility. In the current study, we investigated the effect of the flavonoid isorhamnetin on the production of IL-6 in murine macrophages stimulated with lipopolysaccharide (LPS) from Prevotella intermedia, a pathogen implicated in inflammatory periodontal disease, and its mechanisms of action. Lipopolysaccharide from P. intermedia ATCC 25611 was isolated using the standard hot phenol-water method. Culture supernatants were collected and assayed for IL-6. We used real-time PCR to quantify IL-6 and heme oxygenase-1 (HO-1) mRNA expression. The expression of HO-1 protein and the levels of signaling proteins were monitored using immunoblot analyses. The DNA-binding activity of nuclear factor-κB (NF-κB) was analyzed using ELISA-based assay kits. Isorhamnetin significantly down-regulated P. intermedia LPS-induced production of IL-6 as well as its mRNA expression in RAW264.7 cells. Isorhamnetin up-regulated the expression of HO-1 at both gene transcription and translation levels in cells stimulated with P. intermedia LPS. In addition, inhibition of HO-1 activity by tin protoporphyrin IX blocked the inhibitory effect of isorhamnetin on IL-6 production. Isorhamnetin failed to prevent LPS from activating either c-Jun N-terminal kinase or p38 pathways. Isorhamnetin did not inhibit NF-κB transcriptional activity at the level of inhibitory κB-α degradation. Isorhamnetin suppressed NF-κB signaling through inhibition of nuclear translocation and DNA binding activity of NF-κB p50 subunit and attenuated signal transducer and activator of transcription 1 signaling. Although further research is required to clarify the detailed mechanism of action, we propose

  13. Internode length in Pisum. Gene na may block gibberellin synthesis between ent-7. cap alpha. -hydroxykaurenoic acid and biggerellin A/sub 12/-aldehyde. [Pisum sativum

    Energy Technology Data Exchange (ETDEWEB)

    Ingram, T.J.; Reid, J.B.

    1987-04-01

    The elongation response of the gibberellin (GA) deficient genotypes na, ls, and lh of peas (Pisum sativum L.) to a range of GA-precursors was examined. Plants possessing gene na did not respond to precursors in the GA biosynthetic pathway prior to GA/sub 12/-aldehyde. In contrast, plants possessing lh and ls responded as well as wild-type plants (dwarfed with AMO-1618) to these compounds. The results suggest that GA biosynthesis is blocked prior to ent-kaurene in the lh and ls mutants and between ent-7..cap alpha..-hydroxykaurenoic acid and GA/sub 12/-aldehyde in the na mutant. Feeds of ent(/sup 3/H)kaurenoic acid and (/sup 2/H)GA/sub 12/-aldehyde to a range of genotypes supported the above conclusions. The na line WL1766 was shown by gas chromatography-mass spectrometry (GC-MS) to metabolize(/sup 2/H)GA/sub 12/-aldehyde to a number of (/sup 2/H)C/sub 19/-GAs including GA/sub 1/. However, there was no indication in na genotypes for the metabolism of ent-(/sup 3/H)kaurenoic acid to these GAs. In contrast, the expanding shoot tissue of all Na genotypes examined metabolized ent-(/sup 3/H)kaurenoic acid to radioactive compounds that co-chromatographed with GA/sub 1/, GA/sub 8/, GA/sub 20/, and GA/sub 29/. However, insufficient material was present for unequivocal identification of the metabolites. The radioactive profiles from HPLC of extracts of the node treated with ent-(/sup 3/H)kaurenoic acid were similar for both Na and na plants and contained ent-16..cap alpha..,17-dihydroxykaurenoic acid and ent-6..cap alpha..,7..cap alpha..,16..beta..,17-tetrahydroxykaurenoic acid (both characterized by GC-MS), suggesting that the metabolites arose from side branches of the main GA-biosynthetic pathway. Thus, both Na and na plants appear capable of ent-7..cap alpha..-hydroxylation.

  14. Ultrasound guided supraclavicular block.

    LENUS (Irish Health Repository)

    Hanumanthaiah, Deepak

    2013-09-01

    Ultrasound guided regional anaesthesia is becoming increasingly popular. The supraclavicular block has been transformed by ultrasound guidance into a potentially safe superficial block. We reviewed the techniques of performing supraclavicular block with special focus on ultrasound guidance.

  15. Preventive Effects of Velvet Antler (Cervus elaphus against Lipopolysaccharide-Induced Acute Lung Injury in Mice by Inhibiting MAPK/NF-κB Activation and Inducing AMPK/Nrf2 Pathways

    Directory of Open Access Journals (Sweden)

    Jui-Shu Chang

    2018-01-01

    Full Text Available Velvet antler (Cervus elaphus is a typical traditional animal medicine. It is considered to have various pharmacological effects including stimulation of the immune system, increase in the physical strength, and enhancement of sexual function. This paper aims to investigate the aqueous extract of velvet antler (AVA in the mouse models of LPS-induced ALI. Inhibition of NO, TNF-α, IL-1β, IL-6, and IL-10 productions contributes to the attenuation of LPS-induced lung inflammation by AVA. A 5-day pretreatment of AVA prevented histological alterations and enhanced antioxidant enzyme activity in lung tissues. AVA significantly reduced the material (total number of cells and proteins in the BALF. Western blot analysis revealed that the expression of iNOS and COX-2 and phosphorylation of IκB-α and MAPKs proteins are blocked in LPS-stimulated macrophages as well as LPS-induced lung injury in mice. Consistent with this concept, the phosphorylation of CaMKKβ, LKB1, AMPK, Nrf2, and HO-1 was activated after AVA treatment. The results from this study indicate AVA has anti-inflammatory effects in vivo and AVA is a potential model for the development of health food. In addition, its pathways may be at least partially associated with inhibiting MAPK/NF-κB activation and upregulating AMPK/Nrf2 pathways and the regulation of antioxidant enzyme activity.

  16. A Prenylated Xanthone, Cudratricusxanthone A, Isolated from Cudrania tricuspidata Inhibits Lipopolysaccharide-Induced Neuroinflammation through Inhibition of NF-κB and p38 MAPK Pathways in BV2 Microglia.

    Science.gov (United States)

    Yoon, Chi-Su; Kim, Dong-Cheol; Quang, Tran Hong; Seo, Jungwon; Kang, Dae Gill; Lee, Ho Sub; Oh, Hyuncheol; Kim, Youn-Chul

    2016-09-16

    Cudrania tricuspidata Bureau (Moraceae) is an important source of traditional Korean and Chinese medicines used to treat neuritis and inflammation. Cudratricusxanthone A (1), a prenylated xanthone, isolated from C. tricuspidata, has a variety of biological and therapeutic activities. The goal of this study was to examine the effects of compound 1 on neuroinflammation and characterize its mechanism of action in lipopolysaccharide (LPS)-stimulated BV2 microglia. Cudratricusxanthone A (1) suppressed the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX)-2 enzymes and decreased the production of iNOS-derived nitric oxide and COX-2-derived prostaglandin E2 in LPS-stimulated mouse BV2 microglia. The compound also decreased tumor necrosis factor-α, interleukin (IL)-1β, and IL-12 production; inhibited the phosphorylation and degradation of IκB-α; and blocked the nuclear translocation of p50 and p65 in mouse BV2 microglia induced by LPS. Cudratricusxanthone A (1) had inhibitory effects on nuclear factor kappa B DNA-binding activity. Additionally, it inhibited the p38 mitogen-activated protein kinase signaling pathway. Our data suggests that cudratricusxanthone A (1) may be a useful therapeutic agent in the treatment of neurodegenerative diseases caused by neuroinflammation.

  17. Anti-Inflammatory Effect of Methylpenicinoline from a Marine Isolate of Penicillium sp. (SF-5995: Inhibition of NF-κB and MAPK Pathways in Lipopolysaccharide-Induced RAW264.7 Macrophages and BV2 Microglia

    Directory of Open Access Journals (Sweden)

    Dong-Cheol Kim

    2014-11-01

    Full Text Available In the course of a search for anti-inflammatory metabolites from marine-derived fungi, methylpenicinoline (1 was isolated from a marine isolate of Penicillin sp. Compound 1 inhibited lipopolysaccharide (LPS-stimulated nitric oxide (NO production by suppressing the expression of inducible NO synthase (iNOS in RAW264.7 macrophages and BV2 microglia. It also attenuated prostaglandin E2 (PGE2 production by suppressing cyclooxygenase-2 (COX-2 expression in a concentration-dependent manner (from 10 μM to 80 μM without affecting cell viability. In addition, compound 1 reduced the production of the pro-inflammatory cytokine interleukin-1β (IL-1β. In a further study designed to elucidate the mechanism of its anti-inflammatory effects, compound 1 was shown to block nuclear factor-kappa B (NF-κB activation in LPS-induced RAW264.7 macrophages and BV2 microglia by inhibiting the phosphorylation of inhibitor kappa B-α (IκB-α, thereby suppressing the nuclear translocation of NF-κB dimers, namely p50 and p65, that are known to be crucial molecules associated with iNOS and COX-2 expression. In addition, compound 1 inhibited the activation of mitogen-activated protein kinase (MAPK pathways. Taken together, the results suggest that compound 1 might be a valuable therapeutic agent for the treatment of anti-inflammatory and anti-neuroinflammatory diseases.

  18. Biodegradable Tri-Block Copolymer Poly(lactic acid-poly(ethylene glycol-poly(L-lysine(PLA-PEG-PLL as a Non-Viral Vector to Enhance Gene Transfection

    Directory of Open Access Journals (Sweden)

    Na Zhang

    2011-02-01

    Full Text Available Low cytotoxicity and high gene transfection efficiency are critical issues in designing current non-viral gene delivery vectors. The purpose of the present work was to synthesize the novel biodegradable poly (lactic acid-poly(ethylene glycol-poly(L-lysine (PLA-PEG-PLL copolymer, and explore its applicability and feasibility as a non-viral vector for gene transport. PLA-PEG-PLL was obtained by the ring-opening polymerization of Lys(Z-NCA onto amine-terminated NH2-PEG-PLA, then acidolysis to remove benzyloxycarbonyl. The tri-block copolymer PLA-PEG-PLL combined the characters of cationic polymer PLL, PLA and PEG: the self-assembled nanoparticles (NPs possessed a PEG loop structure to increase the stability, hydrophobic PLA segments as the core, and the primary ε-amine groups of lysine in PLL to electrostatically interact with negatively charged phosphate groups of DNA to deposit with the PLA core. The physicochemical properties (morphology, particle size and surface charge and the biological properties (protection from nuclease degradation, plasma stability, in vitro cytotoxicity, and in vitro transfection ability in HeLa and HepG2 cells of the gene-loaded PLA-PEG-PLL nanoparticles (PLA-PEG-PLL NPs were evaluated, respectively. Agarose gel electrophoresis assay confirmed that the PLA-PEG-PLL NPs could condense DNA thoroughly and protect DNA from nuclease degradation. Initial experiments showed that PLA-PEG-PLL NPs/DNA complexes exhibited almost no toxicity and higher gene expression (up to 21.64% in HepG2 cells and 31.63% in HeLa cells than PEI/DNA complexes (14.01% and 24.22%. These results revealed that the biodegradable tri-block copolymer PLA-PEG-PLL might be a very attractive candidate as a non-viral vector and might alleviate the drawbacks of the conventional cationic vectors/DNA complexes for gene delivery in vivo.

  19. Neuropeptide VGF C-Terminal Peptide TLQP-62 Alleviates Lipopolysaccharide-Induced Memory Deficits and Anxiety-like and Depression-like Behaviors in Mice: The Role of BDNF/TrkB Signaling.

    Science.gov (United States)

    Li, Chenli; Li, Mengmeng; Yu, Hanjie; Shen, Xinbei; Wang, Jinting; Sun, Xin; Wang, Qinwen; Wang, Chuang

    2017-09-20

    Peripheral inflammatory responses affect central nervous system (CNS) function, manifesting in symptoms of memory deficits, depression, and anxiety. Previous studies have revealed that neuropeptide VGF (nonacronymic) C-terminal peptide TLQP-62 rapidly reinforces brain-derived neurotrophic factor (BDNF)/tropomyosin receptor kinase B (TrkB) signaling, regulating memory consolidation and antidepressant-like action. However, whether it is beneficial for lipopolysaccharide (LPS)-induced neuropsychiatric dysfunction in mice is unknown. Herein, we explored the involvement of BDNF/TrkB signaling and biochemical alterations in inflammatory or oxidative stress markers in the alleviating effects of TLQP-62 on LPS-induced neuropsychiatric dysfunction. The mice were treated with TLQP-62 (2 μg/side) via intracerebroventricular (i.c.v.) injection 1 h before LPS (0.5 mg/kg, i.p.) administration. Our results showed that a single treatment with LPS (0.5 mg/kg, i.p) is sufficient to produce recognition memory deficits (in the novel object recognition test), depression-like behavior (in the forced swim test and sucrose preference test), and anxiety-like behavior (in the elevated zero maze). However, pretreatment with TLQP-62 prevented LPS-induced behavioral dysfunction, neuroinflammatory, and oxidative responses. In addition, our results further demonstrated that a reduction in BDNF expression mediated by BDNF-shRNA lentivirus significantly blocked the effects of TLQP-62, suggesting the critical role of BDNF/TrkB signaling in the neuroprotective effects of TLQP-62 in the mice. In conclusion, TLQP-62 could be a therapeutic approach for neuropsychiatric disorders, which are closely associated with neuroinflammation and oxidative stress.

  20. Agomelatine, a MT1/MT2melatonergic receptor agonist with serotonin 5-HT2Creceptor antagonistic properties, suppresses Prevotella intermedia lipopolysaccharide-induced production of proinflammatory mediators in murine macrophages.

    Science.gov (United States)

    Hyeon, Jin-Yi; Choi, Eun-Young; Choe, So-Hui; Park, Hae Ryoun; Choi, Jeom-Il; Choi, In Soon; Kim, Sung-Jo

    2017-10-01

    This study was performed in an attempt to examine the influence of agomelatine in mitigating the generation of proinflammatory mediators in RAW264.7 murine macrophages exposed to lipopolysaccharide (LPS) obtained from Prevotella intermedia, a gram-negative anaerobic bacterium that is related with various types of periodontal diseases, and the molecular mechanisms behind its effects. LPS from P. intermedia strain ATCC 25611 was prepared employing the conventional phenol-water procedure. Conditioned culture media were analyzed for the levels of nitric oxide (NO), interleukin-1β (IL-1β) and IL-6. Real-time PCR analysis was carried out to determine the mRNA levels of inducible NO synthase (iNOS), IL-1β, IL-6 and SOCS1. Protein expression levels were evaluated by immunoblot test. NF-κB-dependent SEAP reporter assay was performed using a reporter cell line. DNA-binding activities of NF-κB subunits were analyzed utilizing the ELISA-based kits. Agomelatine was found to down-regulate significantly the generation of iNOS-derived NO, IL-1β and IL-6 as well as the expression of their mRNAs in cells activated with P. intermedia LPS. Agomelatine decreased NF-κB-dependent SEAP release caused by P. intermedia LPS. Agomelatine did not inhibit NF-κB transcription induced by LPS at the level of IκB-α degradation. Instead, LPS-induced nuclear translocation and DNA binding of NF-κB p50 subunit was blocked by agomelatine. P. intermedia LPS-elicited activation of STAT1 and STAT3 was reduced notably by co-treatment with agomelatine. Agomelatine showed a tendency to enhance mRNA level of SOCS1 in LPS-activated cells as well. Agomelatine merits further evaluation to reveal its usefulness on the host modulation of periodontal disease. Copyright © 2017 Elsevier Ltd. All rights reserved.

  1. Polyinosinic Acid Blocks Adeno-Associated Virus Macrophage Endocytosis In Vitro and Enhances Adeno-Associated Virus Liver-Directed Gene Therapy In Vivo

    NARCIS (Netherlands)

    van Dijk, Remco; Montenegro-Miranda, Paula S.; Riviere, Christel; Schilderink, Ronald; ten Bloemendaal, Lysbeth; van Gorp, Jacqueline; Duijst, Suzanne; de Waart, Dirk R.; Beuers, Ulrich; Haisma, Hidde J.; Bosma, Piter J.

    2013-01-01

    Adeno-associated virus serotype 8 (AAV8) has been demonstrated to be effective for liver-directed gene therapy in humans. Although hepatocytes are the main target cell for AAV8, there is a loss of the viral vector because of uptake by macrophages and Kupffer cells. Reducing this loss would increase

  2. Brachypodium distachyon line Bd3-1 resistance is elicited by the barley stripe mosaic virus triple gene block 1 movement protein

    NARCIS (Netherlands)

    Lee, M.Y.; Yan, L.J.; Gorter, F.A.; Kim, B.Y.T.; Cui, Y.; Hu, Y.; Yuan, C.; Grindheim, J.; Ganesan, U.; Liu, Z.Y.; Han, C.G.; Yu, J.L.; Li, D.W.; Jackson, A.O.

    2012-01-01

    Barley stripe mosaic virus North Dakota 18 (ND18), Beijing (BJ), Xinjiang (Xi), Type (TY) and CV21 strains are unable to infect the Brachypodium distachyon Bd3-1 inbred line, which harbours a resistance gene designated Bsr1, but the Norwich (NW) strain is virulent on Bd3-1. Analysis of ND18 and NW

  3. Homogeneous bilateral block shifts

    Indian Academy of Sciences (India)

    Douglas class were classified in [3]; they are unilateral block shifts of arbitrary block size (i.e. dim H(n) can be anything). However, no examples of irreducible homogeneous bilateral block shifts of block size larger than 1 were known until now.

  4. Estrogen modulates NFκB signaling by enhancing IκBα levels and blocking p65 binding at the promoters of inflammatory genes via estrogen receptor-β.

    Directory of Open Access Journals (Sweden)

    Dongqi Xing

    Full Text Available NFκB signaling is critical for expression of genes involved in the vascular injury response. We have shown that estrogen (17β-estradiol, E2 inhibits expression of these genes in an estrogen receptor (ER-dependent manner in injured rat carotid arteries and in tumor necrosis factor (TNF-α treated rat aortic smooth muscle cells (RASMCs. This study tested whether E2 inhibits NFκB signaling in RASMCs and defined the mechanisms.TNF-α treated RASMCs demonstrated rapid degradation of IκBα (10-30 min, followed by dramatic increases in IκBα mRNA and protein synthesis (40-60 min. E2 enhanced TNF-α induced IκBα synthesis without affecting IκBα degradation. Chromatin immunoprecipitation (ChIP assays revealed that E2 pretreatment both enhanced TNF-α induced binding of NFκB p65 to the IκBα promoter and suppressed TNF-α induced binding of NFκB p65 to and reduced the levels of acetylated histone 3 at promoters of monocyte chemotactic protein (MCP-1 and cytokine-induced neutrophil chemoattractant (CINC-2β genes. ChIP analyses also demonstrated that ERβ can be recruited to the promoters of MCP-1 and CINC-2β during co-treatment with TNF-α and E2.These data demonstrate that E2 inhibits inflammation in RASMCs by two distinct mechanisms: promoting new synthesis of IκBα, thus accelerating a negative feedback loop in NFκB signaling, and directly inhibiting binding of NFκB to the promoters of inflammatory genes. This first demonstration of multifaceted modulation of NFκB signaling by E2 may represent a novel mechanism by which E2 protects the vasculature against inflammatory injury.

  5. Interleukin-10 does not mediate the inhibitory effect of PDE-4 inhibitors and other cAMP-elevating drugs on lipopolysaccharide-induced tumors necrosis factor-alpha generation from human peripheral blood monocytes.

    Science.gov (United States)

    Seldon, P M; Barnes, P J; Giembycz, M A

    1998-01-01

    Lipopolysaccharide (LPS)-induced liver injury in mice and LPS-induced tumor necrosis factor-alpha (TNF-alpha) generation by murine macrophages and hepatocytes are suppressed markedly by agents that elevate intracellular cAMP. Phosphodiesterase (PDE)-4 inhibitors, beta 2-adrenoceptor agonists, and E-series prostaglandins also attenuate the induction of the TNF-alpha gene in human monocytes in response to bacterial LPS. The mechanism of action of cAMP is unclear, but in the mouse, is believed to involve the generation of this anti-inflammatory cytokine, interleukin-10 (IL-10). In this article, we describe the results of studies designed to determine the extent to which IL-10 contributes to the suppression of TNF-alpha generation from LPS-stimulated human monocytes evoked by 8-bromo cyclic AMP (8-Br-cAMP), rolipram, salbutamol, and prostaglandin E2 (PGE2). LPS evoked a time- and concentration-dependent generation of TNF-alpha (t1/2 = 4.5 h; EC50 = 273 pg/mL), which was inhibited by exogenous human recombinant (h) IL-10 (IC50 = 124 pg/mL), and by rolipram (EC50 = 420 nM), 8-Br-cAMP (EC50 = 77 (microM), PGE2 (EC50 = 15 nM) and salbutamol (EC50 = 20 nM). In addition, 8-Br-cAMP, PGE2; and salbutamol (but not rolipram) augmented significantly LPS-induced IL-10 production (two-to-fivefold) under identical experimental conditions. Pretreatment of monocytes with an anti-IL-10 monoclonal antibody (MAb) that abolished the inhibitory action of a maximally effective concentration of exogenous hrIL-10, failed to attenuate the inhibitory effect of rolipram, PGE2, salbutamol, and 8-Br-cAMP. Anti-IL-10 was similarly inactive when the number of monocytes seeded was increased from 0.5 to 4 x 10(6)/mL or when measurements were made at 42 h post-LPS, a time when the concentration of IL-10 released was maximal. Collectively, these data suggest that in contrast to murine hepatocytes and macrophages, IL-10 does not mediate the inhibitory effect of cAMP-elevating drugs on TNF

  6. Inhibition of lipopolysaccharide-induced proinflammatory responses by Buddleja officinalis extract in BV-2 microglial cells via negative regulation of NF-kB and ERK1/2 signaling.

    Science.gov (United States)

    Oh, Won-Jun; Jung, Uhee; Eom, Hyun-Soo; Shin, Hee-June; Park, Hae-Ran

    2013-07-31

    Buddleja officinalis has been traditionally used in the supportive treatment of inflammatory and neuronal diseases in Korea and China. Although several reports have shown the anti-inflammatory effects of Buddleja officinalis, the anti-neuroinflammatory effect has remained unclear. In this study, we aimed to investigate the inhibitory effects of flower buds of B. officinalis Maximowicz water extract (BOWE) on LPS-induced inflammatory processes in BV-2 microglial cells. BOWE dose-dependently inhibited the production of nitric oxide as well as iNOS mRNA expression. Moreover, BOWE prevented IL-1β and IL-6 mRNA expression. However, BOWE had no effect on LPS-induced COX-2 or TNF-a mRNA expression. The extract also had no effect on LPS-stimulated p38 MAPK, JNK, and c-Jun phosphorylation, whereas ERK1/2 phosphorylation was strongly inhibited by BOWE. BOWE also inhibited the LPS-induced degradation of IkB-α, and LPS-induced phosphorylation of p65 NF-kB protein. These data indicate that BOWE inhibited the nitric oxide production and pro-inflammatory gene expression in BV-2 microglial cells, possibly through a negative regulation of the NF-kB and ERK1/2 pathways. Further identification of the direct target molecule(s) of BOWE is required to support its use as an anti-neuroinflammatory agent against the neurodegenerative disorders.

  7. Inhibition of Lipopolysaccharide-Induced Proinflammatory Responses by Buddleja officinalis Extract in BV-2 Microglial Cells via Negative Regulation of NF-kB and ERK1/2 Signaling

    Directory of Open Access Journals (Sweden)

    Hae-Ran Park

    2013-07-01

    Full Text Available Buddleja officinalis has been traditionally used in the supportive treatment of inflammatory and neuronal diseases in Korea and China. Although several reports have shown the anti-inflammatory effects of Buddleja officinalis, the anti-neuroinflammatory effect has remained unclear. In this study, we aimed to investigate the inhibitory effects of flower buds of B. officinalis Maximowicz water extract (BOWE on LPS-induced inflammatory processes in BV-2 microglial cells. BOWE dose-dependently inhibited the production of nitric oxide as well as iNOS mRNA expression. Moreover, BOWE prevented IL-1β and IL-6 mRNA expression. However, BOWE had no effect on LPS-induced COX-2 or TNF-a mRNA expression. The extract also had no effect on LPS-stimulated p38 MAPK, JNK, and c-Jun phosphorylation, whereas ERK1/2 phosphorylation was strongly inhibited by BOWE. BOWE also inhibited the LPS-induced degradation of IkB-α, and LPS-induced phosphorylation of p65 NF-kB protein. These data indicate that BOWE inhibited the nitric oxide production and pro-inflammatory gene expression in BV-2 microglial cells, possibly through a negative regulation of the NF-kB and ERK1/2 pathways. Further identification of the direct target molecule(s of BOWE is required to support its use as an anti-neuroinflammatory agent against the neurodegenerative disorders.

  8. Blocking the Wnt/β-Catenin Pathway by Lentivirus-Mediated Short Hairpin RNA Targeting β-Catenin Gene Suppresses Silica-Induced Lung Fibrosis in Mice

    Science.gov (United States)

    Wang, Xin; Dai, Wujing; Wang, Yanrang; Gu, Qing; Yang, Deyi; Zhang, Ming

    2015-01-01

    Silicosis is a form of occupational lung disease caused by inhalation of crystalline silica dust. While the pathogenesis of silicosis is not clearly understood, the Wnt/β-catenin signaling pathway is thought to play a major role in lung fibrosis. To explore the role of Wnt/β-catenin pathway in silicosis, we blocked Wnt/β-catenin pathway both in silica-treated MLE-12 cells (a mouse pulmonary epithelial cell line) and in a mouse silicosis model by using a lentiviral vector expressing a short hairpin RNA silencing β-catenin (Lv-shβ-catenin). In vitro, Lv-shβ-catenin significantly decreased the expression of β-catenin, MMP2 and MMP9, and secretion of TGF-β1. In vivo, intratracheal treatment with Lv-shβ-catenin significantly reduced expression of β-catenin in the lung and levels of TGF-β1 in bronchoalveolar lavage fluid, and notably attenuated pulmonary fibrosis as evidenced by hydroxyproline content and collagen I\\III synthesis in silica-administered mice. These results indicate that blockade of the Wnt/β-catenin pathway can prevent the development of silica-induced lung fibrosis. Thus Wnt/β-catenin pathway may be a target in prevention and treatment of silicosis. PMID:26340635

  9. Chromogenic in situ hybridization to detect EGFR gene copy number in cell blocks from fine-needle aspirates of non small cell lung carcinomas and lung metastases from colo-rectal cancer

    Directory of Open Access Journals (Sweden)

    Terrenato Irene

    2010-09-01

    Full Text Available Abstract Background Several studies demonstrated that epidermal growth factor receptor (EGFR gene copy number (GCN correlates to the response to tyrosine kinase inhibitors in non small cell lung cancer (NSCLC and to anti-EGFR monoclonal antibodies (MoAbs in metastatic colorectal cancer (CRC. In the presence of lung nodules, cytology is often the only possible diagnostic approach. Chromogenic in situ hybridization (CISH is an alternative technique to fluorescence in situ hybridization (FISH, but its feasibility in detecting EGFR GCN in cell blocks from fine-needle aspiration cytology (FNAC of lung nodules has not yet been established. Methods We evaluated the feasibility of CISH on 33 FNAC from 20 primary NSCLC (5 squamous carcinomas, 8 large cell carcinomas and 7 adenocarcinomas and 13 lung metastases from CRC. Results Of the 33 FNAC analyzed by CISH, 27 (82% presented a balanced increase in EGFR gene and chromosome 7 number: 10 cases (30% showed a low polysomy, 15 (45% a high polysomy and 2 (6% NSCLC were amplified. No significant differences between NSCLC and CRC lung metastases were found in relation to disomic or polysomic status. In addition, no correlation between EGFR GCN and EGFR immunohistochemical overexpression was found. Furthermore, we compared CISH results with those obtained by FISH on the same samples and we found 97% overall agreement between the two assays (k = 0.78, p Conclusions Our study shows that CISH is a valid method to detect EGFR GCN in cell blocks from FNAC of primary NSCLC or metastatic CRC to the lung.

  10. Vitamin D inhibits the growth of and virulence factor gene expression by Porphyromonas gingivalis and blocks activation of the nuclear factor kappa B transcription factor in monocytes.

    Science.gov (United States)

    Grenier, D; Morin, M-P; Fournier-Larente, J; Chen, H

    2016-06-01

    Increasing evidence suggests that 1,25-dihydroxyvitamin D3 (1,25(OH)2 D3 ), a fat-soluble secosteroid hormone, has a positive impact on periodontal health through diverse mechanisms. The present study was aimed at investigating the effect of 1,25(OH)2 D3 on the growth of and virulence factor gene expression by the periodontopathogenic bacterium Porphyromonas gingivalis. The effect of 1,25(OH)2 D3 on P. gingivalis-mediated activation of nuclear factor kappa B (NF-κB) transcription factor in monocytes was also assessed. A broth microdilution assay was used to determine the antibacterial activity of 1,25(OH)2 D3 . The modulation of virulence factor gene expression in P. gingivalis was assessed by quantitative reverse transcription-polymerase chain reaction. NF-κB activation was assessed using a human monocytic cell line stably transfected with a luciferase reporter containing NF-κB binding sites. Minimal inhibitory concentrations of 1,25(OH)2 D3 against P. gingivalis ranged from 3.125 to 6.25 μg/mL. Moreover, a partial synergistic effect was observed when 1,25(OH)2 D3 was used in association with metronidazole. 1,25(OH)2 D3 attenuated the virulence of P. gingivalis by reducing the expression of genes coding for important virulence factors, including adhesins (fimA, hagA and hagB) and proteinases (rgpA, rgpB and kgp). 1,25(OH)2 D3 dose-dependently prevented P. gingivalis-induced NF-κB activation in a monocyte model. Our study suggested that 1,25(OH)2 D3 selectively inhibits the growth of and virulence factor gene expression by P. gingivalis, in addition to attenuating NF-κB activation by this periodontopathogen. This dual action on P. gingivalis and the inflammatory response of host cells may be of particular interest with a view to developing a novel and inexpensive preventive/therapeutic strategy. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  11. Gene

    Data.gov (United States)

    U.S. Department of Health & Human Services — Gene integrates information from a wide range of species. A record may include nomenclature, Reference Sequences (RefSeqs), maps, pathways, variations, phenotypes,...

  12. Plasmodium falciparum merozoite surface protein 1 block 2 gene polymorphism in field isolates along the slope of mount Cameroon: a cross - sectional study.

    Science.gov (United States)

    Apinjoh, Tobias O; Tata, Rolland B; Anchang-Kimbi, Judith K; Chi, Hanesh F; Fon, Eleanor M; Mugri, Regina N; Tangoh, Delphine A; Nyingchu, Robert V; Ghogomu, Stephen M; Nkuo-Akenji, Theresa; Achidi, Eric A

    2015-08-05

    Malaria remains a major global health burden despite the intensification of control efforts, due partly to the lack of an effective vaccine. Information on genetic diversity in natural parasite populations constitutes a major impediment to vaccine development efforts and is limited in some endemic settings. The present study characterized diversity by investigating msp1 block 2 polymorphisms and the relationship between the allele families with ethnodemographic indices and clinical phenotype. Individuals with asymptomatic parasitaemia (AP) or uncomplicated malaria (UM) were enrolled from rural, semi-rural and semi-urban localities at varying altitudes along the slope of mount Cameroon. P. falciparum malaria parasitaemic blood screened by light microscopy was depleted of leucocytes using CF11 cellulose columns and the parasite DNA genotyped by nested PCR. Length polymorphism was assessed in 151 field isolates revealing 64 (5) and 274 (22) distinct recombinant and major msp1 allelic fragments (genotypes) respectively. All family specific allelic types (K1, MAD20 and RO33) as well as MR were observed in the different locations, with K1 being most abundant. Eighty seven (60 %) of individuals harbored more than one parasite clone, with a significant proportion (p = 0.009) in rural compared to other settings. AP individuals had higher (p = 0.007) K1 allele frequencies but lower (p = 0.003) mean multiplicity of genotypes per infection (2.00 ± 0.98 vs. 2.56 ± 1.17) compared to UM patients. These results indicate enormous diversity of P. falciparum in the area and suggests that allele specificity and complexity may be relevant for the progression to symptomatic disease.

  13. VCAM-1-targeted core/shell nanoparticles for selective adhesion and delivery to endothelial cells with lipopolysaccharide-induced inflammation under shear flow and cellular magnetic resonance imaging in vitro.

    Science.gov (United States)

    Yang, Hong; Zhao, Fenglong; Li, Ying; Xu, Mingming; Li, Li; Wu, Chunhui; Miyoshi, Hirokazu; Liu, Yiyao

    2013-01-01

    these VCAM-1-targeted Fe(3)O(4)@SiO2(FITC) nanoparticles targeted to inflammatory endothelial cells could be used in the transfer of therapeutic drugs/genes into these cells or for diagnosis of vascular disease at the molecular and cellular levels in the future.

  14. 14-3-3γ Regulates Lipopolysaccharide-Induced Inflammatory Responses and Lactation in Dairy Cow Mammary Epithelial Cells by Inhibiting NF-κB and MAPKs and Up-Regulating mTOR Signaling

    Science.gov (United States)

    Liu, Lixin; Lin, Ye; Liu, Lili; Bian, Yanjie; Zhang, Li; Gao, Xuejun; Li, Qingzhang

    2015-01-01

    As a protective factor for lipopolysaccharide (LPS)-induced injury, 14-3-3γ has been the subject of recent research. Nevertheless, whether 14-3-3γ can regulate lactation in dairy cow mammary epithelial cells (DCMECs) induced by LPS remains unknown. Here, the anti-inflammatory effect and lactation regulating ability of 14-3-3γ in LPS-induced DCMECs are investigated for the first time, and the molecular mechanisms responsible for their effects are explored. The results of qRT-PCR showed that 14-3-3γ overexpression significantly inhibited the mRNA expression of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), interleukin-1β (IL-1β) and inducible nitric oxide synthase (iNOS). Enzyme-linked immunosorbent assay (ELISA) analysis revealed that 14-3-3γ overexpression also suppressed the production of TNF-α and IL-6 in cell culture supernatants. Meanwhile, CASY-TT Analyser System showed that 14-3-3γ overexpression clearly increased the viability and proliferation of cells. The results of kit methods and western blot analysis showed that 14-3-3γ overexpression promoted the secretion of triglycerides and lactose and the synthesis of β-casein. Furthermore, the expression of genes relevant to nuclear factor-κB (NF-κB) and mitogen-activated protein kinase (MAPKs) and lactation-associated proteins were assessed by western blot, and the results suggested that 14-3-3γ overexpression inactivated the NF-κB and MAPK signaling pathways by down-regulating extracellular signal regulated protein kinase (ERK), p38 mitogen-activated protein kinase (p38MAPK) and inhibitor of NF-κB (IκB) phosphorylation levels, as well as by inhibiting NF-κB translocation. Meanwhile, 14-3-3γ overexpression enhanced the expression levels of β-casein, mammalian target of rapamycin (mTOR), ribosomal protein S6 kinase 1 (S6K1), serine/threonine protein kinase Akt 1 (AKT1), sterol regulatory element binding protein 1 (SREBP1) and peroxisome proliferator-activated receptor gamma (PPAR

  15. VCAM-1-targeted core/shell nanoparticles for selective adhesion and delivery to endothelial cells with lipopolysaccharide-induced inflammation under shear flow and cellular magnetic resonance imaging in vitro

    Directory of Open Access Journals (Sweden)

    Yang H

    2013-05-01

    also significantly greater than that of nontargeted Fe3O4@SiO2(FITC-NH2 nanoparticles. Magnetic resonance images showed that the superparamagnetic iron oxide cores of the VCAM-1-targeted Fe3O4@SiO2(FITC nanoparticles could also act as a contrast agent for magnetic resonance imaging. Taken together, the cumulative adhesion and uptake potential of these VCAM-1-targeted Fe3O4@SiO2(FITC nanoparticles targeted to inflammatory endothelial cells could be used in the transfer of therapeutic drugs/genes into these cells or for diagnosis of vascular disease at the molecular and cellular levels in the future.Keywords: silica nanoparticles, vascular cell adhesion molecule-1, endothelial cells, adhesion, magnetic resonance imaging

  16. Homogeneous bilateral block shifts

    Indian Academy of Sciences (India)

    A new 3-parameter family of homogeneous 2-by-2 block shifts is described. These are the first examples of irreducible homogeneous bilateral block shifts of block size larger than 1. Author Affiliations. Adam Korányi1. Department of Mathematics, The Graduate Center, City University of New York, New York, NY 10016, USA ...

  17. [Establishment of delta block matching technique].

    Science.gov (United States)

    Lü, Qin-Feng; Zhang, Wei; Zhu, Fa-Ming; Yan, Li-Xing

    2006-04-01

    To establish delta block HLA-matching technique, DNA was extracted from whole blood by salting-out method, delta block was amplified by polymerase chain reaction (PCR), and PCR product was detected by GeneScan. The results showed that delta block had polymorphism in 104 samples without sibship of the Han people from Zhejiang province. The range of DNA fragment length was 81-393 bp and could be divided into 4 groups: 81-118 bp, 140-175 bp, 217-301 bp, 340-393 bp. The numbers of DNA fragments were 6-32. It is concluded that the method of delta block matching is reliable and can be applied to select donors for the patients to be transplanted. It is the first time to get delta block data of the Han people in China.

  18. Blocked Randomization with Randomly Selected Block Sizes

    Directory of Open Access Journals (Sweden)

    Jimmy Efird

    2010-12-01

    Full Text Available When planning a randomized clinical trial, careful consideration must be given to how participants are selected for various arms of a study. Selection and accidental bias may occur when participants are not assigned to study groups with equal probability. A simple random allocation scheme is a process by which each participant has equal likelihood of being assigned to treatment versus referent groups. However, by chance an unequal number of individuals may be assigned to each arm of the study and thus decrease the power to detect statistically significant differences between groups. Block randomization is a commonly used technique in clinical trial design to reduce bias and achieve balance in the allocation of participants to treatment arms, especially when the sample size is small. This method increases the probability that each arm will contain an equal number of individuals by sequencing participant assignments by block. Yet still, the allocation process may be predictable, for example, when the investigator is not blind and the block size is fixed. This paper provides an overview of blocked randomization and illustrates how to avoid selection bias by using random block sizes.

  19. Blocked randomization with randomly selected block sizes.

    Science.gov (United States)

    Efird, Jimmy

    2011-01-01

    When planning a randomized clinical trial, careful consideration must be given to how participants are selected for various arms of a study. Selection and accidental bias may occur when participants are not assigned to study groups with equal probability. A simple random allocation scheme is a process by which each participant has equal likelihood of being assigned to treatment versus referent groups. However, by chance an unequal number of individuals may be assigned to each arm of the study and thus decrease the power to detect statistically significant differences between groups. Block randomization is a commonly used technique in clinical trial design to reduce bias and achieve balance in the allocation of participants to treatment arms, especially when the sample size is small. This method increases the probability that each arm will contain an equal number of individuals by sequencing participant assignments by block. Yet still, the allocation process may be predictable, for example, when the investigator is not blind and the block size is fixed. This paper provides an overview of blocked randomization and illustrates how to avoid selection bias by using random block sizes.

  20. 31 CFR 595.301 - Blocked account; blocked property.

    Science.gov (United States)

    2010-07-01

    ... (Continued) OFFICE OF FOREIGN ASSETS CONTROL, DEPARTMENT OF THE TREASURY TERRORISM SANCTIONS REGULATIONS General Definitions § 595.301 Blocked account; blocked property. The terms blocked account and blocked...

  1. Lipopolysaccharide-induced acute renal failure in conscious rats

    DEFF Research Database (Denmark)

    Jonassen, Thomas E N; Graebe, Martin; Promeneur, Dominique

    2002-01-01

    In conscious, chronically instrumented rats we examined 1) renal tubular functional changes involved in lipopolysaccharide (LPS)-induced acute renal failure; 2) the effects of LPS on the expression of selected renal tubular water and sodium transporters; and 3) effects of milrinone......-alpha and lactate, inhibited the LPS-induced tachycardia, and exacerbated the acute LPS-induced fall in GFR. Furthermore, Ro-20-1724-treated rats were unable to maintain MAP. We conclude 1) PDE3 or PDE4 inhibition exacerbates LPS-induced renal failure in conscious rats; and 2) LPS treated rats develop an escape......, a phosphodiesterase type 3 (PDE3) inhibitor, and Ro-20-1724, a PDE4 inhibitor, on LPS-induced changes in renal function. Intravenous infusion of LPS (4 mg/kg b.wt. over 1 h) caused an immediate decrease in glomerular filtration rate (GFR) and proximal tubular outflow without changes in mean arterial pressure (MAP...

  2. Evidence for lipopolysaccharide-induced differentiation of RAW264 ...

    Indian Academy of Sciences (India)

    Flow cytometric studies indicate that the cell surface markers known to be expressed on dendritic cells and involved in antigen presentation and T cell activation (B7.1, B7.2, CD40, MHC class II antigens and CD1d) were also markedly upregulated on LPS-treated RAW264.7 cells. Our results suggest the possibility that LPS ...

  3. Lipopolysaccharide induced inflammation in the perivascular space in lungs

    Directory of Open Access Journals (Sweden)

    Pabst Reinhard

    2008-07-01

    Full Text Available Abstract Background Lipopolysaccharide (LPS contained in tobacco smoke and a variety of environmental and occupational dusts is a toxic agent causing lung inflammation characterized by migration of neutrophils and monocytes into alveoli. Although migration of inflammatory cells into alveoli of LPS-treated rats is well characterized, the dynamics of their accumulation in the perivascular space (PVS leading to a perivascular inflammation (PVI of pulmonary arteries is not well described. Methods Therefore, we investigated migration of neutrophils and monocytes into PVS in lungs of male Sprague-Dawley rats treated intratracheally with E. coli LPS and euthanized after 1, 6, 12, 24 and 36 hours. Control rats were treated with endotoxin-free saline. H&E stained slides were made and immunohistochemistry was performed using a monocyte marker and the chemokine Monocyte-Chemoattractant-Protein-1 (MCP-1. Computer-assisted microscopy was performed to count infiltrating cells. Results Surprisingly, the periarterial infiltration was not a constant finding in each animal although LPS-induced alveolitis was present. A clear tendency was observed that neutrophils were appearing in the PVS first within 6 hours after LPS application and were decreasing at later time points. In contrast, mononuclear cell infiltration was observed after 24 hours. In addition, MCP-1 expression was present in perivascular capillaries, arteries and the epithelium. Conclusion PVI might be a certain lung reaction pattern in the defense to infectious attacks.

  4. Lipopolysaccharide-induced expression of TRAIL promotes dendritic cell differentiation.

    Science.gov (United States)

    Cho, Young S; Challa, Sreerupa; Clancy, Lauren; Chan, Francis K-M

    2010-08-01

    Tumour necrosis factor-related apoptosis inducing ligand (TRAIL) is a death-inducing cytokine whose physiological function is not well understood. Here, we show that TRAIL has a role in programming human dendritic cell (DC) differentiation. TRAIL expression was strongly induced in DCs upon stimulation with lipopolysaccharide (LPS) or Polyinosine-polycytidylic acid (poly(I:C)) stimulation. Blockade of TRAIL with neutralizing antibody partially inhibited LPS-induced up-regulation of co-stimulatory molecules and the expression of inflammatory cytokines including interleukin-12 (IL-12) p70. In addition, neutralization of TRAIL in LPS-treated DCs inhibited the DC-driven differentiation of T cells into interferon-gamma (IFN-gamma) -producing effectors. The effects of TRAIL neutralization in poly(I:C)-treated DCs were similar, except that IL-12 production and the differentiation of effector T cells into IFN-gamma producers were not inhibited. Strikingly, TRAIL stimulation alone was sufficient to induce morphological changes resembling DC maturation, up-regulation of co-stimulatory molecules, and enhancement of DC-driven allogeneic T-cell proliferation. However, TRAIL alone did not induce inflammatory cytokine production. We further show that the effects of TRAIL on DC maturation were not the result of the induction of apoptosis, but may involve p38 activation. Hence, our data demonstrate that TRAIL co-operates with other cytokines to facilitate DC functional maturation in response to Toll-like receptor activation.

  5. Allicin Protects against Lipopolysaccharide-Induced Acute Lung ...

    African Journals Online (AJOL)

    Purpose: To investigate the effect of allicin, an active component of garlic, on lipopolysaccharide (LPS)- induced acute lung injury. Methods: Wistar rats were subjected to LPS intravenous injection with or without allicin treatment to induce acute lung injury (ALI) model. Also, A549 cells were stimulated with LPS in the ...

  6. Intermittent fasting attenuates lipopolysaccharide-induced neuroinflammation and memory impairment.

    Science.gov (United States)

    Vasconcelos, Andrea R; Yshii, Lidia M; Viel, Tania A; Buck, Hudson S; Mattson, Mark P; Scavone, Cristoforo; Kawamoto, Elisa M

    2014-05-06

    Systemic bacterial infections often result in enduring cognitive impairment and are a risk factor for dementia. There are currently no effective treatments for infection-induced cognitive impairment. Previous studies have shown that intermittent fasting (IF) can increase the resistance of neurons to injury and disease by stimulating adaptive cellular stress responses. However, the impact of IF on the cognitive sequelae of systemic and brain inflammation is unknown. Rats on IF for 30 days received 1 mg/kg of lipopolysaccharide (LPS) or saline intravenously. Half of the rats were subjected to behavioral tests and the other half were euthanized two hours after LPS administration and the hippocampus was dissected and frozen for analyses. Here, we report that IF ameliorates cognitive deficits in a rat model of sepsis by a mechanism involving NF-κB activation, suppression of the expression of pro-inflammatory cytokines, and enhancement of neurotrophic support. Treatment of rats with LPS resulted in deficits in cognitive performance in the Barnes maze and inhibitory avoidance tests, without changing locomotor activity, that were ameliorated in rats that had been maintained on the IF diet. IF also resulted in reduced levels of mRNAs encoding the LPS receptor TLR4 and inducible nitric oxide synthase (iNOS) in the hippocampus. Moreover, IF prevented LPS-induced elevation of IL-1α, IL-1β and TNF-α levels, and prevented the LPS-induced reduction of BDNF levels in the hippocampus. IF also significantly attenuated LPS-induced elevations of serum IL-1β, IFN-γ, RANTES, TNF-α and IL-6 levels. Taken together, our results suggest that IF induces adaptive responses in the brain and periphery that can suppress inflammation and preserve cognitive function in an animal model of systemic bacterial infection.

  7. Inhibition of lipopolysaccharide induced acute inflammation in lung by chlorination

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Jinshan; Xue, Jinling; Xu, Bi; Xie, Jiani [Environmental Simulation and Pollution Control State Key Joint Laboratory, School of Environment, Tsinghua University, Beijing 100084 (China); Qiao, Juan, E-mail: qjuan@tsinghua.edu.cn [Department of Chemistry, Tsinghua University, Beijing 100084 (China); Lu, Yun, E-mail: luyun@tsinghua.edu.cn [Environmental Simulation and Pollution Control State Key Joint Laboratory, School of Environment, Tsinghua University, Beijing 100084 (China)

    2016-02-13

    Highlights: • Chlorination is effective to reduce the inflammation inducing capacity of LPS in lung. • LAL-detected endotoxin activity is not correlated to the potency of inflammation induction. • Alkyl chain of LPS was chlorinated in chlorination process. • LPS aggregate size decreases after chlorination. - Abstract: Lipopolysaccharide (LPS, also called endotoxin) is a pro-inflammatory constituent of gram negative bacteria and cyanobacteria, which causes a potential health risk in the process of routine urban application of reclaimed water, such as car wash, irrigation, scenic water refilling, etc. Previous studies indicated that the common disinfection treatment, chlorination, has little effect on endotoxin activity removal measured by Limulus amebocyte lysate (LAL) assay. However, in this study, significant decrease of acute inflammatory effects was observed in mouse lung, while LAL assay still presented a moderate increase of endotoxin activity. To explore the possible mechanisms, the nuclear magnetic resonance (NMR) results showed the chlorination happened in alkyl chain of LPS molecules, which could affect the interaction between LPS and LPS-binding protein. Also the size of LPS aggregates was found to drop significantly after treatment, which could be another results of chlorination caused polarity change. In conclusion, our observation demonstrated that chlorination is effective to reduce the LPS induced inflammation in lung, and it is recommended to use health effect-based methods to assess risk removal of water treatment technologies.

  8. Evidence for lipopolysaccharide-induced differentiation of RAW264 ...

    Indian Academy of Sciences (India)

    Unknown

    Beutler B 2000 Endotoxin, toll-like receptor 4, and the afferent limb of innate immunity; Curr. Opinion Microbiol. 3 23–28. Fenton M J and Golenbock D T 1998 LPS-binding proteins and receptors; J. Leukoc. Biol. 64 25–32. Grabbe S, Kampgen E and Schuler G 2000 Dendritic cells: multi-lineal and multi-functional; Immunol.

  9. Pleurotus eryngii Ameliorates Lipopolysaccharide-Induced Lung Inflammation in Mice

    Directory of Open Access Journals (Sweden)

    Junya Kawai

    2014-01-01

    Full Text Available Pleurotus eryngii (P. eryngii is consumed as a fresh cultivated mushroom worldwide and demonstrated to have multiple beneficial effects. We investigated the anti-inflammatory effect of P. eryngii in mice with acute lung injury (ALI. Intranasal instillation of lipopolysaccharide (LPS (10 μg/site/mouse induced marked lung inflammation (increase in the number of inflammatory cells, protein leakage, and production of nitric oxide in bronchoalveolar lavage fluid as well as histopathological damage in the lung, 6 h after treatment. Mice administered heat-treated P. eryngii (0.3–1 g/kg, p.o. (HTPE 1 h before LPS challenge showed decreased pulmonary inflammation and ameliorated histopathological damage. These results suggest that HTPE has anti-inflammatory effects against ALI. Thus, P. eryngii itself may also have anti-inflammatory effects and could be a beneficial food for the prevention of ALI induced by bacterial infection.

  10. Inhibitory Effects of Ketamine on Lipopolysaccharide-Induced Microglial Activation

    Directory of Open Access Journals (Sweden)

    Yi Chang

    2009-01-01

    Full Text Available Microglia activated in response to brain injury release neurotoxic factors including nitric oxide (NO and proinflammatory cytokines such as tumor necrosis factor-α (TNF-α and interleukin-1β (IL-1β. Ketamine, an anesthetic induction agent, is generally reserved for use in patients with severe hypotension or respiratory depression. In this study, we found that ketamine (100 and 250 μM concentration-dependently inhibited lipopolysaccharide (LPS-induced NO and IL-1β release in primary cultured microglia. However, ketamine (100 and 250 μM did not significantly inhibit the LPS-induced TNF-α production in microglia, except at the higher concentration (500 μM. Further study of the molecular mechanisms revealed that ketamine markedly inhibited extracellular signal-regulated kinase (ERK1/2 phosphorylation but not c-Jun N-terminal kinase or p38 mitogen-activated protein kinase stimulated by LPS in microglia. These results suggest that microglial inactivation by ketamine is at least partially due to inhibition of ERK1/2 phosphorylation.

  11. The Alternaria alternata Mycotoxin Alternariol Suppresses Lipopolysaccharide-Induced Inflammation.

    Science.gov (United States)

    Grover, Shivani; Lawrence, Christopher B

    2017-07-20

    The Alternaria mycotoxins alternariol (AOH) and alternariol monomethyl ether (AME) have been shown to possess genotoxic and cytotoxic properties. In this study, the ability of AOH and AME to modulate innate immunity in the human bronchial epithelial cell line (BEAS-2B) and mouse macrophage cell line (RAW264.7) were investigated. During these studies, it was discovered that AOH and to a lesser extent AME potently suppressed lipopolysaccharide (LPS)-induced innate immune responses in a dose-dependent manner. Treatment of BEAS-2B cells with AOH resulted in morphological changes including a detached pattern of growth as well as elongated arms. AOH/AME-related immune suppression and morphological changes were linked to the ability of these mycotoxins to cause cell cycle arrest at the G2/M phase. This model was also used to investigate the AOH/AME mechanism of immune suppression in relation to aryl hydrocarbon receptor (AhR). AhR was not found to be important for the immunosuppressive properties of AOH/AME, but appeared important for the low levels of cell death observed in BEAS-2B cells.

  12. Lipopolysaccharide induces autotaxin expression in human monocytic THP-1 cells

    International Nuclear Information System (INIS)

    Li Song; Zhang Junjie

    2009-01-01

    Autotaxin (ATX) is a secreted enzyme with lysophospholipase D (lysoPLD) activity, which converts lysophosphatidylcholine (LPC) into lysophosphatidic acid (LPA), a bioactive phospholipid involved in numerous biological activities, including cell proliferation, differentiation, and migration. In the present study, we found that bacterial lipopolysaccharide (LPS), a well-known initiator of the inflammatory response, induced ATX expression in monocytic THP-1 cells. The activation of PKR, JNK, and p38 MAPK was required for the ATX induction. The LPS-induced ATX in THP-1 cells was characterized as the β isoform. In the presence of LPC, ATX could promote the migrations of THP-1 and Jurkat cells, which was inhibited by pertussis toxin (PTX), an inhibitor of Gi-mediated LPA receptor signaling. In summary, LPS induces ATX expression in THP-1 cells via a PKR, JNK and p38 MAPK-mediated mechanism, and the ATX induction is likely to enhance immune cell migration in proinflammatory response by regulating LPA levels in the microenvironment.

  13. Evidence for lipopolysaccharide-induced differentiation of RAW264 ...

    Indian Academy of Sciences (India)

    Unknown

    Dose-dependent morphological transformation of. RAW264⋅7 cells by LPS. RAW264⋅7 cells were cultured on glass slides in a slide chamber in the presence of various given doses of LPS. After two days, slides were fixed and stained as described in § 2. Slides were observed under a microscope with a digital camera and ...

  14. Dexmedetomidine reduces lipopolysaccharide induced neuroinflammation, sickness behavior, and anhedonia.

    Directory of Open Access Journals (Sweden)

    Ching-Hua Yeh

    Full Text Available Peripheral innate immune response may induce sickness behavior through activating microglia, excessive cytokines production, and neuroinflammation. Dexmedetomidine (Dex has anti-inflammatory effect. We investigated the effects of Dex on lipopolysaccharide (LPS-induced neuroinflammation and sickness behavior in mice.BALB/c mice were intraperitoneally (i.p. injected with Dex (50 ug/kg or vehicle. One hour later, the mice were injected (i.p. with Escherichia coli LPS (0.33 mg/kg or saline (n = 6 in each group. We analyzed the food and water intake, body weight loss, and sucrose preference of the mice for 24h. We also determined microglia activation and cytokines expression in the brains of the mice. In vitro, we determine cytokines expression in LPS-treated BV-2 microglial cells with or without Dex treatment.In the Dex-pretreated mice, LPS-induced sickness behavior (anorexia, weight loss, and social withdrawal were attenuated and microglial activation was lower than vehicle control. The mRNA expression of TNF-α, MCP-1, indoleamine 2, 3 dioxygenase (IDO, caspase-3, and iNOS were increased in the brain of LPS-challenged mice, which were reduced by Dex but not vehicle.Dexmedetomidine diminished LPS-induced neuroinflammation in the mouse brain and modulated the cytokine-associated changes in sickness behavior.

  15. Interleukin-15 is required for maximal lipopolysaccharide-induced abortion.

    Science.gov (United States)

    Lee, Amanda J; Kandiah, Nalaayini; Karimi, Khalil; Clark, David A; Ashkar, Ali A

    2013-06-01

    The maternal immune response during pregnancy is critical for the survival of the fetus yet can be detrimental during infection and inflammation. Previously, IL-15 has been observed to mediate inflammation during LPS-induced sepsis. Therefore, we sought to determine whether IL-15 mediates the inflammatory process during LPS-induced abortion through the use of IL-15(-/-) and WT mice. Administration of 2.5 μg LPS i.p. on gd 7.5 drastically reduced fetal viability in WT mice, whereas it had a minimal effect on fetal survival in IL-15(-/-) mice. The uteroplacental sites of LPS-treated WT mice were characterized by vast structural degradation and inflammation compared with treated IL-15(-/-) and untreated controls. This suggests that IL-15 may mediate the inflammation responsible for LPS-induced resorption. As IL-15(-/-) mice are deficient in NK cells and resistant to LPS-induced abortion, these effects suggest that IL-15 may mediate abortion through their homeostatic and/or activation effects on NK cells. WT uteroplacental units exposed to LPS had an increase in the overall number and effector number of NK cells compared with their control counterparts. Furthermore, NK cell depletion before administration of LPS in WT mice partially restored fetal viability. Overall, this paper suggests that IL-15 mediates the inflammatory environment during LPS-induced fetal resorption, primarily through its effects on NK cells.

  16. Generalized Block Failure

    DEFF Research Database (Denmark)

    Jönsson, Jeppe

    2015-01-01

    Block tearing is considered in several codes as a pure block tension or a pure block shear failure mechanism. However in many situations the load acts eccentrically and involves the transfer of a substantial moment in combination with the shear force and perhaps a normal force. A literature study...... shows that no readily available tests with a well-defined substantial eccentricity have been performed. This paper presents theoretical and experimental work leading towards generalized block failure capacity methods. Simple combination of normal force, shear force and moment stress distributions along...

  17. Homogeneous bilateral block shifts

    Indian Academy of Sciences (India)

    Homogeneous bilateral block shifts. ADAM KORÁNYI. Department of Mathematics, The Graduate Center, City University of New York,. New York, NY 10016, USA. E-mail: Adam.Koranyi@lehman.cuny.edu. MS received 18 January 2013. Abstract. A new 3-parameter family of homogeneous 2-by-2 block shifts is described.

  18. Related Drupal Nodes Block

    NARCIS (Netherlands)

    Van der Vegt, Wim

    2010-01-01

    Related Drupal Nodes Block This module exposes a block that uses Latent Semantic Analysis (Lsa) internally to suggest three nodes that are relevant to the node a user is viewing. This module performs three tasks. 1) It periodically indexes a Drupal site and generates a Lsa Term Document Matrix.

  19. Control rod blocking monitor

    International Nuclear Information System (INIS)

    Suzuki, Shigeru.

    1993-01-01

    The number of times for setting up a control rod blocking monitor of a BWR type power plant is remarkably reduced to mitigate operator's burden. In the control rod blocking monitor, trip levels, as a judging standard upon outputting control rod blocking inhibition signals, are set up stepwise depending on the power level around control rods put to blocking control. The present invention comprises an allowance judging means capable of setting up trip levels for each of power levels corresponding to a plurality of control rods at once if the power levels are within the set up allowable range. With such a constitution, the set up allowable range is determined previously in the allowance judging means. Accordingly, when a gang blocking is conducted to control rods, if power levels around the control rods are increased at once into the set up allowable range, the trip levels for each of the control rods are set up at once. (I.S.)

  20. Predictability of blocking

    International Nuclear Information System (INIS)

    Tosi, E.; Ruti, P.; Tibaldi, S.; D'Andrea, F.

    1994-01-01

    Tibaldi and Molteni (1990, hereafter referred to as TM) had previously investigated operational blocking predictability by the ECMWF model and the possible relationships between model systematic error and blocking in the winter season of the Northern Hemisphere, using seven years of ECMWF operational archives of analyses and day 1 to 10 forecasts. They showed that fewer blocking episodes than in the real atmosphere were generally simulated by the model, and that this deficiency increased with increasing forecast time. As a consequence of this, a major contribution to the systematic error in the winter season was shown to derive from the inability of the model to properly forecast blocking. In this study, the analysis performed in TM for the first seven winter seasons of the ECMWF operational model is extended to the subsequent five winters, during which model development, reflecting both resolution increases and parametrisation modifications, continued unabated. In addition the objective blocking index developed by TM has been applied to the observed data to study the natural low frequency variability of blocking. The ability to simulate blocking of some climate models has also been tested

  1. 31 CFR 594.301 - Blocked account; blocked property.

    Science.gov (United States)

    2010-07-01

    ... (Continued) OFFICE OF FOREIGN ASSETS CONTROL, DEPARTMENT OF THE TREASURY GLOBAL TERRORISM SANCTIONS REGULATIONS General Definitions § 594.301 Blocked account; blocked property. The terms blocked account and...

  2. Bundle Branch Block

    Science.gov (United States)

    ... 2015. Bundle branch block Symptoms & causes Diagnosis & treatment Advertisement Mayo Clinic does not endorse companies or products. ... a Job Site Map About This Site Twitter Facebook Google YouTube Pinterest Mayo Clinic is a not- ...

  3. Blocked Urethral Valves

    Science.gov (United States)

    ... the penis. Rarely, small membranes form across the urethra in boys early in pregnancy, and they can block the flow of urine out of the bladder. These membranes are called posterior urethral valves and can have life-threatening consequences ...

  4. Optoelectronics using block copolymers.

    Energy Technology Data Exchange (ETDEWEB)

    Botiz, I.; Darling, S. B.; Center for Nanoscale Materials

    2010-05-01

    Block copolymers, either as semiconductors themselves or as structure directors, are emerging as a promising class of materials for understanding and controlling processes associated with both photovoltaic energy conversion and light emitting devices.

  5. Transcriptional features of genomic regulatory blocks.

    Science.gov (United States)

    Akalin, Altuna; Fredman, David; Arner, Erik; Dong, Xianjun; Bryne, Jan Christian; Suzuki, Harukazu; Daub, Carsten O; Hayashizaki, Yoshihide; Lenhard, Boris

    2009-01-01

    Genomic regulatory blocks (GRBs) are chromosomal regions spanned by highly conserved non-coding elements (HCNEs), most of which serve as regulatory inputs of one target gene in the region. The target genes are most often transcription factors involved in embryonic development and differentiation. GRBs often contain extensive gene deserts, as well as additional 'bystander' genes intertwined with HCNEs but whose expression and function are unrelated to those of the target gene. The tight regulation of target genes, complex arrangement of regulatory inputs, and the differential responsiveness of genes in the region call for the examination of fundamental rules governing transcriptional activity in GRBs. Here we use extensive CAGE tag mapping of transcription start sites across different human tissues and differentiation stages combined with expression data and a number of sequence and epigenetic features to discover these rules and patterns. We show evidence that GRB target genes have properties that set them apart from their bystanders as well as other genes in the genome: longer CpG islands, a higher number and wider spacing of alternative transcription start sites, and a distinct composition of transcription factor binding sites in their core/proximal promoters. Target gene expression correlates with the acetylation state of HCNEs in the region. Additionally, target gene promoters have a distinct combination of activating and repressing histone modifications in mouse embryonic stem cell lines. GRB targets are genes with a number of unique features that are the likely cause of their ability to respond to regulatory inputs from very long distances.

  6. Single-chain antibody-based gene therapy: Inhibition of tumor growth by in situ production of phage-derived antibodies blocking functionally active sites of cell-associated matrices

    DEFF Research Database (Denmark)

    Sanz, Laura; Kristensen, Peter; Blanco, Belén

    2002-01-01

    Experimental evidence suggests that blocking the interactions between endothelial cells and extracellular matrix (ECM) components may provide a potent and general strategy to inhibit tumor neovascularization. Based on these considerations, we have focused our efforts on laminin, component of the ...

  7. Right bundle branch block

    DEFF Research Database (Denmark)

    Bussink, Barbara E; Holst, Anders Gaarsdal; Jespersen, Lasse

    2013-01-01

    AimsTo determine the prevalence, predictors of newly acquired, and the prognostic value of right bundle branch block (RBBB) and incomplete RBBB (IRBBB) on a resting 12-lead electrocardiogram in men and women from the general population.Methods and resultsWe followed 18 441 participants included.......5%/2.3% in women, P Right bundle branch block was associated with significantly...... increased all-cause and cardiovascular mortality in both genders with age-adjusted hazard ratios (HR) of 1.31 [95% confidence interval (CI), 1.11-1.54] and 1.87 (95% CI, 1.48-2.36) in the gender pooled analysis with little attenuation after multiple adjustment. Right bundle branch block was associated...

  8. Amphiphilic block copolymers for drug delivery.

    Science.gov (United States)

    Adams, Monica L; Lavasanifar, Afsaneh; Kwon, Glen S

    2003-07-01

    Amphiphilic block copolymers (ABCs) have been used extensively in pharmaceutical applications ranging from sustained-release technologies to gene delivery. The utility of ABCs for delivery of therapeutic agents results from their unique chemical composition, which is characterized by a hydrophilic block that is chemically tethered to a hydrophobic block. In aqueous solution, polymeric micelles are formed via the association of ABCs into nanoscopic core/shell structures at or above the critical micelle concentration. Upon micellization, the hydrophobic core regions serve as reservoirs for hydrophobic drugs, which may be loaded by chemical, physical, or electrostatic means, depending on the specific functionalities of the core-forming block and the solubilizate. Although the Pluronics, composed of poly(ethylene oxide)-block-poly(propylene oxide)-block-poly(ethylene oxide), are the most widely studied ABC system, copolymers containing poly(L-amino acid) and poly(ester) hydrophobic blocks have also shown great promise in delivery applications. Because each ABC has unique advantages with respect to drug delivery, it may be possible to choose appropriate block copolymers for specific purposes, such as prolonging circulation time, introduction of targeting moieties, and modification of the drug-release profile. ABCs have been used for numerous pharmaceutical applications including drug solubilization/stabilization, alteration of the pharmacokinetic profile of encapsulated substances, and suppression of multidrug resistance. The purpose of this minireview is to provide a concise, yet detailed, introduction to the use of ABCs and polymeric micelles as delivery agents as well as to highlight current and past work in this area. Copyright 2003 Wiley-Liss, Inc. and the American Pharmacists Association

  9. E-Block: A Tangible Programming Tool with Graphical Blocks

    OpenAIRE

    Danli Wang; Yang Zhang; Shengyong Chen

    2013-01-01

    This paper designs a tangible programming tool, E-Block, for children aged 5 to 9 to experience the preliminary understanding of programming by building blocks. With embedded artificial intelligence, the tool defines the programming blocks with the sensors as the input and enables children to write programs to complete the tasks in the computer. The symbol on the programming block's surface is used to help children understanding the function of each block. The sequence information is transfer...

  10. Contaminated soil concrete blocks

    NARCIS (Netherlands)

    de Korte, A.C.J.; Brouwers, Jos; Limbachiya, Mukesh C.; Kew, Hsein Y.

    2009-01-01

    According to Dutch law the contaminated soil needs to be remediated or immobilised. The main focus in this article is the design of concrete blocks, containing contaminated soil, that are suitable for large production, financial feasible and meets all technical and environmental requirements. In

  11. Making Block Grants Accountable.

    Science.gov (United States)

    Chelimsky, Eleanor

    Methods of accountability are presented in considering the Reagan administration plan to consolidate 84 federal health, education and social service grants into six block grant areas and to cut overall funding. After matching aspects of public criticism with proposal objectives, a rationale is developed for building elements of accountability into…

  12. Linoleum Block Printing Revisited.

    Science.gov (United States)

    Chetelat, Frank J.

    1980-01-01

    The author discusses practical considerations of teaching linoleum block printing in the elementary grades (tool use, materials, motivation) and outlines a sequence of design concepts in this area for the primary, intermediate and junior high grades. A short list of books and audiovisual aids is appended. (SJL)

  13. Effects of Block Scheduling

    Directory of Open Access Journals (Sweden)

    William R. Veal

    1999-09-01

    Full Text Available This study examined the effects of a tri-schedule on the academic achievement of students in a high school. The tri-schedule consists of traditional, 4x4 block, and hybrid schedules running at the same time in the same high school. Effectiveness of the schedules was determined from the state mandated test of basic skills in reading, language, and mathematics. Students who were in a particular schedule their freshman year were tested at the beginning of their sophomore year. A statistical ANCOVA test was performed using the schedule types as independent variables and cognitive skill index and GPA as covariates. For reading and language, there was no statistically significant difference in test results. There was a statistical difference mathematics-computation. Block mathematics is an ideal format for obtaining more credits in mathematics, but the block format does little for mathematics achievement and conceptual understanding. The results have content specific implications for schools, administrations, and school boards who are considering block scheduling adoption.

  14. Coding with Blockly

    CERN Document Server

    Lovett, Amber

    2017-01-01

    "Blockly is a fun, graphical programming language designed to get kids interested in creating their own computer programs. Through simple text written to foster creativity and problem solving, students will the art of innovation. Large, colorful images show students how to complete activities. Additional tools, including a glossary and an index, help students learn new vocabulary and locate information."-- Provided by publisher.

  15. [Establishment of beta block matching technique].

    Science.gov (United States)

    Zhu, Fa-Ming; Lü, Qin-Feng; Zhang, Wei; Zhang, Hai-Qin; Fu, Qi-Hua; Yan, Li-Xing

    2005-10-01

    The purpose of this study was to establish beta block matching technique. DNA was extracted from whole blood by salting-out method, beta block matching was performed by PCR and GeneScan technique. The results showed that the length of fragments amplificated in 100 samples was different and the range of them was 91-197 bp. Amplification fragments could be divided into four regions: 91-93, 105-113, 125-139 and 177-197 bp respectively. 91 bp DNA fragments could be found in all of samples. The numbers of DNA fragments with different length have been shown high polymorphism and they focused on the range of seven to twenty four. In conclusion, the beta block matching technique is reliable and applicable to the selection of hematopoietic stem cell transplantation donors.

  16. Block Tridiagonal Matrices in Electronic Structure Calculations

    DEFF Research Database (Denmark)

    Petersen, Dan Erik

    is developed and compared to standard Gaussian elimination, where it is shown to be qualitatively quicker for the task of determining the block tridiagonal portion of the Green’s function matrix. The Sweep algorithm is then parallelized via a straightforward approach in order to enable moderate speedup...... and memory distribution. The well known block cyclic reduction algorithm first developed by Gene Golub is then presented and analyzed for further expanding our parallel options, and finally a new hybrid method that combines block cyclic reduction and a form of Schur complement calculation is introduced....... The parallel algorithms are then benchmarked and the new hybrid method is shown to possess promising speedup characteristics for common cases of problems that need to be modeled....

  17. HomBlocks: A multiple-alignment construction pipeline for organelle phylogenomics based on locally collinear block searching.

    Science.gov (United States)

    Bi, Guiqi; Mao, Yunxiang; Xing, Qikun; Cao, Min

    2018-01-01

    Organelle phylogenomic analysis requires precisely constructed multi-gene alignment matrices concatenated by pre-aligned single gene datasets. For non-bioinformaticians, it can take days to weeks to manually create high-quality multi-gene alignments comprising tens or hundreds of homologous genes. Here, we describe a new and highly efficient pipeline, HomBlocks, which uses a homologous block searching method to construct multiple sequence alignment. This approach can automatically recognize locally collinear blocks among organelle genomes and excavate phylogenetically informative regions to construct multiple sequence alignment in a few hours. In addition, HomBlocks supports organelle genomes without annotation and makes adjustment to different taxon datasets, thereby enabling the inclusion of as many common genes as possible. Topology comparison of trees built by conventional multi-gene and HomBlocks alignments implemented in different taxon categories shows that the same efficiency can be achieved by HomBlocks as when using the traditional method. The availability of Homblocks makes organelle phylogenetic analyses more accessible to non-bioinformaticians, thereby promising to lead to a better understanding of phylogenic relationships at an organelle genome level. HomBlocks is implemented in Perl and is supported by Unix-like operative systems, including Linux and macOS. The Perl source code is freely available for download from https://github.com/fenghen360/HomBlocks.git, and documentation and tutorials are available at https://github.com/fenghen360/HomBlocks. yxmao@ouc.edu.cn or fenghen360@126.com. Copyright © 2017 Elsevier Inc. All rights reserved.

  18. [Masquerading bundle branch block].

    Science.gov (United States)

    Kukla, Piotr; Baranchuk, Adrian; Jastrzębski, Marek; Bryniarski, Leszek

    2014-01-01

    We here describe a surface 12-lead electrocardiogram (ECG) of a 72-year-old female with a prior history of breast cancer and chemotherapy-induced cardiomyopathy. An echocardiogram revealed left ventricular dysfunction, ejection fraction of 23%, with mild enlarged left ventricle. The 12-lead ECG showed atrial fibrillation with a mean heart rate of about 100 bpm, QRS duration 160 ms, QT interval 400 ms, right bundle branch block (RBBB) and left anterior fascicular block (LAFB). The combination of RBBB features in the precordial leads and LAFB features in the limb leads is known as ''masquerading bundle branch block''. In most cases of RBBB and LAFB, the QRS axis deviation is located between - 80 to -120 degrees. Rarely, when predominant left ventricular forces are present, the QRS axis deviation is near about -90 degrees, turning the pattern into an atypical form. In a situation of RBBB associated with LAFB, the S wave can be absent or very small in lead I. Such a situation is the result of not only purely LAFB but also with left ventricular hypertrophy and/or focal block due to scar (extensive anterior myocardial infarction) or fibrosis (cardiomyopathy). Sometimes, this specific ECG pattern is mistaken for LBBB. RBBB with LAFB may imitate LBBB either in the limb leads (known as 'standard masquerading' - absence of S wave in lead I), or in the precordial leads (called 'precordial masquerading' - absence of S wave in leads V₅ and V₆). Our ECG showed both these types of masquerading bundle branch block - absence of S wave in lead I and in leads V₅ and V₆.

  19. SUPERFICIAL CERVICAL PLEXUS BLOCK

    Directory of Open Access Journals (Sweden)

    Komang Mega Puspadisari

    2014-01-01

    Full Text Available Superficial cervical plexus block is one of the regional anesthesia in  neck were limited to thesuperficial fascia. Anesthesia is used to relieve pain caused either during or after the surgery iscompleted. This technique can be done by landmark or with ultrasound guiding. The midpointof posterior border of the Sternocleidomastoid was identified and the prosedure done on thatplace or on the level of cartilage cricoid.

  20. Change Around the Block?

    Science.gov (United States)

    Berlin, Joey

    2017-04-01

    Proponents of a block grant or per-capita cap trumpet them as vehicles for the federal government to give the states a capped amount of funding for Medicaid that legislatures would effectively distribute how they see fit. Questions abound as to what capped Medicaid funding would look like, and what effect it would have on the current Medicaid-eligible population, covered services, and physician payments.

  1. Managing access block.

    Science.gov (United States)

    Cameron, Peter; Scown, Paul; Campbell, Donald

    2002-01-01

    There is pessimism regarding the ability of the Acute Health Sector to manage access block for emergency and elective patients. Melbourne Health suffered an acute bed crisis in 2001 resulting in record ambulance diversions and emergency department (ED) delays. We conducted an observational study to reduce access block for emergency patients whilst maintaining elective throughput at Melbourne Health. This involved a clinician-led taskforce using previously proven principles for organisational change to implement 51 actions to improve patient access over a three-month period. The primary outcome measures were ambulance diversion, emergency patients waiting more than 12 hours for an inpatient bed, elective throughput and theatre cancellations. Despite a reduction in multi-day bed numbers all primary objectives were met, ambulance diversion decreased to minimal levels, 12-hour waits decreased by 40% and elective throughput was maintained. Theatre cancellations were also minimised. We conclude that access block can be improved by clinician-led implementation of proven process improvements over a short time frame. The ability to sustain change over the longer term requires further study.

  2. Paving block study : final report.

    Science.gov (United States)

    1971-10-01

    The Louisiana Department of Highways has conducted field tests with an experimental revetment consisting of cellular concrete revetment blocks used in conjunction with plastic filter cloth and/or vegetation such as grass or vines. The precast blocks ...

  3. Habitat Blocks and Wildlife Corridors

    Data.gov (United States)

    Vermont Center for Geographic Information — Habitat blocks are areas of contiguous forest and other natural habitats that are unfragmented by roads, development, or agriculture. Vermonts habitat blocks are...

  4. Demographic Data - MDC_Block

    Data.gov (United States)

    NSGIC Local Govt | GIS Inventory — A polygon feature class of Miami-Dade Census 2000 Blocks. Census blocks are areas bounded on all sides by visible and/or invisible features shown on a map prepared...

  5. Silence of the Genes

    Indian Academy of Sciences (India)

    Srimath

    tary to the endogenous sense mRNA produced by the normal gene. The antisense strand binds to the sense strand and blocks protein synthesis. This method of gene inhibition was termed antisense technology. The antisense technology soon became a. RNA interference. (RNAi) is a novel mechanism for controlling gene.

  6. Blocking the Hawking radiation

    DEFF Research Database (Denmark)

    Autzen, M.; Kouvaris, C.

    2014-01-01

    grows after its formation (and eventually destroys the star) instead of evaporating. The fate of the black hole is dictated by the two opposite mechanics, i.e., accretion of nuclear matter from the center of the star and Hawking radiation that tends to decrease the mass of the black hole. We study how...... the assumptions for the accretion rate can in fact affect the critical mass beyond which a black hole always grows. We also study to what extent degenerate nuclear matter can impede Hawking radiation due to the fact that emitted particles can be Pauli blocked at the core of the star....

  7. How Artists Overcome Creative Blocks.

    Science.gov (United States)

    Hirst, Barbara

    1992-01-01

    Six practicing artists were interviewed about how they overcome creative blocks. Their responses indicated that feelings of self-doubt, fear, and depression accompany blocks but that relaxing and working on new directions and playing ideas off a supportive person helped to overcome such blocks. (DB)

  8. Block Scheduling in High Schools.

    Science.gov (United States)

    Irmsher, Karen

    1996-01-01

    Block Scheduling has been considered a cure for a lengthy list of educational problems. This report reviews the literature on block schedules and describes some Oregon high schools that have integrated block scheduling. Major disadvantages included resistance to change and requirements that teachers change their teaching strategies. There is…

  9. Abdominal wall blocks in adults

    DEFF Research Database (Denmark)

    Neimann, Jens Dupont Børglum; Gögenür, Ismail; Bendtsen, Thomas F.

    2016-01-01

    Purpose of review Abdominal wall blocks in adults have evolved much during the last decade; that is, particularly with the introduction of ultrasound-guided (USG) blocks. This review highlights recent advances of block techniques within this field and proposes directions for future research.  Rec...

  10. Program structure-based blocking

    Science.gov (United States)

    Bertolli, Carlo; Eichenberger, Alexandre E.; O'Brien, John K.; Sura, Zehra N.

    2017-09-26

    Embodiments relate to program structure-based blocking. An aspect includes receiving source code corresponding to a computer program by a compiler of a computer system. Another aspect includes determining a prefetching section in the source code by a marking module of the compiler. Yet another aspect includes performing, by a blocking module of the compiler, blocking of instructions located in the prefetching section into instruction blocks, such that the instruction blocks of the prefetching section only contain instructions that are located in the prefetching section.

  11. Insulin-like growth factor-I gene delivery to astrocytes reduces their inflammatory response to lipopolysaccharide

    Directory of Open Access Journals (Sweden)

    Goya Rodolfo G

    2011-03-01

    Full Text Available Abstract Background Insulin-like growth factor-I (IGF-I exerts neuroprotective actions in the central nervous system that are mediated at least in part by control of activation of astrocytes. In this study we have assessed the efficacy of exogenous IGF-I and IGF-I gene therapy in reducing the inflammatory response of astrocytes from cerebral cortex. Methods An adenoviral vector harboring the rat IGF-I gene and a control adenoviral vector harboring a hybrid gene encoding the herpes simplex virus type 1 thymidine kinase fused to Aequorea victoria enhanced green fluorescent protein were used in this study. Primary astrocytes from mice cerebral cortex were incubated for 24 h or 72 h with vehicle, IGF-I, the IGF-I adenoviral vector, or control vector; and exposed to bacterial lipopolysaccharide to induce an inflammatory response. IGF-I levels were measured by radioimmunoassay. Levels of interleukin 6, tumor necrosis factor-α, interleukin-1β and toll-like receptor 4 mRNA were assessed by quantitative real-time polymerase chain reaction. Levels of IGF-I receptor and IGF binding proteins 2 and 3 were assessed by western blotting. The subcellular distribution of nuclear factor κB (p65 was assessed by immunocytochemistry. Statistical significance was assessed by one way analysis of variance followed by the Bonferroni pot hoc test. Results IGF-I gene therapy increased IGF-I levels without affecting IGF-I receptors or IGF binding proteins. Exogenous IGF-I, and IGF-I gene therapy, decreased expression of toll-like receptor 4 and counteracted the lipopolysaccharide-induced inflammatory response of astrocytes. In addition, IGF-I gene therapy decreased lipopolysaccharide-induced translocation of nuclear factor κB (p65 to the cell nucleus. Conclusion These findings demonstrate efficacy of exogenous IGF-I and of IGF-I gene therapy in reducing the inflammatory response of astrocytes. IGF-I gene therapy may represent a new approach to reduce inflammatory

  12. Block copolymer investigations

    Science.gov (United States)

    Yufa, Nataliya A.

    The research presented in this thesis deals with various aspects of block copolymers on the nanoscale: their behavior at a range of temperatures, their use as scaffolds, or for creation of chemically striped surfaces, as well as the behavior of metals on block copolymers under the influence of UV light, and the healing behavior of copolymers. Invented around the time of World War II, copolymers have been used for decades due to their macroscopic properties, such as their ability to be molded without vulcanization, and the fact that, unlike rubber, they can be recycled. In recent years, block copolymers (BCPs) have been used for lithography, as scaffolds for nano-objects, to create a magnetic hard drive, as well as in photonic and other applications. In this work we used primarily atomic force microscopy (AFM) and transmission electron microscopy (TEM), described in Chapter II, to conduct our studies. In Chapter III we demonstrate a new and general method for positioning nanoparticles within nanoscale grooves. This technique is suitable for nanodots, nanocrystals, as well as DNA. We use AFM and TEM to demonstrate selective decoration. In Chapters IV and V we use AFM and TEM to study the structure of polymer surfaces coated with metals and self-assembled monolayers. We describe how the surfaces were created, exhibit their structure on the nanoscale, and prove that their macroscopic wetting properties have been altered compared to the original polymer structures. Finally, Chapters VI and VII report out in-situ AFM studies of BCP at high temperatures, made possible only recently with the invention of air-tight high-temperature AFM imaging cells. We locate the transition between disordered films and cylinders during initial ordering. Fluctuations of existing domains leading to domain coarsening are also described, and are shown to be consistent with reptation and curvature minimization. Chapter VII deals with the healing of PS-b-PMMA following AFM-tip lithography or

  13. Two Plastid DNA Lineages—Rapa/Oleracea and Nigra—within the Tribe Brassiceae Can Be Best Explained by Reciprocal Crosses at Hexaploidy: Evidence from Divergence Times of the Plastid Genomes and R-Block Genes of the A and B Genomes of Brassica juncea

    Science.gov (United States)

    Gupta, Vibha; Paritosh, Kumar; Pradhan, Akshay K.; Pental, Deepak

    2014-01-01

    Brassica species (tribe Brassiceae) belonging to U's triangle—B. rapa (AA), B. nigra (BB), B. oleracea (CC), B. juncea (AABB), B. napus (AACC) and B. carinata (BBCC)—originated via two polyploidization rounds: a U event producing the three allopolyploids, and a more ancient b genome-triplication event giving rise to the A-, B-, and C-genome diploid species. Molecular mapping studies, in situ hybridization, and genome sequencing of B. rapa support the genome triplication origin of tribe Brassiceae, and suggest that these three diploid species diversified from a common hexaploid ancestor. Analysis of plastid DNA has revealed two distinct lineages—Rapa/Oleracea and Nigra—that conflict with hexaploidization as a single event defining the tribe Brassiceae. We analysed an R-block region of A. thaliana present in six copies in B. juncea (AABB), three copies each on A- and B-genomes to study gene fractionation pattern and synonymous base substitution rates (Ks values). Divergence time of paralogues within the A and B genomes and homoeologues between the A and B genomes was estimated. Homoeologous R blocks of the A and B genomes exhibited high gene collinearity and a conserved gene fractionation pattern. The three progenitors of diploid Brassicas were estimated to have diverged approximately 12 mya. Divergence of B. rapa and B. nigra, calculated from plastid gene sequences, was estimated to have occurred approximately 12 mya, coinciding with the divergence of the three genomes participating in the b event. Divergence of B. juncea A and B genome homoeologues was estimated to have taken place around 7 mya. Based on divergence time estimates and the presence of distinct plastid lineages in tribe Brassiceae, it is concluded that at least two independent triplication events involving reciprocal crosses at the time of the b event have given rise to Rapa/Oleracea and Nigra lineages. PMID:24691069

  14. Celiac ganglia block

    Energy Technology Data Exchange (ETDEWEB)

    Akinci, Devrim [Department of Radiology, Hacettepe University School of Medicine, Sihhiye, 06100 Ankara (Turkey); Akhan, Okan [Department of Radiology, Hacettepe University School of Medicine, Sihhiye, 06100 Ankara (Turkey)]. E-mail: oakhan@hacettepe.edu.tr

    2005-09-01

    Pain occurs frequently in patients with advanced cancers. Tumors originating from upper abdominal viscera such as pancreas, stomach, duodenum, proximal small bowel, liver and biliary tract and from compressing enlarged lymph nodes can cause severe abdominal pain, which do not respond satisfactorily to medical treatment or radiotherapy. Percutaneous celiac ganglia block (CGB) can be performed with high success and low complication rates under imaging guidance to obtain pain relief in patients with upper abdominal malignancies. A significant relationship between pain relief and degree of tumoral celiac ganglia invasion according to CT features was described in the literature. Performing the procedure in the early grades of celiac ganglia invasion on CT can increase the effectiveness of the CGB, which is contrary to World Health Organization criteria stating that CGB must be performed in patients with advanced stage cancer. CGB may also be effectively performed in patients with chronic pancreatitis for pain palliation.

  15. Photovoltaic building blocks

    DEFF Research Database (Denmark)

    Hanberg, Peter Jesper; Jørgensen, Anders Michael

    2014-01-01

    efficiency of about 15% for commercial Silicon solar cells there is still much to gain. DTU Danchip provides research facilities, equipment and expertise for the building blocks that comprises fabricating the efficient solar cell. In order to get more of the sun light into the device we provide thin film......Photovoltaics (PV), better known as solar cells, are now a common day sight on many rooftops in Denmark.The installed capacity of PV systems worldwide is growing exponentially1 and is the third most importantrenewable energy source today. The cost of PV is decreasing fast with ~10%/year but to make...... it directcompetitive with fossil energy sources a further reduction is needed. By increasing the efficiency of the solar cells one gain an advantage through the whole chain of cost. So that per produced Watt of power less material is spent, installation costs are lower, less area is used etc. With an average...

  16. Atomic Basic Blocks

    Science.gov (United States)

    Scheler, Fabian; Mitzlaff, Martin; Schröder-Preikschat, Wolfgang

    Die Entscheidung, einen zeit- bzw. ereignisgesteuerten Ansatz für ein Echtzeitsystem zu verwenden, ist schwierig und sehr weitreichend. Weitreichend vor allem deshalb, weil diese beiden Ansätze mit äußerst unterschiedlichen Kontrollflussabstraktionen verknüpft sind, die eine spätere Migration zum anderen Paradigma sehr schwer oder gar unmöglich machen. Wir schlagen daher die Verwendung einer Zwischendarstellung vor, die unabhängig von der jeweils verwendeten Kontrollflussabstraktion ist. Für diesen Zweck verwenden wir auf Basisblöcken basierende Atomic Basic Blocks (ABB) und bauen darauf ein Werkzeug, den Real-Time Systems Compiler (RTSC) auf, der die Migration zwischen zeit- und ereignisgesteuerten Systemen unterstützt.

  17. Celiac ganglia block

    International Nuclear Information System (INIS)

    Akinci, Devrim; Akhan, Okan

    2005-01-01

    Pain occurs frequently in patients with advanced cancers. Tumors originating from upper abdominal viscera such as pancreas, stomach, duodenum, proximal small bowel, liver and biliary tract and from compressing enlarged lymph nodes can cause severe abdominal pain, which do not respond satisfactorily to medical treatment or radiotherapy. Percutaneous celiac ganglia block (CGB) can be performed with high success and low complication rates under imaging guidance to obtain pain relief in patients with upper abdominal malignancies. A significant relationship between pain relief and degree of tumoral celiac ganglia invasion according to CT features was described in the literature. Performing the procedure in the early grades of celiac ganglia invasion on CT can increase the effectiveness of the CGB, which is contrary to World Health Organization criteria stating that CGB must be performed in patients with advanced stage cancer. CGB may also be effectively performed in patients with chronic pancreatitis for pain palliation

  18. Dimensional reduction for conformal blocks

    Science.gov (United States)

    Hogervorst, Matthijs

    2016-09-01

    We consider the dimensional reduction of a CFT, breaking multiplets of the d-dimensional conformal group SO( d + 1 , 1) up into multiplets of SO( d, 1). This leads to an expansion of d-dimensional conformal blocks in terms of blocks in d - 1 dimensions. In particular, we obtain a formula for 3 d conformal blocks as an infinite sum over 2 F 1 hypergeometric functions with closed-form coefficients.

  19. Learning Potentials in Number Blocks

    DEFF Research Database (Denmark)

    Majgaard, Gunver; Misfeldt, Morten; Nielsen, Jacob

    2012-01-01

    . The tool is called Number Blocks and it combines physical interaction, learning, and immediate feedback. Number Blocks supports the children's understanding of place value in the sense that it allows them to experiment with creating large numbers. We found the blocks contributed to the learning process...... in several ways. The blocks combined mathematics and play, and they included and supported children at different academic levels. The auditory representation, especially the enhanced rhythmic effects due to using speech synthesis, and the rhythm helped the children to pronounce large numbers. This creates...

  20. Common blocks for ASQS(12

    Directory of Open Access Journals (Sweden)

    Lorenzo Milazzo

    1997-05-01

    Full Text Available An ASQS(v is a particular Steiner system featuring a set of v vertices and two separate families of blocks, B and G, whose elements have a respective cardinality of 4 and 6. It has the property that any three vertices of X belong either to a B-block or to a G-block. The parameter cb is the number of common blocks in two separate ASQSs, both defined on the same set of vertices X . In this paper it is shown that cb ≤ 29 for any pair of ASQSs(12.

  1. Cre-/IoxP-Mediated Recombination between the SIL and SCL Genes Leads to a Block in T-Cell Development at the CD4-CD8- to CD4+CD8+ Transition

    Directory of Open Access Journals (Sweden)

    Yue Cheng

    2007-04-01

    Full Text Available In the most common form of stem cell leukemia (SCL gene rearrangement, an interstitial deletion of 82 kb brings SCL under the control of regulatory elements that normally govern expression of the ubiquitously expressed SCL interrupting locus (SIL gene, which is located directly upstream of SCL. To investigate the effect of this fusion in a mouse model, a bacterial artificial chromosome (BAC clone containing both human SIL and SCL genes was isolated, and IoxP sites were inserted into intron 1 of both the SIL and SCL genes, corresponding to the sites at which recombination occurs in human T-cell acute lymphocytic leukemia patients. This BAC clone was used to generate transgenic SILIoxloxSCL mice. These transgenic mice were subsequently bred to Lck-Cre mice that express the Cre recombinase specifically in the thymus. The BAC transgene was recombined between the two IoxP sites in over 50% of the thymocytes from SILIoxloxSCL/Cre double-transgenic mice, bringing the SCL gene under the direct control of SIL regulatory elements. Aberrant SCL gene expression in the thymus was verified by reverse transcription- polymerase chain reaction. Using FACS analysis, we found that mice carrying both SILIoxloxSCL and Cre transgenes have increased CD4-/CD8- thymocytes compared with transgenenegative mice. In the spleen, these transgenic mice show a marked reduction in the number of mature CD4+ or CD8+ cells. These results demonstrate that conditional activation of SCL under control of SIL regulatory elements can impair normal T-cell development.

  2. 31 CFR 545.301 - Blocked account; blocked property.

    Science.gov (United States)

    2010-07-01

    ... (Continued) OFFICE OF FOREIGN ASSETS CONTROL, DEPARTMENT OF THE TREASURY TALIBAN (AFGHANISTAN) SANCTIONS... name of the Taliban or persons whose property or interests in property are blocked pursuant to § 545.201, or in which the Taliban or persons whose property or interests in property are blocked pursuant...

  3. Small homologous blocks in phytophthora genomes do not point to an ancient whole-genome duplication.

    Science.gov (United States)

    van Hooff, Jolien J E; Snel, Berend; Seidl, Michael F

    2014-05-01

    Genomes of the plant-pathogenic genus Phytophthora are characterized by small duplicated blocks consisting of two consecutive genes (2HOM blocks) and by an elevated abundance of similarly aged gene duplicates. Both properties, in particular the presence of 2HOM blocks, have been attributed to a whole-genome duplication (WGD) at the last common ancestor of Phytophthora. However, large intraspecies synteny-compelling evidence for a WGD-has not been detected. Here, we revisited the WGD hypothesis by deducing the age of 2HOM blocks. Two independent timing methods reveal that the majority of 2HOM blocks arose after divergence of the Phytophthora lineages. In addition, a large proportion of the 2HOM block copies colocalize on the same scaffold. Therefore, the presence of 2HOM blocks does not support a WGD at the last common ancestor of Phytophthora. Thus, genome evolution of Phytophthora is likely driven by alternative mechanisms, such as bursts of transposon activity.

  4. Classical Virasoro irregular conformal block

    Science.gov (United States)

    Rim, Chaiho; Zhang, Hong

    2015-07-01

    Virasoro irregular conformal block with arbitrary rank is obtained for the classical limit or equivalently Nekrasov-Shatashvili limit using the beta-deformed irregular matrix model (Penner-type matrix model for the irregular conformal block). The same result is derived using the generalized Mathieu equation which is equivalent to the loop equation of the irregular matrix model.

  5. Classical Virasoro irregular conformal block

    Energy Technology Data Exchange (ETDEWEB)

    Rim, Chaiho; Zhang, Hong [Department of Physics and Center for Quantum Spacetime (CQUeST), Sogang University,Seoul 121-742 (Korea, Republic of)

    2015-07-30

    Virasoro irregular conformal block with arbitrary rank is obtained for the classical limit or equivalently Nekrasov-Shatashvili limit using the beta-deformed irregular matrix model (Penner-type matrix model for the irregular conformal block). The same result is derived using the generalized Mathieu equation which is equivalent to the loop equation of the irregular matrix model.

  6. Four-block beam collimator

    CERN Document Server

    CERN PhotoLab

    1977-01-01

    The photo shows a four-block collimator installed on a control table for positioning the alignment reference marks. Designed for use with the secondary beams, the collimators operated in vacuum conditions. The blocks were made of steel and had a standard length of 1 m. The maximum aperture had a square coss-section of 144 cm2. (See Annual Report 1976.)

  7. OPAL Various Lead Glass Blocks

    CERN Document Server

    These lead glass blocks were part of a CERN detector called OPAL (one of the four experiments at the LEP particle detector). OPAL uses some 12 000 blocks of glass like this to measure particle energies in the electromagnetic calorimeter. This detector measured the energy deposited when electrons and photons were slowed down and stopped.

  8. Writing Blocks and Tacit Knowledge.

    Science.gov (United States)

    Boice, Robert

    1993-01-01

    A review of the literature on writing block looks at two kinds: inability to write in a timely, fluent fashion, and reluctance by academicians to assist others in writing. Obstacles to fluent writing are outlined, four historical trends in treating blocks are discussed, and implications are examined. (MSE)

  9. Block storage subsystem performance analysis

    CERN Multimedia

    CERN. Geneva

    2016-01-01

    You feel that your service is slow because of the storage subsystem? But there are too many abstraction layers between your software and the raw block device for you to debug all this pile... Let's dive on the platters and check out how the block storage sees your I/Os! We can even figure out what those patterns are meaning.

  10. Criminal Justice Systems. Block I: Law Enforcement. Block II: The Courts. Block III: Corrections. Block IV: Community Relations. Block V: Proficiency Skills. Block VI: Criminalistics. Student Guide.

    Science.gov (United States)

    Florida State Dept. of Education, Tallahassee. Div. of Vocational, Adult, and Community Education.

    This student guide together with an instructor guide comprise a set of curriculum materials on the criminal justice system. The student guide contains self-contained instructional material that students can study at their own pace most of the time. Six major subject areas or blocks, which are further broken down into several units, with some units…

  11. Criminal Justice Systems. Block I: Law Enforcement. Block II: The Courts. Block III: Corrections. Block IV: Community Relations. Block V: Proficiency Skills. Block VI: Criminalistics. Instructor Guide.

    Science.gov (United States)

    Florida State Dept. of Education, Tallahassee. Div. of Vocational, Adult, and Community Education.

    This instructor guide together with a student guide comprise a set of curriculum materials on the criminal justice system. The instructor guide is a resource for planning and managing individualized, competency-based instruction in six major subject areas or blocks, which are further broken down into several units with some units having several…

  12. Block by Block: Civic Action in the Battle of Baghdad

    Science.gov (United States)

    2007-11-01

    bedding, and latrine facilities. Additionally, provide milk , baby formula, diapers, 7 Bogart: Block by Block and infant/family care items such as...viable agricultural businesses. The cattle are a cross breed of a “regular” Iraqi cow and a water buffalo. Chicken farms are mostly egg farms, and...a problem. Contractors did not want to work for fear of being shot or kid - napped. For example, four contractors were shot over the duration of

  13. Harmony of spinning conformal blocks

    Energy Technology Data Exchange (ETDEWEB)

    Schomerus, Volker [DESY Hamburg, Theory Group,Notkestraße 85, 22607 Hamburg (Germany); Sobko, Evgeny [Nordita and Stockholm University,Roslagstullsbacken 23, SE-106 91 Stockholm (Sweden); Isachenkov, Mikhail [Department of Particle Physics and Astrophysics, Weizmann Institute of Science,Rehovot 7610001 (Israel)

    2017-03-15

    Conformal blocks for correlation functions of tensor operators play an increasingly important role for the conformal bootstrap programme. We develop a universal approach to such spinning blocks through the harmonic analysis of certain bundles over a coset of the conformal group. The resulting Casimir equations are given by a matrix version of the Calogero-Sutherland Hamiltonian that describes the scattering of interacting spinning particles in a 1-dimensional external potential. The approach is illustrated in several examples including fermionic seed blocks in 3D CFT where they take a very simple form.

  14. Harmony of spinning conformal blocks

    Energy Technology Data Exchange (ETDEWEB)

    Schomerus, Volker [Deutsches Elektronen-Synchrotron (DESY), Hamburg (Germany). Theory Group; Sobko, Evgeny [Stockholm Univ. (Sweden); Nordita, Stockholm (Sweden); Isachenkov, Mikhail [Weizmann Institute of Science, Rehovoth (Israel). Dept. of Particle Physics and Astrophysics

    2016-12-07

    Conformal blocks for correlation functions of tensor operators play an increasingly important role for the conformal bootstrap programme. We develop a universal approach to such spinning blocks through the harmonic analysis of certain bundles over a coset of the conformal group. The resulting Casimir equations are given by a matrix version of the Calogero-Sutherland Hamiltonian that describes the scattering of interacting spinning particles in a 1-dimensional external potential. The approach is illustrated in several examples including fermionic seed blocks in 3D CFT where they take a very simple form.

  15. Left bundle-branch block

    DEFF Research Database (Denmark)

    Risum, Niels; Strauss, David; Sogaard, Peter

    2013-01-01

    The relationship between myocardial electrical activation by electrocardiogram (ECG) and mechanical contraction by echocardiography in left bundle-branch block (LBBB) has never been clearly demonstrated. New strict criteria for LBBB based on a fundamental understanding of physiology have recently...

  16. The wild tapered block bootstrap

    DEFF Research Database (Denmark)

    Hounyo, Ulrich

    -based method in terms of asymptotic accuracy of variance estimation and distribution approximation. For stationary time series, the asymptotic validity, and the favorable bias properties of the new bootstrap method are shown in two important cases: smooth functions of means, and M-estimators. The first......-order asymptotic validity of the tapered block bootstrap as well as the wild tapered block bootstrap approximation to the actual distribution of the sample mean is also established when data are assumed to satisfy a near epoch dependent condition. The consistency of the bootstrap variance estimator for the sample......In this paper, a new resampling procedure, called the wild tapered block bootstrap, is introduced as a means of calculating standard errors of estimators and constructing confidence regions for parameters based on dependent heterogeneous data. The method consists in tapering each overlapping block...

  17. Recursion Relations for Conformal Blocks

    CERN Document Server

    Penedones, João; Yamazaki, Masahito

    2016-09-12

    In the context of conformal field theories in general space-time dimension, we find all the possible singularities of the conformal blocks as functions of the scaling dimension $\\Delta$ of the exchanged operator. In particular, we argue, using representation theory of parabolic Verma modules, that in odd spacetime dimension the singularities are only simple poles. We discuss how to use this information to write recursion relations that determine the conformal blocks. We first recover the recursion relation introduced in 1307.6856 for conformal blocks of external scalar operators. We then generalize this recursion relation for the conformal blocks associated to the four point function of three scalar and one vector operator. Finally we specialize to the case in which the vector operator is a conserved current.

  18. Defying gravity using Jenga™ blocks

    Science.gov (United States)

    Tan, Yin-Soo; Yap, Kueh-Chin

    2007-11-01

    This paper describes how Jenga™ blocks can be used to demonstrate the physics of an overhanging tower that appears to defy gravity. We also propose ideas for how this demonstration can be adapted for the A-level physics curriculum.

  19. Microbial production of polyhydroxyalkanoate block copolymer by recombinant Pseudomonas putida.

    Science.gov (United States)

    Li, Shi Yan; Dong, Cui Ling; Wang, Shen Yu; Ye, Hai Mu; Chen, Guo-Qiang

    2011-04-01

    Polyhydroxyalkanoate (PHA) synthesis genes phaPCJ(Ac) cloned from Aeromonas caviae were transformed into Pseudomonas putida KTOY06ΔC, a mutant of P. putida KT2442, resulting in the ability of the recombinant P. putida KTOY06ΔC (phaPCJ(A.c)) to produce a short-chain-length and medium-chain-length PHA block copolymer consisting of poly-3-hydroxybutyrate (PHB) as one block and random copolymer of 3-hydroxyvalerate (3HV) and 3-hydroxyheptanoate (3HHp) as another block. The novel block polymer was studied by differential scanning calorimetry (DSC), nuclear magnetic resonance, and rheology measurements. DSC studies showed the polymer to possess two glass transition temperatures (T(g)), one melting temperature (T(m)) and one cool crystallization temperature (T(c)). Rheology studies clearly indicated a polymer chain re-arrangement in the copolymer; these studies confirmed the polymer to be a block copolymer, with over 70 mol% homopolymer (PHB) of 3-hydroxybutyrate (3HB) as one block and around 30 mol% random copolymers of 3HV and 3HHp as the second block. The block copolymer was shown to have the highest tensile strength and Young's modulus compared with a random copolymer with similar ratio and a blend of homopolymers PHB and PHVHHp with similar ratio. Compared with other commercially available PHA including PHB, PHBV, PHBHHx, and P3HB4HB, the short-chain- and medium-chain-length block copolymer PHB-b-PHVHHp showed differences in terms of mechanical properties and should draw more attentions from the PHA research community. © Springer-Verlag 2010

  20. A pH and Redox Dual Responsive 4-Arm Poly(ethylene glycol-block-poly(disulfide histamine Copolymer for Non-Viral Gene Transfection in Vitro and in Vivo

    Directory of Open Access Journals (Sweden)

    Kangkang An

    2014-05-01

    Full Text Available A novel 4-arm poly(ethylene glycol-b-poly(disulfide histamine copolymer was synthesized by Michael addition reaction of poly(ethylene glycol (PEG vinyl sulfone and amine-capped poly(disulfide histamine oligomer, being denoted as 4-arm PEG-SSPHIS. This copolymer was able to condense DNA into nanoscale polyplexes (<200 nm in average diameter with almost neutral surface charge (+(5–10 mV. Besides, these polyplexes were colloidal stable within 4 h in HEPES buffer saline at pH 7.4 (physiological environment, but rapidly dissociated to liberate DNA in the presence of 10 mM glutathione (intracellular reducing environment. The polyplexes also revealed pH-responsive surface charges which markedly increased with reducing pH values from 7.4–6.3 (tumor microenvironment. In vitro transfection experiments showed that polyplexes of 4-arm PEG-SSPHIS were capable of exerting enhanced transfection efficacy in MCF-7 and HepG2 cancer cells under acidic conditions (pH 6.3–7.0. Moreover, intravenous administration of the polyplexes to nude mice bearing HepG2-tumor yielded high transgene expression largely in tumor rather other normal organs. Importantly, this copolymer and its polyplexes had low cytotoxicity against the cells in vitro and caused no death of the mice. The results of this study indicate that 4-arm PEG-SSPHIS has high potential as a dual responsive gene delivery vector for cancer gene therapy.

  1. Effect of interleukin-18 gene polymorphisms on sensitization to wheat flour in bakery workers.

    Science.gov (United States)

    Kim, Seung-Hyun; Hur, Gyu-Young; Jin, Hyun Jung; Choi, Hyunna; Park, Hae-Sim

    2012-04-01

    Lower respiratory symptoms in bakery workers may be induced by wheat flour and endotoxins. We hypothesized that endotoxins from wheat flour may stimulate innate immunity and that interleukin-18 (IL-18) gene polymorphisms may affect their regulatory role in innate immune responses to endotoxins. To investigate the genetic contribution of IL-18 to sensitization to wheat flour, we performed a genetic association study of IL-18 in Korean bakery workers. A total of 373 bakery workers undertook a questionnaire regarding work-related symptoms. Skin prick tests with common and occupational allergens were performed and specific antibodies to wheat flour were measured by ELISA. Three polymorphisms of the IL-18 gene (-607A/C, -137G/C, 8674C/G) were genotyped, and the functional effects of the polymorphisms were analyzed using the luciferase reporter assay. Genotypes of -137G/C (GC or CC) and haplotype ht3 [ACC] showed a significant association with the rate of sensitization to wheat flour. Luciferase activity assay indicated ht3 [AC] as a low transcript haplotype. In conclusion, the regulatory role of IL-18 in lipopolysaccharide-induced responses in bakery workers may be affected by this polymorphism, thus contributing to the development of sensitization to wheat flour and work-related respiratory symptoms.

  2. Analysis of Separated Flow over Blocked Surface

    Directory of Open Access Journals (Sweden)

    Onur YEMENİCİ

    2013-04-01

    Full Text Available In this study, the separated flow over flat and blocked surfaces was investigated experimentally. Velocity and turbulence intensity measurements were carried out by a constanttemperature hot wire anemometer and static pressure measurements by a micro-manometer. The flow separations and reattachments were occurred before the first block, on the first block, between blocks and after the last block, and the presence of the blocks significantly increased the turbulent intensity

  3. Various semiclassical limits of torus conformal blocks

    Energy Technology Data Exchange (ETDEWEB)

    Alkalaev, Konstantin [I.E. Tamm Department of Theoretical Physics, P.N. Lebedev Physical Institute,Leninsky ave. 53, Moscow, 119991 (Russian Federation); Department of General and Applied Physics, Moscow Institute of Physics and Technology,Institutskiy per. 7, Dolgoprudnyi, Moscow region, 141700 (Russian Federation); Geiko, Roman [Mathematics Department, National Research University Higher School of Economics,Usacheva str. 6, Moscow, 119048 (Russian Federation); Rappoport, Vladimir [I.E. Tamm Department of Theoretical Physics, P.N. Lebedev Physical Institute,Leninsky ave. 53, Moscow, 119991 (Russian Federation); Department of Quantum Physics, Institute for Information Transmission Problems,Bolshoy Karetny per. 19, Moscow, 127994 (Russian Federation)

    2017-04-12

    We study four types of one-point torus blocks arising in the large central charge regime. There are the global block, the light block, the heavy-light block, and the linearized classical block, according to different regimes of conformal dimensions. It is shown that the blocks are not independent being connected to each other by various links. We find that the global, light, and heavy-light blocks correspond to three different contractions of the Virasoro algebra. Also, we formulate the c-recursive representation of the one-point torus blocks which is relevant in the semiclassical approximation.

  4. n-Butanol extract from Folium isatidis inhibits lipopolysaccharide-induced inflammatory cytokine production in macrophages and protects mice against lipopolysaccharide-induced endotoxic shock

    Directory of Open Access Journals (Sweden)

    Jiang LL

    2015-10-01

    Full Text Available Lili Jiang,1 Yili Lu,1 Jiahui Jin,1 Lili Dong,1 Fengli Xu,1 Shuangshuang Chen,1 Zhanyue Wang,2 Guang Liang,2 Xiaoou Shan11Department of Pediatrics, The Second Affiliated Hospital, 2Chemical Biology Research Center at The School of Pharmacy, Wenzhou Medical University, Wenzhou, Zhejiang, People’s Republic of ChinaAbstract: Sepsis, which is caused by severe infection, is an important cause of mortality, but effective clinical treatment against sepsis is extremely limited. As the main component of the outer membrane of Gram-negative bacteria, lipopolysaccharide (LPS plays a major role in inflammatory responses. Studies have shown beneficial pharmacological effects for Folium isatidis. The present study further illuminated the effects of n-butanol extract from Folium isatidis in LPS-induced septic shock and identified the main active chemical components. Our study showed that pretreatment with n-butanol extract from Folium isatidis not only significantly inhibited LPS-induced tumor necrosis factor-α and interleukin-6 production but also markedly and dose dependently enhanced the recruitment of MyD88, the phosphorylation of extracellular signal-regulated kinase, and the degradation of IκB-α. Additionally, the extract exhibited dramatic protective effects against lung injury and death in mice with septic shock. Eight main active compounds were identified, including organic acids, glycoside, indolinones, and flavonoids. These findings provide a perspective on the respiratory protection offered by n-butanol extract from Folium isatidis in LPS-induced sepsis and outline a novel therapeutic strategy for the treatment of sepsis.Keywords: Folium isatidis, sepsis, inflammatory cytokine

  5. Formation and structural properties of multi-block copolymer vesicles

    Science.gov (United States)

    Wang, Rong; Ma, Shiying

    2014-03-01

    Due to the unique structure, vesicles have attracted considerable attention for their potential applications, such as gene and drug delivery, microcapsules, nanoreactors, cell membrane mimetic, synthetic organelles, etc. By using dissipative particle dynamics, we studied the self-assembly of amphiphilic multi-block copolymer. The phase diagram was constructed by varying the interaction parameters and the composition of the block copolymers. The results show that the vesicles are stable in a large region which is different from the diblock copolymer or triblock copolymer. The structural properties of vesicles can be controlled by varying the interaction parameters and the length of the hydrophobic block. The relationship between the hydrophilic and hydrophobic block length vs the aqueous cavity size and vesicle size are revealed. The copolymers with shorter hydrophobic blocks length or the higher hydrophilicity are more likely to form vesicles with larger aqueous cavity size and vesicle size as well as thinner wall thickness. However, the increase in hydrophobic-block length results to form vesicles with smaller aqueous cavity size and larger vesicle size. Acknowledgments. This work has been supported by NNSFC (No. 21074053) and NBRPC (No. 2010CB923303).

  6. TMPyP4 porphyrin distorts RNA G-quadruplex structures of the disease-associated r(GGGGCC)n repeat of the C9orf72 gene and blocks interaction of RNA-binding proteins.

    Science.gov (United States)

    Zamiri, Bita; Reddy, Kaalak; Macgregor, Robert B; Pearson, Christopher E

    2014-02-21

    Certain DNA and RNA sequences can form G-quadruplexes, which can affect genetic instability, promoter activity, RNA splicing, RNA stability, and neurite mRNA localization. Amyotrophic lateral sclerosis and frontotemporal dementia can be caused by expansion of a (GGGGCC)n repeat in the C9orf72 gene. Mutant r(GGGGCC)n- and r(GGCCCC)n-containing transcripts aggregate in nuclear foci, possibly sequestering repeat-binding proteins such as ASF/SF2 and hnRNPA1, suggesting a toxic RNA pathogenesis, as occurs in myotonic dystrophy. Furthermore, the C9orf72 repeat RNA was recently demonstrated to undergo the noncanonical repeat-associated non-AUG translation (RAN translation) into pathologic dipeptide repeats in patient brains, a process that is thought to depend upon RNA structure. We previously demonstrated that the r(GGGGCC)n RNA forms repeat tract length-dependent G-quadruplex structures that bind the ASF/SF2 protein. Here we show that the cationic porphyrin (5,10,15,20-tetra(N-methyl-4-pyridyl) porphyrin (TMPyP4)), which can bind some G-quadruplex-forming sequences, can bind and distort the G-quadruplex formed by r(GGGGCC)8, and this ablates the interaction of either hnRNPA1 or ASF/SF2 with the repeat. These findings provide proof of concept that nucleic acid binding small molecules, such as TMPyP4, can distort the secondary structure of the C9orf72 repeat, which may beneficially disrupt protein interactions, which may ablate either protein sequestration and/or RAN translation into potentially toxic dipeptides. Disruption of secondary structure formation of the C9orf72 RNA repeats may be a viable therapeutic avenue, as well as a means to test the role of RNA structure upon RAN translation.

  7. Radial Coordinates for Conformal Blocks

    CERN Document Server

    Hogervorst, Matthijs

    2013-01-01

    We develop the theory of conformal blocks in CFT_d expressing them as power series with Gegenbauer polynomial coefficients. Such series have a clear physical meaning when the conformal block is analyzed in radial quantization: individual terms describe contributions of descendants of a given spin. Convergence of these series can be optimized by a judicious choice of the radial quantization origin. We argue that the best choice is to insert the operators symmetrically. We analyze in detail the resulting "rho-series" and show that it converges much more rapidly than for the commonly used variable z. We discuss how these conformal block representations can be used in the conformal bootstrap. In particular, we use them to derive analytically some bootstrap bounds whose existence was previously found numerically.

  8. Diversity Gain through Antenna Blocking

    Directory of Open Access Journals (Sweden)

    V. Dehghanian

    2012-01-01

    Full Text Available As part of the typical usage mode, interaction between a handheld receiver antenna and the operator's RF absorbing body and nearby objects is known to generate variability in antenna radiation characteristics through blocking and pattern changes. It is counterintuitive that random variations in blocking can result in diversity gain of practical applicability. This diversity gain is quantified from a theoretical and experimental perspective. Measurements carried out at 1947.5 MHz verify the theoretical predictions, and a diversity gain of 3.1 dB was measured through antenna blocking and based on the utilized measurement setup. The diversity gain can be exploited to enhance signal detectability of handheld receivers based on a single antenna in indoor multipath environments.

  9. Cryptanalysis of Selected Block Ciphers

    DEFF Research Database (Denmark)

    Alkhzaimi, Hoda A.

    , pseudorandom number generators, and authenticated encryption designs. For this reason a multitude of initiatives over the years has been established to provide a secure and sound designs for block ciphers as in the calls for Data Encryption Standard (DES) and Advanced Encryption Standard (AES), lightweight...... ciphers initiatives, and the Competition for Authenticated Encryption: Security, Applicability, and Robustness (CAESAR). In this thesis, we first present cryptanalytic results on different ciphers. We propose attack named the Invariant Subspace Attack. It is utilized to break the full block cipher...... on the family of lightweight block cipher SIMON that was published by the U.S National Security Agency (NSA). The ciphers are developed with optimization towards both hardware and software in mind. While the specification paper discusses design requirements and performance of the presented lightweight ciphers...

  10. Climatological features of blocking anticyclones

    International Nuclear Information System (INIS)

    Lupo, A.R.; Smith, P.J.; Oglesby, R.J.

    1994-01-01

    Several climatological studies have been previously performed using large observational data sets (i.e., 10 years or longer) in order to determine the predominant characteristics of blocking anticyclones, including favored development regions, duration, preferred seasonal occurrence, and frequency of occurrence. These studies have shown that blocking anticyclones occur most frequently from October to April over the eastern Atlantic and Pacific oceans downstream from both the North American and Asian continental regions and the storm track regions to the east of these continents. Some studies have also revealed the presence of a third region block formation in western Russia near 40 degrees E which is associated with another storm track region over the Mediterranean and western Asia

  11. Projectors, shadows, and conformal blocks

    Energy Technology Data Exchange (ETDEWEB)

    Simmons-Duffin, David [Jefferson Physical Laboratory, Harvard University,Cambridge, MA 02138 (United States)

    2014-04-24

    We introduce a method for computing conformal blocks of operators in arbitrary Lorentz representations in any spacetime dimension, making it possible to apply bootstrap techniques to operators with spin. The key idea is to implement the “shadow formalism' of Ferrara, Gatto, Grillo, and Parisi in a setting where conformal invariance is manifest. Conformal blocks in d-dimensions can be expressed as integrals over the projective null-cone in the “embedding space' ℝ{sup d+1,1}. Taking care with their analytic structure, these integrals can be evaluated in great generality, reducing the computation of conformal blocks to a bookkeeping exercise. To facilitate calculations in four-dimensional CFTs, we introduce techniques for writing down conformally-invariant correlators using auxiliary twistor variables, and demonstrate their use in some simple examples.

  12. Projectors, Shadows, and Conformal Blocks

    OpenAIRE

    Simmons-Duffin, David

    2012-01-01

    We introduce a method for computing conformal blocks of operators in arbitrary Lorentz representations in any spacetime dimension, making it possible to apply bootstrap techniques to operators with spin. The key idea is to implement the “shadow formalism” of Ferrara, Gatto, Grillo, and Parisi in a setting where conformal invariance is manifest. Conformal blocks in d -dimensions can be expressed as integrals over the projective null-cone in the “embedding space” $ \\mathbb{R} $ d +1,1 . Taking ...

  13. Mitogen activated protein kinases blockade improves lipopolysaccharide-induced ileal motor disturbances El bloqueo de las proteínas cinasas activadas por mitógenos mejora las alteraciones motoras inducidas por el lipopolisacárido en íleon

    Directory of Open Access Journals (Sweden)

    Sergio Gonzalo

    2012-06-01

    Full Text Available Background: several diseases such as sepsis can affect the ileum. Lipopolysaccharide (LPS, an endotoxin present in the cell wall of gram negative bacteria, is a causative agent of sepsis. Objectives: the aims of this study were: a to investigate the role of mitogen activated protein kinases (MAPKs in the effect of LPS on the acetylcholine-induced contractions of rabbit ileum; and b to study the localization of MAPKs in the ileum. Material and methods: ileal contractility was studied in an organ bath and MAPKs were localized by immunohistochemistry. Results: acetylcholine-induced contractions decreased with LPS. SB203580, SP600125 and U0126 blocked the effect of LPS on the acetylcholine-induced contractions. Phosphorylated p38 and ERK were detected in neurons of myenteric plexus and phosphorylated p38 and JNK in smooth muscle cells of ileum. Conclusion: we can suggest that p38, JNK, and ERK MAPKs are involved in the mechanism of action of LPS in the ileum.Introducción: varias enfermedades como la sepsis pueden afectar al íleon. El lipopolisacárido (LPS, una endotoxina presente en la pared celular de las bacterias gram-negativas, es un agente causal de la sepsis. Objetivos: los objetivos del presente estudio fueron: a investigar el papel de las proteína cinasas activadas por mitógenos (MAPKs en los efectos del LPS en las contracciones inducidas por acetilcolina en el íleon de conejo; y b estudiar la localización de las MAPKs en el íleon. Material y métodos: la contractilidad ileal se estudió en un baño de órganos y las MAPKs se localizaron mediante inmunohistoquímica. Resultados: el LPS disminuyó las contracciones inducidas por acetilcolina. El SB203580, el SP600125 y el U0126 bloquearon los efectos del LPS sobre las contracciones inducidas por acetilcolina. La p38 y la ERK fosforiladas se detectaron en las neuronas del plexo mientérico y la p38 y la JNK fosforiladas en las células del músculo liso del íleon. Conclusi

  14. Main-chain supramolecular block copolymers.

    Science.gov (United States)

    Yang, Si Kyung; Ambade, Ashootosh V; Weck, Marcus

    2011-01-01

    Block copolymers are key building blocks for a variety of applications ranging from electronic devices to drug delivery. The material properties of block copolymers can be tuned and potentially improved by introducing noncovalent interactions in place of covalent linkages between polymeric blocks resulting in the formation of supramolecular block copolymers. Such materials combine the microphase separation behavior inherent to block copolymers with the responsiveness of supramolecular materials thereby affording dynamic and reversible materials. This tutorial review covers recent advances in main-chain supramolecular block copolymers and describes the design principles, synthetic approaches, advantages, and potential applications.

  15. Building Blocks for Personal Brands

    Science.gov (United States)

    Thomas, Lisa Carlucci

    2011-01-01

    In this article, the author discusses the four essential building blocks for personal brands: (1) name; (2) message; (3) channels; and (4) bridges. However, outstanding building materials can only take a person so far. The author emphasizes that vision, determination, faith, a sense of humor, and humility are also required.

  16. Control rod removal blocking device

    International Nuclear Information System (INIS)

    Yoshioka, Ritsuo.

    1981-01-01

    Purpose: To prevent excess power increase resulted from erroneous control rod removal during high power operation in BWR type reactor by decreasing the continuous removal enabling distance for the control rods along with increase in the reactor power where the reactor power is greater than a predetermined level. Constitution: When control rod selection signals are supplied from a control unit to a control rod removal blocking device, the blocking device judges whether the reactor core power is greater than a predetermined value A or not, using reactor core power signals outputted from an average power monitor. Where the reactor core power exceeds the predetermined value A and if the reactor core power is relatively low, a large continuous removal enabling distance N 1 is calculated in the blocking device to allow the continuous removal as far as the notch N 1 . The continuous removal enabling distance is shortened as the reactor core power increases and the removal is blocked, for example, at notch N 2 . While on the other hand, if the reactor core power is below the predetermined value A, both of the notchwise removal and the continuous removal are enabled. (Seki, T.)

  17. First Degree Pacemaker Exit Block

    Directory of Open Access Journals (Sweden)

    Johnson Francis

    2016-10-01

    Full Text Available Usually atrial and ventricular depolarizations follow soon after the pacemaker stimulus (spike on the ECG. But there can be an exit block due to fibrosis at the electrode - tissue interface at the lead tip. This can increase the delay between the spike and atrial or ventricular depolarization.

  18. Vagal Blocking for Obesity Control

    DEFF Research Database (Denmark)

    Johannessen, Helene; Revesz, David; Kodama, Yosuke

    2017-01-01

    BACKGROUND: Recently, the US FDA has approved "vagal blocking therapy or vBLoc® therapy" as a new treatment for obesity. The aim of the present study was to study the mechanism-of-action of "VBLOC" in rat models. METHODS: Rats were implanted with VBLOC, an intra-abdominal electrical device...

  19. Thermo-responsive block copolymers

    NARCIS (Netherlands)

    Mocan Cetintas, Merve

    2017-01-01

    Block copolymers (BCPs) are remarkable materials because of their self-assembly behavior into nano-sized regular structures and high tunable properties. BCPs are in used various applications such as surfactants, nanolithography, biomedicine and nanoporous membranes. In these thesis, we aimed to

  20. Scintigraphic visualization of 'Blocking' thyroid

    International Nuclear Information System (INIS)

    Simeonova, A.; Kostadinova, I.

    2006-01-01

    Full text: An important problem in nuclear endocrinology is 'blocking' of thyroid gland, which necessitates postpone of the investigation, adverse clinical effect of stopping medications and a delay of making diagnosis. The aim of the study was to introduce and to determine the clinical value of the scintigraphy with 99mTc-MIBI in patients (Pts) with 'blocked thyroid'. In 365 Pts (aged 38-75 years), indicated for a thyroid scintigraphy after proper preparation, an investigation was performed with 74 MBq 99mTc-pertechnetate, 20 min. p.i. In 14 of them (3.8%), the thyroid was 'blocked' and additional scintigraphy was done with 370-555 MBq 99mTc-MIBI, 15 and 120 min.p.i. It was estimated that in all Pts there was a visualization of thyroid. In 1 of them, a large 'hot' nodule was visualized in the early and late image. Later on a differentiated thyroid carcinoma was proved histologically. In the rest of the patients 'cold' nodules with different size were visualized, eventually as a result of cysts. As a conclusion we consider, that a scintigraphy with 99mTc-MIBI is a useful tool in Pts with 'blocked' thyroid. In addition an evaluation of the thyroid nodule could be done and therefore- a recommendation for therapy

  1. Genes and Gene Therapy

    Science.gov (United States)

    ... correctly, a child can have a genetic disorder. Gene therapy is an experimental technique that uses genes to ... or prevent disease. The most common form of gene therapy involves inserting a normal gene to replace an ...

  2. Aconitum pseudo-laeve var. erectum Inhibits Receptor Activator of Nuclear Factor Kappa-B Ligand-Induced Osteoclastogenesis via the c-Fos/nuclear Factor of Activated T-Cells, Cytoplasmic 1 Signaling Pathway and Prevents Lipopolysaccharide-Induced Bone Loss in Mice

    Directory of Open Access Journals (Sweden)

    Jong Min Baek

    2014-08-01

    Full Text Available Aconitum pseudo-laeve var. erectum (APE has been widely shown in herbal medicine to have a therapeutic effect on inflammatory conditions. However, there has been no evidence on whether the extract of APE is involved in the biological bone metabolism process, particularly osteoclast-mediated bone resorption. In this study, we confirmed that the administration of APE could restore normal skeletal conditions in a murine model of lipopolysaccharide (LPS-induced bone loss via a decrease in the receptor activator of nuclear factor kappa-B ligand (RANKL/osteoprotegerin (OPG ratio and osteoclast number. We then investigated the effect of APE on the RANKL-induced formation and function of osteoclasts to elucidate its underlying molecular mechanisms. APE suppressed the formation of tartrate-resistant acid phosphatase (TRAP-positive cells, as well as the bone-resorbing activity of mature osteoclasts. Furthermore, APE attenuated nuclear factor of activated T-cells, cytoplasmic 1 (NFATc1 and c-Fos without affecting any early signal pathway of osteoclastogenesis. Subsequently, APE significantly downregulated the expression of various genes exclusively expressed in osteoclasts. These results demonstrate that APE restores LPS-induced bone loss through a decrease of the serum RANKL/OPG ratio, and inhibits osteoclast differentiation and function, suggesting the promise of APE as a potential cure for various osteoclast-associated bone diseases.

  3. Congenital and childhood atrioventricular blocks: pathophysiology and contemporary management.

    Science.gov (United States)

    Baruteau, Alban-Elouen; Pass, Robert H; Thambo, Jean-Benoit; Behaghel, Albin; Le Pennec, Solène; Perdreau, Elodie; Combes, Nicolas; Liberman, Leonardo; McLeod, Christopher J

    2016-09-01

    Atrioventricular block is classified as congenital if diagnosed in utero, at birth, or within the first month of life. The pathophysiological process is believed to be due to immune-mediated injury of the conduction system, which occurs as a result of transplacental passage of maternal anti-SSA/Ro-SSB/La antibodies. Childhood atrioventricular block is therefore diagnosed between the first month and the 18th year of life. Genetic variants in multiple genes have been described to date in the pathogenesis of inherited progressive cardiac conduction disorders. Indications and techniques of cardiac pacing have also evolved to allow safe permanent cardiac pacing in almost all patients, including those with structural heart abnormalities. Early diagnosis and appropriate management are critical in many cases in order to prevent sudden death, and this review critically assesses our current understanding of the pathogenetic mechanisms, clinical course, and optimal management of congenital and childhood AV block. • Prevalence of congenital heart block of 1 per 15,000 to 20,000 live births. AV block is defined as congenital if diagnosed in utero, at birth, or within the first month of life, whereas childhood AV block is diagnosed between the first month and the 18th year of life. As a result of several different etiologies, congenital and childhood atrioventricular block may occur in an entirely structurally normal heart or in association with concomitant congenital heart disease. Cardiac pacing is indicated in symptomatic patients and has several prophylactic indications in asymptomatic patients to prevent sudden death. • Autoimmune, congenital AV block is associated with a high neonatal mortality rate and development of dilated cardiomyopathy in 5 to 30 % cases. What is New: • Several genes including SCN5A have been implicated in autosomal dominant forms of familial progressive cardiac conduction disorders. • Leadless pacemaker technology and gene therapy for

  4. Unrelated donors selected prospectively by block-matching have superior bone marrow transplant outcome.

    Science.gov (United States)

    Witt, C; Sayer, D; Trimboli, F; Saw, M; Herrmann, R; Cannell, P; Baker, D; Christiansen, F

    2000-02-01

    Previous retrospective studies have demonstrated improved outcome in patients whose donors were matched for non-HLA markers in the MHC as well as for HLA genes. Forty patients receiving transplants from unrelated donors were typed prospectively for HLA and non-HLA markers. Non-HLA markers near HLA-B (beta-block markers) and in the DRB1 introns (delta-block markers) were used to assess MHC match between donors and recipient. Patients whose donors were matched at the beta- and delta-blocks had improved event free survival (63%) compared to patients whose donors were mismatched at one or both blocks (25%) (p matched at the beta-block had significantly less severe acute graft versus host disease (p block matching was correlated with HLA matching as determined by DNA sequencing. Beta-block matching was highly correlated with matching for exons 2 and 3 of HLA-B but less so for HLA-C. Delta-block matching was highly correlated with matching for exon 2 of HLA DRB1. It is concluded that matching for non-HLA markers in the MHC improves matching for HLA genes. Further studies are required to determine whether matching for non-HLA markers improves outcome to a greater extent than matching for the HLA genes alone.

  5. 31 CFR 585.216 - Expenses of maintaining blocked property; liquidation into blocked account.

    Science.gov (United States)

    2010-07-01

    ... property; liquidation into blocked account. 585.216 Section 585.216 Money and Finance: Treasury Regulations... blocked property; liquidation into blocked account. (a) Except as otherwise authorized, and... expenses incident to the blocking and maintenance of property blocked pursuant to § 585.201 or § 585.215(a...

  6. On the Eigenvalues and Eigenvectors of Block Triangular Preconditioned Block Matrices

    KAUST Repository

    Pestana, Jennifer

    2014-01-01

    Block lower triangular matrices and block upper triangular matrices are popular preconditioners for 2×2 block matrices. In this note we show that a block lower triangular preconditioner gives the same spectrum as a block upper triangular preconditioner and that the eigenvectors of the two preconditioned matrices are related. © 2014 Society for Industrial and Applied Mathematics.

  7. MicroRNA mimicry blocks pulmonary fibrosis

    Science.gov (United States)

    Montgomery, Rusty L; Yu, Guoying; Latimer, Paul A; Stack, Christianna; Robinson, Kathryn; Dalby, Christina M; Kaminski, Naftali; van Rooij, Eva

    2014-01-01

    Over the last decade, great enthusiasm has evolved for microRNA (miRNA) therapeutics. Part of the excitement stems from the fact that a miRNA often regulates numerous related mRNAs. As such, modulation of a single miRNA allows for parallel regulation of multiple genes involved in a particular disease. While many studies have shown therapeutic efficacy using miRNA inhibitors, efforts to restore or increase the function of a miRNA have been lagging behind. The miR-29 family has gained a lot of attention for its clear function in tissue fibrosis. This fibroblast-enriched miRNA family is downregulated in fibrotic diseases which induces a coordinate increase of many extracellular matrix genes. Here, we show that intravenous injection of synthetic RNA duplexes can increase miR-29 levels in vivo for several days. Moreover, therapeutic delivery of these miR-29 mimics during bleomycin-induced pulmonary fibrosis restores endogenous miR-29 function whereby decreasing collagen expression and blocking and reversing pulmonary fibrosis. Our data support the feasibility of using miRNA mimics to therapeutically increase miRNAs and indicate miR-29 to be a potent therapeutic miRNA for treating pulmonary fibrosis. PMID:25239947

  8. Calcitonin gene-related peptide promotes the wound healing of human bronchial epithelial cells via PKC and MAPK pathways.

    Science.gov (United States)

    Zhou, Yong; Zhang, Min; Sun, Guo-Ying; Liu, Yong-Ping; Ran, Wen-Zhuo; Peng, Li; Guan, Cha-Xiang

    2013-06-10

    Calcitonin gene-related peptide (CGRP) is a 37-amino acid neuropeptide derived from the calcitonin gene. CGRP is widely distributed in the central and peripheral neuronal systems. In the lung, CGRP could modulate dendritic cell function, stimulate proliferation of alveolar epithelial cells and mediate lung injury in mice. In this study, we investigated the effect of CGRP on the wound healing of human bronchial epithelial cells (HBECs) in vitro. The results showed that CGRP accelerated the recovery of wound area of monolayer HBECs in a dose-dependent manner. CGRP inhibited the lipopolysaccharide-induced apoptosis in HBECs. The percentage of S phase and G2/M phase was increased in HBECs after CGRP treatment. CGRP upregulated the expression of Ki67 in a dose-dependent manner. Some pathway inhibitors were used to investigate the signal pathway in which CGRP was involved. We found out that PKC pathway inhibitor (H-7) and MAPK pathway inhibitor (PD98059) could partially attenuate the effect of CGRP, which indicated that CGRP might promote the wound healing of HBECs via PKC and/or MAPK dependent pathway by accelerating migration and proliferation, and inhibiting apoptosis. Copyright © 2013 Elsevier B.V. All rights reserved.

  9. Block-Matching Based Multifocus Image Fusion

    Directory of Open Access Journals (Sweden)

    Feng Zhu

    2015-01-01

    Full Text Available A new multifocus image fusion method is proposed. Two image blocks are selected by sliding the window from the two source images at the same position, discrete cosine transform (DCT is implemented, respectively, on these two blocks, and the alternating component (AC energy of these blocks is then calculated to decide which is the well-focused one. In addition, block matching is used to determine a group of image blocks that are all similar to the well-focused reference block. Finally, all the blocks are returned to their original positions through weighted average. The weight is decided with the AC energy of the well-focused block. Experimental results demonstrate that, unlike other spatial methods, the proposed method effectively avoids block artifacts. The proposed method also significantly improves the objective evaluation results, which are obtained by some transform domain methods.

  10. Blocking incidental frustration during bargaining.

    Science.gov (United States)

    Vargas, Maria Esperanza S; Brown, Anna-Leigh; Durkee, Cassandra M; Sim, Hoeun

    2018-02-08

    The current study examined the effects of an intervention aimed at blocking the transfer of frustration from a previous experience (i.e. recall task) to a subsequent and unrelated task (i.e. ultimatum bargaining task). Participants who went through the intervention were more likely to accept unfair offers in the ultimatum bargaining task than those who did not go through the intervention. These results show that participants who were blocked from transferring their feelings of frustration from the recall task to the subsequent bargaining task (no-transfer condition) more likely accepted unfair offers than those who inadvertently transferred their feelings of frustration (transfer condition). The effect of conditions on accept-reject decisions in the ultimatum bargaining was mediated by reported feelings of frustration.

  11. UAV PHOTOGRAMMETRY: BLOCK TRIANGULATION COMPARISONS

    Directory of Open Access Journals (Sweden)

    R. Gini

    2013-08-01

    Full Text Available UAVs systems represent a flexible technology able to collect a big amount of high resolution information, both for metric and interpretation uses. In the frame of experimental tests carried out at Dept. ICA of Politecnico di Milano to validate vector-sensor systems and to assess metric accuracies of images acquired by UAVs, a block of photos taken by a fixed wing system is triangulated with several software. The test field is a rural area included in an Italian Park ("Parco Adda Nord", useful to study flight and imagery performances on buildings, roads, cultivated and uncultivated vegetation. The UAV SenseFly, equipped with a camera Canon Ixus 220HS, flew autonomously over the area at a height of 130 m yielding a block of 49 images divided in 5 strips. Sixteen pre-signalized Ground Control Points, surveyed in the area through GPS (NRTK survey, allowed the referencing of the block and accuracy analyses. Approximate values for exterior orientation parameters (positions and attitudes were recorded by the flight control system. The block was processed with several software: Erdas-LPS, EyeDEA (Univ. of Parma, Agisoft Photoscan, Pix4UAV, in assisted or automatic way. Results comparisons are given in terms of differences among digital surface models, differences in orientation parameters and accuracies, when available. Moreover, image and ground point coordinates obtained by the various software were independently used as initial values in a comparative adjustment made by scientific in-house software, which can apply constraints to evaluate the effectiveness of different methods of point extraction and accuracies on ground check points.

  12. Carrying-over effects of GVBD blocking on post-blocking meiotic progression of oocytes: species difference and the signaling pathway leading to MPF activation.

    Directory of Open Access Journals (Sweden)

    Guang-Zhong Jiao

    Full Text Available Efforts to improve the quality of in vitro matured oocytes by blocking germinal vesicle breakdown (GVBD and allowing more time for ooplasmic maturation have achieved little due to a lack of knowledge on the molecular events during GVBD blocking. Such knowledge is also important for studies aimed at regulating gene expression in maturing oocytes prior to GVBD. We studied species difference and signaling pathways leading to the carrying-over effect of GVBD blocking on post-blocking meiotic progression (PBMP. Overall, GVBD-blocking with roscovitine decelerated PBMP of mouse oocytes but accelerated that of pig oocytes. During blocking culture, whereas cyclin B of pig oocytes increased continuously, that of mouse oocytes declined first and then increased slowly. In both species, (a whereas active CDC2A showed a dynamics similar to cyclin B, inactive CDC2A decreased continuously; (b when oocytes were blocked in blocking medium containing cycloheximide, PBMP was decelerated significantly while cyclin B and active CDC2A decreasing to the lowest level; (c whereas sodium vanadate in blocking medium reduced PBMP, epidermal growth factor (EGF in blocking medium accelerated PBMP significantly with no effect on cyclin B levels. In conclusion, the EGF signaling cascade accelerated PBMP by promoting the pre-MPF (M-phase-promoting factor to MPF conversion during GVBD blocking with roscovitine. The significant difference in PBMP observed between mouse and pig oocytes was caused by species difference in cyclin B dynamics during blocking culture as no species difference was observed in either pre-MPF to MPF conversion or the EGF signaling activity.

  13. Curcumin blocks interleukin-1 signaling in chondrosarcoma cells.

    Directory of Open Access Journals (Sweden)

    Thomas Kalinski

    Full Text Available Interleukin (IL-1 signaling plays an important role in inflammatory processes, but also in malignant processes. The essential downstream event in IL-1 signaling is the activation of nuclear factor (NF-κB, which leads to the expression of several genes that are involved in cell proliferation, invasion, angiogenesis and metastasis, among them VEGF-A. As microenvironment-derived IL-1β is required for invasion and angiogenesis in malignant tumors, also in chondrosarcomas, we investigated IL-1β-induced signal transduction and VEGF-A expression in C3842 and SW1353 chondrosarcoma cells. We additionally performed in vitro angiogenesis assays and NF-κB-related gene expression analyses. Curcumin is a substance which inhibits IL-1 signaling very early by preventing the recruitment of IL-1 receptor associated kinase (IRAK to the IL-1 receptor. We demonstrate that IL-1 signaling and VEGF-A expression are blocked by Curcumin in chondrosarcoma cells. We further show that Curcumin blocks IL-1β-induced angiogenesis and NF-κB-related gene expression. We suppose that IL-1 blockade is an additional treatment option in chondrosarcoma, either by Curcumin, its derivatives or other IL-1 blocking agents.

  14. [THE TECHNOLOGY "CELL BLOCK" IN CYTOLOGICAL PRACTICE].

    Science.gov (United States)

    Volchenko, N N; Borisova, O V; Baranova, I B

    2015-08-01

    The article presents summary information concerning application of "cell block" technology in cytological practice. The possibilities of implementation of various modern techniques (immune cytochemnical analysis. FISH, CISH, polymerase chain reaction) with application of "cell block" method are demonstrated. The original results of study of "cell block" technology made with gelatin, AgarCyto and Shadon Cyoblock set are presented. The diagnostic effectiveness of "cell block" technology and common cytological smear and also immune cytochemical analysis on samples of "cell block" technology and fluid cytology were compared. Actually application of "cell block" technology is necessary for ensuring preservation of cell elements for subsequent immune cytochemical and molecular genetic analysis.

  15. DNMT1-interacting RNAs block gene-specific DNA methylation

    Czech Academy of Sciences Publication Activity Database

    Di Ruscio, A.; Ebralidze, A.; Benoukraf, T.; Amabile, G.; Goff, L.A.; Terragni, J.; Figueroa, M.E.; Pontes, L.L.D.; Alberich-Jorda, Meritxell; Zhang, P.; Wu, M.C.; D´Alo, F.; Melnick, A.; Leone, G.; Ebralidze, K.K.; Pradhan, S.; Rinn, J.L.; Tenen, D.G.

    2013-01-01

    Roč. 503, č. 7476 (2013), s. 371-376 ISSN 0028-0836 R&D Projects: GA MŠk LK21307 Institutional support: RVO:68378050 Keywords : DNA methylation * non-coding RNA * DNMT1 Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 42.351, year: 2013

  16. Blocking device especially for circulating pumps

    International Nuclear Information System (INIS)

    Susil, J.; Vychodil, V.; Lorenc, P.

    1976-01-01

    The claim of the invention is a blocking device which blocks reverse flow occurring after the shutdown of circulating pumps, namely in the operation of nuclear power plants or in pumps with a high delivery head. (F.M.)

  17. Demographic Data - MDC_BlockGroup

    Data.gov (United States)

    NSGIC Local Govt | GIS Inventory — A polygon feature class of Miami-Dade County Census 2000 Block Groups. A census Block Group is a statistical subdivision of a census Tract consisting of a cluster of...

  18. Used, Blocking and Sleeping Patents

    DEFF Research Database (Denmark)

    Torrisi, Salvatore; Gambardella, Alfonso; Giuri, Paola

    2016-01-01

    patents are being utilized. A substantial share of patents is neither used internally nor for market transactions, which confirms the importance of strategic patenting and inefficiency in the management of intellectual property. We investigate different types of unused patents—unused blocking patents...... and sleeping patents. We also examine the association between used and unused patents and their characteristics such as family size, scope, generality and overlapping claims, technology area, type of applicant, and the competitive environment from where these patents originate. We discuss our results...

  19. Large block test status report

    International Nuclear Information System (INIS)

    Wilder, D.G.; Lin, W.; Blair, S.C.

    1997-01-01

    This report is intended to serve as a status report, which essentially transmits the data that have been collected to date on the Large Block Test (LBT). The analyses of data will be performed during FY98, and then a complete report will be prepared. This status report includes introductory material that is not needed merely to transmit data but is available at this time and therefore included. As such, this status report will serve as the template for the future report, and the information is thus preserved

  20. Micellization and Dynamics of a Block Copolymer

    DEFF Research Database (Denmark)

    Hvidt, Søren

    2006-01-01

    Triblock copolymers of the type EPE, where E and P denote ethylene oxide and propylene oxide blocks, respectively, are industrially important copolymers often called Pluronics or Poloxamers. EPE copolymers form micelles with a core of P blocks and different micellar shapes depending on block leng...

  1. 31 CFR 515.319 - Blocked account.

    Science.gov (United States)

    2010-07-01

    ... 31 Money and Finance: Treasury 3 2010-07-01 2010-07-01 false Blocked account. 515.319 Section 515... § 515.319 Blocked account. The term blocked account shall mean an account in which any designated national has an interest, with respect to which account payments, transfers or withdrawals or other...

  2. 31 CFR 500.319 - Blocked account.

    Science.gov (United States)

    2010-07-01

    ... 31 Money and Finance: Treasury 3 2010-07-01 2010-07-01 false Blocked account. 500.319 Section 500... § 500.319 Blocked account. The term blocked account shall mean an account in which any designated national has an interest, with respect to which account payments, transfers or withdrawals of other...

  3. Bullet-Block Science Video Puzzle

    Science.gov (United States)

    Shakur, Asif

    2015-01-01

    A science video blog, which has gone viral, shows a wooden block shot by a vertically aimed rifle. The video shows that the block hit dead center goes exactly as high as the one shot off-center. (Fig. 1). The puzzle is that the block shot off-center carries rotational kinetic energy in addition to the gravitational potential energy. This leads a…

  4. 21 CFR 882.5070 - Bite block.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Bite block. 882.5070 Section 882.5070 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES NEUROLOGICAL DEVICES Neurological Therapeutic Devices § 882.5070 Bite block. (a) Identification. A bite block...

  5. Escitalopram block of hERG potassium channels.

    Science.gov (United States)

    Chae, Yun Ju; Jeon, Ji Hyun; Lee, Hong Joon; Kim, In-Beom; Choi, Jin-Sung; Sung, Ki-Wug; Hahn, Sang June

    2014-01-01

    Escitalopram, a selective serotonin reuptake inhibitor, is the pharmacologically active S-enantiomer of the racemic mixture of RS-citalopram and is widely used in the treatment of depression. The effects of escitalopram and citalopram on the human ether-a-go-go-related gene (hERG) channels expressed in human embryonic kidney cells were investigated using voltage-clamp and Western blot analyses. Both drugs blocked hERG currents in a concentration-dependent manner with an IC50 value of 2.6 μM for escitalopram and an IC50 value of 3.2 μM for citalopram. The blocking of hERG by escitalopram was voltage-dependent, with a steep increase across the voltage range of channel activation. However, voltage independence was observed over the full range of activation. The blocking by escitalopram was frequency dependent. A rapid application of escitalopram induced a rapid and reversible blocking of the tail current of hERG. The extent of the blocking by escitalopram during the depolarizing pulse was less than that during the repolarizing pulse, suggesting that escitalopram has a high affinity for the open state of the hERG channel, with a relatively lower affinity for the inactivated state. Both escitalopram and citalopram produced a reduction of hERG channel protein trafficking to the plasma membrane but did not affect the short-term internalization of the hERG channel. These results suggest that escitalopram blocked hERG currents at a supratherapeutic concentration and that it did so by preferentially binding to both the open and the inactivated states of the channels and by inhibiting the trafficking of hERG channel protein to the plasma membrane.

  6. Isostatic compression of buffer blocks. Middle scale

    International Nuclear Information System (INIS)

    Ritola, J.; Pyy, E.

    2012-01-01

    Manufacturing of buffer components using isostatic compression method has been studied in small scale in 2008 (Laaksonen 2010). These tests included manufacturing of buffer blocks using different bentonite materials and different compression pressures. Isostatic mould technology was also tested, along with different methods to fill the mould, such as vibration and partial vacuum, as well as a stepwise compression of the blocks. The development of manufacturing techniques has continued with small-scale (30 %) blocks (diameter 600 mm) in 2009. This was done in a separate project: Isostatic compression, manufacturing and testing of small scale (D = 600 mm) buffer blocks. The research on the isostatic compression method continued in 2010 in a project aimed to test and examine the isostatic manufacturing process of buffer blocks at 70 % scale (block diameter 1200 to 1300 mm), and the aim was to continue in 2011 with full-scale blocks (diameter 1700 mm). A total of nine bentonite blocks were manufactured at 70 % scale, of which four were ring-shaped and the rest were cylindrical. It is currently not possible to manufacture full-scale blocks, because there is no sufficiently large isostatic press available. However, such a compression unit is expected to be possible to use in the near future. The test results of bentonite blocks, produced with an isostatic pressing method at different presses and at different sizes, suggest that the technical characteristics, for example bulk density and strength values, are somewhat independent of the size of the block, and that the blocks have fairly homogenous characteristics. Water content and compression pressure are the two most important properties determining the characteristics of the compressed blocks. By adjusting these two properties it is fairly easy to produce blocks at a desired density. The commonly used compression pressure in the manufacturing of bentonite blocks is 100 MPa, which compresses bentonite to approximately

  7. Coastal protection using topological interlocking blocks

    Science.gov (United States)

    Pasternak, Elena; Dyskin, Arcady; Pattiaratchi, Charitha; Pelinovsky, Efim

    2013-04-01

    The coastal protection systems mainly rely on the self-weight of armour blocks to ensure its stability. We propose a system of interlocking armour blocks, which form plate-shape assemblies. The shape and the position of the blocks are chosen in such a way as to impose kinematic constraints that prevent the blocks from being removed from the assembly. The topological interlocking shapes include simple convex blocks such as platonic solids, the most practical being tetrahedra, cubes and octahedra. Another class of topological interlocking blocks is so-called osteomorphic blocks, which form plate-like assemblies tolerant to random block removal (almost 25% of blocks need to be removed for the assembly to loose integrity). Both classes require peripheral constraint, which can be provided either by the weight of the blocks or post-tensioned internal cables. The interlocking assemblies provide increased stability because lifting one block involves lifting (and bending) the whole assembly. We model the effect of interlocking by introducing an equivalent additional self-weight of the armour blocks. This additional self-weight is proportional to the critical pressure needed to cause bending of the interlocking assembly when it loses stability. Using beam approximation we find an equivalent stability coefficient for interlocking. It is found to be greater than the stability coefficient of a structure with similar blocks without interlocking. In the case when the peripheral constraint is provided by the weight of the blocks and for the slope angle of 45o, the effective stability coefficient for a structure of 100 blocks is 33% higher than the one for a similar structure without interlocking. Further increase in the stability coefficient can be reached by a specially constructed peripheral constraint system, for instance by using post-tension cables.

  8. Isostatic compression of buffer blocks. Middle scale

    Energy Technology Data Exchange (ETDEWEB)

    Ritola, J.; Pyy, E. [VTT Technical Research Centre of Finland, Espoo (Finland)

    2012-01-15

    Manufacturing of buffer components using isostatic compression method has been studied in small scale in 2008 (Laaksonen 2010). These tests included manufacturing of buffer blocks using different bentonite materials and different compression pressures. Isostatic mould technology was also tested, along with different methods to fill the mould, such as vibration and partial vacuum, as well as a stepwise compression of the blocks. The development of manufacturing techniques has continued with small-scale (30 %) blocks (diameter 600 mm) in 2009. This was done in a separate project: Isostatic compression, manufacturing and testing of small scale (D = 600 mm) buffer blocks. The research on the isostatic compression method continued in 2010 in a project aimed to test and examine the isostatic manufacturing process of buffer blocks at 70 % scale (block diameter 1200 to 1300 mm), and the aim was to continue in 2011 with full-scale blocks (diameter 1700 mm). A total of nine bentonite blocks were manufactured at 70 % scale, of which four were ring-shaped and the rest were cylindrical. It is currently not possible to manufacture full-scale blocks, because there is no sufficiently large isostatic press available. However, such a compression unit is expected to be possible to use in the near future. The test results of bentonite blocks, produced with an isostatic pressing method at different presses and at different sizes, suggest that the technical characteristics, for example bulk density and strength values, are somewhat independent of the size of the block, and that the blocks have fairly homogenous characteristics. Water content and compression pressure are the two most important properties determining the characteristics of the compressed blocks. By adjusting these two properties it is fairly easy to produce blocks at a desired density. The commonly used compression pressure in the manufacturing of bentonite blocks is 100 MPa, which compresses bentonite to approximately

  9. Randomized Block Cubic Newton Method

    KAUST Repository

    Doikov, Nikita

    2018-02-12

    We study the problem of minimizing the sum of three convex functions: a differentiable, twice-differentiable and a non-smooth term in a high dimensional setting. To this effect we propose and analyze a randomized block cubic Newton (RBCN) method, which in each iteration builds a model of the objective function formed as the sum of the natural models of its three components: a linear model with a quadratic regularizer for the differentiable term, a quadratic model with a cubic regularizer for the twice differentiable term, and perfect (proximal) model for the nonsmooth term. Our method in each iteration minimizes the model over a random subset of blocks of the search variable. RBCN is the first algorithm with these properties, generalizing several existing methods, matching the best known bounds in all special cases. We establish ${\\\\cal O}(1/\\\\epsilon)$, ${\\\\cal O}(1/\\\\sqrt{\\\\epsilon})$ and ${\\\\cal O}(\\\\log (1/\\\\epsilon))$ rates under different assumptions on the component functions. Lastly, we show numerically that our method outperforms the state-of-the-art on a variety of machine learning problems, including cubically regularized least-squares, logistic regression with constraints, and Poisson regression.

  10. ALS insertion device block measurement and inspection

    International Nuclear Information System (INIS)

    Marks, S.; Carrieri, J.; Cook, C.; Hassenzahl, W.V.; Hoyer, E.; Plate, D.

    1991-05-01

    The performance specifications for ALS insertion devices require detailed knowledge and strict control of the Nd-Fe-B permanent magnet blocks incorporated in these devices. This paper describes the measurement and inspection apparatus and the procedures designed to qualify and characterize these blocks. A detailed description of a new, automated Helmholtz coil facility for measurement of the three components of magnetic moment is included. Physical block inspection and magnetic moment measurement procedures are described. Together they provide a basis for qualifying blocks and for specifying placement of blocks within an insertion devices' magnetic structures. 1 ref., 4 figs

  11. Adaptive motion compensation without blocking artifacts

    Science.gov (United States)

    Terriberry, Timothy B.

    2015-03-01

    The Block Matching Algorithms used in most popular video codec standards introduce blocking artifacts which must be removed via residual coding or deblocking filters. Alternative transform stages that do not cause blocking artifacts, such as lapped transforms or wavelets, require motion compensation methods that do not produce blocking artifacts, since they are expensive to remove. We design a new Overlapped Block Motion Compensation (OBMC) scheme that avoids these artifacts while allowing adaptive blending window sizes. This has the potential to show significant visual quality improvements over traditional OBMC.

  12. Misgivings about the Matching Familiar Figures Test: A Brief Reply to Block, Gjerde, and Block (1986).

    Science.gov (United States)

    Kagan, Jerome

    1987-01-01

    Reply by Jerome Kagan to a recent article by Block, Gjerde, and Block (1986) which questions the validity of the construct of reflection-impulsivity. Kagan alleges flaws in the logic of the authors' (Block, Gjerde, Block) position and in the inferences drawn from their data. (Author/RWB)

  13. 31 CFR 544.204 - Expenses of maintaining blocked physical property; liquidation of blocked property.

    Science.gov (United States)

    2010-07-01

    ... physical property; liquidation of blocked property. 544.204 Section 544.204 Money and Finance: Treasury... maintaining blocked physical property; liquidation of blocked property. (a) Except as otherwise authorized..., all expenses incident to the maintenance of physical property blocked pursuant to § 544.201(a) shall...

  14. 31 CFR 547.204 - Expenses of maintaining blocked physical property; liquidation of blocked property.

    Science.gov (United States)

    2010-07-01

    ... physical property; liquidation of blocked property. 547.204 Section 547.204 Money and Finance: Treasury... maintaining blocked physical property; liquidation of blocked property. (a) Except as otherwise authorized..., all expenses incident to the maintenance of physical property blocked pursuant to § 547.201(a) shall...

  15. 31 CFR 593.204 - Expenses of maintaining blocked physical property; liquidation of blocked account.

    Science.gov (United States)

    2010-07-01

    ... physical property; liquidation of blocked account. 593.204 Section 593.204 Money and Finance: Treasury... maintaining blocked physical property; liquidation of blocked account. (a) Except as otherwise authorized, and... to the maintenance of physical property blocked pursuant to § 593.201(a) shall be the responsibility...

  16. 31 CFR 587.205 - Expenses of maintaining blocked property; liquidation of blocked account.

    Science.gov (United States)

    2010-07-01

    ... property; liquidation of blocked account. 587.205 Section 587.205 Money and Finance: Treasury Regulations....205 Expenses of maintaining blocked property; liquidation of blocked account. (a) Except as otherwise... standard time, January 19, 2001, all expenses incident to the maintenance of physical property blocked...

  17. Plasma and tissue disposition of florfenicol in Escherichia coli lipopolysaccharide-induced endotoxaemic sheep.

    Science.gov (United States)

    Pérez-Fernández, Rubén; Cazanga, Victoria; Jeldres, Jessie Ana; Silva, Pedro P; Riquelme, José; Quiroz, Fernando; Palma, Cristina; Carretta, Maria D; Burgos, Rafael A

    2017-05-01

    1. The purpose of this study was to understand the effects of the acute inflammatory response (AIR) induced by Escherichia coli lipopolysaccharide (LPS) on florfenicol (FFC) and FFC-amine (FFC-a) plasma and tissue concentrations. 2. Ten Suffolk Down sheep, 60.5 ± 4.7 kg, were distributed into two experimental groups: group 1 (LPS) treated with three intravenous doses of 1 μg/kg bw of LPS at 24, 16, and 0.75 h (45 min) before FFC treatment; group 2 (Control) was treated with saline solution (SS) in parallel to group 1. An IM dose of 20 mg FFC/kg was administered at 0.75 h after the last injection of LPS or SS. Blood and tissue samples were taken after FFC administration. 3. The plasma AUC 0-4 h values of FFC were higher (p = 0.0313) in sheep treated with LPS (21.8 ± 2.0 μg·min/mL) compared with the control group (12.8 ± 2.3 μg·min/mL). Lipopolysaccharide injections increased FFC concentrations in kidneys, spleen, and brain. Low levels of plasma FFC-a were observed in control sheep (C max  = 0.14 ± 0.01 μg/mL) with a metabolite ratio (MR) of 4.0 ± 0.87%. While in the LPS group, C max increased slightly (0.25 ± 0.01 μg/mL), and MR decreased to 2.8 ± 0.17%. 4. The changes observed in the plasma and tissue concentrations of FFC were attributed to the pathophysiological effects of LPS on renal hemodynamics that modified tissue distribution and reduced elimination of the drug.

  18. Effect of methanolic extract of Asparagus racemosus Willd. on lipopolysaccharide induced-oxidative stress in rats.

    Science.gov (United States)

    Ahmad, Mohammad Parwez; Hussain, Arshad; Siddiqui, Hefazat Hussain; Wahab, Shadma; Adak, Manoranjan

    2015-03-01

    Lipopolysaccharide (LPS) induced oxidative stress and impairment of normal physiological function generally categorized by increased anxiety and reduced mobility. Therefore, the present study was to find out the effect Methanolic extract of Asparagus racemosus (MEAR ) in lipopolysaccharide (LPS)-induced oxidative stress in rats . LPS-induced oxidative stress in rats was measured by locomotor activity by photoactometer test, anxiety with elevated plus maze test and also studied the oxidative stress markers, nitric oxide and cytokines. The obtained data shows that LPS markedly exhausted (pAsparagus racemosus Willd. is a functionally newer type of cerebroprotective agent.

  19. Effect of anti-podoplanin antibody administration during lipopolysaccharide-induced lung injury in mice.

    Science.gov (United States)

    Lax, Sian; Rayes, Julie; Thickett, David R; Watson, Steve P

    2017-01-01

    Acute respiratory distress syndrome (ARDS) is a devastating pulmonary condition in the critically ill patient. A therapeutic intervention is yet to be found that can prevent progression to ARDS. We recently demonstrated that the interaction between podoplanin expressed on inflammatory alveolar macrophages (iAMs) and its endogenous ligand, platelet C-type lectin-like 2 (CLEC-2), protects against exaggerated lung inflammation during a mouse model of ARDS. In this study, we aim to investigate the therapeutic use of a crosslinking/activating anti-podoplanin antibody (α-PDPN, clone 8.1.1) during lipopolysaccharide (LPS)-induced lung inflammation in mice. Intravenous administration of α-PDPN was performed 6 hours after intratracheal LPS in wildtype, C57Bl/6 mice. Lung function decline was measured by pulse oximetry as well as markers of local inflammation including bronchoalveolar lavage neutrophilia and cytokine/chemokine expression. In parallel, alveolar macrophages were isolated and cultured in vitro from haematopoietic-specific podoplanin-deficient mice (Pdpn fl/fl VAV1cre + ) and floxed-only controls treated with or without LPS in the presence or absence of α-PDPN. Lung function decline as well as alveolar neutrophil recruitment was significantly decreased in mice treated with the crosslinking/activating α-PDPN in vivo. Furthermore, we demonstrate that, in vitro, activation of podoplanin on iAMs regulates their secretion of proinflammatory cytokines and chemokines. These data confirm the importance of the CLEC-2-podoplanin pathway during intratracheal (IT)-LPS and demonstrate the beneficial effect of targeting podoplanin during IT-LPS in mice possibly via modulation of local cytokine/chemokine expression. Moreover, these data suggest that podoplanin-targeted therapies may have a beneficial effect in patients at risk of developing ARDS.

  20. Moderate Exercise Attenuates Lipopolysaccharide-Induced Inflammation and Associated Maternal and Fetal Morbidities in Pregnant Rats.

    Directory of Open Access Journals (Sweden)

    Karina T Kasawara

    Full Text Available Fetal growth restriction (FGR and coagulopathies are often associated with aberrant maternal inflammation. Moderate-intensity exercise during pregnancy has been shown to increase utero-placental blood flow and to enhance fetal nutrition as well as fetal and placental growth. Furthermore, exercise is known to reduce inflammation. To evaluate the effect of moderate-intensity exercise on inflammation associated with the development of maternal coagulopathies and FGR, Wistar rats were subjected to an exercise regime before and during pregnancy. To model inflammation-induced FGR, pregnant rats were administered daily intraperitoneal injections of E. coli lipopolysaccharide (LPS on gestational days (GD 13.5-16.5 and sacrificed at GD 17.5. Control rats were injected with saline. Maternal hemostasis was assessed by thromboelastography. Moderate-intensity exercise prevented LPS-mediated increases in white blood cell counts measured on GD 17.5 and improved maternal hemostasis profiles. Importantly, our data reveal that exercise prevented LPS-induced FGR. Moderate-intensity exercise initiated before and maintained during pregnancy may decrease the severity of maternal and perinatal complications associated with abnormal maternal inflammation.

  1. Establishment of hydrochloric acid/lipopolysaccharide-induced pelvic inflammatory disease model

    Science.gov (United States)

    Oh, Yeonsu; Lee, Jaehun; Kim, Hyeon-Cheol; Hahn, Tae-Wook; Yoon, Byung-Il; Han, Jeong-Hee; Kwon, Yong-Soo; Park, Joung Jun; Koo, Deog-Bon; Rhee, Ki-Jong

    2016-01-01

    Pelvic inflammatory disease (PID), which is one of the most problematic complications experienced by women with sexually transmitted diseases, frequently causes secondary infections after reproductive abnormalities in veterinary animals. Although the uterus is self-protective, it becomes fragile during periods or pregnancy. To investigate PID, bacteria or lipopolysaccharide (LPS) extracted from gram negative bacteria has been used to induce the disease in several animal models. However, when LPS is applied to the peritoneum, it often causes systemic sepsis leading to death and the PID was not consistently demonstrated. Hydrochloric acid (HCl) has been used to induce inflammation in the lungs and stomach but not tested for reproductive organs. In this study, we developed a PID model in mice by HCl and LPS sequential intracervical (i.c.) administration. The proinflammatory cytokines, interleukin (IL)-1β, IL-6 and tumor necrosis factor-α, were detected in the mouse uterus by western blot analysis and cytokine enzyme-linked immunosorbent assay after HCl (25 mg/kg) administration i.c. followed by four LPS (50 mg/kg) treatments. Moreover, mice exhibited increased infiltration of neutrophils in the endometrium and epithelial layer. These results suggest that ic co-administration of HCl and LPS induces PID in mice. This new model may provide a consistent and reproducible PID model for future research. PMID:26726020

  2. Dietary Supplementation with Lactobacillus casei Alleviates Lipopolysaccharide-Induced Liver Injury in a Porcine Model

    Directory of Open Access Journals (Sweden)

    Di Zhao

    2017-11-01

    Full Text Available This study aims to determine whether Lactobacillus casei (L. casei could relieve liver injury in piglets challenged with lipopolysaccharide (LPS. Piglets were randomly allocated into one of the three groups: control, LPS, and L. casei. The control and LPS groups were fed a corn- and soybean meal-based diet, whereas the L. casei group was fed the basal diet supplemented with 6 × 106 cfu/g L. casei. On Day 31 of the trial, piglets in the LPS and L. casei groups received intraperitoneal administration of LPS (100 µg/kg body weight, while the control group received the same volume of saline. Blood and liver samples were collected for analysis. Results showed that L. casei supplementation decreased the feed/gain ratio (p = 0.027 and diarrhea incidence (p < 0.001, and attenuated LPS-induced liver histomorphological abnormalities. Compared with the control group, LPS challenge dramatically increased glutamyl transpeptidase activity (p = 0.001 in plasma as well as the concentrations of Interleukin 6 (IL-6 (p = 0.048, Tumor necrosis factor-alpha (TNF-α (p = 0.041, and Malondialdehyde (MDA (p = 0.001 in the liver, while decreasing the hepatic SOD activity. LPS also increased (p < 0.05 the mRNA levels for IL-6, IL-8, TNF-α, Toll-like receptors 4 (TLR4, Nuclear factor κB (NF-κB and Heat shock protein 70 (HSP70 in the liver. The adverse effects of LPS challenge were ameliorated by L. casei supplementation. In conclusion, dietary L. casei alleviates LPS-induced liver injury via reducing pro-inflammatory cytokines and increasing anti-oxidative capacity.

  3. Modulation by gamithromycin and ketoprofen of in vitro and in vivo porcine lipopolysaccharide-induced inflammation.

    Science.gov (United States)

    Wyns, Heidi; Meyer, Evelyne; Plessers, Elke; Watteyn, Anneleen; van Bergen, Thomas; Schauvliege, Stijn; De Baere, Siegrid; Devreese, Mathias; De Backer, Patrick; Croubels, Siska

    2015-12-15

    The immunomodulatory properties of gamithromycin (GAM), ketoprofen (KETO) and their combination (GAM-KETO) were investigated after both in vitro and in vivo lipopolysaccharide (LPS)-induced inflammation. The influence of these drugs was measured on the production of prostaglandin E2 (PGE2) and the pro-inflammatory cytokines tumour necrosis factor (TNF)-α, interleukin (IL)-6 and IL-1β in both LPS-stimulated porcine peripheral blood mononuclear cells (PBMCs) and LPS-challenged pigs. Additionally, effects on the production of acute phase proteins (APPs), including pig major acute phase protein (pig-MAP) and C-reactive protein (CRP), as well as on the development of fever, pulmonary symptoms and sickness behaviour were investigated. Dexamethasone was included as a positive control in the in vitro research. Following an 18h-incubation period with 1.25μg/mL LPS, the levels of TNF-α, IL-1β and IL-6 (p<0.05) measured in the PBMC supernatants were significantly increased. Incubation with a high concentration of both GAM and KETO significantly reduced the in vitro levels of all three cytokines. Maximal plasma concentrations of TNF-α and IL-6 were observed at 1h and 2.5h following LPS challenge in pigs, respectively. Neither GAM, nor KETO nor the combination GAM-KETO was able to inhibit the in vivo LPS-induced cytokine production. Furthermore, none of the drugs influenced the subsequent APPs production. In contrast, administration of KETO significantly reduced PGE2 production both in vitro and in vivo (p<0.05 and p<0.001, respectively) and prevented the development of fever and severe symptoms, including dyspnoea, anorexia, vomiting and lateral decubitus. Copyright © 2015 Elsevier B.V. All rights reserved.

  4. Misoprostol Inhibits Lipopolysaccharide-Induced Pro-inflammatory Cytokine Production by Equine Leukocytes

    Directory of Open Access Journals (Sweden)

    Emily Medlin Martin

    2017-09-01

    Full Text Available Pro-inflammatory cytokines including tumor necrosis factor α (TNFα, IL-1β, IL-6, and IL-8 are potent immune mediators that exacerbate multiple equine diseases such as sepsis and laminitis. Unfortunately, safe and effective cytokine-targeting therapies are lacking in horses; therefore, novel mechanisms of inhibiting cytokine production are critically needed. One potential mechanism for inhibiting cytokine synthesis is elevation of intracellular cyclic AMP (cAMP. In human leukocytes, intracellular cAMP production is induced by activation of E-prostanoid (EP receptors 2 and 4. These receptors can be targeted by the EP2/4 agonist and prostaglandin E1 analog, misoprostol. Misoprostol is currently used as a gastroprotectant in horses but has not been evaluated as a cytokine-targeting therapeutic. Thus, we hypothesized that misoprostol treatment would inhibit pro-inflammatory cytokine production by lipopolysaccharide (LPS-stimulated equine leukocytes in an in vitro inflammation model. To test this hypothesis, equine leukocyte-rich plasma (LRP was collected from 12 healthy adult horses and used to model LPS-mediated inflammatory signaling. LRP was treated with varying concentrations of misoprostol either before (pretreated or following (posttreated LPS stimulation. LRP supernatants were assayed for 23 cytokines using an equine-specific multiplex bead immunoassay. Leukocytes were isolated from LRP, and leukocyte mRNA levels of four important cytokines were evaluated via RT-PCR. Statistical differences between treatments were determined using one-way RM ANOVA (Holm–Sidak post hoc testing or Friedman’s RM ANOVA on Ranks (SNK post hoc testing, where appropriate (p < 0.05, n = 3–6 horses. These studies revealed that misoprostol pre- and posttreatment inhibited LPS-induced TNFα and IL-6 protein production in equine leukocytes but had no effect on IL-8 protein. Interestingly, misoprostol pretreatment enhanced IL-1β protein synthesis following 6 h of LPS stimulation, while misoprostol posttreatment inhibited IL-1β protein production after 24 h of LPS stimulation. At the mRNA level, misoprostol pre- and posttreatment inhibited LPS-induced TNFα, IL-1β, and IL-6 mRNA production but did not affect IL-8 mRNA. These results indicate that misoprostol exerts anti-inflammatory effects on equine leukocytes when applied before or after a pro-inflammatory stimulus. However, the effects we observed were cytokine-specific and sometimes differed at the mRNA and protein levels. Further studies are warranted to establish the inhibitory effects of misoprostol on equine cytokine production in vivo.

  5. Misoprostol Inhibits Lipopolysaccharide-Induced Pro-inflammatory Cytokine Production by Equine Leukocytes

    Science.gov (United States)

    Martin, Emily Medlin; Messenger, Kristen M.; Sheats, Mary Katherine; Jones, Samuel L.

    2017-01-01

    Pro-inflammatory cytokines including tumor necrosis factor α (TNFα), IL-1β, IL-6, and IL-8 are potent immune mediators that exacerbate multiple equine diseases such as sepsis and laminitis. Unfortunately, safe and effective cytokine-targeting therapies are lacking in horses; therefore, novel mechanisms of inhibiting cytokine production are critically needed. One potential mechanism for inhibiting cytokine synthesis is elevation of intracellular cyclic AMP (cAMP). In human leukocytes, intracellular cAMP production is induced by activation of E-prostanoid (EP) receptors 2 and 4. These receptors can be targeted by the EP2/4 agonist and prostaglandin E1 analog, misoprostol. Misoprostol is currently used as a gastroprotectant in horses but has not been evaluated as a cytokine-targeting therapeutic. Thus, we hypothesized that misoprostol treatment would inhibit pro-inflammatory cytokine production by lipopolysaccharide (LPS)-stimulated equine leukocytes in an in vitro inflammation model. To test this hypothesis, equine leukocyte-rich plasma (LRP) was collected from 12 healthy adult horses and used to model LPS-mediated inflammatory signaling. LRP was treated with varying concentrations of misoprostol either before (pretreated) or following (posttreated) LPS stimulation. LRP supernatants were assayed for 23 cytokines using an equine-specific multiplex bead immunoassay. Leukocytes were isolated from LRP, and leukocyte mRNA levels of four important cytokines were evaluated via RT-PCR. Statistical differences between treatments were determined using one-way RM ANOVA (Holm–Sidak post hoc testing) or Friedman’s RM ANOVA on Ranks (SNK post hoc testing), where appropriate (p equine leukocytes but had no effect on IL-8 protein. Interestingly, misoprostol pretreatment enhanced IL-1β protein synthesis following 6 h of LPS stimulation, while misoprostol posttreatment inhibited IL-1β protein production after 24 h of LPS stimulation. At the mRNA level, misoprostol pre- and posttreatment inhibited LPS-induced TNFα, IL-1β, and IL-6 mRNA production but did not affect IL-8 mRNA. These results indicate that misoprostol exerts anti-inflammatory effects on equine leukocytes when applied before or after a pro-inflammatory stimulus. However, the effects we observed were cytokine-specific and sometimes differed at the mRNA and protein levels. Further studies are warranted to establish the inhibitory effects of misoprostol on equine cytokine production in vivo. PMID:29034249

  6. Milk Thistle Extract and Silymarin Inhibit Lipopolysaccharide Induced Lamellar Separation of Hoof Explants in Vitro

    Directory of Open Access Journals (Sweden)

    Nicole Reisinger

    2014-10-01

    Full Text Available The pathogenesis of laminitis is not completely identified and the role of endotoxins (lipopolysaccharides, LPS in this process remains unclear. Phytogenic substances, like milk thistle (MT and silymarin, are known for their anti-inflammatory and antioxidant properties and might therefore have the potential to counteract endotoxin induced effects on the hoof lamellar tissue. The aim of our study was to investigate the influence of endotoxins on lamellar tissue integrity and to test if MT and silymarin are capable of inhibiting LPS-induced effects in an in vitro/ex vivo model. In preliminary tests, LPS neutralization efficiency of these phytogenics was determined in an in vitro neutralization assay. Furthermore, tissue explants gained from hooves of slaughter horses were tested for lamellar separation after incubation with different concentrations of LPS. By combined incubation of explants with LPS and either Polymyxin B (PMB; positive control, MT or silymarin, the influence of these substances on LPS-induced effects was assessed. In the in vitro neutralization assay, MT and silymarin reduced LPS concentrations by 64% and 75%, respectively, in comparison PMB reduced 98% of the LPS concentration. In hoof explants, LPS led to a concentration dependent separation. Accordantly, separation force was significantly decreased by 10 µg/mL LPS. PMB, MT and silymarin could significantly improve tissue integrity of explants incubated with 10 µg/mL LPS. This study showed that LPS had a negative influence on the structure of hoof explants in vitro. MT and silymarin reduced endotoxin activity and inhibited LPS-induced effects on the lamellar tissue. Hence, MT and silymarin might be used to support the prevention of laminitis and should be further evaluated for this application.

  7. LIPOPOLYSACCHARIDE INDUCES THE PRODUCTION OF DIAGNOSTIC MONOCLONAL ANTIBODY BY HYBRIDOMA CELLS AGAINST CONGENITAL ADRENAL HYPERPLASIA

    Directory of Open Access Journals (Sweden)

    GEK KEE CHUA

    2017-11-01

    Full Text Available The purpose of this research is to screen and identify the potential inducers in maximizing the production of monoclonal antibody by hybridoma 192 cell line for Congenital Adrenal Hyperplasia diagnostic. There are nine inducers used in this research, namely lysozyme, aldolase, sodium butyrate, sodium phosphate, potassium phosphate, dimethyl sulfoxide, lipopolysaccharide, essential amino acids, and nonessential amino acids. Hybridoma 192 cell was cultured in 5% CO2 incubator at 37°C and ˃80% humidity in the medium with different concentrations of inducer agents. The inducers were added at the beginning of the culture and the samples were taken after 72 h of culture. The performance of these inducer agents was assessed based on the maximum monoclonal antibody titer achieved using Enzyme-linked Immunosorbent Assay. Lipopolysaccharide was found to increase the maximum monoclonal antibody titer when supplemented at 8 to 12 µg/mL. After optimization using one-factor central composite design at this range, the optimum point was determined to be 8 µg/mL. Verification experiments shows that lipopolysaccharide enhanced the average specific monoclonal antibody production rate by 56% relative to control. In conclusion, lipopolysaccharide at 8 µg/mL is able to increase the monoclonal antibody specific production of hybridoma 192 cell line.

  8. Lipopolysaccharide-Induced Spatial Memory and Synaptic Plasticity Impairment Is Preventable by Captopril

    Directory of Open Access Journals (Sweden)

    Azam Abareshi

    2016-01-01

    Full Text Available Introduction. Renin-angiotensin system has a role in inflammation and also is involved in many brain functions such as learning, memory, and emotion. Neuroimmune factors have been proposed as the contributors to the pathogenesis of memory impairments. In the present study, the effect of captopril on spatial memory and synaptic plasticity impairments induced by lipopolysaccharide (LPS was investigated. Methods. The rats were divided and treated into control (saline, LPS (1 mg/kg, LPS-captopril (LPS-Capto; 50 mg/kg captopril before LPS, and captopril groups (50 mg/kg before saline. Morris water maze was done. Long-term potentiation (LTP from CA1 area of hippocampus was assessed by 100 Hz stimulation in the ipsilateral Schaffer collateral pathway. Results. In the LPS group, the spent time and traveled path to reach the platform were longer than those in the control, while, in the LPS-Capto group, they were shorter than those in the LPS group. Moreover, the slope and amplitude of field excitatory postsynaptic potential (fEPSP decreased in the LPS group, as compared to the control group, whereas, in the LPS-Capto group, they increased compared to the LPS group. Conclusion. The results of the present study showed that captopril improved the LPS-induced memory and LTP impairments induced by LPS in rats. Further investigations are required in order to better understand the exact responsible mechanism(s.

  9. Taraxacum officinale protects against lipopolysaccharide-induced acute lung injury in mice.

    Science.gov (United States)

    Liu, Liben; Xiong, Huanzhang; Ping, Jiaqi; Ju, Yulin; Zhang, Xuemei

    2010-07-20

    Taraxacum officinale has been frequently used as a remedy for inflammatory diseases. In the present study, we investigated the in vivo protective effect of Taraxacum officinale on acute lung injury (ALI) induced by lipopolysaccharide (LPS) in mice. Taraxacum officinale at 2.5, 5 and 10 mg/kg was orally administered once per day for 5 days consecutively, followed by 500 microg/kg LPS was instilled intranasally. The lung wet/dry weight (W/D) ratio, protein concentration and the number of inflammatory cells in bronchoalveolar lavage fluid (BALF) were determined. Superoxidase dismutase (SOD) and myeloperoxidase (MPO) activities, and histological change in the lungs were examined. The levels of inflammatory cytokine tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) in the BALF were measured using ELISA. We found that Taraxacum officinale decreased the lung W/D ratio, protein concentration and the number of neutrophils in the BALF at 24 h after LPS challenge. Taraxacum officinale decreased LPS-induced MPO activity and increased SOD activity in the lungs. In addition, histopathological examination indicated that Taraxacum officinale attenuated tissue injury of the lungs in LPS-induced ALI. Furthermore, Taraxacum officinale also inhibited the production of inflammatory cytokines TNF-alpha and IL-6 in the BALF at 6h after LPS challenge in a dose-dependent manner. These results suggest that Taraxacum officinale protects against LPS-induced ALI in mice. Copyright 2010 Elsevier Ireland Ltd. All rights reserved.

  10. Bee venom ameliorates lipopolysaccharide-induced memory loss by preventing NF-kappaB pathway

    OpenAIRE

    Gu, Sun Mi; Park, Mi Hee; Hwang, Chul Ju; Song, Ho Sueb; Lee, Ung Soo; Han, Sang Bae; Oh, Ki Wan; Ham, Young Wan; Song, Min Jong; Son, Dong Ju; Hong, Jin Tae

    2015-01-01

    Background Accumulation of beta-amyloid and neuroinflammation trigger Alzheimer?s disease. We previously found that lipopolysaccharide (LPS) caused neuroinflammation with concomitant accumulation of beta-amyloid peptides leading to memory loss. A variety of anti-inflammatory compounds inhibiting nuclear factor kappaB (NF-?B) activation have showed efficacy to hinder neuroinflammation and amyloidogenesis. We also found that bee venom (BV) inhibits NF-?B. Methods A mouse model of LPS-induced me...

  11. Omega-3 Fatty Acid Intervention Suppresses Lipopolysaccharide-Induced Inflammation and Weight Loss in Mice

    Directory of Open Access Journals (Sweden)

    Ying-Hua Liu

    2015-02-01

    Full Text Available Bacterial endotoxin lipopolysaccharide (LPS-induced sepsis is a critical medical condition, characterized by a severe systemic inflammation and rapid loss of muscle mass. Preventive and therapeutic strategies for this complex disease are still lacking. Here, we evaluated the effect of omega-3 (n-3 polyunsaturated fatty acid (PUFA intervention on LPS-challenged mice with respect to inflammation, body weight and the expression of Toll-like receptor 4 (TLR4 pathway components. LPS administration induced a dramatic loss of body weight within two days. Treatment with n-3 PUFA not only stopped loss of body weight but also gradually reversed it back to baseline levels within one week. Accordingly, the animals treated with n-3 PUFA exhibited markedly lower levels of inflammatory cytokines or markers in plasma and tissues, as well as down-regulation of TLR4 pathway components compared to animals without n-3 PUFA treatment or those treated with omega-6 PUFA. Our data demonstrate that n-3 PUFA intervention can suppress LPS-induced inflammation and weight loss via, at least in part, down-regulation of pro-inflammatory targets of the TLR4 signaling pathway, and highlight the therapeutic potential of n-3 PUFA in the management of sepsis.

  12. The effects of a novel botanical agent on lipopolysaccharide-induced alveolar bone loss in rats.

    Science.gov (United States)

    Lee, Bo-Ah; Lee, Hwa-Sun; Jung, Young-Suk; Kim, Se-Won; Lee, Yong-Wook; Chang, Sun-Hwa; Chung, Hyun-Ju; Kim, Ok-Su; Kim, Young-Joon

    2013-08-01

    The development of host-modulatory agents with low risk of adverse effects has been needed to treat periodontitis, a chronic inflammatory disease. A botanical mixture of extracts from two natural substances, Panax notoginseng and Rehmannia glutinosa Libosch, was developed as a novel botanical agent synthesized with anti-inflammatory effect. The aim of this study is to evaluate the effects of the botanical mixture on the release of inflammatory cytokines and its inhibitory effect on lipopolysaccharide (LPS)-induced alveolar bone loss (ABL) in a rat model. Cytotoxicity was assessed by 3-(4,5-dimethylthiazol-2yl)-5(3-carboxymethoxyphenol)-2-(4-sulfophenyl)-2H-tetrazolium assay using human gingival fibroblast (hGF) and human periodontal ligament (hPDL) cells. Human acute monocytic leukemia cell line and hGF cells were cultured to assay tumor necrosis factor (TNF)-α and interleukin (IL)-6, respectively. Microcomputed tomography analysis and immunofluoresence analysis were performed to evaluate the efficacy of the botanical mixture to inhibit the destruction of alveolar bone and connective tissue in a rat model. The botanical mixture is cytotoxic at concentrations exceeding 2.5 mg/mL (P botanical mixture to be used in all subsequent in vitro and in vivo experiments. The botanical mixture reduced the release of TNF-α and IL-6 from human monocytic cells and hGF cells in a dose-dependent manner (P botanical mixture significantly reduced the alveolar bone loss in a rat model (P botanical mixture, matrix metalloproteinase (MMP)-9 was detected along the alveolar bone crest (ABC), but not around the gingival connective tissue, while in the group with LPS-induced ABL, pronounced expression of MMP-9 around the ABC, periodontal ligament, and gingival connective tissue was found. The botanical mixture showed a potential adjunctive effect in the treatment of periodontitis. However, the present findings are obtained in vitro and in a rat model, so further clinical study is needed for its clinical application.

  13. Cardiac-Specific Overexpression of Catalase Attenuates Lipopolysaccharide-Induced Myocardial Contractile Dysfunction: Role of Autophagy

    Science.gov (United States)

    Turdi, Subat; Han, Xuefeng; Huff, Anna F.; Roe, Nathan D.; Hu, Nan; Gao, Feng; Ren, Jun

    2012-01-01

    Lipopolysaccharide (LPS) from Gram-negative bacteria is a major initiator of sepsis, leading to cardiovascular collapse. Accumulating evidence has indicated a role of reactive oxygen species (ROS) in cardiovascular complication in sepsis. This study was designed to examine the effect of cardiac-specific overexpression of catalase in LPS-induced cardiac contractile dysfunction and the underlying mechanism(s) with a focus on autophagy. Catalase transgenic and wild-type FVB mice were challenged with LPS (6 mg/kg) and cardiac function was evaluated. Levels of oxidative stress, autophagy, apoptosis and protein damage were examined using fluorescence microscopy, Western blot, TUNEL assay, caspase-3 activity and carbonyl formation. Kaplan-Meier curve was constructed for survival following LPS treatment. Our results revealed a lower mortality in catalase mice compared with FVB mice following LPS challenge. LPS injection led to depressed cardiac contractile capacity as evidenced by echocardiography and cardiomyocyte contractile function, the effect of which was ablated by catalase overexpression. LPS treatment induced elevated TNF-α level, autophagy, apoptosis (TUNEL, caspase-3 activation, cleaved caspase-3), production of ROS and O2−, and protein carbonyl formation, the effects of which were significantly attenuated by catalase overexpression. Electron microscopy revealed focal myocardial damage characterized by mitochondrial injury following LPS treatment, which was less severe in catalase mice. Interestingly, LPS-induced cardiomyocyte contractile dysfunction was prevented by antioxidant NAC and the autophagy inhibitor 3-methyladenine. Taken together, our data revealed that catalase protects against LPS-induced cardiac dysfunction and mortality, which may be associated with inhibition of oxidative stress and autophagy. PMID:22902401

  14. Cardiac-specific overexpression of catalase attenuates lipopolysaccharide-induced myocardial contractile dysfunction: role of autophagy.

    Science.gov (United States)

    Turdi, Subat; Han, Xuefeng; Huff, Anna F; Roe, Nathan D; Hu, Nan; Gao, Feng; Ren, Jun

    2012-09-15

    Lipopolysaccharide (LPS) from gram-negative bacteria is a major initiator of sepsis, leading to cardiovascular collapse. Accumulating evidence has indicated a role of reactive oxygen species (ROS) in cardiovascular complications in sepsis. This study was designed to examine the effect of cardiac-specific overexpression of catalase in LPS-induced cardiac contractile dysfunction and the underlying mechanism(s) with a focus on autophagy. Catalase transgenic and wild-type FVB mice were challenged with LPS (6 mg/kg) and cardiac function was evaluated. Levels of oxidative stress, autophagy, apoptosis, and protein damage were examined using fluorescence microscopy, Western blot, TUNEL assay, caspase-3 activity, and carbonyl formation. A Kaplan-Meier curve was constructed for survival after LPS treatment. Our results revealed a lower mortality in catalase mice compared with FVB mice after LPS challenge. LPS injection led to depressed cardiac contractile capacity as evidenced by echocardiography and cardiomyocyte contractile function, the effect of which was ablated by catalase overexpression. LPS treatment induced elevated TNF-α level, autophagy, apoptosis (TUNEL, caspase-3 activation, cleaved caspase-3), production of ROS and O(2)(-), and protein carbonyl formation, the effects of which were significantly attenuated by catalase overexpression. Electron microscopy revealed focal myocardial damage characterized by mitochondrial injury after LPS treatment, which was less severe in catalase mice. Interestingly, LPS-induced cardiomyocyte contractile dysfunction was prevented by the antioxidant N-acetylcysteine and the autophagy inhibitor 3-methyladenine. Taken together, our data revealed that catalase protects against LPS-induced cardiac dysfunction and mortality, which may be associated with inhibition of oxidative stress and autophagy. Copyright © 2012 Elsevier Inc. All rights reserved.

  15. Cardiac-Specific Overexpression of Catalase Attenuates Lipopolysaccharide-Induced Myocardial Contractile Dysfunction: Role of Autophagy

    OpenAIRE

    Turdi, Subat; Han, Xuefeng; Huff, Anna F.; Roe, Nathan D.; Hu, Nan; Gao, Feng; Ren, Jun

    2012-01-01

    Lipopolysaccharide (LPS) from Gram-negative bacteria is a major initiator of sepsis, leading to cardiovascular collapse. Accumulating evidence has indicated a role of reactive oxygen species (ROS) in cardiovascular complication in sepsis. This study was designed to examine the effect of cardiac-specific overexpression of catalase in LPS-induced cardiac contractile dysfunction and the underlying mechanism(s) with a focus on autophagy. Catalase transgenic and wild-type FVB mice were challenged ...

  16. Lipopolysaccharide-induced biliary factors enhance invasion of Salmonella enteritidis in a rat model.

    Science.gov (United States)

    Islam, A F; Moss, N D; Dai, Y; Smith, M S; Collins, A M; Jackson, G D

    2000-01-01

    In this study, the role of the hepatobiliary system in the early pathogenesis of Salmonella enteritidis infection was investigated in a rat model. Intravenous (i.v.) challenge with lipopolysaccharide (LPS) has previously been shown to enhance the translocation of normal gut flora. We first confirmed that LPS can similarly promote the invasion of S. enteritidis. Oral infection of outbred Australian Albino Wistar rats with 10(6) to 10(7) CFU of S. enteritidis led to widespread tissue invasion after days. If animals were similarly challenged after intravenous administration of S. enteritidis LPS (3 to 900 microg/kg of body weight), significant invasion of the livers and mesenteric lymph nodes (MLN) occurred within 24 h, with invasion of the liver increasing in a dose-dependent fashion (P < 0.01). If bile was prevented from reaching the intestine by bile duct ligation or cannulation, bacterial invasion of the liver and MLN was almost totally abrogated (P < 0.001). As i.v. challenge with LPS could induce the delivery of inflammatory mediators into the bile, biliary tumor necrosis factor alpha (TNF-alpha) concentrations were measured by bioassay. Biliary concentrations of TNF-alpha rose shortly after LPS challenge, peaked with a mean concentration of 27.0 ng/ml at around 1 h postchallenge, and returned to baseline levels (3.1 ng/ml) after 2.5 h. Although TNF-alpha cannot be directly implicated in the invasion process, we conclude that the invasiveness of the enteric pathogen S. enteritidis is enhanced by the presence of LPS in the blood and that this enhanced invasion is at least in part a consequence of the delivery of inflammatory mediators to the gastrointestinal tract by the hepatobiliary system.

  17. Protective effects of kaempferol on lipopolysaccharide-induced mastitis in mice.

    Science.gov (United States)

    Cao, Rongfeng; Fu, Kaiqiang; Lv, Xiaopei; Li, Weishi; Zhang, Naisheng

    2014-10-01

    Kaempferol isolated from the root of Zingiberaceae plants galangal and other Chinese herbal medicines have been reported to have anti-inflammatory properties. However, the anti-inflammatory effects of kaempferol on lipopolysaccharide (LPS)-induced mastitis are unknown and their underlying molecular mechanisms remain to be explored. The aim of this study was to evaluate the effects of kaempferol on LPS-induced mouse mastitis. The mouse model of mastitis was induced by injection of LPS through the duct of mammary gland. Kaempferol was injected 1 h before and 12 h after induction of LPS intraperitoneally. The present results showed that kaempferol markedly reduced infiltration of neutrophilic granulocyte, activation of myeloperoxidase (MPO), expression of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-1β (IL-1β) in a dose-dependent manner, which were increased in LPS-induced mouse mastitis. Furthermore, kaempferol suppressed the phosphorylation of nuclear factor-κB (NF-κB) p65 subunit and the degradation of its inhibitor IκBα. All results suggest that anti-inflammatory effects of kaempferol against the LPS-induced mastitis possibly through inhibition of the NF-κB signaling pathway. Kaempferol may be a potential therapeutic agent for mastitis.

  18. Establishment of hydrochloric acid/lipopolysaccharide-induced pelvic inflammatory disease model.

    Science.gov (United States)

    Oh, Yeonsu; Lee, Jaehun; Kim, Hyeon-Cheol; Hahn, Tae-Wook; Yoon, Byung-Il; Han, Jeong-Hee; Kwon, Yong-Soo; Park, Joung Jun; Koo, Deog-Bon; Rhee, Ki-Jong; Jung, Bae Dong

    2016-09-30

    Pelvic inflammatory disease (PID), which is one of the most problematic complications experienced by women with sexually transmitted diseases, frequently causes secondary infections after reproductive abnormalities in veterinary animals. Although the uterus is self-protective, it becomes fragile during periods or pregnancy. To investigate PID, bacteria or lipopolysaccharide (LPS) extracted from gram negative bacteria has been used to induce the disease in several animal models. However, when LPS is applied to the peritoneum, it often causes systemic sepsis leading to death and the PID was not consistently demonstrated. Hydrochloric acid (HCl) has been used to induce inflammation in the lungs and stomach but not tested for reproductive organs. In this study, we developed a PID model in mice by HCl and LPS sequential intracervical (i.c.) administration. The proinflammatory cytokines, interleukin (IL)-1β, IL-6 and tumor necrosis factor-α, were detected in the mouse uterus by western blot analysis and cytokine enzyme-linked immunosorbent assay after HCl (25 mg/kg) administration i.c. followed by four LPS (50 mg/kg) treatments. Moreover, mice exhibited increased infiltration of neutrophils in the endometrium and epithelial layer. These results suggest that ic co-administration of HCl and LPS induces PID in mice. This new model may provide a consistent and reproducible PID model for future research.

  19. [FcγRIis involved in lipopolysaccharide-induced apoptosis of PC12 cells].

    Science.gov (United States)

    Chen, Yanjie; Liang, Yingxia; Zhang, Yan

    2017-06-01

    Objective To investigate the role of IgG Fc receptorI (FcγRI) in lipopolysaccharide (LPS)-induced apoptosis of the rat PC12 cells. Methods PC12 cells were treated with different concentrations of LPS (50, 125, 250, 500, 1000 μg/mL) for 24 hours and cell viability was analyzed by MTT assay. The appropriate concentration of LPS (500 μg/mL) was chosen for the following experiments. PC12 cells in the logarithmic growth phase were divided randomly into three groups: the control group without LPS, the 500 μg/mL LPS treated group and the 500 μg/mL LPS plus 0.2 μg/mL FcγRI neutralizer group. After24-hour different treatments, the mRNA and protein levels of FcγRIwere detected by quantitative real-time PCR and Western blotting, respectively. The apoptosis rate of PC12 cells was determined by flow cytometry combined with annexinV-FITC/PI double staining. The protein expression levels of caspase-3, Bcl-2 and BAX were measured by immunohistochemistry. Results PC12 cell viability decreased in a LPS dose-dependent manner. Compared to the control group, the protein and mRNA expression of FcγRI were upregulated, the expression levels of caspase-3, Bcl-2 and BAX proteins were elevated, and the apoptosis rate of PC12 cells was raised as well in the LPS treated group. Compared to the LPS treated group, the protein and mRNA levels of FcγRI were significantly lower along with significantly reduced expressions of Caspase-3 and BAX and inhibited cell apoptosis in the FcγRIneutralizer treated group, while Bcl-2 protein expression was upregulated. Conclusion FcγRIis involved in the LPS-induced apoptosis in PC12 cells.

  20. Acrolein inhalation suppresses lipopolysaccharide-induced inflammatory cytokine production but does not affect acute airways neutrophilia.

    Science.gov (United States)

    Kasahara, David Itiro; Poynter, Matthew E; Othman, Ziryan; Hemenway, David; van der Vliet, Albert

    2008-07-01

    Acrolein is a reactive unsaturated aldehyde that is produced during endogenous oxidative processes and is a major bioactive component of environmental pollutants such as cigarette smoke. Because in vitro studies demonstrate that acrolein can inhibit neutrophil apoptosis, we evaluated the effects of in vivo acrolein exposure on acute lung inflammation induced by LPS. Male C57BL/6J mice received 300 microg/kg intratracheal LPS and were exposed to acrolein (5 parts per million, 6 h/day), either before or after LPS challenge. Exposure to acrolein either before or after LPS challenge did not significantly affect the overall extent of LPS-induced lung inflammation, or the duration of the inflammatory response, as observed from recovered lung lavage leukocytes and histology. However, exposure to acrolein after LPS instillation markedly diminished the LPS-induced production of several inflammatory cytokines, specifically TNF-alpha, IL-12, and the Th1 cytokine IFN-gamma, which was associated with reduction in NF-kappaB activation. Our data demonstrate that acrolein exposure suppresses LPS-induced Th1 cytokine responses without affecting acute neutrophilia. Disruption of cytokine signaling by acrolein may represent a mechanism by which smoking contributes to chronic disease in chronic obstructive pulmonary disease and asthma.

  1. Role for macrophage inflammatory protein-2 in lipopolysaccharide-induced lung injury in rats

    DEFF Research Database (Denmark)

    Schmal, H; Shanley, T P; Jones, M L

    1996-01-01

    Macrophage inflammatory protein-2 (MIP-2) is a C-X-C chemokine that possesses chemotactic activity for neutrophils. Rat MIP-2 was cloned and expressed as a 7.9-kDa peptide that exhibited dose-dependent neutrophil chemotactic activity at concentrations from 10 to 250 nM. Rabbit polyclonal Ab...

  2. Pseudomonas aeruginosa lipopolysaccharide induces CF-like alteration of protein secretion by human tracheal gland cells.

    Science.gov (United States)

    Kammouni, W; Figarella, C; Baeza, N; Marchand, S; Merten, M D

    1997-12-18

    Human tracheal gland (HTG) serous cells are now believed to play a major role in the physiopathology of cystic fibrosis. Because of the persistent inflammation and the specific infection by Pseudomonas aeruginosa in the lung, we looked for the action of the lipopolysaccharide (LPS) of this bacteria on human tracheal gland cells in culture by studying the secretion of the secretory leukocyte proteinase inhibitor (SLPI) which is a specific serous secretory marker of these cells. Treatment with Pseudomonas aeruginosa LPS resulted in a significant dose-dependent increase in the basal production of SLPI (+ 250 +/- 25%) whilst the SLPI transcript mRNA levels remained unchanged. This LPS-induced increase in secretion was inhibited by glucocorticoides. Furthermore, LPS treatment of HTG cells induces a loss of responsiveness to carbachol and isoproterenol but not to adenosine triphosphate. These findings indicate that HTG cells treated by Pseudomonas aeruginosa LPS have the same behavior as those previously observed with CF-HTG cells. Exploration by using reverse transcriptase polymerase chain reaction amplification showed that LPS downregulated cystic fibrosis transmembrane conductance regulator (CFTR) mRNA expression in HTG cells indicative of a link between CFTR function and consequent CF-like alteration in protein secretory process.

  3. Static Magnetic Field Attenuates Lipopolysaccharide-Induced Inflammation in Pulp Cells by Affecting Cell Membrane Stability

    Directory of Open Access Journals (Sweden)

    Sung-Chih Hsieh

    2015-01-01

    Full Text Available One of the causes of dental pulpitis is lipopolysaccharide- (LPS- induced inflammatory response. Following pulp tissue inflammation, odontoblasts, dental pulp cells (DPCs, and dental pulp stem cells (DPSCs will activate and repair damaged tissue to maintain homeostasis. However, when LPS infection is too serious, dental repair is impossible and disease may progress to irreversible pulpitis. Therefore, the aim of this study was to examine whether static magnetic field (SMF can attenuate inflammatory response of dental pulp cells challenged with LPS. In methodology, dental pulp cells were isolated from extracted teeth. The population of DPSCs in the cultured DPCs was identified by phenotypes and multilineage differentiation. The effects of 0.4 T SMF on DPCs were observed through MTT assay and fluorescent anisotropy assay. Our results showed that the SMF exposure had no effect on surface markers or multilineage differentiation capability. However, SMF exposure increases cell viability by 15%. In addition, SMF increased cell membrane rigidity which is directly related to higher fluorescent anisotropy. In the LPS-challenged condition, DPCs treated with SMF demonstrated a higher tolerance to LPS-induced inflammatory response when compared to untreated controls. According to these results, we suggest that 0.4 T SMF attenuates LPS-induced inflammatory response to DPCs by changing cell membrane stability.

  4. Lipopolysaccharide-induced Pulpitis Up-regulates TRPV1 in Trigeminal Ganglia

    Science.gov (United States)

    Chung, M.-K.; Lee, J.; Duraes, G.; Ro, J.Y.

    2011-01-01

    Tooth pain often accompanies pulpitis. Accumulation of lipopolysaccharides (LPS), a product of Gram-negative bacteria, is associated with painful clinical symptoms. However, the mechanisms underlying LPS-induced tooth pain are not clearly understood. TRPV1 is a capsaicin- and heat-gated nociceptive ion channel implicated in thermosensation and hyperalgesia under inflammation or injury. Although TRPV1 is expressed in pulpal afferents, it is not known whether the application of LPS to teeth modulates TRPV1 in trigeminal nociceptors. By assessing the levels of protein and transcript of TRPV1 in mouse trigeminal ganglia, we demonstrate that dentinal application of LPS increases the expression of TRPV1. Our results suggest that the up-regulation of TRPV1 in trigeminal nociceptors following bacterial infection could contribute to hyperalgesia under pulpitis conditions. PMID:21712529

  5. OPTICAL IMAGING OF LIPOPOLYSACCHARIDE-INDUCED OXIDATIVE STRESS IN ACUTE LUNG INJURY FROM HYPEROXIA AND SEPSIS

    Directory of Open Access Journals (Sweden)

    REYHANEH SEPEHR

    2013-07-01

    Full Text Available Reactive oxygen species (ROS have been implicated in the pathogenesis of many acute and chronic pulmonary disorders such as acute lung injury (ALI in adults and bronchopulmonary dysplasia (BPD in premature infants. Bacterial infection and oxygen toxicity, which result in pulmonary vascular endothelial injury, contribute to impaired vascular growth and alveolar simplification seen in the lungs of premature infants with BPD. Hyperoxia induces ALI, reduces cell proliferation, causes DNA damage and promotes cell death by causing mitochondrial dysfunction. The objective of this study was to use an optical imaging technique to evaluate the variations in fluorescence intensities of the auto-fluorescent mitochondrial metabolic coenzymes, NADH and FAD in four different groups of rats. The ratio of these fluorescence signals (NADH/FAD, referred to as NADH redox ratio (NADH RR has been used as an indicator of tissue metabolism in injuries. Here, we investigated whether the changes in metabolic state can be used as a marker of oxidative stress caused by hyperoxia and bacterial lipopolysaccharide (LPS exposure in neonatal rat lungs. We examined the tissue redox states of lungs from four groups of rat pups: normoxic (21% O2 pups, hyperoxic (90% O2 pups, pups treated with LPS (normoxic + LPS, and pups treated with LPS and hyperoxia (hyperoxic + LPS. Our results show that hyperoxia oxidized the respiratory chain as reflected by a ~ 31% decrease in lung tissue NADH RR as compared to that for normoxic lungs. LPS treatment alone or with hyperoxia had no significant effect on lung tissue NADH RR as compared to that for normoxic or hyperoxic lungs, respectively. Thus, NADH RR serves as a quantitative marker of oxidative stress level in lung injury caused by two clinically important conditions: hyperoxia and LPS exposure.

  6. CELECOXIB ATTENUATES SYSTEMIC LIPOPOLYSACCHARIDE-INDUCED BRAIN INFLAMMATION AND WHITE MATTER INJURY IN THE NEONATAL RATS

    Science.gov (United States)

    FAN, L.-W.; KAIZAKI, A.; TIEN, L.-T.; PANG, Y.; TANAKA, S.; NUMAZAWA, S.; BHATT, A. J.; CAI, Z.

    2013-01-01

    Lipopolysaccharide (LPS)-induced white matter injury in the neonatal rat brain is associated with inflammatory processes. Cyclooxygenase-2 (COX-2) can be induced by inflammatory stimuli, such as cytokines and pro-inflammatory molecules, suggesting that COX-2 may be considered as the target for anti-inflammation. The objective of the present study was to examine whether celecoxib, a selective COX-2 inhibitor, can reduce systemic LPS-induced brain inflammation and brain damage. Intraperitoneal (i.p.) injection of LPS (2 mg/kg) was performed in postnatal day 5 (P5) of Sprague-Dawley rat pups and celecoxib (20 mg/kg) or vehicle was administered i.p. 5 min after LPS injection. The body weight and wire hanging maneuver test were performed 24 hr after the LPS exposure, and brain injury was examined after these tests. Systemic LPS exposure resulted in an impairment of behavioral performance and acute brain injury, as indicated by apoptotic death of oligodendrocytes (OLs) and loss of OL immunoreactivity in the neonatal rat brain. Treatments with celecoxib significantly reduced systemic LPS-induced neurobehavioral disturbance and brain damage. Celecoxib administration significantly attenuated systemic LPS-induced increments in the number of activated microglia and astrocytes, concentrations of IL-1β and TNFα, and protein levels of phosphorylated-p38 MAPK in the neonatal rat brain. The protection of celecoxib was also associated with a reduction of systemic LPS-induced COX-2+ cells which were double labeled with GFAP+ (astrocyte) cells. The overall results suggest that celecoxib was capable of attenuating the brain injury and neurobehavioral disturbance induced by systemic LPS exposure, and the protective effects are associated with its anti-inflammatory properties. PMID:23485816

  7. NPS 2143, a selective calcium-sensing receptor antagonist inhibits lipopolysaccharide-induced pulmonary inflammation.

    Science.gov (United States)

    Lee, Jae-Won; Park, Hyun Ah; Kwon, Ok-Kyoung; Park, Ji-Won; Lee, Gilhye; Lee, Hee Jae; Lee, Seung Jin; Oh, Sei-Ryang; Ahn, Kyung-Seop

    2017-10-01

    NPS 2143, a novel and selective antagonist of calcium-sensing receptor (CaSR) has been reported to possess anti-inflammatory activity. In the present study, we examined the protective effect of NPS 2143 on lipopolysaccharide (LPS)-induced acute lung injury (ALI). NPS 2143 pretreatment significantly inhibited the influx of inflammatory cells and the expression of monocyte chemoattractant protein-1 (MCP-1) in the lung of mice with LPS-induced ALI. NPS 2143 decreased the levels of neutrophil elastase (NE) and protein concentration in the bronchoalveolar lavage fluid (BALF). NPS 2143 also reduced the production of inflammatory cytokines such as tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in the BALF and serum. In addition, NPS 2143 attenuated the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2), and increased the activation of AMP-activated protein kinase (AMPK) in the lung. NPS 2143 also downregulated the activation of nuclear factor-kappa B (NF-κB) in the lung. In LPS-stimulated H292 airway epithelial cells, NPS 2143 attenuated the releases of IL-6 and MCP-1. Furthermore, NPS 2143 upregulated the activation of AMPK and downregulated the activation of NF-κB. These results suggest that NPS 2143 could be potential agent for the treatment of inflammatory diseases including ALI. Copyright © 2017 Elsevier Ltd. All rights reserved.

  8. Lipopolysaccharide induces multinuclear cell from RAW264.7 line with increased phagocytosis activity

    Energy Technology Data Exchange (ETDEWEB)

    Nakanishi-Matsui, Mayumi, E-mail: nakanim@iwate-med.ac.jp [Department of Biochemistry, Faculty of Pharmaceutical Sciences, Iwate Medical University, Futai Special Laboratory, Yahaba, Iwate 028-3694 (Japan); Yano, Shio; Matsumoto, Naomi; Futai, Masamitsu [Department of Biochemistry, Faculty of Pharmaceutical Sciences, Iwate Medical University, Futai Special Laboratory, Yahaba, Iwate 028-3694 (Japan)

    2012-08-24

    Highlights: Black-Right-Pointing-Pointer LPS induces multinuclear cells from murine macrophage-derived RAW264.7 cells. Black-Right-Pointing-Pointer The multinuclear cells are formed through cell-cell fusion in the presence of Ca{sup 2+}. Black-Right-Pointing-Pointer The multinuclear cells do not express osteoclast-specific enzymes. Black-Right-Pointing-Pointer They internalized more and larger beads than mononuclear cells and osteoclasts. -- Abstract: Lipopolysaccharide (LPS), an outer membrane component of Gram-negative bacteria, induces strong proinflammatory responses, including the release of cytokines and nitric oxide from macrophage. In this study, we found that a murine macrophage-derived line, RAW264.7, became multinuclear through cell-cell fusion after incubation with highly purified LPS or synthetic lipid A in the presence of Ca{sup 2+}. The same cell line is known to differentiate into multinuclear osteoclast, which expresses a specific proton pumping ATPase together with osteoclast markers on stimulation by the extracellular domain of receptor activator of nuclear factor {kappa}B ligand (Toyomura, T., Murata, Y., Yamamoto, A., Oka, T., Sun-Wada, G.-H., Wada, Y. and Futai, M., 2003). The LPS-induced multinuclear cells did not express osteoclast-specific enzymes including tartrate-resistant acid phosphatase and cathepsin K. During multinuclear cell formation, the cells internalized more and larger polystyrene beads (diameter 6-15 {mu}m) than mononuclear cells and osteoclasts. The internalized beads were located in lysosome-marker positive organelles, which were probably phagolysosomes. The LPS-induced multinuclear cell could be a good model system to study phagocytosis of large foreign bodies.

  9. Biochanin A inhibits lipopolysaccharide-induced inflammation in human umbilical vein endothelial cells.

    Science.gov (United States)

    Ming, Xiaodong; Ding, Mingfeng; Zhai, Bo; Xiao, Lei; Piao, Taikui; Liu, Ming

    2015-09-01

    Biochanin A, an isoflavone isolated from red clover, cabbage or alfalfa, has been reported to have anti-inflammatory activity. However, the effects of biochanin A on vascular inflammation have not been investigated. In this study, we investigate the anti-inflammatory effects of biochanin A on lipopolysaccharide (LPS)-induced inflammatory response in human umbilical vein endothelial cells (HUVEC cells). The HUVEC cells were treated with biochanin A for 12h before exposure to LPS. The expression of ECAMs, including VCAM-1, ICAM-1, E-selectin, NF-κB and PPAR-γ was detected by Western blotting. The expression of cytokines TNF-α and IL-8 was detected by ELISA. The results showed that biochanin A inhibited LPS-induced TNF-α and IL-8 production. Meanwhile, biochanin A also suppressed VCAM-1, ICAM-1, and E-selectin expression induced by LPS. We also found that biochanin A inhibited NF-κB activation induced by LPS. Furthermore, biochanin A could activate PPAR-γ and the anti-inflammatory effects of biochanin A can be reversed by GW9662, a specific antagonist for PPAR-γ. In conclusion, the anti-inflammatory effect of biochanin A is associated with activating PPAR-γ, thereby attenuating NF-κB activation and LPS-induced inflammatory response. These findings suggest that biochanin A may be a therapeutic agent for inflammatory cardiovascular disease. Copyright © 2015 Elsevier Inc. All rights reserved.

  10. Decrease of plasma platelet-activating factor acetylhydrolase activity in lipopolysaccharide induced mongolian gerbil sepsis model.

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    Junwei Yang

    Full Text Available Platelet-activating factor (PAF plays an important role in the pathogenesis of sepsis, and the level of plasma PAF acetylhydrolase (pPAF-AH, which inactivates PAF, decreases in sepsis patients except for the sepsis caused by severe leptospirosis. Usually, increase of pPAF-AH activity was observed in lipopolysaccharide (LPS-induced Syrian hamster and rat sepsis models, while contradictory effects were reported for mouse model in different studies. Here, we demonstrated the in vivo effects of LPS upon the change of pPAF-AH activity in C57BL/6 mice and Mongolian gerbils. After LPS-treatment, the clinical manifestations of Mongolian gerbil model were apparently similar to that of C57BL/6 mouse sepsis model. The pPAF-AH activity increased in C57BL/6 mice after LPS induction, but decreased in Mongolian gerbils, which was similar to that of the human sepsis. It thus suggests that among the LPS-induced rodent sepsis models, only Mongolian gerbil could be used for the study of pPAF-AH related to the pathogenesis of human sepsis. Proper application of this model might enable people to clarify the underline mechanism accounted for the contradictory results between the phase II and phase III clinical trials for the administration of recombinant human pPAF-AH in the sepsis therapy.

  11. Lipopolysaccharide-induced metabolome signature in Arabidopsis thaliana reveals dynamic reprogramming of Phytoalexin and Phytoanticipin pathways

    CSIR Research Space (South Africa)

    Finnegan, T

    2016-09-01

    Full Text Available tentatively identified. These include the phytohormones salicylic acid and jasmonic acid, and also the associated methyl esters and sugar conjugates. The induced defensive state resulted in increases in indoleÐand other glucosinolates, indole derivatives...

  12. Bacterial lipopolysaccharide induces osteoclast formation in RAW 264.7 macrophage cells

    International Nuclear Information System (INIS)

    Islam, Shamima; Hassan, Ferdaus; Tumurkhuu, Gantsetseg; Dagvadorj, Jargalsaikhan; Koide, Naoki; Naiki, Yoshikazu; Mori, Isamu; Yoshida, Tomoaki; Yokochi, Takashi

    2007-01-01

    Lipopolysaccharide (LPS) is a potent bone resorbing factor. The effect of LPS on osteoclast formation was examined by using murine RAW 264.7 macrophage cells. LPS-induced the formation of multinucleated giant cells (MGC) in RAW 264.7 cells 3 days after the exposure. MGCs were positive for tartrate-resistant acid phosphatase (TRAP) activity. Further, MGC formed resorption pits on calcium-phosphate thin film that is a substrate for osteoclasts. Therefore, LPS was suggested to induce osteoclast formation in RAW 264.7 cells. LPS-induced osteoclast formation was abolished by anti-tumor necrosis factor (TNF)-α antibody, but not antibodies to macrophage-colony stimulating factor (M-CSF) and receptor activator of nuclear factor (NF)-κB ligand (RANKL). TNF-α might play a critical role in LPS-induced osteoclast formation in RAW 264.7 cells. Inhibitors of NF-κB and stress activated protein kinase (SAPK/JNK) prevented the LPS-induced osteoclast formation. The detailed mechanism of LPS-induced osteoclast formation is discussed

  13. Activation of PPARα by Wy-14643 ameliorates systemic lipopolysaccharide-induced acute lung injury

    Energy Technology Data Exchange (ETDEWEB)

    Yoo, Seong Ho, E-mail: yoosh@snu.ac.kr [Seoul National University Hospital, Biomedical Research Institute and Institute of Forensic Medicine, Seoul National University College of Medicine, Seoul (Korea, Republic of); Abdelmegeed, Mohamed A. [Laboratory of Membrane Biochemistry and Biophysics, National Institute on Alcohol Abuse and Alcoholism, Bethesda, MD (United States); Song, Byoung-Joon, E-mail: bj.song@nih.gov [Laboratory of Membrane Biochemistry and Biophysics, National Institute on Alcohol Abuse and Alcoholism, Bethesda, MD (United States)

    2013-07-05

    Highlights: •Activation of PPARα attenuated LPS-mediated acute lung injury. •Pretreatment with Wy-14643 decreased the levels of IFN-γ and IL-6 in ALI. •Nitrosative stress and lipid peroxidation were downregulated by PPARα activation. •PPARα agonists may be potential therapeutic targets for acute lung injury. -- Abstract: Acute lung injury (ALI) is a major cause of mortality and morbidity worldwide. The activation of peroxisome proliferator-activated receptor-α (PPARα) by its ligands, which include Wy-14643, has been implicated as a potential anti-inflammatory therapy. To address the beneficial efficacy of Wy-14643 for ALI along with systemic inflammation, the in vivo role of PPARα activation was investigated in a mouse model of lipopolysaccharide (LPS)-induced ALI. Using age-matched Ppara-null and wild-type mice, we demonstrate that the activation of PPARα by Wy-14643 attenuated LPS-mediated ALI. This was evidenced histologically by the significant alleviation of inflammatory manifestations and apoptosis observed in the lung tissues of wild-type mice, but not in the corresponding Ppara-null mice. This protective effect probably resulted from the inhibition of LPS-induced increases in pro-inflammatory cytokines and nitroxidative stress levels. These results suggest that the pharmacological activation of PPARα might have a therapeutic effect on LPS-induced ALI.

  14. Activation of PPARα by Wy-14643 ameliorates systemic lipopolysaccharide-induced acute lung injury

    International Nuclear Information System (INIS)

    Yoo, Seong Ho; Abdelmegeed, Mohamed A.; Song, Byoung-Joon

    2013-01-01

    Highlights: •Activation of PPARα attenuated LPS-mediated acute lung injury. •Pretreatment with Wy-14643 decreased the levels of IFN-γ and IL-6 in ALI. •Nitrosative stress and lipid peroxidation were downregulated by PPARα activation. •PPARα agonists may be potential therapeutic targets for acute lung injury. -- Abstract: Acute lung injury (ALI) is a major cause of mortality and morbidity worldwide. The activation of peroxisome proliferator-activated receptor-α (PPARα) by its ligands, which include Wy-14643, has been implicated as a potential anti-inflammatory therapy. To address the beneficial efficacy of Wy-14643 for ALI along with systemic inflammation, the in vivo role of PPARα activation was investigated in a mouse model of lipopolysaccharide (LPS)-induced ALI. Using age-matched Ppara-null and wild-type mice, we demonstrate that the activation of PPARα by Wy-14643 attenuated LPS-mediated ALI. This was evidenced histologically by the significant alleviation of inflammatory manifestations and apoptosis observed in the lung tissues of wild-type mice, but not in the corresponding Ppara-null mice. This protective effect probably resulted from the inhibition of LPS-induced increases in pro-inflammatory cytokines and nitroxidative stress levels. These results suggest that the pharmacological activation of PPARα might have a therapeutic effect on LPS-induced ALI

  15. Protein Kinase C is a Mediator of Lipopolysaccharide-Induced Vascular Suppression in the Rat Aorta

    Science.gov (United States)

    1994-01-01

    vascular suppression. INTRODUCTION activator phorbol 12-myristate 13-acetate. or exposure to 20c% Cardiovascular tissue from septic animals shows...15 nun at ll’C). The supernatanut tra~s recovered and (Escltsric/tiui ictu LPS serouvpe 1155:B5i) wNas obtained fromt Difeo.Dto.Ml estr ~ieted threLe

  16. Prostaglandins E1 and E2 inhibit lipopolysaccharide-induced interleukin-18 production in monocytes.

    Science.gov (United States)

    Takahashi, Hideo K; Iwagaki, Hiromi; Mori, Shuji; Yoshino, Tadashi; Tanaka, Noriaki; Nishibori, Masahiro

    2005-07-11

    The purpose of this present study was to explore the therapeutic potential of prostaglandins E1 and E2 on the systemic inflammatory response evoked by endotoxin. Since interleukin-18, a monocyte-derived cytokine, is increased during sepsis, decreasing the production of interleukin-18 is important in treating this condition. Prostaglandin E1 and E2 inhibited interleukin-18 production in human monocytes treated with lipopolysaccharide and prostanoid IP-, EP2- and EP4-receptor agonists mimicked the effects of prostaglandins E1 and E2. Therefore, prostanoid IP, EP2- and EP4-receptors might be involved in the decrease in interleukin-18 production during sepsis.

  17. Ameliorating effects of traditional Chinese medicine on lipopolysaccharide -induced microcirculatory disturbances and organ injury.

    Science.gov (United States)

    Sun, Kai; Pan, Chun-Sui; Li, Quan; Furukawa, Osamu; Fan, Jing-Yu; Han, Jing-Yan

    2015-03-16

    Gram-negative bacteria are one of the major pathogens associated with severe sepsis and septic shock. LPS is a component of the outer membrane of gram-negative bacteria, which causes a systemic, uncontrolled inflammatory response in infected subjects. In microcirculation it manifests multiple insults, including leukocyte and platelet adhesion, ROS and protease overproduction, mast cell degranulation, endothelium hyperpermeabilty, hemorrhage, and microthrombi formation, ultimately results in multiorgan dysfunction, DIC, refractory shock and even death. TCM has been used in China, Korea, Japan and other Asian countries for treatment of a wide range of diseases. In China, the usage of compound traditional preparation to treat inflammation-related diseases dates back to the Han Dynasty and the medical formulary had been developed thousands of years before, which recorded a great number of classical prescriptions for treatment with infectious diseases. This review will summarize the up to date works with respect to the ameliorating effects of compound and single traditional Chinese medicine and active components on LPS-induced inflammation, including clinical trial and experimental studies regarding multiorgan injury and underlying mechanisms.

  18. Improved Hepatoprotective Effect of Liposome-Encapsulated Astaxanthin in Lipopolysaccharide-Induced Acute Hepatotoxicity

    Directory of Open Access Journals (Sweden)

    Chun-Hung Chiu

    2016-07-01

    Full Text Available Lipopolysaccharide (LPS-induced acute hepatotoxicity is significantly associated with oxidative stress. Astaxanthin (AST, a xanthophyll carotenoid, is well known for its potent antioxidant capacity. However, its drawbacks of poor aqueous solubility and low bioavailability have limited its utility. Liposome encapsulation is considered as an effective alternative use for the improvement of bioavailability of the hydrophobic compound. We hypothesized that AST encapsulated within liposomes (LA apparently shows improved stability and transportability compared to that of free AST. To investigate whether LA administration can efficiently prevent the LPS-induced acute hepatotoxicity, male Sprague-Dawley rats (n = six per group were orally administered liposome-encapsulated AST at 2, 5 or 10 mg/kg-day (LA-2, LA-5, and LA-10 for seven days and then were LPS-challenged (i.p., 5 mg/kg. The LA-10 administered group, but not the other groups, exhibited a significant amelioration of serum glutamic pyruvic transaminase (GPT, glutamic oxaloacetic transaminase (GOT, blood urea nitrogen (BUN, creatinine (CRE, hepatic malondialdehyde (MDA and glutathione peroxidase (GSH-Px, IL-6, and hepatic nuclear NF-κB and inducible nitric oxide synthase (iNOS, suggesting that LA at a 10 mg/kg-day dosage renders hepatoprotective effects. Moreover, the protective effects were even superior to that of positive control N-acetylcysteine (NAC, 200 mg/kg-day. Histopathologically, NAC, free AST, LA-2 and LA-5 partially, but LA-10 completely, alleviated the acute inflammatory status. These results indicate that hydrophobic AST after being properly encapsulated by liposomes improves bioavailability and can also function as potential drug delivery system in treating hepatotoxicity.

  19. Lipopolysaccharide induces immune activation and SIV replication in rhesus macaques of Chinese origin.

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    Rong Bao

    Full Text Available BACKGROUND: Chronic immune activation is a hallmark of progressive HIV infection and a key determinant of immunodeficiency in HIV-infected individuals. Bacterial lipopolysaccharide (LPS in the circulation has been implicated as a key factor in HIV infection-related systemic immune activation. We thus investigate the impact of LPS on systemic immune activation in simian immunodeficiency virus (SIV-infected rhesus macaques of Chinese origin. METHODS: The animals were inoculated intravenously with SIVmac239. The levels of plasma viral load and host inflammatory cytokines in PBMC were measured by real-time RT-PCR. CD4/CD8 ratio and systemic immune activation markers were examined by flow cytometric analysis of PBMCs. White blood cell and neutrophil counts and C Reactive Protein levels were determined using biochemistry analyzer. The plasma levels of LPS were determined by Tachypleus Amebocyte Lysate (TAL test. RESULTS: The animals inoculated with SIVmac239 became infected as evidenced by the increased plasma levels of SIV RNA and decreased CD4/CD8 ratio. LPS administration of SIV-infected animals induced a transient increase of plasma SIV RNA and immune activation, which was indicated by the elevated expression of the inflammatory cytokines and CD4+HLA-DR+ T cells in PBMCs. CONCLUSIONS: These data support the concept that LPS is a driving factor in systemic immune activation of HIV disease.

  20. Equine colostral carbohydrates reduce lipopolysaccharide-induced inflammatory responses in equine peripheral blood mononuclear cells.

    Science.gov (United States)

    Vendrig, J C; Coffeng, L E; Fink-Gremmels, J

    2012-12-01

    Increasing evidence suggests that reactions to lipopolysaccharide (LPS), particularly in the gut, can be partly or completely mitigated by colostrum- and milk-derived oligosaccharides. Confirmation of this hypothesis could lead to the development of new therapeutic concepts. To demonstrate the influence of equine colostral carbohydrates on the inflammatory response in an in vitro model with equine peripheral blood mononuclear cells (PBMCs). Carbohydrates were extracted from mare colostrum, and then evaluated for their influence on LPS-induced inflammatory responses in PBMCs isolated from the same mares, mRNA expression of tumour necrosis factor-alpha, interleukin-6 and interleukin-10 was measured as well as the protein levels of tumour necrosis factor-alpha (TNF-alpha) and interleukin-10 (IL-10). Equine colostral carbohydrates significantly reduced LPS-induced TNF-alpha protein at both times measured and significantly reduced LPS-induced TNF-alpha, IL-6 and IL-10 mRNA expression by PBMCs. Moreover, cell viability significantly increased in the presence of high concentrations of colostral carbohydrates. Carbohydrates derived from equine colostrum reduce LPS-induced inflammatory responses of equine PBMCs. Colostrum and milk-derived carbohydrates are promising candidates for new concepts in preventive and regenerative medicine.

  1. Cerium oxide nanoparticles inhibit lipopolysaccharide induced MAP kinase/NF-kB mediated severe sepsis

    Directory of Open Access Journals (Sweden)

    Vellaisamy Selvaraj

    2015-09-01

    Full Text Available The life threatening disease of sepsis is associated with high mortality. Septic patient survivability with currently available treatments has failed to improve. The purpose of this study was to evaluate whether lipopolysaccharide (LPS induced sepsis mortality and associated hepatic dysfunction can be prevented by cerium oxide nanoparticles (CeO2NPs treatment in male Sprague Dawley rats. Here we provide the information about the methods processing of raw data related to our study published in Biomaterials (Selvaraj et al., Biomaterials, 2015, In press and Data in Brief (Selvaraj et al., Data in Brief, 2015, In Press. The data present here provides confirmation of cerium oxide nanoparticle treatments ability to prevent the LPS induced sepsis associated changes in physiological, blood cell count, inflammatory protein and growth factors in vivo. In vitro assays investigation the treated of macrophages cells with different concentrations of cerium oxide nanoparticle demonstrate that concentration of cerium oxide nanoparticles below 1 µg/ml did not significantly influence cell survival as determined by the MTT assay.

  2. Lipopolysaccharide induced MAP kinase activation in RAW 264.7 cells attenuated by cerium oxide nanoparticles

    Directory of Open Access Journals (Sweden)

    Vellaisamy Selvaraj

    2015-09-01

    Full Text Available High mortality rates are associated with the life threatening disease of sepsis. Improvements in septic patient survivability have failed to materialize with currently available treatments. This article represents data regarding a study published in biomaterials (Vellaisamy et al., Biomaterials, 2015, in press. with the purpose of evaluating whether severe sepsis mortality and associated hepatic dysfunction induced by lipopolysaccharide (LPS can be prevented by cerium oxide nanoparticles (CeO2NPs treatment in male Sprague Dawley rats. Here we provide the information about the method and processing of raw data related to our study publish in Biomaterials and Data in Brief (Vellaisamy et al., Biomaterials, 2015, in press; Vellaisamy et al., Data in Brief, 2015, in press.. The data contained in this article evaluates the contribution of MAPK signaling in LPS induced sepsis. Macrophage cells (RAW 264.7 were treated with a range of cerium oxide nanoparticle concentration in the presence and absence of LPS. Immunoblotting was performed on the cell lysates to evaluate the effect of cerium oxide nanoparticle treatment on LPS induced changes in Mitogen Activated Protein Kinases (MAPK p-38, ERK 1/2, and SAPK/JNK phosphorylation.

  3. A dibenzoylmethane derivative inhibits lipopolysaccharide-induced NO production in mouse microglial cell line BV-2.

    Science.gov (United States)

    Takano, Katsura; Ishida, Natsumi; Kawabe, Kenji; Moriyama, Mitsuaki; Hibino, Satoshi; Choshi, Tominari; Hori, Osamu; Nakamura, Yoichi

    2017-04-05

    Microglial activation has been suggested to play important roles in various neurodegenerative diseases by phagocytosis and producing various factors such as nitric oxide (NO), proinflammatory cytokines. Excessive production of NO, as a consequence of increased inducible nitric oxide synthase (iNOS) in microglia, contributes to the neurodegeneration. During a search for compounds that regulate endoplasmic reticulum (ER) stress, a dibenzoylmethane derivative, 2,2'-dimethoxydibenzoylmethane (DBM 14-26) was identified as a novel neuroprotective agent (Takano et al., Am. J. Physiol. Cell Physiol. 293, C1884-1894, 2007). We previously reported in cultured astrocytes that DBM 14-26 protected hydrogen peroxide-induced cell death and inhibited lipopolysaccharide (LPS)-induced NO production (Takano et al., J. Neurosci. Res. 89, 955-965, 2011). In the present study, we assessed the effects of DBM 14-26 on microglia using the mouse cell line BV-2 and found that DBM 14-26 inhibited LPS-induced iNOS expression and NO production also in microglia. DBM 14-26 also suppressed LPS-induced IL-1β expression. Conditioned medium of BV-2 cells stimulated by LPS significantly decreased cell viability of neuron (human neuroblastoma SH-SY5Y cells) compared with the absence of LPS. Conditioned medium of BV-2 cells stimulated by LPS in the presence of DBM 14-26 did not significantly decreased cell viability of neuron. These results indicate that microglial activation by LPS causes neuronal cell death and DBM 14-26 protect neuron through the inhibition of microglial activation. Functional regulation of microglia by DBM 14-26 could be a therapeutic candidate for the treatment of neurodegenerative diseases. Copyright © 2017 Elsevier Ltd. All rights reserved.

  4. The inhibitory principle of lipopolysaccharide-induced nitric oxide production from Inula britannica var. chinensis.

    Science.gov (United States)

    Je, Kang-Hoon; Han, Ah-Reum; Lee, Hyun-Tai; Mar, Woongchon; Seo, Eun-Kyoung

    2004-01-01

    A sesquiterpene lactone, 1-O-acetyl-4R,6S-britannilactone (1) isolated from the flowers of Inula britannica L. var. chinensis (Rupr.) Reg. (Compositae), was found as an iNOS inhibitory constituent for the first time with an IC50 value of 22.1 microM which is more potent than the positive control, L-N6-(1-iminoethyl)lysine (IC50 = 33.7 microM). Structure of compound 1 was identified by 1D and 2D NMR experiments and by comparison with the reference standard.

  5. Rabdosia japonica var. glaucocalyx Flavonoids Fraction Attenuates Lipopolysaccharide-Induced Acute Lung Injury in Mice

    Directory of Open Access Journals (Sweden)

    Chun-jun Chu

    2014-01-01

    Full Text Available Rabdosia japonica var. glaucocalyx (Maxim. Hara, belonging to the Labiatae family, is widely used as an anti-inflammatory and antitumor drug for the treatment of different inflammations and cancers. Aim of the Study. To investigate therapeutic effects and possible mechanism of the flavonoids fraction of Rabdosia japonica var. glaucocalyx (Maxim. Hara (RJFs in acute lung injury (ALI mice induced by lipopolysaccharide (LPS. Materials and Methods. Mice were orally administrated with RJFs (6.4, 12.8, and 25.6 mg/kg per day for 7 days, consecutively, before LPS challenge. Lung specimens and the bronchoalveolar lavage fluid (BALF were isolated for histopathological examinations and biochemical analysis. The level of complement 3 (C3 in serum was quantified by a sandwich ELISA kit. Results. RJFs significantly attenuated LPS-induced ALI via reducing productions of the level of inflammatory mediators (TNF-α, IL-6, and IL-1β, and significantly reduced complement deposition with decreasing the level of C3 in serum, which was exhibited together with the lowered myeloperoxidase (MPO activity and nitric oxide (NO and protein concentration in BALF. Conclusions. RJFs significantly attenuate LPS-induced ALI via reducing productions of proinflammatory mediators, decreasing the level of complement, and reducing radicals.

  6. Beneficial effect of honokiol on lipopolysaccharide induced anxiety-like behavior and liver damage in mice.

    Science.gov (United States)

    Sulakhiya, Kunjbihari; Kumar, Parveen; Gurjar, Satendra S; Barua, Chandana C; Hazarika, Naba K

    2015-02-26

    Anxiety disorders are commonly occurring co-morbid neuropsychiatric disorders with chronic inflammatory conditions such as live damage. Numerous studies revealed that peripheral inflammation, oxidative stress and brain derived neurotrophic factor (BDNF) play important roles in the pathophysiology of anxiety disorders. Honokiol (HNK) is a polyphenol, possessing multiple biological activities including antioxidant, anti-inflammatory, anxiolytic, antidepressant and hepatoprotection. The present study was designed to investigate the effect of HNK, in lipopolysaccharide (LPS)-induced anxiety-like behavior and liver damage in mice. Mice (n=6-10/group) were pre-treated with different doses of HNK (2.5 and 5mg/kg; i.p.) for two days, and challenged with saline or LPS (0.83mg/kg; i.p.) on third day. Anxiety-like behavior was monitored using elevated plus maze (EPM) and open field test (OFT). Animals were sacrificed to evaluate various biochemical parameters in plasma and liver. HNK pre-treatment provided significant (P<0.01) protection against LPS-induced reduction in body weight, food and water intake in mice. HNK at higher dose significantly (P<0.05) attenuated LPS-induced anxiety-like behavior by increasing the number of entries and time spent in open arm in EPM test, and by increasing the frequency in central zone in OFT. HNK pre-treatment ameliorated LPS-induced peripheral inflammation by reducing plasma IL-1β, IL-6, TNF-α level, and also improved the plasma BDNF level, prevented liver damage via attenuating transaminases (AST, ALT), liver oxidative stress and TNF-α activity in LPS challenged mice. In conclusion, the current investigation suggests that HNK provided beneficial effect against LPS-induced anxiety-like behavior and liver damage which may be governed by inhibition of cytokines production, oxidative stress and depletion of plasma BDNF level. Our result suggests that HNK could be a therapeutic approach for the treatment of anxiety and other neuropsychiatric disorders associated with inflammation and oxidative stress. Copyright © 2015 Elsevier Inc. All rights reserved.

  7. Cepharanthine attenuates lipopolysaccharide-induced mice mastitis by suppressing the NF-κB signaling pathway.

    Science.gov (United States)

    Ershun, Zhou; Yunhe, Fu; Zhengkai, Wei; Yongguo, Cao; Naisheng, Zhang; Zhengtao, Yang

    2014-04-01

    Cepharanthine (CEP), a biscoclaurine alkaloid isolated from Stephania cepharantha Hayata, has been reported to have potent anti-inflammatory properties. However, the anti-inflammatory effects of CEP on a mouse model of lipopolysaccharide (LPS)-induced mastitis and its underlying molecular mechanisms remain to be elucidated. The purpose of the present study was to investigate the effects of CEP on LPS-induced mouse mastitis. The mouse model of mastitis was induced by inoculation of LPS through the canals of the mammary gland. CEP was administered intraperitoneally at 1 h before and 12 h after induction of LPS. The results show that CEP significantly attenuates the infiltration of neutrophils, suppresses myeloperoxidase activity, and reduces the levels of TNF-α, IL-1β, and IL-6 in LPS-induced mouse mastitis. Furthermore, CEP inhibited the phosphorylation of NF-κB p65 subunit and the degradation of its inhibitor IκBα. All the results suggest that CEP exerts potent anti-inflammatory effects on LPS-induced mouse mastitis. Accordingly, CEP might be a potential therapeutic agent for mastitis.

  8. Protective effects of melatonin on lipopolysaccharide-induced mastitis in mice.

    Science.gov (United States)

    Shao, Guoxi; Tian, Yinggang; Wang, Haiyu; Liu, Fangning; Xie, Guanghong

    2015-12-01

    Melatonin, a secretory product of the pineal gland, has been reported to have antioxidant and anti-inflammatory effects. However, the protective effects of melatonin on lipopolysaccharide (LPS)-induced mastitis have not been reported. The purpose of this study was to investigate the anti-inflammatory effects and the underlying mechanisms of melatonin on LPS-induced mastitis both in vivo and in vitro. In vivo, our results showed that melatonin attenuated LPS-induced mammary histopathologic changes and myeloperoxidase (MPO) activity. Melatonin also inhibited LPS-induced inflammatory cytokines tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and interleukin-6 (IL-6) production in mammary tissues. In vitro, melatonin was found to inhibit LPS-induced TNF-α and IL-6 production in mouse mammary epithelial cells. Melatonin also suppressed LPS-induced Toll-like receptor 4 (TLR4) expression and nuclear factor-kappaB (NF-κB) activation in a dose-dependent manner. In addition, melatonin was found to up-regulate the expression of PPAR-γ. Inhibition of PPAR-γ by GW9662 reduced the anti-inflammatory effects of melatonin. In conclusion, we found that melatonin, for the first time, had protective effects on LPS-induced mastitis in mice. The anti-inflammatory mechanism of melatonin was through activating PPAR-γ which subsequently inhibited LPS-induced inflammatory responses. Copyright © 2015 Elsevier B.V. All rights reserved.

  9. Dietary L-arginine supplementation modulates lipopolysaccharide-induced systemic inflammatory response in broiler chickens

    Science.gov (United States)

    This study was conducted to evaluate whether dietary supplementation with L-arginine (Arg) could attenuate lipopolysaccharide (LPS)-induced systemic inflammatory response through LPS/TLR-4 signaling pathway in broilers. The experiment was designed as a 2 × 3 factorial arrangement (n = 8 cages/treatm...

  10. Dietary L-arginine supplementation attenuates lipopolysaccharide-induced inflammatory response in broiler chickens.

    Science.gov (United States)

    Tan, Jianzhuang; Liu, Shasha; Guo, Yuming; Applegate, Todd J; Eicher, Susan D

    2014-04-28

    In the present study, two experiments were conducted to investigate the effect of dietary L-arginine (Arg) supplementation on the inflammatory response and innate immunity of broiler chickens. Expt 1 was designed as a 2 × 3 factorial arrangement (n 8 cages/treatment; n 6 birds/cage) with three dietary Arg concentrations (1.05, 1.42 and 1.90%) and two immune treatments (injection of lipopolysaccharide (LPS) or saline) given at an interval of 48 h between 14 and 21 d of age. In Expt 2, correlation between dietary Arg concentration (0.99, 1.39, 1.76, 2.13 or 2.53%) and percentage of circulating B cells (percentage of circulating lymphocytes) was determined. In Expt 1, LPS injection decreased body-weight gain and feed intake and increased feed conversion ratio of the challenged broilers (14-21 d; Psupplementation linearly decreased the percentages of CD11+, CD14+ and B cells in the spleen (Psupplementation decreased (Psupplementation attenuated the overexpression of pro-inflammatory cytokines probably through the suppression of the TLR4 pathway and CD14+ cell percentage. Furthermore, excessive Arg supplementation (1.76%) suppressed the percentages of circulating and splenic B cells.

  11. Dietary L-arginine supplementation attenuates lipopolysaccharide-induced inflammatory response in broiler chickens

    Science.gov (United States)

    Two experiments were conducted to investigate the effect of dietary L-arginine (Arg) supplementation on inflammatory response and innate immunity of broilers. Experiment 1 was designed as a 2 × 3 factorial arrangement (n = 8 cages/treatment; 6 birds/cage) with 3 dietary Arg concentrations (1.05, 1.4...

  12. Effect of azithromycin on Prevotella intermedia lipopolysaccharide-induced production of interleukin-6 in murine macrophages.

    Science.gov (United States)

    Choi, Eun-Young; Jin, Ji-Young; Choi, Jeom-Il; Choi, In Soon; Kim, Sung-Jo

    2014-04-15

    Interleukin-6 (IL-6) is a key proinflammatory cytokine which plays a central role in the pathogenesis of periodontal disease. Host modulatory agents targeting at inhibiting IL-6, therefore, appear to be beneficial in slowing the progression of periodontal disease and potentially reducing destructive aspects of the host response. The present study was designed to investigate the effect of the macrolide antibiotic azithromycin on IL-6 generation in murine macrophages treated with lipopolysaccharide (LPS) from Prevotella intermedia, a pathogen implicated in inflammatory periodontal disease, and its mechanisms of action. Azithromycin significantly suppressed IL-6 production as well as its mRNA expression in P. intermedia LPS-activated RAW264.7 cells. LPS-induced activation of JNK and p38 was not affected by azithromycin treatment. Azithromycin failed to prevent P. intermedia LPS from degrading IκB-α. Instead, azithromycin significantly diminished nuclear translocation and DNA binding activity of NF-κB p50 subunit induced with LPS. Azithromycin inhibited P. intermedia LPS-induced STAT1 and STAT3 phosphorylation. In addition, azithromycin up-regulated the mRNA level of SOCS1 in cells treated with LPS. In conclusion, azithromycin significantly attenuated P. intermedia LPS-induced production of IL-6 in murine macrophages via inhibition of NF-κB, STAT1 and STAT3 activation, which is possibly related to the activation of SOCS1 signaling. Further in vivo studies are required to better evaluate the potential of azithromycin in the treatment of periodontal disease. Copyright © 2014 Elsevier B.V. All rights reserved.

  13. Lipopolysaccharide-induced neuronal activation in the paraventricular and dorsomedial hypothalamus depends on ambient temperature.

    Directory of Open Access Journals (Sweden)

    Samuel P Wanner

    Full Text Available Systemic inflammatory response syndrome is associated with either fever or hypothermia, but the mechanisms responsible for switching from one to the other are unknown. In experimental animals, systemic inflammation is often induced by bacterial lipopolysaccharide (LPS. To identify the diencephalic and brainstem structures involved in the fever-hypothermia switch, we studied the expression of c-Fos protein, a marker of neuronal activation, in rats treated with the same high dose of LPS (0.5 mg/kg, intravenously either in a thermoneutral (30 °C or cool (24 °C environment. At 30 °C, LPS caused fever; at 24 °C, the same dose caused profound hypothermia. Both fever and hypothermia were associated with the induction of c-Fos in many brain areas, including several structures of the anterior preoptic, paraventricular, lateral, and dorsal hypothalamus, the bed nucleus of the stria terminalis, the posterior pretectal nucleus, ventrolateral periaqueductal gray, lateral parabrachial nucleus, area postrema, and nucleus of the solitary tract. Every brain area studied showed a comparable response to LPS at the two different ambient temperatures used, with the exception of two areas: the dorsomedial hypothalamic nucleus (DMH, which we studied together with the adjacent dorsal hypothalamic area (DA, and the paraventricular hypothalamic nucleus (PVH. Both structures had much stronger c-Fos expression during LPS hypothermia than during fever. We propose that PVH and DMH/DA neurons are involved in a circuit, which - depending on the ambient temperature - determines whether the thermoregulatory response to bacterial LPS will be fever or hypothermia.

  14. Poly(Adp-ribose) synthetase inhibition prevents lipopolysaccharide-induced peroxynitrite mediated damage in diaphragm.

    Science.gov (United States)

    Ozdülger, Ali; Cinel, Ismail; Unlü, Ali; Cinel, Leyla; Mavioglu, Ilhan; Tamer, Lülüfer; Atik, Ugur; Oral, Ugur

    2002-07-01

    Although the precise mechanism by which sepsis causes impairment of respiratory muscle contractility has not been fully elucidated, oxygen-derived free radicals are thought to play an important role. In our experimental study, the effects of poly(ADP-ribose) synthetase (PARS) inhibition on the diaphragmatic Ca(2+)-ATPase, malondialdehyde (MDA), and 3-nitrotyrosine (3-NT) levels and additionally histopathology of the diaphragm in lipopolysaccharide (LPS)-induced endotoxemia are investigated.Thirty-two male Wistar rats, weighing between 180-200 g were randomly divided into four groups. The first group (control; n=8) received saline solution and the second (LPS group; n=8) 10 mgkg(-1) LPS i.p. 3-Aminobenzamide (3-AB) as a PARS inhibitor; was given to the third group (C+3-AB, n=8) 20 min before administration of saline solution while the fourth group (LPS+3-AB, n=8) received 3-AB 20 min before LPS injection. Six hours later, under ketamin/xylasine anesthesia diapraghmatic specimens were obtained and the rats were decapitated. Diaphragmatic specimens were divided into four parts, three for biochemical analyses and one for histopathologic assessment. In the LPS group, tissue Ca(2+)-ATPase levels were found to be decreased and tissue MDA and 3-NT levels were found to be increased (P<0.05). In the LPS+3-AB group, 3-AB pretreatment inhibited the increase in MDA and 3-NT levels and Ca(2+)-ATPase activity remained similar to those in the control group (P<0.05). Histopathologic examination of diaphragm showed edema between muscle fibers only in LPS group. PARS inhibition with 3-AB prevented not only lipid peroxidation but also the decrease of Ca(2+)-ATPase activity in endotoxemia. These results highlights the importance of nitric oxide (NO)-peroxynitrite (ONOO(-))-PARS pathway in preventing free radical mediated injury. PARS inhibitors should further be investigated as a new thearapetic alternative in sepsis treatment.

  15. Cigarette smoke and lipopolysaccharide induce a proliferative airway smooth muscle phenotype

    Directory of Open Access Journals (Sweden)

    Zaagsma Johan

    2010-04-01

    Full Text Available Abstract Background A major feature of chronic obstructive pulmonary disease (COPD is airway remodelling, which includes an increased airway smooth muscle (ASM mass. The mechanisms underlying ASM remodelling in COPD are currently unknown. We hypothesized that cigarette smoke (CS and/or lipopolysaccharide (LPS, a major constituent of CS, organic dust and gram-negative bacteria, that may be involved in recurrent airway infections and exacerbations in COPD patients, would induce phenotype changes of ASM. Methods To this aim, using cultured bovine tracheal smooth muscle (BTSM cells and tissue, we investigated the direct effects of CS extract (CSE and LPS on ASM proliferation and contractility. Results Both CSE and LPS induced a profound and concentration-dependent increase in DNA synthesis in BTSM cells. CSE and LPS also induced a significant increase in BTSM cell number, which was associated with increased cyclin D1 expression and dependent on activation of ERK 1/2 and p38 MAP kinase. Consistent with a shift to a more proliferative phenotype, prolonged treatment of BTSM strips with CSE or LPS significantly decreased maximal methacholine- and KCl-induced contraction. Conclusions Direct exposure of ASM to CSE or LPS causes the induction of a proliferative, hypocontractile ASM phenotype, which may be involved in airway remodelling in COPD.

  16. Effects of propofol on lipopolysaccharide-induced expression and release of HMGB1 in macrophages

    Energy Technology Data Exchange (ETDEWEB)

    Wang, T.; Wei, X.Y.; Liu, B.; Wang, L.J.; Jiang, L.H. [Department of Anesthesiology, the Third Affiliated Hospital, Zhengzhou University, Zhengzhou (China)

    2015-02-24

    This study aimed to determine the effects of different concentrations of propofol (2,6-diisopropylphenol) on lipopolysaccharide (LPS)-induced expression and release of high-mobility group box 1 protein (HMGB1) in mouse macrophages. Mouse macrophage cell line RAW264.7 cells were randomly divided into 5 treatment groups. Expression levels of HMGB1 mRNA were detected using RT-PCR, and cell culture supernatant HMGB1 protein levels were detected using enzyme-linked immunosorbent assay (ELISA). Translocation of HMGB1 from the nucleus to the cytoplasm in macrophages was observed by Western blotting and activity of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) in the nucleus was detected using ELISA. HMGB1 mRNA expression levels increased significantly in the cell culture supernatant and in cells after 24 h of stimulating RAW264.7 cells with LPS (500 ng/mL). However, HMGB1 mRNA expression levels in the P2 and P3 groups, which received 500 ng/mL LPS with 25 or 50 μmol/mL propofol, respectively, were significantly lower than those in the group receiving LPS stimulation (P<0.05). After stimulation by LPS, HMGB1 protein levels were reduced significantly in the nucleus but were increased in the cytoplasm (P<0.05). Simultaneously, the activity of NF-κB was enhanced significantly (P<0.05). After propofol intervention, HMGB1 translocation from the nucleus to the cytoplasm and NF-κB activity were inhibited significantly (each P<0.05). Thus, propofol can inhibit the LPS-induced expression and release of HMGB1 by inhibiting HMGB1 translocation and NF-κB activity in RAW264.7 cells, suggesting propofol may be protective in patients with sepsis.

  17. Protein Phosphatase 2A in Lipopolysaccharide-Induced Cyclooxygenase-2 Expression in Murine Lymphatic Endothelial Cells.

    Directory of Open Access Journals (Sweden)

    Yu-Fan Chuang

    Full Text Available The lymphatic endothelium plays an important role in the maintenance of tissue fluid homeostasis. It also participates in the pathogenesis of several inflammatory diseases. However, little is known about the underlying mechanisms by which lymphatic endothelial cell responds to inflammatory stimuli. In this study, we explored the mechanisms by which lipopolysaccharide (LPS induces cyclooxygenase (COX-2 expression in murine lymphatic endothelial cells (SV-LECs. LPS caused increases in cox-2 mRNA and protein levels, as well as in COX-2 promoter luciferase activity in SV-LECs. These actions were associated with protein phosphatase 2A (PP2A, apoptosis signal-regulating kinase 1 (ASK1, JNK1/2 and p38MAPK activation, and NF-κB subunit p65 and C/EBPβ phosphorylation. PP2A-ASK1 signaling blockade reduced LPS-induced JNK1/2, p38MAPK, p65 and C/EBPβ phosphorylation. Transfection with PP2A siRNA reduced LPS's effects on p65 and C/EBPβ binding to the COX-2 promoter region. Transfected with the NF-κB or C/EBPβ site deletion of COX-2 reporter construct also abrogated LPS's enhancing effect on COX-2 promoter luciferase activity in SV-LECs. Taken together, the induction of COX-2 in SV-LECs exposed to LPS may involve PP2A-ASK1-JNK and/or p38MAPK-NF-κB and/or C/EBPβ cascade.

  18. Antioxidant properties of lutein contribute to the protection against lipopolysaccharide-induced uveitis in mice

    Directory of Open Access Journals (Sweden)

    Yao Xin-Sheng

    2011-10-01

    Full Text Available Abstract Background Lutein is an important eye-protective nutrient. This study investigates the protective effects and mechanisms of lutein on lipopolysaccharides (LPS-induced uveitis in mice. Methods Lutein, suspended in drinking water at a final concentration of 12.5 and 25 mg/mL, was administered to mice at 0.1 mL/10 g body weight for five consecutive days. Control and model group received drinking water only. Uveitis was induced by injecting LPS (100 mg per mouse into the footpad in the model and lutein groups on day 5 after the last drug administration. Eyes of the mice were collected 24 hours after the LPS injection for the detection of indicators using commercial kits and reverse transcription-polymerase chain reaction. Results LPS-induced uveitis was confirmed by significant pathological damage and increased the nitric oxide level in eye tissue of BALB/C mice 24 hours after the footpad injection. The elevated nitric oxide level was significantly reduced by oral administration of lutein (125 and 500 mg/kg/d for five days before LPS injection. Moreover, lutein decreased the malondialdehyde content, increased the oxygen radical absorbance capacity level, glutathione, the vitamin C contents and total superoxide dismutase (SOD and glutathione peroxidase (GPx activities. Lutein further increased expressions of copper-zinc SOD, manganese SOD and GPx mRNA. Conclusion The antioxidant properties of lutein contribute to the protection against LPS-induced uveitis, partially through the intervention of inflammation process.

  19. Chondroitin Sulfate-Rich Extract of Skate Cartilage Attenuates Lipopolysaccharide-Induced Liver Damage in Mice

    Science.gov (United States)

    Song, Yeong Ok; Kim, Mijeong; Woo, Minji; Baek, Jang-Mi; Kang, Keon-Hee; Kim, Sang-Ho; Roh, Seong-Soo; Park, Chan Hum; Jeong, Kap-Seop; Noh, Jeong-Sook

    2017-01-01

    The protective effects of a chondroitin sulfate-rich extract (CSE) from skate cartilage against lipopolysaccharide (LPS)-induced hepatic damage were investigated, and its mechanism of action was compared with that of chondroitin sulfate (CS) from shark cartilage. ICR mice were orally administrated 200 mg/kg body weight (BW) of CS or 400 mg/kg BW of CSE for 3 consecutive days, followed by a one-time intraperitoneal injection of LPS (20 mg/kg BW). The experimental groups were vehicle treatment without LPS injection (NC group), vehicle treatment with LPS injection (LPS group), CS pretreatment with LPS injection (CS group), and CSE pretreatment with LPS injection (CSE group). Hepatic antioxidant enzyme expression levels in the CS and CSE groups were increased relative to those in the LPS group. In LPS-insulted hepatic tissue, inflammatory factors were augmented relative to those in the NC group, but were significantly suppressed by pretreatment with CS or CSE. Moreover, CS and CSE alleviated the LPS-induced apoptotic factors and mitogen-activated protein kinase (MAPK). In addition, CS and CSE effectively decreased the serum lipid concentrations and downregulated hepatic sterol regulatory element-binding proteins expression. In conclusion, the skate CSE could protect against LPS-induced hepatic dyslipidemia, oxidative stress, inflammation, and apoptosis, probably through the regulation of MAPK signaling. PMID:28617322

  20. Ficolins do not alter host immune responses to lipopolysaccharide-induced inflammation in vivo

    DEFF Research Database (Denmark)

    Genster, Ninette; Østrup, Olga; Schjalm, Camilla

    2017-01-01

    Ficolins are a family of pattern recognition molecules that are capable of activating the lectin pathway of complement. A limited number of reports have demonstrated a protective role of ficolins in animal models of infection. In addition, an immune modulatory role of ficolins has been suggested....... Yet, the contribution of ficolins to inflammatory disease processes remains elusive. To address this, we investigated ficolin deficient mice during a lipopolysaccharide (LPS)-induced model of systemic inflammation. Although murine serum ficolin was shown to bind LPS in vitro, there was no difference...... an unaltered spleen transcriptome profile in ficolin deficient mice compared to wildtype mice. Collectively, results from this study demonstrate that ficolins are not involved in host response to LPS-induced systemic inflammation....

  1. Early Effects of Lipopolysaccharide-Induced Inflammation on Foetal Brain Development in Rat

    Directory of Open Access Journals (Sweden)

    Cristina A Ghiani

    2011-10-01

    Full Text Available Studies in humans and animal models link maternal infection and imbalanced levels of inflammatory mediators in the foetal brain to the aetiology of neuropsychiatric disorders. In a number of animal models, it was shown that exposure to viral or bacterial agents during a period that corresponds to the second trimester in human gestation triggers brain and behavioural abnormalities in the offspring. However, little is known about the early cellular and molecular events elicited by inflammation in the foetal brain shortly after maternal infection has occurred. In this study, maternal infection was mimicked by two consecutive intraperitoneal injections of 200 μg of LPS (lipopolysaccharide/kg to timed-pregnant rats at GD15 (gestational day 15 and GD16. Increased thickness of the CP (cortical plate and hippocampus together with abnormal distribution of immature neuronal markers and decreased expression of markers for neural progenitors were observed in the LPS-exposed foetal forebrains at GD18. Such effects were accompanied by decreased levels of reelin and the radial glial marker GLAST (glial glutamate transporter, and elevated levels of pro-inflammatory cytokines in maternal serum and foetal forebrains. Foetal inflammation elicited by maternal injections of LPS has discrete detrimental effects on brain development. The early biochemical and morphological changes described in this work begin to explain the sequelae of early events that underlie the neurobehavioural deficits reported in humans and animals exposed to prenatal insults.

  2. Aspirin reduces lipopolysaccharide-induced pulmonary inflammation in human models of ARDS.

    Science.gov (United States)

    Hamid, U; Krasnodembskaya, A; Fitzgerald, M; Shyamsundar, M; Kissenpfennig, A; Scott, C; Lefrancais, E; Looney, M R; Verghis, R; Scott, J; Simpson, A J; McNamee, J; McAuley, D F; O'Kane, C M

    2017-11-01

    Platelets play an active role in the pathogenesis of acute respiratory distress syndrome (ARDS). Animal and observational studies have shown aspirin's antiplatelet and immunomodulatory effects may be beneficial in ARDS. To test the hypothesis that aspirin reduces inflammation in clinically relevant human models that recapitulate pathophysiological mechanisms implicated in the development of ARDS. Healthy volunteers were randomised to receive placebo or aspirin 75  or 1200 mg (1:1:1) for seven days prior to lipopolysaccharide (LPS) inhalation, in a double-blind, placebo-controlled, allocation-concealed study. Bronchoalveolar lavage (BAL) was performed 6 hours after inhaling 50 µg of LPS. The primary outcome measure was BAL IL-8. Secondary outcome measures included markers of alveolar inflammation (BAL neutrophils, cytokines, neutrophil proteases), alveolar epithelial cell injury, systemic inflammation (neutrophils and plasma C-reactive protein (CRP)) and platelet activation (thromboxane B2, TXB2). Human lungs, perfused and ventilated ex vivo (EVLP) were randomised to placebo or 24 mg aspirin and injured with LPS. BAL was carried out 4 hours later. Inflammation was assessed by BAL differential cell counts and histological changes. In the healthy volunteer (n=33) model, data for the aspirin groups were combined. Aspirin did not reduce BAL IL-8. However, aspirin reduced pulmonary neutrophilia and tissue damaging neutrophil proteases (Matrix Metalloproteinase (MMP)-8/-9), reduced BAL concentrations of tumour necrosis factor α and reduced systemic and pulmonary TXB2. There was no difference between high-dose and low-dose aspirin. In the EVLP model, aspirin reduced BAL neutrophilia and alveolar injury as measured by histological damage. These are the first prospective human data indicating that aspirin inhibits pulmonary neutrophilic inflammation, at both low and high doses. Further clinical studies are indicated to assess the role of aspirin in the prevention and treatment of ARDS. NCT01659307 Results. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

  3. Impact of lipopolysaccharide-induced acute inflammation on baroreflex-controlled sympathetic arterial pressure regulation.

    Science.gov (United States)

    Tohyama, Takeshi; Saku, Keita; Kawada, Toru; Kishi, Takuya; Yoshida, Keimei; Nishikawa, Takuya; Mannoji, Hiroshi; Kamada, Kazuhiro; Sunagawa, Kenji; Tsutsui, Hiroyuki

    2018-01-01

    Lipopolysaccharide (LPS) induces acute inflammation, activates sympathetic nerve activity (SNA) and alters hemodynamics. Since the arterial baroreflex is a negative feedback system to stabilize arterial pressure (AP), examining the arterial baroreflex function is a prerequisite to understanding complex hemodynamics under LPS challenge. We investigated the impact of LPS-induced acute inflammation on SNA and AP regulation by performing baroreflex open-loop analysis. Ten anesthetized Sprague-Dawley rats were used. Acute inflammation was induced by an intravenous injection of LPS (60 μg/kg). We isolated the carotid sinuses from the systemic circulation and controlled carotid sinus pressure (CSP) by a servo-controlled piston pump. We matched CSP to AP to establish the baroreflex closed-loop condition, whereas we decoupled CSP from AP to establish the baroreflex open-loop condition and changed CSP stepwise to evaluate the baroreflex open-loop function. We recorded splanchnic SNA and hemodynamic parameters under baroreflex open- and closed-loop conditions at baseline and at 60 and 120 min after LPS injection. In the baroreflex closed-loop condition, SNA continued to increase after LPS injection, reaching three-fold the baseline value at 120 min (baseline: 94.7 ± 3.6 vs. 120 min: 283.9 ± 31.9 a.u.). In contrast, AP increased initially (until 75 min), then declined to the baseline level. In the baroreflex open-loop condition, LPS reset the neural arc (CSP-SNA relationship) upward to higher SNA, while shifted the peripheral arc (SNA-AP relationship) downward at 120 min after the injection. As a result, the operating point determined by the intersection between function curves of neural arc and peripheral arc showed marked sympatho-excitation without substantial changes in AP. LPS-induced acute inflammation markedly increased SNA via resetting of the baroreflex neural arc, and suppressed the peripheral arc. The balance between the augmented neural arc and suppressed peripheral arc determines SNA and hemodynamics in LPS-induced acute inflammation.

  4. Inhibition of Lipopolysaccharide-Induced iNOS, COX- 2, and TNF ...

    African Journals Online (AJOL)

    Methods: The expression of mRNA and protein using RT-PCR and Western blot analysis was investigated. The level of nitric oxide (NO) production was analyzed using Griess reaction. Release of prostaglandin E2 (PGE2) and tumor necrosis factor- (TNF-) was determined using sandwich ELISA. Results: AEOJ potently ...

  5. RGD-tagged helical rosette nanotubes aggravate acute lipopolysaccharide-induced lung inflammation

    Directory of Open Access Journals (Sweden)

    Suri SS

    2011-12-01

    Full Text Available Sarabjeet Singh Suri1, Steven Mills1, Gurpreet Kaur Aulakh1, Felaniaina Rakotondradany2, Hicham Fenniri2, Baljit Singh11Department of Veterinary Biomedical Sciences, University of Saskatchewan, Saskatoon; 2National Institute for Nanotechnology and Department of Chemistry, Edmonton, CanadaAbstract: Rosette nanotubes (RNT are a novel class of self-assembled biocompatible nanotubes that offer a built-in strategy for engineering structure and function through covalent tagging of synthetic self-assembling modules (G∧C motif. In this report, the G∧C motif was tagged with peptide Arg-Gly-Asp-Ser-Lys (RGDSK-G∧C and amino acid Lys (K-G∧C which, upon co-assembly, generate RNTs featuring RGDSK and K on their surface in predefined molar ratios. These hybrid RNTs, referred to as Kx/RGDSKy-RNT, where x and y refer to the molar ratios of K-G∧C and RGDSK–G∧C, were designed to target neutrophil integrins. A mouse model was used to investigate the effects of intravenous Kx/RGDSKy-RNT on acute lipopolysaccharide (LPS-induced lung inflammation. Healthy male C57BL/6 mice were treated intranasally with Escherichia coli LPS 80 µg and/or intravenously with K90/RGDSK10-RNT. Here we provide the first evidence that intravenous administration of K90/RGDSK10-RNT aggravates the proinflammatory effect of LPS in the mouse. LPS and K90/RGDSK10-RNT treatment groups showed significantly increased infiltration of polymorphonuclear cells in bronchoalveolar lavage fluid at all time points compared with the saline control. The combined effect of LPS and K90/RGDSK10-RNT was more pronounced than LPS alone, as shown by a significant increase in the expression of interleukin-1ß, MCP-1, MIP-1, and KC-1 in the bronchoalveolar lavage fluid and myeloperoxidase activity in the lung tissues. We conclude that K90/RGDSK10-RNT promotes acute lung inflammation, and when used along with LPS, leads to exaggerated immune response in the lung.Keywords: RGD peptide, helical rosette nanotubes, neutrophils, macrophages, chemokines, inflammation

  6. Atomic force microscopy observation of lipopolysaccharide-induced cardiomyocyte cytoskeleton reorganization.

    Science.gov (United States)

    Wang, Liqun; Chen, Tangting; Zhou, Xiang; Huang, Qiaobing; Jin, Chunhua

    2013-08-01

    We applied atomic force microscopy (AFM) to observe lipopolysaccharide (LPS)-induced intracellular cytoskeleton reorganization in primary cardiomyocytes from neonatal mouse. The nonionic detergent Triton X-100 was used to remove the membrane, soluble proteins, and organelles from the cell. The remaining cytoskeleton can then be directly visualized by AFM. Using three-dimensional technique of AFM, we were able to quantify the changes of cytoskeleton by the "density" and total "volume" of the cytoskeleton fibers. Compared to the control group, the density of cytoskeleton was remarkably decreased and the volume of cytoskeleton was significantly increased after LPS treatment, which suggests that LPS may induce the cytoskeleton reorganization and change the cardiomyocyte morphology. Copyright © 2013 Elsevier Ltd. All rights reserved.

  7. Possible Mechanisms Involved in Attenuation of Lipopolysaccharide-Induced Memory Deficits by Methyl Jasmonate in Mice.

    Science.gov (United States)

    Eduviere, Anthony Taghogho; Umukoro, Solomon; Adeoluwa, Olusegun A; Omogbiya, Itivere Adrian; Aluko, Oritoke Modupe

    2016-12-01

    This present study was carried out to investigate the likely mechanisms by which methyl jasmonate (MJ), 'an agent widely used in aromatherapy for neurological disorders, attenuates lipopolysaccharide (LPS)-induced memory deficits in mice. Mice were given intraperitoneal administration of LPS (250 µg/kg) alone or in combination with MJ (10-40 mg/kg), donepezil, DP (1 mg/kg), or vehicle for 7 successive days. Thereafter, memory was assessed using object recognition test (ORT). Acetylcholinesterase and myeloperoxidase activities were estimated in brain tissue homogenates. Brain levels of nitric oxide and markers of oxidative stress as well as histopathologic changes of the prefrontal cortex and cornu ammonis 1 (CA1) of the hippocampal region were also assessed. MJ (10-40 mg/kg) attenuated LPS-induced memory impairment in ORT. Moreover, the increased brain activities of acetylcholinesterase and myeloperoxidase enzymes were suppressed by MJ when compared with control (p memory deficits via mechanisms related to inhibition of acetylcholinesterase, myeloperoxidase, oxidative stress and neuronal degeneration.

  8. Methyl jasmonate attenuated lipopolysaccharide-induced depressive-like behaviour in mice.

    Science.gov (United States)

    Adebesin, Adaeze; Adeoluwa, Olusegun A; Eduviere, Anthony T; Umukoro, Solomon

    2017-11-01

    Depression is a recurrent neuropsychiatric disorder that affects millions of individuals worldwide and impact negatively on the patients' social functions and quality of life. Studies have shown that i.p injection of lipopolysaccharide (LPS) induces depressive-like behavior in rodents via induction of oxidative stress and neuroinflammation. Methyl jasmonate (MJ), an isolated compound from jasmine plant has gained reputation in aromatherapy for treatment of depression, nervousness and memory deficits. This study was designed to evaluate the effects of MJ on LPS-induced depressive-like behavior in mice. Mice were given MJ (5-20 mg/kg), imipramine (10 mg/kg) or vehicle (10 mL/kg) intraperitoneally for 7 consecutive days. On day 7, treatment was carried out 30 min prior to i.p injection of LPS (830 μg/kg). Twenty four hours after LPS administration, tail suspension, forced swim and sucrose preference tests were carried out. Thereafter, serum corticosterone levels were determined using ELISA. The levels of malondialdehyde (MDA), glutathione (GSH) and tumor necrosis factor-alpha (TNF-α) were determined in brain tissue homogenates. LPS significantly increased immobility time in the tail suspension and forced swim tests when compared with vehicle (p < 0.05), which indicates depressive-like syndromes. However, the increased immobility time was significantly reduced by MJ (5-20 mg/kg) when compared with LPS-treated group. LPS administration also altered the levels of MDA, GSH, corticosterone and TNF alpha in mice, which was significantly reversed by MJ. These findings suggest that attenuation of LPS-induced depressive-like behavior by MJ may be related to suppression of oxidative stress and release of TNF alpha. Copyright © 2017 Elsevier Ltd. All rights reserved.

  9. A sharp recovery condition for block sparse signals by block orthogonal multi-matching pursuit

    OpenAIRE

    Chen, Wengu; Ge, Huanmin

    2016-01-01

    We consider the block orthogonal multi-matching pursuit (BOMMP) algorithm for the recovery of block sparse signals. A sharp bound is obtained for the exact reconstruction of block $K$-sparse signals via the BOMMP algorithm in the noiseless case, based on the block restricted isometry constant (block-RIC). Moreover, we show that the sharp bound combining with an extra condition on the minimum $\\ell_2$ norm of nonzero blocks of block $K-$sparse signals is sufficient to recover the true support ...

  10. Blocking for Sequential Political Experiments.

    Science.gov (United States)

    Moore, Ryan T; Moore, Sally A

    2013-10-01

    In typical political experiments, researchers randomize a set of households, precincts, or individuals to treatments all at once, and characteristics of all units are known at the time of randomization. However, in many other experiments, subjects "trickle in" to be randomized to treatment conditions, usually via complete randomization. To take advantage of the rich background data that researchers often have (but underutilize) in these experiments, we develop methods that use continuous covariates to assign treatments sequentially. We build on biased coin and minimization procedures for discrete covariates and demonstrate that our methods outperform complete randomization, producing better covariate balance in simulated data. We then describe how we selected and deployed a sequential blocking method in a clinical trial and demonstrate the advantages of our having done so. Further, we show how that method would have performed in two larger sequential political trials. Finally, we compare causal effect estimates from differences in means, augmented inverse propensity weighted estimators, and randomization test inversion.

  11. Exercising with blocked muscle glycogenolysis

    DEFF Research Database (Denmark)

    Nielsen, Tue L; Pinós, Tomàs; Brull, Astrid

    2018-01-01

    of expression and activation of proteins involved in glycolytic flux revealed that in glycolytic, but not oxidative muscle from exercised McArdle mice, the glycolytic flux had changed compared to that in wild-type mice. Specifically, exercise triggered in glycolytic muscle a differentiated activation of insulin......BACKGROUND: McArdle disease (glycogen storage disease type V) is an inborn error of skeletal muscle metabolism, which affects glycogen phosphorylase (myophosphorylase) activity leading to an inability to break down glycogen. Patients with McArdle disease are exercise intolerant, as muscle glycogen......-derived glucose is unavailable during exercise. Metabolic adaptation to blocked muscle glycogenolysis occurs at rest in the McArdle mouse model, but only in highly glycolytic muscle. However, it is unknown what compensatory metabolic adaptations occur during exercise in McArdle disease. METHODS: In this study, 8...

  12. Analyzing block placement errors in SADP patterning

    Science.gov (United States)

    Kobayashi, Shinji; Okada, Soichiro; Shimura, Satoru; Nafus, Kathleen; Fonseca, Carlos; Demand, Marc; Biesemans, Serge; Versluijs, Janko; Ercken, Monique; Foubert, Philippe; Miyazaki, Shinobu

    2016-03-01

    We discuss edge placement errors (EPE) for multi-patterning of Mx critical layers using ArF lithography. Specific focus is placed on the block formation part of the process. While plenty of literature characterization data exist on spacer formation, only limited published data is available on block processes. We analyze the accuracy of placing blocks relative to narrow spacers. Many publications calculate EPE assuming Gaussian distributions for key process variations contributing to EPE. For practical reasons, each contributor is measured on dedicated test structures. In this work, we complement such analysis and directly measure the EPE in product. We perform high density sampling of blocks using CDSEM images and analyze all feature edges of interest. We find that block placement errors can be very different depending on their local design context. Specifically we report on 2 block populations (further called block A and B) which have a 4x different standard deviation. We attribute this to differences in local topography (spacer shape) and interaction with the plasma-etch process design. Block A (on top of the `core space' S1) has excellent EPE uniformity of ~1 nm while block B (on top of `gap space' S2) has degraded EPE control of ~4 nm. Finally, we suggest that the SOC etch process is at the origin on positioning blocks accurately on slim spacers, helping the manufacturability of spacer-based patterning techniques, and helping its extension toward the 5nm node.

  13. Block-structured grids for Eulerian gyrokinetic simulations

    Science.gov (United States)

    Jarema, D.; Bungartz, H. J.; Görler, T.; Jenko, F.; Neckel, T.; Told, D.

    2016-01-01

    In order to predict the turbulent transport in magnetic fusion experiments, global (i.e., full-torus) gyrokinetic simulations are often carried out. In this context, one frequently encounters situations in which the plasma temperature varies by large factors across the radial simulation domain. In grid-based Eulerian codes, this enforces the use of a very large number of grid points in the two-dimensional velocity space, and, thus, an enormous computational effort. To minimize the computational requirements, one may employ block-structured grids, adapted to the radial changes of the temperature. As the block-structured grids rely on a general approach, they can be applied to different Eulerian gyrokinetic implementations. In this paper, we explain the construction and implementation of such grids in the gyrokinetic code GENE, F. Jenko et al. (2000), and present corresponding simulation results.

  14. Sample size calculation for microarray experiments with blocked one-way design

    Directory of Open Access Journals (Sweden)

    Jung Sin-Ho

    2009-05-01

    Full Text Available Abstract Background One of the main objectives of microarray analysis is to identify differentially expressed genes for different types of cells or treatments. Many statistical methods have been proposed to assess the treatment effects in microarray experiments. Results In this paper, we consider discovery of the genes that are differentially expressed among K (> 2 treatments when each set of K arrays consists of a block. In this case, the array data among K treatments tend to be correlated because of block effect. We propose to use the blocked one-way ANOVA F-statistic to test if each gene is differentially expressed among K treatments. The marginal p-values are calculated using a permutation method accounting for the block effect, adjusting for the multiplicity of the testing procedure by controlling the false discovery rate (FDR. We propose a sample size calculation method for microarray experiments with a blocked one-way design. With FDR level and effect sizes of genes specified, our formula provides a sample size for a given number of true discoveries. Conclusion The calculated sample size is shown via simulations to provide an accurate number of true discoveries while controlling the FDR at the desired level.

  15. A block for nuclear reactor reflector covers

    International Nuclear Information System (INIS)

    Helm, H.

    1980-01-01

    The graphite block with hexagonal profile is provided with cylindrical channels passing from the corners of the upper end face towards the diagonally opposed corners of the lower end face. These channels enable gas cooling of the blocks joined together and avoid direct escape of neutrons. The blocks can also be joined together in such way that they form even-cylindrical channel for control rods for example. (GL) [de

  16. The Learning Potentials of Number Blocks

    DEFF Research Database (Denmark)

    Majgaard, Gunver; Nielsen, Jacob; Misfeldt, Morten

    2012-01-01

    . The tool is called Number Blocks and it combines physical interaction, learning, and immediate feedback. Number Blocks supports the children's understanding of place value in the sense that it allows them to experiment with creating large numbers. We found the blocks contributed to the learning process...... in several ways. The blocks combined mathematics and play, and they included and supported children at different academic levels. The auditory representation, especially the enhanced rhythmic effects due to using speech synthesis, and the rhythm helped the children to pronounce large numbers. This creates...

  17. Modelling of multi-block data

    DEFF Research Database (Denmark)

    Høskuldsson, Agnar; Svinning, K.

    2006-01-01

    Here is presented a unified approach to modelling multi-block regression data. The starting point is a partition of the data X into L data blocks, X = (X-1, X-2,...X-L), and the data Y into M data-blocks, Y = (Y-1, Y-2,...,Y-M). The methods of linear regression, X -> Y, are extended to the case...... these methods can be extended to a network of data blocks. Examples of the optimisation procedures in a network are shown. The examples chosen are the ones that are useful to work within industrial production environments. The methods are illustrated by simulated data and data from cement production....

  18. Using Interference to Block RFID Tags

    DEFF Research Database (Denmark)

    Krigslund, Rasmus; Popovski, Petar; Pedersen, Gert Frølund

    We propose a novel method to block RFID tags from responding, using intentional interference. We focus on the experimental evaluation, where we impose interference on the download and uplink, respectively. The results are positive, where modulated CCI shows most effective to block a tag.......We propose a novel method to block RFID tags from responding, using intentional interference. We focus on the experimental evaluation, where we impose interference on the download and uplink, respectively. The results are positive, where modulated CCI shows most effective to block a tag....

  19. Recent developments in paediatric neuraxial blocks

    Directory of Open Access Journals (Sweden)

    Vrushali Chandrashekhar Ponde

    2012-01-01

    Full Text Available Paediatric anaesthesia and paediatric regional anaesthesia are intertwined. Almost all surgeries unless contradicted could be and should be supplemented with a regional block. The main objective of this review is to elaborate on the recent advances of the central neuraxial blocks, such as application of ultrasound guidance and electrical stimulation in the pursuit of safety and an objective end point. This review also takes account of the traditional technique and understand the benefits as well the risk of each as compared with the recent technique. The recent trends in choosing the most appropriate peripheral block for a given surgery thereby sparing the central neuroaxis is considered. A penile block for circumcision or a sciatic block for unilateral foot surgery, rather than caudal epidural would have a better risk benefit equation. Readers will find a special mention on the recent thoughts on continuous epidural analgesia in paediatrics, especially its rise and fall, yet its unique importance. Lastly, the issue of block placements under sedation or general anaesthesia with its implication in this special population is dealt with. We conducted searches in MEDLINE (PubMed and assessed the relevance of the abstracts of citations identified from literature searches. The search was carried out in English, for last 10 years, with the following key words: Recent advances in paediatric regional anaesthesia; ultrasound guidance for central neuraxial blocks in children; role of electrical stimulation in neuraxial blocks in children; complications in neuraxial block. Full-text articles of potentially relevant abstracts were retrieved for further review.

  20. A MAC Mode for Lightweight Block Ciphers

    DEFF Research Database (Denmark)

    Luykx, Atul; Preneel, Bart; Tischhauser, Elmar Wolfgang

    2016-01-01

    Lightweight cryptography strives to protect communication in constrained environments without sacrificing security. However, security often conflicts with efficiency, shown by the fact that many new lightweight block cipher designs have block sizes as low as 64 or 32 bits. Such low block sizes lead...... no effect on the security bound, allowing an order of magnitude more data to be processed per key. Furthermore, LightMAC is incredibly simple, has almost no overhead over the block cipher, and is parallelizable. As a result, LightMAC not only offers compact authentication for resource-constrained platforms...

  1. Building blocks of the universe

    International Nuclear Information System (INIS)

    Malamud, E.; O'Connor, C.; Cooper, A.

    1990-01-01

    COSI [Ohio's Center for Science and Industry], a well established science center, and SciTech, an emerging one, have formed a collaboration to develop a group of original interactive exhibits conveying to a wide audience the nature of the most fundamental features of the Universe, as revealed in the fascinating world of nuclear and particle science. These new exhibits will add to, and be supported by, the basic science exhibits which have already attracted large numbers of visitors to both centers. The new project, called Building Blocks of the Universe, aims to foster an appreciation of the way all features of the Universe arise from simple, basic rules and to lead the visitor from the perceived complexities of our surroundings, to the unperceived, but simpler features of the sub-nuclear world. It has already become apparent from individual prototypes that these simple but immensely far-reaching ideas can indeed be conveyed by hands-on exhibits. These exhibits will be linked and enhanced by an effective museum environment, using pictorial diagrams, accurate non-technical text, and artistic displays to create an atmosphere in which visitors can learn about phenomena beyond the range of direct perception. This paper describes the goals, content and organization of the exhibition. The authors also outline their experience with prototype exhibits, and thereby invite additional input into the development process

  2. Capturing Reality at Centre Block

    Science.gov (United States)

    Boulanger, C.; Ouimet, C.; Yeomans, N.

    2017-08-01

    The Centre Block of Canada's Parliament buildings, National Historic Site of Canada is set to undergo a major rehabilitation project that will take approximately 10 years to complete. In preparation for this work, Heritage Conservation Services (HCS) of Public Services and Procurement Canada has been completing heritage documentation of the entire site which includes laser scanning of all interior rooms and accessible confined spaces such as attics and other similar areas. Other documentation completed includes detailed photogrammetric documentation of rooms and areas of high heritage value. Some of these high heritage value spaces present certain challenges such as accessibility due to the height and the size of the spaces. Another challenge is the poor lighting conditions, requiring the use of flash or strobe lighting to either compliment or completely eliminate the available ambient lighting. All the spaces captured at this higher level of detail were also captured with laser scanning. This allowed the team to validate the information and conduct a quality review of the photogrammetric data. As a result of this exercise, the team realized that in most, if not all cases, the photogrammetric data was more detailed and at a higher quality then the terrestrial laser scanning data. The purpose and motivation of this paper is to present these findings, as well provide the advantages and disadvantages of the two methods and data sets.

  3. CAPTURING REALITY AT CENTRE BLOCK

    Directory of Open Access Journals (Sweden)

    C. Boulanger

    2017-08-01

    Full Text Available The Centre Block of Canada’s Parliament buildings, National Historic Site of Canada is set to undergo a major rehabilitation project that will take approximately 10 years to complete. In preparation for this work, Heritage Conservation Services (HCS of Public Services and Procurement Canada has been completing heritage documentation of the entire site which includes laser scanning of all interior rooms and accessible confined spaces such as attics and other similar areas. Other documentation completed includes detailed photogrammetric documentation of rooms and areas of high heritage value. Some of these high heritage value spaces present certain challenges such as accessibility due to the height and the size of the spaces. Another challenge is the poor lighting conditions, requiring the use of flash or strobe lighting to either compliment or completely eliminate the available ambient lighting. All the spaces captured at this higher level of detail were also captured with laser scanning. This allowed the team to validate the information and conduct a quality review of the photogrammetric data. As a result of this exercise, the team realized that in most, if not all cases, the photogrammetric data was more detailed and at a higher quality then the terrestrial laser scanning data. The purpose and motivation of this paper is to present these findings, as well provide the advantages and disadvantages of the two methods and data sets.

  4. Comparative study between ultrasound guided tap block and paravertebral block in upper abdominal surgeries. Randomized controlled trial

    Directory of Open Access Journals (Sweden)

    Ruqaya M. Elsayed

    2017-01-01

    Conclusion: We concluded that ultrasound guided transversus abdominis plane block and thoracic paravertebral block were safe and effective anesthetic technique for upper abdominal surgery with longer and potent postoperative analgesia in thoracic paravertebral block than transversus abdominis block.

  5. Ionization of amphiphilic acidic block copolymers.

    Science.gov (United States)

    Colombani, Olivier; Lejeune, Elise; Charbonneau, Céline; Chassenieux, Christophe; Nicolai, Taco

    2012-06-28

    The ionization behavior of an amphiphilic diblock copolymer poly(n-butyl acrylate(50%)-stat-acrylic acid(50%))(100)-block-poly(acrylic acid)(100) (P(nBA(50%)-stat-AA(50%))(100)-b-PAA(100), DH50) and of its equivalent triblock copolymer P(nBA(50%)-stat-AA(50%))(100)-b-PAA(200)-b-P(nBA(50%)-stat-AA(50%))(100) (TH50) were studied by potentiometric titration either in pure water or in 0.5 M NaCl. These polymers consist of a hydrophilic acidic block (PAA) connected to a hydrophobic block, P(nBA(50%)-stat-AA(50%))(100), whose hydrophobic character has been mitigated by copolymerization with hydrophilic units. We show that all AA units, even those in the hydrophobic block could be ionized. However, the AA units within the hydrophobic block were less acidic than those in the hydrophilic block, resulting in the preferential ionization of the latter block. The preferential ionization of PAA over that of P(nBA(50%)-stat-AA(50%))(100) was stronger at higher ionic strength. Remarkably, the covalent bonds between the PAA and P(nBA(50%)-stat-AA(50%))(100) blocks in the diblock or the triblock did not affect the ionization of each block, although the self-association of the block copolymers into spherical aggregates modified the environment of the PAA blocks compared to when PAA was molecularly dispersed.

  6. Approximate design theory for a simple block design with random block effects

    OpenAIRE

    Christof, Karin

    1985-01-01

    Approximate design theory for a simple block design with random block effects / K. Christof ; F. Pukelsheim. - In: Linear statistical inference / ed. by T. Calinski ... - Berlin u. a. : Springer, 1985. - S. 20-28. - (Lecture notes in statistics ; 35)

  7. Micellar aggregates of amylose-block-polystyrene rod-coil block copolymers in water and THF

    NARCIS (Netherlands)

    Loos, Katja; Böker, Alexander; Zettl, Heiko; Zhang, Mingfu; Krausch, Georg; Müller, Axel H.E.; Boker, A.; Zhang, A.F.

    2005-01-01

    Amylose-block-polystyrenes with various block copolymer compositions were investigated in water and in THF solution. Fluorescence correlation spectroscopy, dynamic light, scattering (DLS), and asymmetric flow field-flow fractionation with multiangle light scattering detection indicate the presence

  8. Substrate tolerant direct block copolymer nanolithography

    DEFF Research Database (Denmark)

    Li, Tao; Wang, Zhongli; Schulte, Lars

    2016-01-01

    Block copolymer (BC) self-assembly constitutes a powerful platform for nanolithography. However, there is a need for a general approach to BC lithography that critically considers all the steps from substrate preparation to the final pattern transfer. We present a procedure that significantly...... plasma treatment enables formation of the oxidized PDMS hard mask, PS block removal and polymer or graphene substrate patterning....

  9. Pixel Decimation in Block Matching Techniques

    Directory of Open Access Journals (Sweden)

    D. Levicky

    2000-12-01

    Full Text Available Block motion estimation using full search algorithm is computationallyextensive. Previously proposed fast algorithms reduce the computationcost by limiting the number of locations searched. In this paper wepresent algorithms for block motion estimation that produce similarperformance to that full search algorithm. The algorithms are based onthe pixel decimation.

  10. Block Gas Sol Unit in Haderslev

    DEFF Research Database (Denmark)

    Vejen, Niels Kristian

    2000-01-01

    Investigation of a SDHW system based on a Block Gas Sol Unit from Baxi A/S installed by a consumer i Haderslev, Denmark.......Investigation of a SDHW system based on a Block Gas Sol Unit from Baxi A/S installed by a consumer i Haderslev, Denmark....

  11. Light extraction block with curved surface

    Science.gov (United States)

    Levermore, Peter; Krall, Emory; Silvernail, Jeffrey; Rajan, Kamala; Brown, Julia J.

    2016-03-22

    Light extraction blocks, and OLED lighting panels using light extraction blocks, are described, in which the light extraction blocks include various curved shapes that provide improved light extraction properties compared to parallel emissive surface, and a thinner form factor and better light extraction than a hemisphere. Lighting systems described herein may include a light source with an OLED panel. A light extraction block with a three-dimensional light emitting surface may be optically coupled to the light source. The three-dimensional light emitting surface of the block may includes a substantially curved surface, with further characteristics related to the curvature of the surface at given points. A first radius of curvature corresponding to a maximum principal curvature k.sub.1 at a point p on the substantially curved surface may be greater than a maximum height of the light extraction block. A maximum height of the light extraction block may be less than 50% of a maximum width of the light extraction block. Surfaces with cross sections made up of line segments and inflection points may also be fit to approximated curves for calculating the radius of curvature.

  12. CONJUGATED BLOCK-COPOLYMERS FOR ELECTROLUMINESCENT DIODES

    NARCIS (Netherlands)

    Hilberer, A; Gill, R.E; Herrema, J.K; Malliaras, G.G; Wildeman, J.; Hadziioannou, G

    In this article we review results obtained in our laboratory on the design and study of new light-emitting polymers. We are interested in the synthesis and characterisation of block copolymers with regularly alternating conjugated and non conjugated sequences. The blocks giving rise to luminescence

  13. C++ application development with Code::Blocks

    CERN Document Server

    Modak, Biplab Kumar

    2013-01-01

    This is a comprehensive tutorial with step-by-step instructions on how to develop applications with Code::Blocks.This book is for C++ developers who wish to use Code::Blocks to create applications with a consistent look and feel across multiple platforms. This book assumes that you are familiar with the basics of the C++ programming language.

  14. Ground reaction curve based upon block theory

    International Nuclear Information System (INIS)

    Yow, J.L. Jr.; Goodman, R.E.

    1985-09-01

    Discontinuities in a rock mass can intersect an excavation surface to form discrete blocks (keyblocks) which can be unstable. Once a potentially unstable block is identified, the forces affecting it can be calculated to assess its stability. The normal and shear stresses on each block face before displacement are calculated using elastic theory and are modified in a nonlinear way by discontinuity deformations as the keyblock displaces. The stresses are summed into resultant forces to evaluate block stability. Since the resultant forces change with displacement, successive increments of block movement are examined to see whether the block ultimately becomes stable or fails. Two-dimensional (2D) and three-dimensional (3D) analytic models for the stability of simple pyramidal keyblocks were evaluated. Calculated stability is greater for 3D analyses than for 2D analyses. Calculated keyblock stability increases with larger in situ stress magnitudes, larger lateral stress ratios, and larger shear strengths. Discontinuity stiffness controls blocks displacement more strongly than it does stability itself. Large keyblocks are less stable than small ones, and stability increases as blocks become more slender

  15. PEO-related block copolymer surfactants

    DEFF Research Database (Denmark)

    Mortensen, K.

    2001-01-01

    Non-ionic block copolymer systems based on hydrophilic poly(ethylene oxide) and more hydrophobic co-polymer blocks are used intensively in a variety of industrial and personal applications. A brief description on the applications is presented. The physical properties of more simple model systems ...

  16. Benchmarking Block Ciphers for Wireless Sensor Networks

    NARCIS (Netherlands)

    Law, Y.W.; Doumen, J.M.; Hartel, Pieter H.

    2004-01-01

    Choosing the most storage- and energy-efficient block cipher specifically for wireless sensor networks (WSNs) is not as straightforward as it seems. To our knowledge so far, there is no systematic evaluation framework for the purpose. We have identified the candidates of block ciphers suitable for

  17. The Cognitive Dimension of Writer's Block.

    Science.gov (United States)

    Rose, Mike

    A study investigated cognitive behaviors and processes that contribute to writer's block. Subjects were 10 college undergraduates who had scored at the extreme ends of a writer's block measurement instrument. The 10, 6 "high-blockers" and 4 "low-blockers," varied in their English experience, class standing, and majors. Each was given a writing…

  18. Programs for the calculi of blocks permeabilities

    International Nuclear Information System (INIS)

    Gomez Hernandez, J.J.; Sovero Sovero, H.F.

    1993-01-01

    This report studies the stochastic analysis of radionuclide transport. The permeability values of blocks are necessary to do a numeric model for the flux and transport problems in ground soils. The determination of block value by function on grill value is the objective of this program

  19. Micellization and Characterization of Block Copolymer Detergents

    DEFF Research Database (Denmark)

    Hvidt, Søren

    Triblock copolymers of the type EPE, where E and P denote ethylene oxide and propylene oxide blocks, respectively, are used widely in industry as emulsifiers, anti-foaming agents, and in delayed drug release. EPE copolymers form micelles with a core of P blocks and different micellar shapes depen...

  20. Blending of styrene-block-butadiene-block-styrene copolymer with sulfonated vinyl aromatic polymers

    OpenAIRE

    Ruggeri, Giacomo; Passaglia, Elisa; Giorgi, Ivan; Picchioni, Francesco; Aglietto, Mauro

    2001-01-01

    Different polymers containing sulfonic groups attached to the phenyl rings were prepared by sulfonation of polystyrene (PS) and styrene-block-(ethylene-co-1-butene)-block-styrene (SEBS). The sulfonation degree (SD) was varied between 1 and 20 mol% of the styrene units. Polyphase materials containing sulfonated units were prepared by blending styrene-block-butadiene-block-styrene (SBS), with both sulfonated PS and sulfonated SEBS in a Brabender mixer. Such a procedure was performed as an alter...

  1. Block information and topology in memory networks

    Science.gov (United States)

    Dominguez, David

    2007-02-01

    The retrieval abilities of spatially uniform attractor networks can be measured by the average overlap between patterns and neural states. Metric networks (with local connections), like small-world graphs, modelled by the parameters: connectivity γ and randomness ω, however, display a richer distribution of memory attractors. We found that metric networks can carry information structured in blocks without any global overlap. There is a competition between global and blocks attractors. We propose a way to measure the block information, related to the fluctuations of the overlap over the blocks. The phase-diagram with the transition from local to global information, shows that the stability of blocks grows with dilution, but decreases with the storage rate and disappears for random topologies.

  2. The undesirable effects of neuromuscular blocking drugs

    DEFF Research Database (Denmark)

    Claudius, C; Garvey, L H; Viby-Mogensen, J

    2009-01-01

    Neuromuscular blocking drugs are designed to bind to the nicotinic receptor at the neuromuscular junction. However, they also interact with other acetylcholine receptors in the body. Binding to these receptors causes adverse effects that vary with the specificity for the cholinergic receptor...... in question. Moreover, all neuromuscular blocking drugs may cause hypersensitivity reactions. Often the symptoms are mild and self-limiting but massive histamine release can cause systematic reactions with circulatory and respiratory symptoms and signs. At the end of anaesthesia, no residual effect...... of a neuromuscular blocking drug should be present. However, the huge variability in response to neuromuscular blocking drugs makes it impossible to predict which patient will suffer postoperative residual curarization. This article discusses the undesirable effects of the currently available neuromuscular blocking...

  3. Syncope and Idiopathic (Paroxysmal) AV Block.

    Science.gov (United States)

    Brignole, Michele; Deharo, Jean-Claude; Guieu, Regis

    2015-08-01

    Syncope due to idiopathic AV block is characterized by: 1) ECG documentation (usually by means of prolonged ECG monitoring) of paroxysmal complete AV block with one or multiple consecutive pauses, without P-P cycle lengthening or PR interval prolongation, not triggered by atrial or ventricular premature beats nor by rate variations; 2) long history of recurrent syncope without prodromes; 3) absence of cardiac and ECG abnormalities; 4) absence of progression to persistent forms of AV block; 5) efficacy of cardiac pacing therapy. The patients affected by idiopathic AV block have low baseline adenosine plasma level values and show an increased susceptibility to exogenous adenosine. The APL value of the patients with idiopathic AV block is much lower than patients affected by vasovagal syncope who have high adenosine values. Copyright © 2015 Elsevier Inc. All rights reserved.

  4. Block copolymer structures in nano-pores

    Science.gov (United States)

    Pinna, Marco; Guo, Xiaohu; Zvelindovsky, Andrei

    2010-03-01

    We present results of coarse-grained computer modelling of block copolymer systems in cylindrical and spherical nanopores on Cell Dynamics Simulation. We study both cylindrical and spherical pores and systematically investigate structures formed by lamellar, cylinders and spherical block copolymer systems for various pore radii and affinity of block copolymer blocks to the pore walls. The obtained structures include: standing lamellae and cylinders, ``onions,'' cylinder ``knitting balls,'' ``golf-ball,'' layered spherical, ``virus''-like and mixed morphologies with T-junctions and U-type defects [1]. Kinetics of the structure formation and the differences with planar films are discussed. Our simulations suggest that novel porous nano-containers can be formed by confining block copolymers in pores of different geometries [1,2]. [4pt] [1] M. Pinna, X. Guo, A.V. Zvelindovsky, Polymer 49, 2797 (2008).[0pt] [2] M. Pinna, X. Guo, A.V. Zvelindovsky, J. Chem. Phys. 131, 214902 (2009).

  5. Sympathetic blocks for visceral cancer pain management

    DEFF Research Database (Denmark)

    Mercadante, Sebastiano; Klepstad, Pal; Kurita, Geana Paula

    2015-01-01

    The neurolytic blocks of sympathetic pathways, including celiac plexus block (CPB) and superior hypogastric plexus block (SHPB) , have been used for years. The aim of this review was to assess the evidence to support the performance of sympathetic blocks in cancer patients with abdominal visceral...... pain. Only comparison studies were included. All data from the eligible trials were analyzed using the GRADE system. Twenty-seven controlled studies were considered. CPB, regardless of the technique used, improved analgesia and/or decrease opioid consumption, and decreased opioid-induced adverse...... effects in comparison with a conventional analgesic treatment. In one study patients treated with superior hypogastric plexus block (SHPB) had a decrease in pain intensity and a less morphine consumption, while no statistical differences in adverse effects were found. The quality of these studies...

  6. 31 CFR 542.204 - Expenses of maintaining blocked property; liquidation of blocked property.

    Science.gov (United States)

    2010-07-01

    ... property; liquidation of blocked property. 542.204 Section 542.204 Money and Finance: Treasury Regulations... SYRIAN SANCTIONS REGULATIONS Prohibitions § 542.204 Expenses of maintaining blocked property; liquidation of blocked property. (a) Except as otherwise authorized, and notwithstanding the existence of any...

  7. 31 CFR 548.204 - Expenses of maintaining blocked physical property; liquidation of blocked property.

    Science.gov (United States)

    2010-07-01

    ... physical property; liquidation of blocked property. 548.204 Section 548.204 Money and Finance: Treasury... property; liquidation of blocked property. (a) Except as otherwise authorized, and notwithstanding the... maintenance of physical property blocked pursuant to § 548.201(a) shall be the responsibility of the owners or...

  8. 31 CFR 537.209 - Expenses of maintaining blocked property; liquidation of blocked account.

    Science.gov (United States)

    2010-07-01

    ... property; liquidation of blocked account. 537.209 Section 537.209 Money and Finance: Treasury Regulations... BURMESE SANCTIONS REGULATIONS Prohibitions § 537.209 Expenses of maintaining blocked property; liquidation... the maintenance of physical property blocked pursuant to § 537.201(a) shall be the responsibility of...

  9. 31 CFR 594.206 - Expenses of maintaining blocked property; liquidation of blocked property.

    Science.gov (United States)

    2010-07-01

    ... property; liquidation of blocked property. 594.206 Section 594.206 Money and Finance: Treasury Regulations... GLOBAL TERRORISM SANCTIONS REGULATIONS Prohibitions § 594.206 Expenses of maintaining blocked property; liquidation of blocked property. (a) Except as otherwise authorized, and notwithstanding the existence of any...

  10. 31 CFR 543.204 - Expenses of maintaining blocked physical property; liquidation of blocked property.

    Science.gov (United States)

    2010-07-01

    ... physical property; liquidation of blocked property. 543.204 Section 543.204 Money and Finance: Treasury... physical property; liquidation of blocked property. (a) Except as otherwise authorized, and notwithstanding... to the maintenance of physical property blocked pursuant to § 543.201(a) shall be the responsibility...

  11. 31 CFR 541.205 - Expenses of maintaining blocked property; liquidation of blocked account.

    Science.gov (United States)

    2010-07-01

    ... property; liquidation of blocked account. 541.205 Section 541.205 Money and Finance: Treasury Regulations... ZIMBABWE SANCTIONS REGULATIONS Prohibitions § 541.205 Expenses of maintaining blocked property; liquidation... maintenance of physical property blocked pursuant to § 541.201(a) shall be the responsibility of the owners or...

  12. 31 CFR 546.204 - Expenses of maintaining blocked physical property; liquidation of blocked property.

    Science.gov (United States)

    2010-07-01

    ... physical property; liquidation of blocked property. 546.204 Section 546.204 Money and Finance: Treasury... property; liquidation of blocked property. (a) Except as otherwise authorized, and notwithstanding the... maintenance of physical property blocked pursuant to § 546.201(a) shall be the responsibility of the owners or...

  13. 31 CFR 588.205 - Expenses of maintaining blocked property; liquidation of blocked account.

    Science.gov (United States)

    2010-07-01

    ... property; liquidation of blocked account. 588.205 Section 588.205 Money and Finance: Treasury Regulations... WESTERN BALKANS STABILIZATION REGULATIONS Prohibitions § 588.205 Expenses of maintaining blocked property; liquidation of blocked account. (a) Except as otherwise authorized, and notwithstanding the existence of any...

  14. 31 CFR 545.207 - Expenses of maintaining blocked property; liquidation of blocked account.

    Science.gov (United States)

    2010-07-01

    ... property; liquidation of blocked account. 545.207 Section 545.207 Money and Finance: Treasury Regulations... property; liquidation of blocked account. (a) Except as otherwise authorized, and notwithstanding the... expenses incident to the maintenance of physical property blocked pursuant to § 545.201 shall be the...

  15. Data on macrophage mediated muscle transfection upon delivery of naked plasmid DNA with block copolymers

    Directory of Open Access Journals (Sweden)

    Vivek Mahajan

    2016-06-01

    Full Text Available The data contains 14 figures supporting the research article “Horizontal gene transfer from macrophages to ischemic muscles upon delivery of naked DNA with Pluronic block copolymers” [1]. The data explains the surgical procedure and histological characterization of Murine Hind Limb Ischemia. The data also shows the kinetics of luciferase gene expression, spread of GFP expression through muscle and the colocalization of GFP with cellular markers in ischemic muscles injected with pDNA alone or pDNA/Pluronic. Finally the data shows the effect of Pluronic Block Copolymer to enhance total gene expression (cmv-promoter driven luciferase gene in coculture of DNA transfected MØs with muscle cells.

  16. Block Copolymers: Synthesis and Applications in Nanotechnology

    Science.gov (United States)

    Lou, Qin

    This study is focused on the synthesis and study of (block) copolymers using reversible deactivation radical polymerizations (RDRPs), including atom transfer radical polymerization (ATRP) and reversible addition-fragmentation chain transfer (RAFT) polymerization. In particular, two primary areas of study are undertaken: (1) a proof-of-concept application of lithographic block copolymers, and (2) the mechanistic study of the deposition of titania into block copolymer templates for the production of well-ordered titania nanostructures. Block copolymers have the ability to undergo microphase separation, with an average size of each microphase ranging from tens to hundreds of nanometers. As such, block copolymers have been widely considered for nanotechnological applications over the past two decades. The development of materials for various nanotechnologies has become an increasingly studied area as improvements in many applications, such as those found in the semiconductor and photovoltaic industries are constantly being sought. Significant growth in developments of new synthetic methods ( i.e. RDRPs) has allowed the production of block copolymers with molecular (and sometimes atomic) definition. In turn, this has greatly expanded the use of block copolymers in nanotechnology. Herein, we describe the synthesis of statistical and block copolymers of 193 nm photolithography methacrylate and acrylate resist monomers with norbornyl and adamantyl moieties using RAFT polymerization.. For these resist (block) copolymers, the phase separation behaviors were examined by atomic force microscopy (AFM). End groups were removed from the polymers to avoid complications during the photolithography since RAFT end groups absorb visible light. Poly(glycidyl methacrylate-block-polystyrene) (PGMA-b-PS) was synthesize by ATRP and demonstrated that this block copolymer acts as both a lithographic UV (365 nm) photoresist and a self-assembly material. The PGMA segments can undergo cationic

  17. A functional SNP in the regulatory region of the decay-accelerating factor gene associates with extraocular muscle pareses in myasthenia gravis

    KAUST Repository

    Heckmann, J M

    2009-08-13

    Complement activation in myasthenia gravis (MG) may damage muscle endplate and complement regulatory proteins such as decay-accelerating factor (DAF) or CD55 may be protective. We hypothesize that the increased prevalence of severe extraocular muscle (EOM) dysfunction among African MG subjects reported earlier may result from altered DAF expression. To test this hypothesis, we screened the DAF gene sequences relevant to the classical complement pathway and found an association between myasthenics with EOM paresis and the DAF regulatory region c.-198CG SNP (odds ratio8.6; P0.0003). This single nucleotide polymorphism (SNP) results in a twofold activation of a DAF 5?-flanking region luciferase reporter transfected into three different cell lines. Direct matching of the surrounding SNP sequence within the DAF regulatory region with the known transcription factor-binding sites suggests a loss of an Sp1-binding site. This was supported by the observation that the c.-198CG SNP did not show the normal lipopolysaccharide-induced DAF transcriptional upregulation in lymphoblasts from four patients. Our findings suggest that at critical periods during autoimmune MG, this SNP may result in inadequate DAF upregulation with consequent complement-mediated EOM damage. Susceptible individuals may benefit from anti-complement therapy in addition to immunosuppression. © 2010 Macmillan Publishers Limited. All rights reserved.

  18. Heuristic algorithms for feature selection under Bayesian models with block-diagonal covariance structure.

    Science.gov (United States)

    Foroughi Pour, Ali; Dalton, Lori A

    2018-03-21

    Many bioinformatics studies aim to identify markers, or features, that can be used to discriminate between distinct groups. In problems where strong individual markers are not available, or where interactions between gene products are of primary interest, it may be necessary to consider combinations of features as a marker family. To this end, recent work proposes a hierarchical Bayesian framework for feature selection that places a prior on the set of features we wish to select and on the label-conditioned feature distribution. While an analytical posterior under Gaussian models with block covariance structures is available, the optimal feature selection algorithm for this model remains intractable since it requires evaluating the posterior over the space of all possible covariance block structures and feature-block assignments. To address this computational barrier, in prior work we proposed a simple suboptimal algorithm, 2MNC-Robust, with robust performance across the space of block structures. Here, we present three new heuristic feature selection algorithms. The proposed algorithms outperform 2MNC-Robust and many other popular feature selection algorithms on synthetic data. In addition, enrichment analysis on real breast cancer, colon cancer, and Leukemia data indicates they also output many of the genes and pathways linked to the cancers under study. Bayesian feature selection is a promising framework for small-sample high-dimensional data, in particular biomarker discovery applications. When applied to cancer data these algorithms outputted many genes already shown to be involved in cancer as well as potentially new biomarkers. Furthermore, one of the proposed algorithms, SPM, outputs blocks of heavily correlated genes, particularly useful for studying gene interactions and gene networks.

  19. The mixed block/event-related design.

    Science.gov (United States)

    Petersen, Steven E; Dubis, Joseph W

    2012-08-15

    Neuroimaging studies began using block design and event-related design experiments. While providing many insights into brain functions, these fMRI design types ignore components of the BOLD signal that can teach us additional elements. The development of the mixed block/event-related fMRI design allowed for a fuller characterization of nonlinear and time-sensitive neuronal responses: for example, the interaction between block and event related factors and the simultaneous extraction of transient activity related to trials and block transitions and sustained activity related to task-level processing. This review traces the origins of the mixed block/event-related design from conceptual precursors to a seminal paper and on to subsequent studies using the method. The review also comments on aspects of the experimental design that must be considered when attempting to use the mixed block/event-related design. When taking into account these considerations, the mixed block/event-related design allows fuller utilization of the BOLD signal allowing deeper interpretation of how regions of the brain function on multiple timescales. Copyright © 2011 Elsevier Inc. All rights reserved.

  20. Development of Alkali Activated Geopolymer Masonry Blocks

    Science.gov (United States)

    Venugopal, K.; Radhakrishna; Sasalatti, Vinod

    2016-09-01

    Cement masonry units are not considered as sustainable since their production involves consumption of fuel, cement and natural resources and therefore it is essential to find alternatives. This paper reports on making of geopolymer solid & hollow blocks and masonry prisms using non conventional materials like fly ash, ground granulated blast furnace slag (GGBFS) and manufactured sand and curing at ambient temperature. They were tested for water absorption, initial rate of water absorption, dry density, dimensionality, compressive, flexural and bond-strength which were tested for bond strength with and without lateral confinement, modulus of elasticity, alternative drying & wetting and masonry efficiency. The properties of geopolymer blocks were found superior to traditional masonry blocks and the masonry efficiency was found to increase with decrease in thickness of cement mortar joints. There was marginal difference in strength between rendered and unrendered geopolymer masonry blocks. The percentage weight gain after 7 cycles was less than 6% and the percentage reduction in strength of geopolymer solid blocks and hollow blocks were 26% and 28% respectively. Since the properties of geopolymer blocks are comparatively better than the traditional masonry they can be strongly recommended for structural masonry.

  1. A revisit of transthecal digital block and traditional digital block for anesthesia of the finger

    Directory of Open Access Journals (Sweden)

    Mohammad Dehghani

    2007-12-01

    Full Text Available BACKGROUND: Finger injuries are very common and the majority can be treated under digital block anesthesia. Traditional digital block is one of the most commonly performed blocks by care providers in several medical fields. There is another less known method, transthecal (Pulley block, in which local anesthesia is injected into the flexor tendon sheath.
    METHODS: A randomized clinical trial was performed to compare the transthecal (Pulley and traditional digital block with regard to the length of anesthesia and the need for another anesthetic method (due to insufficient anesthesia as a supplement. We divided 100 patients who needed digital block due to finger injury, into two groups randomly. In each group the patients were anesthetized either by traditional or transthecal digital block. All blocks were performed by the same investigator.
    RESULTS: Mean length of anesthesia was 34.2 minutes in the transthecal digital block method versus 33.8 minutes in the traditional digital block method (P>0.05. A repeated injection or local infiltration as a supplement was necessary only in 5 instances in the traditional digital block method (P<0.05.
    CONCLUSIONS: Regarding fewer injections and reduced amounts of lidocaine, absence of neurovascular bundles damage and comparable length of anesthesia and no need to supplemental anesthesia, transthecal digital block is an appropriate alternative to traditional digital block.
    KEY WORDS: Digital block, transthecal, pulley, finger, flexor tendon sheath.

  2. Exploring Energy Efficiency of Lightweight Block Ciphers

    DEFF Research Database (Denmark)

    Banik, Subhadeep; Bogdanov, Andrey; Regazzoni, Francesco

    2016-01-01

    is the encryption of one plaintext. By studying the energy consumption model of a CMOS gate, we arrive at the conclusion that the energy consumed per cycle during the encryption operation of an r-round unrolled architecture of any block cipher is a quadratic function in r. We then apply our model to 9 well known......In the last few years, the field of lightweight cryptography has seen an influx in the number of block ciphers and hash functions being proposed. One of the metrics that define a good lightweight design is the energy consumed per unit operation of the algorithm. For block ciphers, this operation...

  3. Evaluative Conditioning is Insensitive to Blocking

    Directory of Open Access Journals (Sweden)

    Tom Beckers

    2009-01-01

    Full Text Available Evaluative conditioning has been claimed to have a number of functional characteristics that set it apart from other forms of associative learning in humans, such as insensitivity to extinction and contingency, independence of contingency awareness, and insensitivity to modulation. Despite its potential theoretical importance, until now few data are available concerning the susceptibility of evaluative conditioning to cue competition effects such as blocking. In the present study, we assessed the susceptibility of acquired preferences and evaluations to blocking in a candy game. Results suggest that evaluative conditioning is not susceptible to blocking. We discuss this observation in the light of theoretical accounts of evaluative conditioning and associative learning in humans.

  4. Blocks and families for cyclotomic Hecke algebras

    CERN Document Server

    Chlouveraki, Maria

    2009-01-01

    The definition of Rouquier for the families of characters introduced by Lusztig for Weyl groups in terms of blocks of the Hecke algebras has made possible the generalization of this notion to the case of complex reflection groups. The aim of this book is to study the blocks and to determine the families of characters for all cyclotomic Hecke algebras associated to complex reflection groups. This volume offers a thorough study of symmetric algebras, covering topics such as block theory, representation theory and Clifford theory, and can also serve as an introduction to the Hecke algebras of complex reflection groups.

  5. Measurement of soil moisture using gypsum blocks

    DEFF Research Database (Denmark)

    Friis Dela, B.

    For the past 50 years, gypsum blocks have been used to determine soil moisture content. This report describes a method for calibrating gypsum blocks for soil moisture measurements. Moisture conditions inside a building are strongly influenced by the moisture conditions in the soil surrounding...... the building. Consequently, measuring the moisture of the surrounding soil is of great importance for detecting the source of moisture in a building. Up till now, information has been needed to carry out individual calibrations for the different types of gypsum blocks available on the market and to account...

  6. Parallel block inversion of geophysical data

    Science.gov (United States)

    Pereyra, Victor L.

    1993-12-01

    We present an automatic blocking algorithm for some medium size nonlinear least squares problems that arise in the inversion of travel time data in geophysics. This blocking leads to a nonlinear Gauss-Seidel type iteration which can be distributed to a network of computers. The low dimensional blocks are also amenable to global optimization methods which leads to further parallelization. All this is necessary because the original problem is generally non- convex, ill-conditioned, with a goal functional that is very expensive to evaluate.

  7. Productivity assessment of Angola's oil blocks

    International Nuclear Information System (INIS)

    Barros, Carlos Pestana; Managi, Shunsuke

    2009-01-01

    This paper analyzes the change in productivity as a result of Angola oil policy from 2001 to 2007. Angola oil blocks are the main source of tax receipts and, therefore, strategically important for public finances. A Malmquist index with the input technological bias is applied to measure productivity change. Oil blocks on average became both more efficient and experienced technological progress. Our results indicate that the traditional growth accounting method, which assumes Hicks neutral technological change, is not appropriate for analyzing changes in productivity for Angola oil blocks. Policy implications are derived. (author)

  8. Combining writing block treatments: theory and research.

    Science.gov (United States)

    Boice, R

    1992-03-01

    Four traditional formats of treatment for writing blocks (automaticity, regimen, self-control, and social skills training) proved insufficient to maintain unblocking in professorial writers for periods of an academic year. A combined application of the four historically prominent interventions was clearly more effective in terms of stable productivity, manuscripts finished and submitted, and manuscripts accepted for publication. Because writing blocks are too often conceptualized and treated by way of lore, a theory of blocking is proposed that clarifies the fundamental steps in effecting lasting unblocking.

  9. Theory of circuit block switch-off

    Directory of Open Access Journals (Sweden)

    S. Henzler

    2004-01-01

    Full Text Available Switching-off unused circuit blocks is a promising approach to supress static leakage currents in ultra deep sub-micron CMOS digital systems. Basic performance parameters of Circuit Block Switch-Off (CBSO schemes are defined and their dependence on basic circuit parameters is estimated. Therefore the design trade-off between strong leakage suppression in idle mode and adequate dynamic performance in active mode can be supported by simple analytic investigations. Additionally, a guideline for the estimation of the minimum time for which a block deactivation is useful is derived.

  10. Seismic proof test of shielding block walls

    International Nuclear Information System (INIS)

    Ohte, Yukio; Watanabe, Takahide; Watanabe, Hiroyuki; Maruyama, Kazuhide

    1989-01-01

    Most of the shielding block walls used for building nuclear facilities are built by dry process. When a nuclear facility is designed, seismic waves specific at each site are set as input seismic motions and they are adopted in the design. Therefore, it is necessary to assure safety of the shielding block walls for earthquake by performing anti-seismic experiments under the conditions at each site. In order to establish the normal form that can be applied to various seismic conditions in various areas, Shimizu Corp. made an actual-size test samples for the shielding block wall and confirmed the safety for earthquake and validity of normalization. (author)

  11. Traveling Rocky Roads: The Consequences of Transcription-Blocking DNA Lesions on RNA Polymerase II

    NARCIS (Netherlands)

    B. Steurer (Barbara); J.A. Marteijn (Jurgen)

    2016-01-01

    textabstractThe faithful transcription of eukaryotic genes by RNA polymerase II (RNAP2) is crucial for proper cell function and tissue homeostasis. However, transcription-blocking DNA lesions of both endogenous and environmental origin continuously challenge the progression of elongating RNAP2. The

  12. Comparison of Two Techniques of Brachial Plexus Block for Upper ...

    African Journals Online (AJOL)

    The study compared trans-arterial approach and mid-humeral technique of axillary brachial plexus block in terms of the clinical benefit of each method; adequacy of block, onset of sensory and motor block, duration of block and complications. .In a prospective randomized study, axillary plexus block was carried out in 50 ...

  13. EnviroAtlas - Memphis, TN - Block Groups

    Data.gov (United States)

    U.S. Environmental Protection Agency — This EnviroAtlas dataset is the base layer for the Memphis, TN EnviroAtlas community. The block groups are from the US Census Bureau and are included/excluded based...

  14. Packaging of Power Electronics Building Blocks

    National Research Council Canada - National Science Library

    Van

    2000-01-01

    The major objective of the PEBB research at CPES remains to support ONR's program to develop a new generation of electric ships based on the building block concept utilizing high voltage dc distribution...

  15. EnviroAtlas - Woodbine, IA - Block Groups

    Data.gov (United States)

    U.S. Environmental Protection Agency — This EnviroAtlas dataset is the base layer for the Woodbine, IA EnviroAtlas area. The block groups are from the US Census Bureau and are included/excluded based on...

  16. Dynamic code block size for JPEG 2000

    Science.gov (United States)

    Tsai, Ping-Sing; LeCornec, Yann

    2008-02-01

    Since the standardization of the JPEG 2000, it has found its way into many different applications such as DICOM (digital imaging and communication in medicine), satellite photography, military surveillance, digital cinema initiative, professional video cameras, and so on. The unified framework of the JPEG 2000 architecture makes practical high quality real-time compression possible even in video mode, i.e. motion JPEG 2000. In this paper, we present a study of the compression impact using dynamic code block size instead of fixed code block size as specified in the JPEG 2000 standard. The simulation results show that there is no significant impact on compression if dynamic code block sizes are used. In this study, we also unveil the advantages of using dynamic code block sizes.

  17. EnviroAtlas - Fresno, CA - Block Groups

    Data.gov (United States)

    U.S. Environmental Protection Agency — This EnviroAtlas dataset is the base layer for the Fresno, CA EnviroAtlas area. The block groups are from the US Census Bureau and are included/excluded based on...

  18. Blocking Detection Based on Synoptic Filters

    Directory of Open Access Journals (Sweden)

    Bernd Schalge

    2011-01-01

    minimum zonal width, and (iii a persistence filter to extract events with a minimum duration. Practical filter application is analysed in two case studies and the blocking climatologies for the Northern and the Southern Hemisphere.

  19. EnviroAtlas - Portland, OR - Block Groups

    Data.gov (United States)

    U.S. Environmental Protection Agency — This EnviroAtlas dataset is the base layer for the Portland, OR EnviroAtlas area. The block groups are from the US Census Bureau and are included/excluded based on...

  20. EnviroAtlas - Cleveland, OH - Block Groups

    Data.gov (United States)

    U.S. Environmental Protection Agency — This EnviroAtlas dataset is the base layer for the Cleveland, OH EnviroAtlas community. The block groups are from the US Census Bureau and are included/excluded...

  1. Two-block crossflow experiments, 2

    International Nuclear Information System (INIS)

    Takizuka, Takakazu; Kaburaki, Hideo

    1985-08-01

    Two-block crossflow experiments were conducted to obtain quantitative information on the characteristics of crossflow through the interface gaps between fuel elements in the VHTR core. Overall crossflow rates and pressure drops were measured on a full-scale two-block model with shims inserted to simulate the interface gap between the blocks. Atmospheric air at ambient temperature was used as a working fluid. Further objective of the experiments were to evaluate the effect of contact pressure on the crossflow and to determine the permeation flow rate through the blocks. The experimental results were expressed by a relation between crossflow loss coefficient factor and Reynolds number. Empirical equations, which accurately reproduce the experimental crossflow coefficient correlations, were devised for the thermal hydraulic design of the VHTR core. (author)

  2. Electrostatic control of block copolymer morphology

    Science.gov (United States)

    Sing, Charles E.; Zwanikken, Jos W.; Olvera de La Cruz, Monica

    2014-07-01

    Energy storage is at present one of the foremost issues society faces. However, material challenges now serve as bottlenecks in technological progress. Lithium-ion batteries are the current gold standard to meet energy storage needs; however, they are limited owing to the inherent instability of liquid electrolytes. Block copolymers can self-assemble into nanostructures that simultaneously facilitate ion transport and provide mechanical stability. The ions themselves have a profound, yet previously unpredictable, effect on how these nanostructures assemble and thus the efficiency of ion transport. Here we demonstrate that varying the charge of a block copolymer is a powerful mechanism to predictably tune nanostructures. In particular, we demonstrate that highly asymmetric charge cohesion effects can induce the formation of nanostructures that are inaccessible to conventional uncharged block copolymers, including percolated phases desired for ion transport. This vastly expands the design space for block copolymer materials and is informative for the versatile design of battery electrolyte materials.

  3. Studying Genes

    Science.gov (United States)

    ... NIGMS NIGMS Home > Science Education > Studying Genes Studying Genes Tagline (Optional) Middle/Main Content Area PDF Version (382 KB) Other Fact Sheets What are genes? Genes are segments of DNA that contain instructions ...

  4. Capacitor blocks for linear transformer driver stages.

    Science.gov (United States)

    Kovalchuk, B M; Kharlov, A V; Kumpyak, E V; Smorudov, G V; Zherlitsyn, A A

    2014-01-01

    In the Linear Transformer Driver (LTD) technology, the low inductance energy storage components and switches are directly incorporated into the individual cavities (named stages) to generate a fast output voltage pulse, which is added along a vacuum coaxial line like in an inductive voltage adder. LTD stages with air insulation were recently developed, where air is used both as insulation in a primary side of the stages and as working gas in the LTD spark gap switches. A custom designed unit, referred to as a capacitor block, was developed for use as a main structural element of the transformer stages. The capacitor block incorporates two capacitors GA 35426 (40 nF, 100 kV) and multichannel multigap gas switch. Several modifications of the capacitor blocks were developed and tested on the life time and self breakdown probability. Blocks were tested both as separate units and in an assembly of capacitive module, consisting of five capacitor blocks. This paper presents detailed design of capacitor blocks, description of operation regimes, numerical simulation of electric field in the switches, and test results.

  5. Direct block scheduling technology: Analysis of Avidity

    Directory of Open Access Journals (Sweden)

    Felipe Ribeiro Souza

    Full Text Available Abstract This study is focused on Direct Block Scheduling testing (Direct Multi-Period Scheduling methodology which schedules mine production considering the correct discount factor of each mining block, resulting in the final pit. Each block is analyzed individually in order to define the best target period. This methodology presents an improvement of the classical methodology derived from Lerchs-Grossmann's initial proposition improved by Whittle. This paper presents the differences between these methodologies, specially focused on the algorithms' avidity. Avidity is classically defined by the voracious search algorithms, whereupon some of the most famous greedy algorithms are Branch and Bound, Brutal Force and Randomized. Strategies based on heuristics can accentuate the voracity of the optimizer system. The applied algorithm use simulated annealing combined with Tabu Search. The most avid algorithm can select the most profitable blocks in early periods, leading to higher present value in the first periods of mine operation. The application of discount factors to blocks on the Lerchs-Grossmann's final pit has an accentuated effect with time, and this effect may make blocks scheduled for the end of the mine life unfeasible, representing a trend to a decrease in reported reserves.

  6. Block copolymer membranes for aqueous solution applications

    KAUST Repository

    Nunes, Suzana Pereira

    2016-03-22

    Block copolymers are known for their intricate morphology. We review the state of the art of block copolymer membranes and discuss perspectives in this field. The main focus is on pore morphology tuning with a short introduction on non-porous membranes. The two main strategies for pore formation in block copolymer membranes are (i) film casting and selective block sacrifice and (ii) self-assembly and non-solvent induced phase separation (SNIPS). Different fundamental aspects involved in the manufacture of block copolymer membranes are considered, including factors affecting the equilibrium morphology in solid films, self-assembly of copolymer in solutions and macrophase separation by solvent-non-solvent exchange. Different mechanisms are proposed for different depths of the SNIPS membrane. Block copolymer membranes can be prepared with much narrower pore size distribution than homopolymer membranes. Open questions and indications of what we consider the next development steps are finally discussed. They include the synthesis and application of new copolymers and specific functionalization, adding characteristics to respond to stimuli and chemical environment, polymerization-induced phase separation, and the manufacture of organic-inorganic hybrids.

  7. Gene Therapy

    Science.gov (United States)

    Gene therapy Overview Gene therapy involves altering the genes inside your body's cells in an effort to treat or stop disease. Genes contain your ... that don't work properly can cause disease. Gene therapy replaces a faulty gene or adds a new ...

  8. Haplotype block partitioning as a tool for dimensionality reduction in SNP association studies.

    Science.gov (United States)

    Pattaro, Cristian; Ruczinski, Ingo; Fallin, Danièle M; Parmigiani, Giovanni

    2008-08-29

    Identification of disease-related genes in association studies is challenged by the large number of SNPs typed. To address the dilution of power caused by high dimensionality, and to generate results that are biologically interpretable, it is critical to take into consideration spatial correlation of SNPs along the genome. With the goal of identifying true genetic associations, partitioning the genome according to spatial correlation can be a powerful and meaningful way to address this dimensionality problem. We developed and validated an MCMC Algorithm To Identify blocks of Linkage DisEquilibrium (MATILDE) for clustering contiguous SNPs, and a statistical testing framework to detect association using partitions as units of analysis. We compared its ability to detect true SNP associations to that of the most commonly used algorithm for block partitioning, as implemented in the Haploview and HapBlock software. Simulations were based on artificially assigning phenotypes to individuals with SNPs corresponding to region 14q11 of the HapMap database. When block partitioning is performed using MATILDE, the ability to correctly identify a disease SNP is higher, especially for small effects, than it is with the alternatives considered. Advantages can be both in terms of true positive findings and limiting the number of false discoveries. Finer partitions provided by LD-based methods or by marker-by-marker analysis are efficient only for detecting big effects, or in presence of large sample sizes. The probabilistic approach we propose offers several additional advantages, including: a) adapting the estimation of blocks to the population, technology, and sample size of the study; b) probabilistic assessment of uncertainty about block boundaries and about whether any two SNPs are in the same block; c) user selection of the probability threshold for assigning SNPs to the same block. We demonstrate that, in realistic scenarios, our adaptive, study-specific block partitioning

  9. Atheroprotective Effects of Tumor Necrosis Factor–Stimulated Gene-6

    Directory of Open Access Journals (Sweden)

    Rena Watanabe, MS

    2016-10-01

    Full Text Available Tumor necrosis factor–stimulated gene-6 (TSG-6, an anti-inflammatory protein, was shown to be localized in the neointima of injury-induced rat arteries. However, the modulatory effect of TSG-6 on atherogenesis has not yet been reported. We aimed to evaluate the atheroprotective effects of TSG-6 on human endothelial cells (HECs, human monocyte-derived macrophages (HMDMs, human aortic smooth muscle cells (HASMCs in vitro, and aortic lesions in apolipoprotein E–deficient mice, along with expression levels of TSG-6 in coronary lesions and plasma from patients with coronary artery disease (CAD. TSG-6 was abundantly expressed in HECs, HMDMs, and HASMCs in vitro. TSG-6 significantly suppressed cell proliferation and lipopolysaccharide-induced up-regulation of monocyte chemotactic protein-1, intercellular adhesion molecule-1, and vascular adhesion molecule-1 in HECs. TSG-6 significantly suppressed inflammatory M1 phenotype and suppressed oxidized low-density lipoprotein–induced foam cell formation associated with down-regulation of CD36 and acyl-CoA:cholesterol acyltransferase-1 in HMDMs. In HASMCs, TSG-6 significantly suppressed migration and proliferation, but increased collagen-1 and -3 expressions. Four-week infusion of TSG-6 into apolipoprotein E–deficient mice significantly retarded the development of aortic atherosclerotic lesions with decreased vascular inflammation, monocyte/macrophage, and SMC contents and increased collagen fibers. In addition, it decreased peritoneal M1 macrophages with down-regulation of inflammatory molecules and lowered plasma total cholesterol levels. In patients with CAD, plasma TSG-6 levels were significantly increased, and TSG-6 was highly expressed in the fibrous cap within coronary atherosclerotic plaques. These results suggest that TSG-6 contributes to the prevention and stability of atherosclerotic plaques. Thus, TSG-6 may serve as a novel therapeutic target for CAD.

  10. Synthesis of segmented (pb(ps-block-pb)(n)) and (pb(san-block- pb)(n)) block-copolymers via polymeric thermal iniferters

    NARCIS (Netherlands)

    Kroeze, E; ten Brinke, G.; Hadziioannou, G

    1995-01-01

    A technique is described for the synthesis of segmented poly(butadiene-block-styrene) block copolymers and segmented poly(butadiene-block-(styrene-co-acrylonitrile)) block copolymers through polybutadiene-based thermal iniferters. Dihydroxy- and dicarboxy-terminated polybutadienes were transformed

  11. Shift in epitope dominance of IgM and IgG responses to Plasmodium falciparum MSP1 block 4

    Directory of Open Access Journals (Sweden)

    Leke Rose GF

    2010-01-01

    Full Text Available Abstract Background Plasmodium falciparum merozoite surface protein-1 (MSP1 has been extensively studied as a blood-stage malaria vaccine candidate, with most work focused on the conserved 19 kDa and semi-conserved 42 kDa C-terminal regions (blocks 16-17 and the hypervariable N-terminal repeat region (block 2. However, recent genotyping studies suggest that additional regions of MSP1 may be under selective pressure, including a locus of intragenic recombination designated as block 4 within the 3' region of the gene. Methods The current study examined the antibody response to the two parental and two recombinant forms of block 4 and to blocks 16-17 (3D7 in study populations from Colombia, Papua New Guinea and Cameroon that differ in malaria transmission intensity and ethnic composition. Results IgM and IgG antibodies were detected against parental and recombinant MSP1 block 4 peptides in all three populations. Overall, 32-44% of the individuals produced IgM to one or more of the peptides, with most individuals having IgM antibodies reactive with both parental and recombinant forms. In contrast, IgG seropositivity to block 4 varied among populations (range 15-65%, with the majority of antibodies showing specificity for one or a pair of block 4 peptides. The IgG response to block 4 was significantly lower than that to blocks 16-17, indicating block 4 is subdominant. Antibodies to block 4 and blocks 16-17 displayed distinct IgG subclass biases, with block 4 responses biased toward IgG3 and blocks 16-17 toward IgG1. These patterns of responsiveness were consistently observed in the three study populations. Conclusions Production of antibodies specific for each parental and recombinant MSP1 block 4 allele in different populations exposed to P. falciparum is consistent with balancing selection of the MSP1 block 4 region by the immune response of individuals in areas of both low and high malaria transmission. MSP1 block 4 determinants may be important

  12. Turbulence Interface Simulation by Lagrangian Blocks

    Science.gov (United States)

    Chu, V. H.

    2015-12-01

    Most computational fluid-dynamics codes are developed using the Eulerian description. To find the numerical solution, fluxes are estimated on the surface of the finite volume using a truncation series. Spurious numerical oscillations and artificial numerical diffusion are consequences, particularly in regions across flow discontinuities. Diffusion often is introduced synthetically in many schemes to gain computational stability. Occasional switching to a diffusive upwind scheme, for example, is one classic strategy to manage the numerical oscillations [see e.g., Ghannadi & Chu 2015]. Lagrangian-block simulation offers an alternative that could minimize the spurious oscillations and false diffusive error. The blocks move in the direction of the flow. The squares of the block widths expand in proportion to the diffusivities. The block simulation procedure consists of (i) Lagrangian advection and diffusion, (ii) division into portions, and (iii) reassembly of the portions into new blocks. The blocks are renewed in each time increment to prevent excessive distortion. Details of the Lagrangian-block simulations method have been given in a series of papers by Tan & Chu (2012), Chu & Altai (2012, 2015}. In this paper, the exchanges across turbulence interfaces are considered for two problems. The first series of the simulations are conducted to find the mass and momentum exchanges across a shallow flow of two different depth. In the simulations, the advection and diffusion of three separated systems of blocks that contain the mass, momentum and potential vorticity are carried out using the Lagrangian-block simulation method. The simulation results are compared with data obtained from a previous laboratory investigation and related to the shear instability problem in rotating shear flow previously considered by Chu (2014). The second problem involves the turbulence generation across the interface of an internal waves. The simulation shows the development of gravitational

  13. Implicit Block Diagonal Low-Rank Representation.

    Science.gov (United States)

    Xie, Xingyu; Guo, Xianglin; Liu, Guangcan; Wang, Jun

    2017-10-17

    While current block diagonal constrained subspace clustering methods are performed explicitly on the original data space, in practice it is often more desirable to embed the block diagonal prior into the reproducing kernel Hilbert feature space by kernelization techniques, as the underlying data structure in reality is usually nonlinear. However, it is still unknown how to carry out the embedding and kernelization in the models with block diagonal constraints. In this work, we shall take a step in this direction. First, we establish a novel model termed Implicit Block Diagonal Low-Rank Representation (IBDLR), by incorporating the implicit feature representation and block diagonal prior into the prevalent Low-Rank Representation (LRR) method. Second, mostly important, we show that the model in IBDLR could be kernelized by making use of a smoothed dual representation and the specifics of a proximal gradient based optimization algorithm. Finally, we provide some theoretical analyses for the convergence of our optimization algorithm. Comprehensive experiments on synthetic and realworld datasets demonstrate the superiorities of our IBDLR over state-of-the-art methods.While current block diagonal constrained subspace clustering methods are performed explicitly on the original data space, in practice it is often more desirable to embed the block diagonal prior into the reproducing kernel Hilbert feature space by kernelization techniques, as the underlying data structure in reality is usually nonlinear. However, it is still unknown how to carry out the embedding and kernelization in the models with block diagonal constraints. In this work, we shall take a step in this direction. First, we establish a novel model termed Implicit Block Diagonal Low-Rank Representation (IBDLR), by incorporating the implicit feature representation and block diagonal prior into the prevalent Low-Rank Representation (LRR) method. Second, mostly important, we show that the model in IBDLR could be

  14. Demographic Data - MDC_LowModerateBlockGroup

    Data.gov (United States)

    NSGIC Local Govt | GIS Inventory — A polygon feature class of Miami-Dade Low-Moderate Block Groups also referred to as Community Development Block Group (CDBG). Identify only those census block groups...

  15. Adductor canal block versus femoral nerve block for analgesia after total knee arthroplasty

    DEFF Research Database (Denmark)

    Jaeger, Pia; Zaric, Dusanka; Fomsgaard, Jonna Storm

    2013-01-01

    Femoral nerve block (FNB), a commonly used postoperative pain treatment after total knee arthroplasty (TKA), reduces quadriceps muscle strength essential for mobilization. In contrast, adductor canal block (ACB) is predominately a sensory nerve block. We hypothesized that ACB preserves quadriceps...... muscle strength as compared with FNB (primary end point) in patients after TKA. Secondary end points were effects on morphine consumption, pain, adductor muscle strength, morphine-related complications, and mobilization ability....

  16. Combined KHFAC + DC nerve block without onset or reduced nerve conductivity after block

    Science.gov (United States)

    Franke, Manfred; Vrabec, Tina; Wainright, Jesse; Bhadra, Niloy; Bhadra, Narendra; Kilgore, Kevin

    2014-10-01

    Objective. Kilohertz frequency alternating current (KHFAC) waveforms have been shown to provide peripheral nerve conductivity block in many acute and chronic animal models. KHFAC nerve block could be used to address multiple disorders caused by neural over-activity, including blocking pain and spasticity. However, one drawback of KHFAC block is a transient activation of nerve fibers during the initiation of the nerve block, called the onset response. The objective of this study is to evaluate the feasibility of using charge balanced direct current (CBDC) waveforms to temporarily block motor nerve conductivity distally to the KHFAC electrodes to mitigate the block onset-response. Approach. A total of eight animals were used in this study. A set of four animals were used to assess feasibility and reproducibility of a combined KHFAC + CBDC block. A following randomized study, conducted on a second set of four animals, compared the onset response resulting from KHFAC alone and combined KHFAC + CBDC waveforms. To quantify the onset, peak forces and the force-time integral were measured during KHFAC block initiation. Nerve conductivity was monitored throughout the study by comparing muscle twitch forces evoked by supra-maximal stimulation proximal and distal to the block electrodes. Each animal of the randomized study received at least 300 s (range: 318-1563 s) of cumulative dc to investigate the impact of combined KHFAC + CBDC on nerve viability. Main results. The peak onset force was reduced significantly from 20.73 N (range: 18.6-26.5 N) with KHFAC alone to 0.45 N (range: 0.2-0.7 N) with the combined CBDC and KHFAC block waveform (p conductivity was observed after application of the combined KHFAC + CBDC block relative to KHFAC waveforms. Significance. The distal application of CBDC can significantly reduce or even completely prevent the KHFAC onset response without a change in nerve conductivity.

  17. Efficient Eulerian gyrokinetic simulations with block-structured grids

    Energy Technology Data Exchange (ETDEWEB)

    Jarema, Denis

    2017-01-20

    applied to different Eulerian gyrokinetic simulation codes, as the technique relies on a general approach. We implemented and tested our block-structured grids in GENE (http://genecode.org), a highly parallel and heavily used gyrokinetic code, for which it is crucial to keep the good parallel characteristic of the implementation and allow developers to easily port the code written for the original grid to the block-structured counterpart. The presented scenarios clearly demonstrate benefits of the block-structured grids: a high speedup, a tremendously reduced memory footprint and size of diagnostic output data, and the capability to significantly advance the frontier of feasible simulations.

  18. Morbillivirus v proteins exhibit multiple mechanisms to block type 1 and type 2 interferon signalling pathways.

    Directory of Open Access Journals (Sweden)

    Senthil K Chinnakannan

    Full Text Available Morbilliviruses form a closely related group of pathogenic viruses which encode three non-structural proteins V, W and C in their P gene. Previous studies with rinderpest virus (RPV and measles virus (MeV have demonstrated that these non-structural proteins play a crucial role in blocking type I (IFNα/β and type II (IFNγ interferon action, and various mechanisms have been proposed for these effects. We have directly compared four important morbilliviruses, rinderpest (RPV, measles virus (MeV, peste des petits ruminants virus (PPRV and canine distemper virus (CDV. These viruses and their V proteins could all block type I IFN action. However, the viruses and their V proteins had varying abilities to block type II IFN action. The ability to block type II IFN-induced gene transcription correlated with co-precipitation of STAT1 with the respective V protein, but there was no correlation between co-precipitation of either STAT1 or STAT2 and the abilities of the V proteins to block type I IFN-induced gene transcription or the creation of the antiviral state. Further study revealed that the V proteins of RPV, MeV, PPRV and CDV could all interfere with phosphorylation of the interferon-receptor-associated kinase Tyk2, and the V protein of highly virulent RPV could also block the phosphorylation of another such kinase, Jak1. Co-precipitation studies showed that morbillivirus V proteins all form a complex containing Tyk2 and Jak1. This study highlights the ability of morbillivirus V proteins to target multiple components of the IFN signalling pathways to control both type I and type II IFN action.

  19. An ancient genomic regulatory block conserved across bilaterians and its dismantling in tetrapods by retrogene replacement.

    Science.gov (United States)

    Maeso, Ignacio; Irimia, Manuel; Tena, Juan J; González-Pérez, Esther; Tran, David; Ravi, Vydianathan; Venkatesh, Byrappa; Campuzano, Sonsoles; Gómez-Skarmeta, José Luis; Garcia-Fernàndez, Jordi

    2012-04-01

    Developmental genes are regulated by complex, distantly located cis-regulatory modules (CRMs), often forming genomic regulatory blocks (GRBs) that are conserved among vertebrates and among insects. We have investigated GRBs associated with Iroquois homeobox genes in 39 metazoans. Despite 600 million years of independent evolution, Iroquois genes are linked to ankyrin-repeat-containing Sowah genes in nearly all studied bilaterians. We show that Iroquois-specific CRMs populate the Sowah locus, suggesting that regulatory constraints underlie the maintenance of the Iroquois-Sowah syntenic block. Surprisingly, tetrapod Sowah orthologs are intronless and not associated with Iroquois; however, teleost and elephant shark data demonstrate that this is a derived feature, and that many Iroquois-CRMs were ancestrally located within Sowah introns. Retroposition, gene, and genome duplication have allowed selective elimination of Sowah exons from the Iroquois regulatory landscape while keeping associated CRMs, resulting in large associated gene deserts. These results highlight the importance of CRMs in imposing constraints to genome architecture, even across large phylogenetic distances, and of gene duplication-mediated genetic redundancy to disentangle these constraints, increasing genomic plasticity.

  20. Periodic titania nanostructures using block copolymer templates.

    Science.gov (United States)

    Chinthamanipeta, Pavan S; Lou, Qin; Shipp, Devon A

    2011-01-25

    The deposition of periodic titania nanostructures, templated by a polystyrene-block-poly(4-vinylpyridine) (PS-b-P4VP) block copolymer, is reported. When cast as a thin film (30-50 nm thick), the PS-b-P4VP forms a morphology that consists of P4VP cylinders that are orientated perpendicular to the substrate. The P4VP phase was lightly cross-linked by exposing the film to diiodobutane. When the block copolymer film was exposed to the sol-gel titania precursor, titanium(IV) bis(ammonium lactate) dihydroxide (TALH), titania was formed in the P4VP phase. The resulting titania structures were identical in size to the P4VP cylinders and only formed (under the deposition conditions used in this study) when the block copolymer film was present on the substrate, thus providing evidence that the block copolymer indeed acts as a template. The process works for both silicon and indium tin oxide substrates.

  1. Rapid ordering of block copolymer thin films.

    Science.gov (United States)

    Majewski, Pawel W; Yager, Kevin G

    2016-10-12

    Block-copolymers self-assemble into diverse morphologies, where nanoscale order can be finely tuned via block architecture and processing conditions. However, the ultimate usage of these materials in real-world applications may be hampered by the extremely long thermal annealing times-hours or days-required to achieve good order. Here, we provide an overview of the fundamentals of block-copolymer self-assembly kinetics, and review the techniques that have been demonstrated to influence, and enhance, these ordering kinetics. We discuss the inherent tradeoffs between oven annealing, solvent annealing, microwave annealing, zone annealing, and other directed self-assembly methods; including an assessment of spatial and temporal characteristics. We also review both real-space and reciprocal-space analysis techniques for quantifying order in these systems.

  2. Recent advances in neuromuscular block during anesthesia.

    Science.gov (United States)

    Boon, Martijn; Martini, Christian; Dahan, Albert

    2018-01-01

    Muscle relaxation is a routine part of anesthesia and has important advantages. However, the lingering effects of muscle relaxants in the postoperative period have historically been associated with postoperative adverse events. Neuromuscular reversal, together with neuromuscular monitoring, is a recognized strategy to reduce the rate of postoperative residual relaxation but has only marginally improved outcome in the past few decades. Sugammadex, a novel reversal agent with unique encapsulating properties, has changed the landscape of neuromuscular reversal and opened up new opportunities to improve patient care. By quickly and completely reversing any depth of neuromuscular block, it may reduce the rate of residual relaxation and improve respiratory recovery. In addition, sugammadex has made the use of deep neuromuscular block possible during surgery. Deep neuromuscular block may improve surgical working conditions and allow for a reduction in insufflation pressures during selected laparoscopic procedures. However, whether and how this may impact outcomes is not well established.

  3. Effects of 4X4 Block Scheduling

    Directory of Open Access Journals (Sweden)

    R. Brian Cobb

    1999-02-01

    Full Text Available The effects of a 4 X 4 block scheduling program in a middle school on a variety of student measures were investigated. These measures included standardized achievement tests in mathematics, reading, and writing, cumulative and semester grades in middle school and high school, attendance rates, and enrollment rates in advanced high school courses (in mathematics only. The block scheduling program had been in effect for four years allowing analyses of current middle and high school students who had experienced a minimum of one and one-half years of block scheduling while in middle school. The primary research design was a post-test only, matched pairs design. Students were matched on school characteristics, gender, ethnicity, grade level, and 5th grade standardized reading scores. Results were relatively consistent with the extant literature and generally positive.

  4. Thoracal paravertebral block for breast surgery

    Directory of Open Access Journals (Sweden)

    Serbülent Gökhan Beyaz

    2012-12-01

    Full Text Available Thoracic paravertebral block (TPVB is an alternativemethod to general anesthesia because of provides a safeanesthesia with balanced hemodynamic response, allowspostoperative pain control by means of catheter and haslow side effect profile. TPVB performed safely for the patientsundergoing breast cancer surgery with the samereason, has used in too few center instead of general anesthesia.This technique provides an adequate anesthesiafor the patients undergoing breast surgery and in additionprovides stable hemodynamic status with unilateralsomatic and sympathetic blockade, near-perfect controlof postoperative pain, minimal nausea and vomiting rate,early discharge and low cost. For this reason, thoracicparavertebral block which is a standard method in breastsurgeries for some centers should be known by all anesthesiologists.We believe that, thoracic paravertebralblock is a method can be applied instead of general anesthesia.Key words: Paravertebral block, thoracic, breast surgery,regional anesthesia

  5. Radial expansion for spinning conformal blocks

    CERN Document Server

    Costa, Miguel S.; Penedones, João; Trevisani, Emilio

    2016-07-12

    This paper develops a method to compute any bosonic conformal block as a series expansion in the optimal radial coordinate introduced by Hogervorst and Rychkov. The method reduces to the known result when the external operators are all the same scalar operator, but it allows to compute conformal blocks for external operators with spin. Moreover, we explain how to write closed form recursion relations for the coefficients of the expansions. We study three examples of four point functions in detail: one vector and three scalars; two vectors and two scalars; two spin 2 tensors and two scalars. Finally, for the case of two external vectors, we also provide a more efficient way to generate the series expansion using the analytic structure of the blocks as a function of the scaling dimension of the exchanged operator.

  6. Blending of styrene-block-butadiene-block-styrene copolymer with sulfonated vinyl aromatic polymers

    NARCIS (Netherlands)

    Ruggeri, Giacomo; Passaglia, Elisa; Giorgi, Ivan; Picchioni, Francesco; Aglietto, Mauro

    2001-01-01

    Different polymers containing sulfonic groups attached to the phenyl rings were prepared by sulfonation of polystyrene (PS) and styrene-block-(ethylene-co-1-butene)-block-styrene (SEBS). The sulfonation degree (SD) was varied between 1 and 20 mol% of the styrene units. Polyphase materials containing

  7. Arthroscopic medial meniscus trimming or repair under nerve blocks: Which nerves should be blocked?

    Science.gov (United States)

    Taha, AM; Abd-Elmaksoud, AM

    2016-01-01

    Background: This study aimed to determine the role of the sciatic and obturator nerve blocks (in addition to femoral block) in providing painless arthroscopic medial meniscus trimming/repair. Materials and Methods: One hundred and twenty patients with medial meniscus tear, who had been scheduled to knee arthroscopy, were planned to be included in this controlled prospective double-blind study. The patients were randomly allocated into three equal groups; FSO, FS, and FO. The femoral, sciatic, and obturator nerves were blocked in FSO groups. The femoral and sciatic nerves were blocked in FS group, while the femoral and obturator nerves were blocked in FO group. Intraoperative pain and its causative surgical maneuver were recorded. Results: All the patients (n = 7, 100%) in FO group had intraoperative pain. The research was terminated in this group but completed in FS and FSO groups (40 patients each). During valgus positioning of the knee for surgical management of the medial meniscus tear, the patients in FS group experienced pain more frequently than those in FSO group (P = 0.005). Conclusion: Adding a sciatic nerve block to the femoral nerve block is important for painless knee arthroscopy. Further adding of an obturator nerve block may be needed when a valgus knee position is required to manage the medial meniscus tear. PMID:27375382

  8. Production blocking and idea generation : Does blocking interfere with cognitive processes?

    NARCIS (Netherlands)

    Nijstad, BA; Stroebe, W; Lodewijkx, HFM

    2003-01-01

    Production blocking (group members must take turns expressing their ideas) is an important cause of productivity loss in brainstorming groups. However, it is not yet clear why production blocking has this detrimental effect. We hypothesized that delays between the generation and articulation of

  9. Fabrication and handling of bentonite blocks

    International Nuclear Information System (INIS)

    1978-06-01

    In accordance with the project for the final storage of spent nuclear fuel, the waste will be encapsulated into copper canisters, which will be deposited in a final repository located in rock 500 m below ground level. The canisters will be placed in vertical holes in the bottoms of the tunnels, where the copper cylinders will be surrounded by blocks of highly compacted bentonite. When the blocks are saturated with water and expansion is essentially retained as in the actual case, a very high swelling pressure will arise. The bentonite will be extremely impermeable and thus it will form a barrier against transport of corrosive matters to the canister. The blocks are fabricated by means of cold isostatic pressing of bentonite powder. The base material in the form of powder is enclosed in flexible forms, which are introduced into pressure vessels where the forms are surrounded by oil or water. Thus the powder is compacted into rigid bodies with a bulk density of about 2.2 t/m 3 for ''air dry'' bentonite, which might be compared with a specific density of about 2.7 t/m 3 . The placing of a canister is preceded by piling up bentonite blocks to a level just below the canister lid position, after which the slot around the blocks is filled with bentonite powder. The rest of the blocks are mounted after filling bentonite powder into the inner slot around the canister as well. Finally the storage tunnels will be sealed by filling them with a mixture o02067NRM 0000181 45

  10. Breast Cancer Gene Therapy: Development of Novel Non-Invasive Magnetic Resonance Assay to Optimize Efficacy

    National Research Council Canada - National Science Library

    Mason, Ralph P

    2005-01-01

    Gene therapy holds great promise for treatment of breast cancer. In particular; clinical trials are underway to apply therapeutic genes related to pro-drug activation or to modulate the activity of oncogenes by blocking promoter sites...

  11. Breast Cancer Gene Therapy: Development of Novel Non-Invasive Magnetic Resonance Assay to Optimize Efficacy

    National Research Council Canada - National Science Library

    Mason, Ralph

    2004-01-01

    Gene therapy holds great promise for treatment of breast cancer. In particular, clinical trials are underway to apply therapeutic genes related to pro-drug activation or to modulate the activity of oncogenes by blocking promoter sites...

  12. Breast Cancer Gene Therapy: Development of Novel Non-Invasive Magnetic Resonance Assay to Optimize Efficacy

    National Research Council Canada - National Science Library

    Mason, Ralph P

    2007-01-01

    Gene therapy holds great promise for treatment of breast cancer. In particular clinical trials are underway to apply therapeutic genes related to pro-drug activation or to modulate the activity of oncogenes by blocking promoter sites...

  13. Breast Cancer Gene Therapy: Development of Novel Non-Invasive Magnetic Resonance Assay to Optimize Efficacy

    National Research Council Canada - National Science Library

    Mason, Ralph P

    2006-01-01

    Gene therapy holds great promise for treatment of breast cancer. In particular clinical trials are underway to apply therapeutic genes related to pro-drug activation or to modulate the activity of oncogenes by blocking promoter sites...

  14. Cutaneous Sensory Block Area, Muscle-Relaxing Effect, and Block Duration of the Transversus Abdominis Plane Block

    DEFF Research Database (Denmark)

    Støving, Kion; Rothe, Christian; Rosenstock, Charlotte V

    2015-01-01

    and the abdominal muscle-relaxing effect. RESULTS: The lateral part of the cutaneous sensory block area was a median of 266 cm2 (interquartile range, 191-310 cm2) and the medial part 76 cm 2(interquartile range, 54-127 cm2). In all the volunteers, lateral wall muscle thickness decreased significantly by 9.2 mm (6...

  15. Nanoscale freestanding gratings for ultraviolet blocking filters

    Energy Technology Data Exchange (ETDEWEB)

    van Beek, J.T.; Fleming, R.C.; Hindle, P.S.; Prentiss, J.D.; Schattenburg, M.L. [Massachusetts Institute of Technology, Cambridge, Massachusetts 02139 (United States); Ritzau, S. [Los Alamos National Laboratory, Los Alamos, New Mexico 87545 (United States)

    1998-11-01

    Ultraviolet (UV) blocking filters are needed for atomic flux imaging in environments where high levels of ultraviolet radiation are present. Freestanding gratings are a promising candidate for UV filtering. They have a high aspect ratio ({approximately}13), narrow ({approximately}40 nm) slots, and effectively block UV radiation. The grating fabrication process makes use of several etching, electroplating, and lithographic steps and includes an optional step to plug pinholes induced by particles during processing. Gratings were successfully manufactured and tested. Measured UV transmissions of {approximately}10{sup {minus}5} and particle transmissions of {approximately}10{percent} are in agreement with theoretical predictions. {copyright} {ital 1998 American Vacuum Society.}

  16. WZW superconformal blocks from three dimensions

    International Nuclear Information System (INIS)

    McArthur, I.N.

    1991-05-01

    A three-dimensional theory whose canonical quantization yields wavefunctions which can be identified with the superconformal blocks of two-dimensional super-Wess-Zumino-Witten theory is presented. In particular, the anomalous Ward identities satisfied by the superconformal blocks in the presence of a supergauge background are reproduced in terms of constraints obeyed by the wavefunctions of the three-dimensional theory. The action contains the bosonic Chern-Simons action but does not possess a three-dimensional supersymmetry. The 'time' coordinate plays the role of an interpolating parameter between two-dimensional superconnections. The structure of the Hilbert space of the theory is examined. (orig.)

  17. Block floating point for radar data

    DEFF Research Database (Denmark)

    Christensen, Erik Lintz

    1999-01-01

    Integer, floating point, and block floating point (BFP) data formats are analyzed and compared in order to establish the mathematical tools for selection of an optimal format which fulfils the demands of high resolution radar (SAR) data to large dynamic range and adequate S/N. The analysis takes...... quantization noise and saturation distortion into account and concludes that it is preferred to use small blocks and a (new) modified BFP format applying fractional exponents. Data from the EMISAR radar system are applied to illustrate the merits of the different schemes....

  18. Wilson loop invariants from WN conformal blocks

    Directory of Open Access Journals (Sweden)

    Oleg Alekseev

    2015-12-01

    Full Text Available Knot and link polynomials are topological invariants calculated from the expectation value of loop operators in topological field theories. In 3D Chern–Simons theory, these invariants can be found from crossing and braiding matrices of four-point conformal blocks of the boundary 2D CFT. We calculate crossing and braiding matrices for WN conformal blocks with one component in the fundamental representation and another component in a rectangular representation of SU(N, which can be used to obtain HOMFLY knot and link invariants for these cases. We also discuss how our approach can be generalized to invariants in higher-representations of WN algebra.

  19. Infinite-degree-corrected stochastic block model

    DEFF Research Database (Denmark)

    Herlau, Tue; Schmidt, Mikkel Nørgaard; Mørup, Morten

    2014-01-01

    In stochastic block models, which are among the most prominent statistical models for cluster analysis of complex networks, clusters are defined as groups of nodes with statistically similar link probabilities within and between groups. A recent extension by Karrer and Newman [Karrer and Newman...... corrected stochastic block model as a nonparametric Bayesian model, incorporating a parameter to control the amount of degree correction that can then be inferred from data. Additionally, our formulation yields principled ways of inferring the number of groups as well as predicting missing links...

  20. Study of the block/grout interface in concrete and clay block masonry structures

    Directory of Open Access Journals (Sweden)

    O. S. Izquierdo

    Full Text Available ABSTRACT This work aims to study the behavior of the block/grout interface for concrete and clay block masonry. This was achieved by push-out and pull-out experimental tests including reinforcement bar in the latter one. The experimental result showed that there is a good bond between the concrete blocks internal faces and the grout, enough to prevent infill-slippage, and that the whole tensile strength of the usual reinforcement bars is achieved provided they are properly anchored. Nevertheless, for clay blocks there is a low bond between the clay blocks internal faces and the grout, allowing the infill-slippage before the reinforcement bars reach their yield stress.

  1. Blocking protein quality control to counter hereditary cancers

    DEFF Research Database (Denmark)

    Kampmeyer, Caroline; Nielsen, Sofie V.; Clausen, Lene

    2017-01-01

    imbalance, which makes them more dependent on protein quality control (PQC) mechanisms than normal cells. Accordingly, blocking PQC, e.g. by proteasome inhibitors, may cause a lethal proteotoxic crisis in cancer cells, while leaving normal cells unaffected. Evidence, however, suggests that the PQC system......Inhibitors of molecular chaperones and the ubiquitin-proteasome system have already been clinically implemented to counter certain cancers, including multiple myeloma and mantle cell lymphoma. The efficacy of this treatment relies on genomic alterations in cancer cells causing a proteostatic...... cancer susceptibility syndromes, such as Lynch syndrome and von Hippel-Lindau disease, are caused by missense mutations in tumor suppressor genes, and in some cases, the resulting amino acid substitutions in the encoded proteins cause the cellular PQC system to target them for degradation, although...

  2. A Variable Block Insertion Heuristic for the Blocking Flowshop Scheduling Problem with Total Flowtime Criterion

    Directory of Open Access Journals (Sweden)

    Mehmet Fatih Tasgetiren

    2016-10-01

    Full Text Available In this paper, we present a variable block insertion heuristic (VBIH algorithm to solve the blocking flowshop scheduling problem with the total flowtime criterion. In the VBIH algorithm, we define a minimum and a maximum block size. After constructing the initial sequence, the VBIH algorithm starts with a minimum block size being equal to one. It removes the block from the current sequence and inserts it into the partial sequence sequentially with a predetermined move size. The sequence, which is obtained after several block moves, goes under a variable local search (VLS, which is based on traditional insertion and swap neighborhood structures. If the new sequence obtained after the VLS local search is better than the current sequence, it replaces the current sequence. As long as it improves, it keeps the same block size. However, if it does not improve, the block size is incremented by one and a simulated annealing-type of acceptance criterion is used to accept the current sequence. This process is repeated until the block size reaches at the maximum block size. Furthermore, we present a novel constructive heuristic, which is based on the profile fitting heuristic from the literature. The proposed constructive heuristic is able to further improve the best known solutions for some larger instances in a few seconds. Parameters of the constructive heuristic and the VBIH algorithm are determined through a design of experiment approach. Extensive computational results on the Taillard’s well-known benchmark suite show that the proposed VBIH algorithm outperforms the discrete artificial bee colony algorithm, which is one of the most efficient algorithms recently in the literature. Ultimately, 52 out of the 150 best known solutions are further improved with substantial margins.

  3. gene structure, gene expression

    Indian Academy of Sciences (India)

    and seedling leaves were sampled at 6 h after the treatment. For cold stress, the seedlings were transferred to 4◦C growth chamber for 30 min. Control seedlings were exposed to none of these treatments. To examine the expression patterns of these predicted genes in Poplar and to further confirm their stress responsive-.

  4. Assessment of Structural Strength of Commercial Sandcrete Blocks ...

    African Journals Online (AJOL)

    makorede

    blocks which describes solid, hollow and cellular blocks: See. Table 1. Type. Void percent of total volume. Solid ... also deals with solid bricks, hollow bricks and cellular bricks. It states that the minimum requirement for blocks ..... bricks and blocks of fired brick earth, clay or shale. Ejeh, S. P. (1982). Comparative strength of ...

  5. What Happens When Things Go Wrong: Women and Writing Blocks.

    Science.gov (United States)

    Cayton, Mary Kupiec

    1990-01-01

    Describes a college instructor's observations of her students' writing blocks. Suggests that female students' writing blocks differ from males'. Asserts that females' blocks last longer and cause greater distress than do males' writing blocks. Notes that female students also appear to experience difficulty in utilizing secondary sources and…

  6. Improving Parent-Child Relationships through Block Play

    Science.gov (United States)

    Lin, Yen-Chun

    2010-01-01

    Blocks are one of the most popular playthings for children. The purpose of this article is to describe the use of block play in developing parent-child relations. This paper has two major parts. First, a brief historical overview highlights the critical roles of child's block play in learning and development. Block play contributes to children's…

  7. Compaction of bentonite blocks. Development of techniques for production of blocks with different shapes and sizes

    International Nuclear Information System (INIS)

    Johannesson, Lars-Erik; Boergesson, Lennart

    1998-09-01

    In this report useful techniques for producing both smaller blocks manageable by man (10-15 kg) and larger blocks which need special equipment for handling (weight up to 600 kg) are described. Tests for producing blocks with a weight of approximately 10 kg were carried out at Hoeganaes Bjuf AB in Bjuv. This industry is normally producing refractory bricks and other refractory products. The plant has facilities for handling large volumes of clay. It also has machines suitable for producing uniaxially compacted blocks. Tests performed at the plant show that it is possible to compact blocks with good quality. The best quality was reached with a coarsely ground bentonite at a water ratio of 17 %. The compaction rate was high and performed with lubricated form and stepwise loading. Tests, in order to find a technique for producing larger blocks with a diameter of the same size as a deposition hole (about 1.65 m), were also made. The technique was developed in a smaller scale (250 mm). Ring-shaped blocks with the same outer diameter and with an inner diameter of about 156 mm were also compacted. The compaction was made with vacuum in the form. The outer surface of the form was conical and most of the tests were performed with a lubricated form. Tests were performed with different water ratios of the bentonite. All the blocks had a good quality. In consequence of the good test results a form with a 1000 mm diameter was constructed and a number of compaction tests were performed. The same technique was used as for the smaller blocks. The compaction pressure in most tests was 100 MPa (maximum compaction load 80.000 kN). The tests were performed at HYDROWELD in Ystad in a press with a maximum capacity of 300.000 kN. All tests were performed with MX-80. Most of the blocks had a good quality. A small damage close to the upper surface of all blocks was observed but is considered to be of no importance for the possibility to handle the blocks and is not affecting the properties

  8. Preparation of amphiphilic block copolymer containing triazene ...

    Indian Academy of Sciences (India)

    The lower rate constant in film state (film = 1.3 × 10−3 s-1), shows that the higher mobility of polymeric chains in solution allow a more rapid orientation, favourable to the triazene bond cleavage. The capability of block copolymer to form micelles in aqueous environment and implicitly, its critical micelle concentration (CMC) ...

  9. Network Operations Control Center Block 3 modifications

    Science.gov (United States)

    Garcia, E. A.

    1978-01-01

    The Network Operations Control Center (NOCC) Block 3 configuration is in the process of being upgraded to provide the capabilities required to support Voyager and Pioneer Venus 1978 Project commitments as well as to support Deep Space Station changes arising from the Mark 3 DSN Data Subsystem implementation. Information is given on the hardware and software changes necessary to implement such capabilities.

  10. Preparation of amphiphilic block copolymer containing triazene ...

    Indian Academy of Sciences (India)

    −7. M). Experiments of fluorescence quenching with various metal cations (UO2+. 2 , Fe2+, Fe3+, Ni2+, Cu2+, Co2+, Pb2+ and Hg2+) suggested that such a block copolymer could ..... from the intersection of straight-line segments, drawn through the points on ... copolymer displays a strong emission around 400 nm, which is ...

  11. Building Blocks for Control System Software

    NARCIS (Netherlands)

    Broenink, Johannes F.; Hilderink, G.H.; Amerongen van, J.; Jonker, B.; Regtien, P.P.L

    2001-01-01

    Software implementation of control laws for industrial systems seem straightforward, but is not. The computer code stemming from the control laws is mostly not more than 10 to 30% of the total. A building-block approach for embedded control system development is advocated to enable a fast and

  12. Role of dexamethasone in brachial plexus block

    International Nuclear Information System (INIS)

    Dawood, M.

    2015-01-01

    To evaluate the effect of dexamethasone added to (lignocaine) on the onset and duration of axillary brachial plexus block. Study Design: Randomized controlled trial. Place and Duration of Study: Combined Military Hospital Rawalpindi, from September 2009 to March 2010. Patients and Methods: A total of 100 patients, who were scheduled for elective hand and forearm surgery under axillary brachial plexus block, were randomly allocated to group A in which patients received 40 ml 1.5% lidocaine with 2 ml of isotonic saline (0.9%) and group B in which patients received 40 ml 1.5% lidocaine with 2 ml of dexamethasone (8 mg). Nerve stimulator with insulated needle for multiple stimulations technique was used to locate the brachial plexus nerves. After the injection onset of action and duration of sensory blockade of brachial plexus were recorded at 5 minutes and 15 minutes interval. Results: Group A showed the onset of action of 21.64 ± 2.30 min and in group B it was 15.42 ± 1.44 min (p< 0.001). Duration of nerve block was 115.08 ± 10.92 min in group A and 265.42 ± 16.56 min in group B (p < 0.001). Conclusion: The addition of dexamethasone to 1.5% lignocaine solution in axillary brachial plexus block prolongs the duration of sensory blockade significantly. (author)

  13. 49 CFR 236.709 - Block, absolute.

    Science.gov (United States)

    2010-10-01

    ... 49 Transportation 4 2010-10-01 2010-10-01 false Block, absolute. 236.709 Section 236.709 Transportation Other Regulations Relating to Transportation (Continued) FEDERAL RAILROAD ADMINISTRATION, DEPARTMENT OF TRANSPORTATION RULES, STANDARDS, AND INSTRUCTIONS GOVERNING THE INSTALLATION, INSPECTION...

  14. 49 CFR 236.708 - Block.

    Science.gov (United States)

    2010-10-01

    ... 49 Transportation 4 2010-10-01 2010-10-01 false Block. 236.708 Section 236.708 Transportation Other Regulations Relating to Transportation (Continued) FEDERAL RAILROAD ADMINISTRATION, DEPARTMENT OF TRANSPORTATION RULES, STANDARDS, AND INSTRUCTIONS GOVERNING THE INSTALLATION, INSPECTION, MAINTENANCE, AND REPAIR...

  15. 49 CFR 236.710 - Block, latch.

    Science.gov (United States)

    2010-10-01

    ... 49 Transportation 4 2010-10-01 2010-10-01 false Block, latch. 236.710 Section 236.710 Transportation Other Regulations Relating to Transportation (Continued) FEDERAL RAILROAD ADMINISTRATION, DEPARTMENT OF TRANSPORTATION RULES, STANDARDS, AND INSTRUCTIONS GOVERNING THE INSTALLATION, INSPECTION...

  16. Orientation: Automotive Mechanics Instructional Program. Block 1.

    Science.gov (United States)

    O'Brien, Ralph D.

    The first six instructional blocks in automotive mechanics, the lessons and supportive information in the document provide a guide for teachers in planning an instructional program in the basic theory and practice of a beginning course at the secondary and post-secondary level. The material, as organized, is a suggested sequence of instruction…

  17. Contemporary block tectonics: California and Nevada.

    Science.gov (United States)

    Hill, D.P.

    1982-01-01

    Well-determined fault plane solution and the gross pattern of late-Cenozoic faulting in California and Nevada show a systematic relation between the orientation of fault planes and slip directions. In general, normal faults have N strikes, reverse faults have E strikes, and dextral and sinstral strike slip faults have NW and NE strikes, respectively. Kinematically, this relation is consistent with the response of clusters of fault-bounded crustal blocks to a regional stress field generated by the relative motion between the Pacific and N American plates. In this stress field, the greatest and least principal (compressive) stresses are restricted to N and E striking vertical planes, respectively. Simple arrangements of block clusters mimic the gross kinematic pattern of Quaternary faulting in California and Nevada. Some implications for contemporary tectonics emphasized by this model involve the W displacement of the Sierra Nevada block with respect to the stable interior of the N American plates, oblique thrusting of the Salinian block over the Pacific plate, and a progressive increase in the offset of the San Andreas fault represented by the 'big bend' through the Transverse Ranges. -from Author

  18. Raster Forming Block in Scanning Television Microscope

    OpenAIRE

    Vasylyuk, Volodymyr; Goy, Vitaliy; Shkliarskyi, Volodymyr

    2010-01-01

    The ways of construction of raster forming block, which provides television and little-frame modes, are considered. The analog and digital methods of formation of signals are analyzed. Ways of change of amplitude and displacement of signals of a raster are shown with the purpose of maintenance of scaling of the image of researched microobject.

  19. Neuraxial block and postoperative epidural analgesia

    DEFF Research Database (Denmark)

    Leslie, K; McIlroy, D; Kasza, J

    2016-01-01

    BACKGROUND: We assessed associations between intraoperative neuraxial block and postoperative epidural analgesia, and a composite primary outcome of death or non-fatal myocardial infarction, at 30 days post-randomization in POISE-2 Trial subjects. METHODS: 10 010 high-risk noncardiac surgical pat...

  20. Colour Blocking: Disregarding Traditional Artistic Colour Harmonies ...

    African Journals Online (AJOL)

    The trending phenomenon popularly referred to as 'colour blocking' involves the use of bright 'expressive' colours for finishing in the decorative and utilitarian arts. In this practice, complimentary and contrasting colours are liberally used in the visual field to engage the attention of the viewer. This paper seeks, in the first ...